HSCR1
MCID: HRS035
MIFTS: 65

Hirschsprung Disease 1 (HSCR1)

Categories: Fetal diseases, Gastrointestinal diseases, Genetic diseases, Neuronal diseases, Rare diseases

Aliases & Classifications for Hirschsprung Disease 1

MalaCards integrated aliases for Hirschsprung Disease 1:

Name: Hirschsprung Disease 1 56 52 73 29 6 71
Hirschsprung Disease 56 12 74 24 25 58 36 29 54 6 43 71 32
Aganglionic Megacolon 56 12 24 52 25 58 73 29 6
Hscr 56 24 52 25 58
Hirschsprung's Disease 12 52 25 15
Hirschsprung Disease, Protection Against 56 29 6
Congenital Intestinal Aganglionosis 25 58 71
Total Intestinal Aganglionosis 12 54 6
Congenital Megacolon 12 74 25
Hirschsprung Disease, Susceptibility to, 1 56 13
Colonic Aganglionosis 73 54
Hscr1 56 73
Mgc 56 73
Congenital Dilatation of Colon 71
Hirschsprung Disease, Type 1 39
Megacolon, Aganglionic; Mgc 56
Hirschsprung Disease Type 1 52
Hirschsprung Disease; Hscr 56
Megacolon, Aganglionic 56
Pelvirectal Achalasia 12
Macrocolon 12
Hscr 1 52

Characteristics:

Orphanet epidemiological data:

58
hirschsprung disease
Inheritance: Autosomal dominant,Autosomal recessive,Multigenic/multifactorial,Not applicable; Prevalence: 1-9/100000 (Europe),1-9/100000 (Belgium),1-5/10000 (Croatia),1-5/10000 (Denmark),1-5/10000 (France),1-5/10000 (Germany),1-9/100000 (Hungary),1-5/10000 (Ireland),1-5/10000 (Italy),1-5/10000 (Netherlands),1-9/100000 (Poland),1-9/100000 (Portugal),1-9/100000 (Spain),1-5/10000 (Switzerland),1-5/10000 (Ukraine),1-5/10000 (Europe),1-9/100000 (Austria),1-5/10000 (Malta),1-5/10000 (Norway),1-5/10000 (United Kingdom); Age of onset: Infancy,Neonatal; Age of death: any age;

OMIM:

56
Inheritance:
autosomal dominant

Miscellaneous:
male predominance of 3:1 to 5:1
familial (10%) and isolated cases


HPO:

31
hirschsprung disease 1:
Inheritance autosomal dominant inheritance


Classifications:

Orphanet: 58  
Rare gastroenterological diseases


External Ids:

Disease Ontology 12 DOID:10487
OMIM 56 142623
OMIM Phenotypic Series 56 PS142623
KEGG 36 H00910
MeSH 43 D006627
NCIt 49 C34700
SNOMED-CT 67 6687001
ICD10 32 Q43.1
MESH via Orphanet 44 D006627
ICD10 via Orphanet 33 Q43.1
UMLS via Orphanet 72 C0019569 C3661523
Orphanet 58 ORPHA388
UMLS 71 C0019569 C0266209 C2931876 more

Summaries for Hirschsprung Disease 1

Genetics Home Reference : 25 Hirschsprung disease is an intestinal disorder characterized by the absence of nerves in parts of the intestine. This condition occurs when the nerves in the intestine (enteric nerves) do not form properly during development before birth (embryonic development). This condition is usually identified in the first two months of life, although less severe cases may be diagnosed later in childhood. Enteric nerves trigger the muscle contractions that move stool through the intestine. Without these nerves in parts of the intestine, the material cannot be pushed through, causing severe constipation or complete blockage of the intestine in people with Hirschsprung disease. Other signs and symptoms of this condition include vomiting, abdominal pain or swelling, diarrhea, poor feeding, malnutrition, and slow growth. People with this disorder are at risk of developing more serious conditions such as inflammation of the intestine (enterocolitis) or a hole in the wall of the intestine (intestinal perforation), which can cause serious infection and may be fatal. There are two main types of Hirschsprung disease, known as short-segment disease and long-segment disease, which are defined by the region of the intestine lacking nerve cells. In short-segment disease, nerve cells are missing from only the last segment of the large intestine (colon). This type is most common, occurring in approximately 80 percent of people with Hirschsprung disease. For unknown reasons, short-segment disease is four times more common in men than in women. Long-segment disease occurs when nerve cells are missing from most of the large intestine and is the more severe type. Long-segment disease is found in approximately 20 percent of people with Hirschsprung disease and affects men and women equally. Very rarely, nerve cells are missing from the entire large intestine and sometimes part of the small intestine (total colonic aganglionosis) or from all of the large and small intestine (total intestinal aganglionosis). Hirschsprung disease can occur in combination with other conditions, such as Waardenburg syndrome, type IV; Mowat-Wilson syndrome; or congenital central hypoventilation syndrome. These cases are described as syndromic. Hirschsprung disease can also occur without other conditions, and these cases are referred to as isolated or nonsyndromic.

MalaCards based summary : Hirschsprung Disease 1, also known as hirschsprung disease, is related to peripheral demyelinating neuropathy, central dysmyelination, waardenburg syndrome, and hirschsprung disease and waardenburg syndrome, type 4a. An important gene associated with Hirschsprung Disease 1 is RET (Ret Proto-Oncogene), and among its related pathways/superpathways are Calcium signaling pathway and Neuroactive ligand-receptor interaction. The drugs Vaccines and Pharmaceutical Solutions have been mentioned in the context of this disorder. Affiliated tissues include colon, thyroid and heart, and related phenotypes are nausea and vomiting and constipation

Disease Ontology : 12 A megacolon that is characterized by a blockage of the large intestine due to improper muscle movement in the bowel.

NIH Rare Diseases : 52 Hirschsprung disease (HSCR) is a disease of the large intestine or colon. People with this disease do not have the nerve cells in the intestine required to pass stools from the body normally. Symptoms of Hirschsprung disease usually start in very young children, but may occur later. The symptoms may vary with age, but often involve constipation and/or obstruction of the bowel . Other signs and symptoms include vomiting, abdominal pain or swelling, diarrhea, poor feeding, malnutrition, and slow growth. There are two main types of Hirschsprung disease , known as short-segment disease and long-segment disease, defined by the region of the intestine lacking nerve cells (aganglionic segments). HSCR is considered a neurocristopathy, a disorder of cells and tissues derived from the neural crest, (a group of embryonic cells of the neural tube that forms several structures, of the body). HSCR may occur as an isolated finding or as part of a another disorder. Isolated HSCR is associated with mutations in several genes . Treatment is with surgery, removing the aganglionic intestinal segment.

OMIM : 56 The disorder described by Hirschsprung (1888) and known as Hirschsprung disease or aganglionic megacolon is characterized by congenital absence of intrinsic ganglion cells in the myenteric (Auerbach) and submucosal (Meissner) plexuses of the gastrointestinal tract. Patients are diagnosed with the short-segment form (S-HSCR, approximately 80% of cases) when the aganglionic segment does not extend beyond the upper sigmoid, and with the long-segment form (L-HSCR) when aganglionosis extends proximal to the sigmoid (Amiel et al., 2008). Total colonic aganglionosis and total intestinal HSCR also occur. (142623)

KEGG : 36 Hirschsprung disease (HD) is a relatively common cause of intestinal obstruction in the newborn. It is characterized by absence of ganglion cells in the distal bowel and extending proximally for varying distances. Recently, several genes have been identified to be associated with HD. The functions of the gene products include transcription factors regulating gene expression in neural crest cells and in participants in signaling pathways between intestinal mesenchymal cells and neural crest cells.

UniProtKB/Swiss-Prot : 73 Hirschsprung disease 1: A disorder of neural crest development characterized by absence of enteric ganglia along a variable length of the intestine. It is the most common cause of congenital intestinal obstruction. Early symptoms range from complete acute neonatal obstruction, characterized by vomiting, abdominal distention and failure to pass stool, to chronic constipation in the older child.

Wikipedia : 74 Hirschsprung's disease (HD or HSCR) is a birth defect in which nerves are missing from parts of the... more...

GeneReviews: NBK1439

Related Diseases for Hirschsprung Disease 1

Diseases in the Hirschsprung Disease 1 family:

Hirschsprung Disease 2 Hirschsprung Disease 5
Hirschsprung Disease 6 Hirschsprung Disease 7
Hirschsprung Disease 8 Hirschsprung Disease 9
Hirschsprung Disease 3 Hirschsprung Disease 4

Diseases related to Hirschsprung Disease 1 via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 487)
# Related Disease Score Top Affiliating Genes
1 peripheral demyelinating neuropathy, central dysmyelination, waardenburg syndrome, and hirschsprung disease 35.2 SOX10 EDNRB EDN3
2 waardenburg syndrome, type 4a 34.5 SOX10 RET EDNRB EDN3
3 waardenburg syndrome, type 4c 34.4 SOX10 EDNRB EDN3
4 waardenburg syndrome, type 4b 34.4 SOX10 EDNRB EDN3 ECE1
5 waardenburg syndrome type 4 34.2 SOX10 EDNRB EDN3
6 goldberg-shprintzen syndrome 33.7 RET GDNF EDNRB EDN3
7 waardenburg's syndrome 33.4 SOX10 RET EDNRB EDN3
8 central hypoventilation syndrome, congenital 33.3 SOX10 RET NRTN GFRA1 GDNF EDNRB
9 hypoganglionosis 33.3 RET GDNF
10 hirschsprung disease 5 33.2 RET HSCR5
11 waardenburg syndrome, type 2a 32.8 SOX10 EDNRB EDN3
12 waardenburg syndrome, type 3 32.8 SOX10 EDNRB EDN3
13 waardenburg syndrome, type 2b 32.7 SOX10 EDN3
14 constipation 32.4 RET NRTN GDNF EDNRB EDN3
15 megacolon 32.3 SOX10 RET NRTN HSCR5 GFRA1 GDNF
16 intestinal obstruction 32.1 RET NRTN GDNF EDNRB EDN3
17 thyroid carcinoma, familial medullary 31.9 RET NRTN GFRA1 GDNF
18 multiple endocrine neoplasia, type iia 31.5 RET GFRA1 GDNF
19 achalasia 31.5 RET GDNF EDN3
20 intestinal pseudo-obstruction 31.5 SOX10 RET EDNRB EDN3
21 multiple endocrine neoplasia, type iib 31.4 RET NRTN GFRA1 GDNF
22 renal hypodysplasia/aplasia 1 31.3 RET GFRA1 GDNF
23 waardenburg syndrome, type 1 31.1 SOX10 EDNRB EDN3
24 piebald trait 31.0 SOX10 EDNRB EDN3
25 cakut 30.9 RET GFRA1 GDNF
26 waardenburg syndrome, type 2e 30.8 SOX10 EDNRB EDN3
27 hirschsprung disease 3 12.7
28 hirschsprung disease 4 12.7
29 hirschsprung disease, cardiac defects, and autonomic dysfunction 12.7
30 hirschsprung disease with type d brachydactyly 12.6
31 mowat-wilson syndrome 12.6
32 hirschsprung disease with polydactyly, renal agenesis, and deafness 12.5
33 hirschsprung disease ganglioneuroblastoma 12.5
34 hirschsprung disease with hypoplastic nails and dysmorphic facial features 12.4
35 hirschsprung disease with heart defects, laryngeal anomalies, and preaxial polydactyly 12.2
36 hirschsprung disease with ulnar polydactyly, polysyndactyly of big toes, and ventricular septal defect 12.2
37 rare disorder with hirschsprung disease as a major feature 12.2
38 ifap syndrome with or without bresheck syndrome 12.1
39 neuroblastoma 2 11.6
40 santos mateus leal syndrome 11.6
41 aganglionosis, total intestinal 11.6
42 cartilage-hair hypoplasia 11.4
43 hirschsprung disease 2 11.4
44 hirschsprung disease 6 11.4
45 hirschsprung disease 7 11.4
46 hirschsprung disease 8 11.4
47 hirschsprung disease 9 11.4
48 intestinal pseudoobstruction, neuronal, chronic idiopathic, x-linked 11.3
49 al-gazali-donnai-mueller syndrome 11.2
50 ramos arroyo clark syndrome 11.2

Graphical network of the top 20 diseases related to Hirschsprung Disease 1:



Diseases related to Hirschsprung Disease 1

Symptoms & Phenotypes for Hirschsprung Disease 1

Human phenotypes related to Hirschsprung Disease 1:

58 31 (show all 20)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 nausea and vomiting 58 31 hallmark (90%) Very frequent (99-80%) HP:0002017
2 constipation 58 31 hallmark (90%) Very frequent (99-80%) HP:0002019
3 abdominal pain 58 31 hallmark (90%) Very frequent (99-80%) HP:0002027
4 intestinal obstruction 58 31 hallmark (90%) Very frequent (99-80%) HP:0005214
5 aganglionic megacolon 58 31 hallmark (90%) Very frequent (99-80%) HP:0002251
6 weight loss 58 31 frequent (33%) Frequent (79-30%) HP:0001824
7 intellectual disability 58 31 occasional (7.5%) Occasional (29-5%) HP:0001249
8 short stature 58 31 occasional (7.5%) Occasional (29-5%) HP:0004322
9 sensorineural hearing impairment 58 31 occasional (7.5%) Occasional (29-5%) HP:0000407
10 failure to thrive in infancy 58 31 occasional (7.5%) Occasional (29-5%) HP:0001531
11 diarrhea 58 31 occasional (7.5%) Occasional (29-5%) HP:0002014
12 sepsis 58 31 occasional (7.5%) Occasional (29-5%) HP:0100806
13 adducted thumb 58 31 occasional (7.5%) Occasional (29-5%) HP:0001181
14 intestinal polyposis 58 31 occasional (7.5%) Occasional (29-5%) HP:0200008
15 neoplasm of the thyroid gland 58 31 occasional (7.5%) Occasional (29-5%) HP:0100031
16 vomiting 31 HP:0002013
17 abdominal distention 31 HP:0003270
18 functional abnormality of the gastrointestinal tract 58 Very frequent (99-80%)
19 enterocolitis 31 HP:0004387
20 abnormality of enteric ganglion morphology 31 HP:0004362

Symptoms via clinical synopsis from OMIM:

56
Abdomen Gastrointestinal:
constipation
vomiting
abdominal distention
enterocolitis
failure to pass meconium in first 48 hours of life
more
Laboratory Abnormalities:
absent enteric ganglia beginning at the rectum and extends proximally by varying degrees
acetylcholinesterase staining reveals nerve trunk hypertrophy

Clinical features from OMIM:

142623

MGI Mouse Phenotypes related to Hirschsprung Disease 1:

45
# Description MGI Source Accession Score Top Affiliating Genes
1 digestive/alimentary MP:0005381 9.23 ECE1 EDN3 EDNRB GDNF GFRA1 NRTN

Drugs & Therapeutics for Hirschsprung Disease 1

Drugs for Hirschsprung Disease 1 (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 18)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1 Vaccines Phase 4
2 Pharmaceutical Solutions Phase 4
3 Liver Extracts Phase 4
4 Soybean oil, phospholipid emulsion Phase 4
5 Parenteral Nutrition Solutions Phase 4
6 Fat Emulsions, Intravenous Phase 4
7 Soy Bean Phase 4
8 Cola Phase 3
9
Mineral oil Approved, Vet_approved 8042-47-5
10
Lactulose Approved 4618-18-2 11333
11
tannic acid Approved 1401-55-4
12
Benzocaine Approved, Investigational 1994-09-7, 94-09-7 2337
13
Metronidazole Approved 443-48-1 4173
14 Anesthetics
15 Central Nervous System Depressants
16 Gastrointestinal Agents
17 Dermatologic Agents
18 Emollients

Interventional clinical trials:

(show all 35)
# Name Status NCT ID Phase Drugs
1 Probiotics for Prophylaxis of Postoperative Hirschsprungs Associated Enterocolitis Recruiting NCT02343562 Phase 4
2 Immunodeficiency in Cartilage-hair Hypoplasia: Correlation With Pulmonary Disease, Infections and Malignancy Active, not recruiting NCT02383797 Phase 4
3 Low Dose Parenteral Fat for the Prevention of Parenteral Nutrition Associated Cholestasis in Neonates With Congenital/Acquired Gastrointestinal Disorders Terminated NCT01373918 Phase 4 Intralipid;Intralipid
4 Effects of Butyrate Enemas on Postoperative Intestinal Mobility Disorders in Hirschsprung's Not yet recruiting NCT03660176 Phase 3 butyrate enemas + routine management
5 Endoscopic Mucosal Resection for the Diagnosis of a-Ganglionosis, a Controlled Prospective Trial Unknown status NCT00671684 Phase 1, Phase 2
6 Probiotic Prophylaxis of Hirschprung's Disease Associated Enterocolitis (HAEC) Completed NCT00630838 Phase 2 VSL#3;Placebo
7 Fast-track Surgery in the Treatment of Hirschsprung's Disease Unknown status NCT02350088 probiotics;placebo
8 A Prospective Multi-center Randomized Controlled Clinical Trials of Enhanced Recovery After Surgery in Hirschsprung Disease. Unknown status NCT02776176
9 Laparoscopic Assisted Pull-through Versus Other Surgical Procedures for Treatment of Hirschsprung Disease. Unknown status NCT03269812
10 Efficacy and Accuracy of a New Diagnostic Scoring System to Differentiate Hirschsprung Disease From Hirschsprung Disease Allied Disorders in the Patients With Suspected Intestinal Dysganglinosis: a Prospective Study Unknown status NCT02216994 high dose lactulose;paraffin oil
11 The Elactrophysiological Response of the Colon, in Normal Bowel, and Large Bowel Lacking Ganglia in Children With Suspected Hirschsprungs Disease. Unknown status NCT02342457
12 The Effect of Combined General-epidural vs General Anaesthesia on Postoperative Intestinal Function Recovery and Infection in Neonates and Infants Undergoing Gastrointestinal Surgery: a Prospective, Randomised, Controlled Trial Unknown status NCT03056261
13 Endoscopic Mucosal Resection for the Diagnosis of a-Ganglionosis, a Controlled Prospective Trial (EDGE Trial) Completed NCT01515501
14 A Prospective Multicenter Randomized Controlled Trial on Probiotics in Preventing Hirschsprung's Disease Associated Entercolitis Completed NCT01934959 Early Phase 1 Bifico
15 3D High Resolution Anorectal Manometry in Children After Surgery for Anorectal Disorders Completed NCT02296008
16 A Prospective, Randomized Controlled Trial of Conservative Versus Surgery Treatment of Normal and Short-segment Hirschsprung Disease for Infants Completed NCT01985646 Early Phase 1 oral probiotic
17 MICROPRUNG : Intestinal Microbiota Analysis in Patients With or Without Hirschsprung's Associated EnteroColitis Completed NCT02857205
18 A Proposed Physical Activity and Diet Control to Manage Constipation in Middle Age Obese Women Completed NCT03106857
19 Randomized Controlled Trial: Rapid Learning Healthcare System in Pediatric Surgery Completed NCT03131180
20 Infectious Agents in Pediatric Crohn's Disease Completed NCT00237055
21 Genetic Analysis of Hirschsprung Disease Recruiting NCT00478712
22 Comparison of Circular(Soave) and Heart-shaped Anastomosis in Hirschsprung's Disease: A Prospective Multicenter Randomized Controlled Trial Recruiting NCT02234219 Probiotics
23 Genetics of Hirschsprung's Disease - Can Genetic Mosaicism Due to Early Somatic Mutations, Explain Disease Development? Recruiting NCT01927809
24 Identification of Genetic, Immunologic and Microbial Markers of Hirschsprung Associated Enterocolitis in Children With Hirschsprung Disease Recruiting NCT02193685
25 Neuropsychological Development and Functional Outcome Sin Children With Hirschsprung Disease at School Age - Hirschsprung Recruiting NCT03406741
26 Management and Outcomes of Congenital Anomalies in Low-, Middle- and High-Income Countries: A Multi-Centre, International, Prospective Cohort Study Recruiting NCT03666767
27 The Enteric Nervous System as Modulator of Mucosal Immune Cells Recruiting NCT03617640
28 Transition of Care for Patients With Hirschsprung Disease and Anorectal Malformations Recruiting NCT04106947
29 Evaluating the Alimentary and Respiratory Tracts in Health and Disease (EARTH) Research Program. Recruiting NCT04071314
30 International Congenital Central Hypoventilation Syndrome (CCHS) REDCap Registry Recruiting NCT03088020
31 Neurocognitive Outcome as a Metric for Evaluating Therapeutic Intervention and Treatment Mechanisms in Congenital Central Hypoventilation Syndrome (CCHS): A Multi-Site Study Using The NIH Toolbox Recruiting NCT03568669
32 Prospective Evaluation of the Efficacy and Safety of Submucosal Endoscopy Enrolling by invitation NCT03626350
33 eHealth as an Aid for Facilitating and Supporting Self-management in Families With Long-term Childhood Illness - Development, Evaluation and Implementation in Clinical Practice Enrolling by invitation NCT04150120
34 The Association Between Calretinin and the Function of Ganglion Cells in Long Segment and Total Hirschsprung Disease Not yet recruiting NCT04149093
35 The Role of Indocyanine Green Angiography Fluorescence on Intestinal Resections in Pediatric Surgery. Not yet recruiting NCT04020939 Indocyanine Green

Search NIH Clinical Center for Hirschsprung Disease 1

Cochrane evidence based reviews: hirschsprung disease

Genetic Tests for Hirschsprung Disease 1

Genetic tests related to Hirschsprung Disease 1:

# Genetic test Affiliating Genes
1 Hirschsprung Disease 29 NRTN
2 Hirschsprung Disease 1 29 RET
3 Aganglionic Megacolon 29
4 Hirschsprung Disease, Protection Against 29

Anatomical Context for Hirschsprung Disease 1

MalaCards organs/tissues related to Hirschsprung Disease 1:

40
Colon, Thyroid, Heart, Small Intestine, Kidney, Testes, Brain

Publications for Hirschsprung Disease 1

Articles related to Hirschsprung Disease 1:

(show top 50) (show all 1743)
# Title Authors PMID Year
1
A common variant located in the 3'UTR of the RET gene is associated with protection from Hirschsprung disease. 54 61 56 6
16986122 2007
2
A common sex-dependent mutation in a RET enhancer underlies Hirschsprung disease risk. 54 61 56 6
15829955 2005
3
Diversity of RET proto-oncogene mutations in familial and sporadic Hirschsprung disease. 54 61 56 6
7581377 1995
4
A missense mutation of the endothelin-B receptor gene in multigenic Hirschsprung's disease. 24 56 6
8001158 1994
5
Close linkage with the RET protooncogene and boundaries of deletion mutations in autosomal dominant Hirschsprung disease. 54 61 56 6
7904208 1993
6
RET genotypes comprising specific haplotypes of polymorphic variants predispose to isolated Hirschsprung disease. 61 56 6
10922382 2000
7
A human model for multigenic inheritance: phenotypic expression in Hirschsprung disease requires both the RET gene and a new 9q31 locus. 54 61 24 56
10618407 2000
8
Mutations in Hirschsprung disease: when does a mutation contribute to the phenotype. 61 56 6
9359036 1997
9
Germline mutations in glial cell line-derived neurotrophic factor (GDNF) and RET in a Hirschsprung disease patient. 54 61 24 6
8896568 1996
10
Germline mutations of the RET ligand GDNF are not sufficient to cause Hirschsprung disease. 54 61 24 6
8896569 1996
11
Hirschsprung disease, associated syndromes and genetics: a review. 61 24 56
17965226 2008
12
Polyalanine expansion and frameshift mutations of the paired-like homeobox gene PHOX2B in congenital central hypoventilation syndrome. 61 24 6
12640453 2003
13
Oncological implications of RET gene mutations in Hirschsprung's disease. 54 24 56
9824583 1998
14
Defects in the kidney and enteric nervous system of mice lacking the tyrosine kinase receptor Ret. 56 6
8114940 1994
15
A genetic study of Hirschsprung disease. 61 24 56
2309705 1990
16
New roles of EDNRB and EDN3 in the pathogenesis of Hirschsprung disease. 54 61 6
20009762 2010
17
Phenotype-genotype correlation in Hirschsprung disease is illuminated by comparative analysis of the RET protein sequence. 54 61 56
15956201 2005
18
Specific polymorphisms in the RET proto-oncogene are over-represented in patients with Hirschsprung disease and may represent loci modifying phenotypic expression. 54 61 56
10528857 1999
19
Double heterozygosity for a RET substitution interfering with splicing and an EDNRB missense mutation in Hirschsprung disease. 54 61 6
10090908 1999
20
Point nucleotidic changes in both the RET proto-oncogene and the endothelin-B receptor gene in a Hirschsprung disease patient associated with Down syndrome. 54 61 56
10458491 1999
21
Mutation of the RET ligand, neurturin, supports multigenic inheritance in Hirschsprung disease. 54 61 6
9700200 1998
22
Mutations of the RET-GDNF signaling pathway in Ondine's curse. 24 6
9497256 1998
23
Genetic predisposition to phaeochromocytoma: analysis of candidate genes GDNF, RET and VHL. 54 61 6
9215674 1997
24
Frequency of RET mutations in long- and short-segment Hirschsprung disease. 54 61 6
9090527 1997
25
De novo mutation of GDNF, ligand for the RET/GDNFR-alpha receptor complex, in Hirschsprung disease. 54 61 6
8968758 1996
26
DNA polymorphisms and conditions for SSCP analysis of the 20 exons of the ret proto-oncogene. 54 61 6
8084609 1994
27
Hirschsprung's disease associated with a deletion of chromosome 10 (q11.2q21.2): a further link with the neurocristopathies? 24 56
7915329 1994
28
Involvement of DNMT3B in the pathogenesis of Hirschsprung disease and its possible role as a regulator of neurogenesis in the human enteric nervous system. 61 56
24577265 2014
29
Differential contributions of rare and common, coding and noncoding Ret mutations to multifactorial Hirschsprung disease liability. 61 6
20598273 2010
30
Localizing a putative mutation as the major contributor to the development of sporadic Hirschsprung disease to the RET genomic sequence between the promoter region and exon 2. 61 56
15138456 2004
31
Hirschsprung disease is linked to defects in neural crest stem cell function. 61 56
12920301 2003
32
A rare haplotype of the RET proto-oncogene is a risk-modifying allele in hirschsprung disease. 61 56
12214285 2002
33
Genome-wide association study and mouse model identify interaction between RET and EDNRB pathways in Hirschsprung disease. 61 56
12355085 2002
34
Hirschsprung Disease Overview 61 6
20301612 2002
35
Segregation at three loci explains familial and population risk in Hirschsprung disease. 61 56
11953745 2002
36
Dissecting Hirschsprung disease. 61 56
11953748 2002
37
Hirschsprung disease and L1CAM: is the disturbed sex ratio caused by L1CAM mutations? 54 61 24
11897831 2002
38
Hydrocephalus and intestinal aganglionosis: is L1CAM a modifier gene in Hirschsprung disease? 54 61 24
11857550 2002
39
Large-scale deletions and SMADIP1 truncating mutations in syndromic Hirschsprung disease with involvement of midline structures. 54 61 24
11595972 2001
40
Hirschsprung disease in an infant with a contiguous gene syndrome of chromosome 13. 54 61 24
11484199 2001
41
Analysis of the RET, GDNF, EDN3, and EDNRB genes in patients with intestinal neuronal dysplasia and Hirschsprung disease. 54 61 24
11302967 2001
42
Mutations in SIP1, encoding Smad interacting protein-1, cause a form of Hirschsprung disease. 54 61 24
11279515 2001
43
A single-nucleotide polymorphic variant of the RET proto-oncogene is underrepresented in sporadic Hirschsprung disease. 61 56
10980580 2000
44
Mutational analysis of RET/GDNF/NTN genes in children with total colonic aganglionosis with small bowel involvement. 54 61 24
10946353 2000
45
Association of RET protooncogene codon 45 polymorphism with Hirschsprung disease. 61 6
10521317 1999
46
A consanguineous family with Hirschsprung disease, microcephaly, and mental retardation (Goldberg-Shprintzen syndrome). 54 61 24
10874640 1999
47
A heterozygous frameshift mutation in the endothelin-3 (EDN-3) gene in isolated Hirschsprung's disease. 54 6
10231870 1999
48
Phenotypic variation in a family with mutations in two Hirschsprung-related genes (RET and endothelin receptor B). 61 6
9760196 1998
49
Association of multiple endocrine neoplasia type 2 and Hirschsprung disease. 54 61 24
9681852 1998
50
Endothelin-3 gene mutations in isolated and syndromic Hirschsprung disease. 61 6
9359047 1997

Variations for Hirschsprung Disease 1

ClinVar genetic disease variations for Hirschsprung Disease 1:

6 (show top 50) (show all 157) ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 RET NM_020975.6(RET):c.95C>T (p.Ser32Leu)SNV Likely pathogenic,risk factor 13923 rs76764689 10:43595928-43595928 10:43100480-43100480
2 SOX10 NM_001301131.1(POLR2F):c.294-27388_*10734deldeletion Pathogenic 156718 22:38409687-38447833 22:38013680-38051826
3 RET NM_020975.6(RET):c.1858T>C (p.Cys620Arg)SNV Pathogenic 13915 rs77316810 10:43609102-43609102 10:43113654-43113654
4 RET NM_020975.6(RET):c.1859G>A (p.Cys620Tyr)SNV Pathogenic 13916 rs77503355 10:43609103-43609103 10:43113655-43113655
5 RET NM_020975.6(RET):c.1825T>C (p.Cys609Arg)SNV Pathogenic 13944 rs77558292 10:43609069-43609069 10:43113621-43113621
6 RET NM_020975.6(RET):c.1858T>G (p.Cys620Gly)SNV Pathogenic 24905 rs77316810 10:43609102-43609102 10:43113654-43113654
7 RET NM_020975.6(RET):c.1196C>T (p.Pro399Leu)SNV Pathogenic 274004 rs1554818362 10:43604611-43604611 10:43109163-43109163
8 RET NM_020975.6(RET):c.1276_1277TG[2] (p.Val427fs)short repeat Pathogenic 590798 rs1564494285 10:43606667-43606668 10:43111219-43111220
9 RET NM_020975.6(RET):c.860G>A (p.Arg287Gln)SNV Pathogenic 560625 rs1564491460 10:43600634-43600634 10:43105186-43105186
10 RET NM_020975.6(RET):c.1852T>G (p.Cys618Gly)SNV Pathogenic 13905 rs76262710 10:43609096-43609096 10:43113648-43113648
11 RET NM_020975.6(RET):c.111G>A (p.Trp37Ter)SNV Pathogenic 599630 rs1564489315 10:43595944-43595944 10:43100496-43100496
12 RET NM_020975.6(RET):c.2865dup (p.Pro956fs)duplication Pathogenic 599634 rs1564500612 10:43619180-43619181 10:43123732-43123733
13 RET NM_020975.6(RET):c.3143del (p.Leu1048fs)deletion Pathogenic 599635 rs1564501934 10:43622126-43622126 10:43126678-43126678
14 RET NM_020975.6(RET):c.712G>T (p.Glu238Ter)SNV Pathogenic 692052 10:43600486-43600486 10:43105038-43105038
15 RET NM_020975.6(RET):c.2410G>A (p.Val804Met)SNV Pathogenic/Likely pathogenic 37102 rs79658334 10:43614996-43614996 10:43119548-43119548
16 RET NM_020975.6(RET):c.1947G>A (p.Ser649=)SNV Pathogenic/Likely pathogenic 24929 rs377767412 10:43609995-43609995 10:43114547-43114547
17 RET NM_020975.6(RET):c.1831T>C (p.Cys611Arg)SNV Pathogenic/Likely pathogenic 24896 rs377767391 10:43609075-43609075 10:43113627-43113627
18 RET NM_020975.6(RET):c.1880-2A>GSNV Likely pathogenic 36725 rs193922699 10:43609926-43609926 10:43114478-43114478
19 RET NM_020975.6(RET):c.73+9277T>CSNV risk factor 13952 rs2435357 10:43582056-43582056 10:43086608-43086608
20 RET NM_020975.6(RET):c.2914A>G (p.Arg972Gly)SNV risk factor 13922 rs76534745 10:43619231-43619231 10:43123783-43123783
21 RET NM_020975.6(RET):c.406G>T (p.Glu136Ter)SNV risk factor 13912 rs79014735 10:43597858-43597858 10:43102410-43102410
22 RET NM_020975.6(RET):c.692G>A (p.Arg231His)SNV risk factor 13937 rs79661516 10:43600466-43600466 10:43105018-43105018
23 SOX10 NM_001301130.2(POLR2F):c.453-24860G>ASNV Likely pathogenic 156720 rs606231342 22:38412215-38412215 22:38016208-38016208
24 RET NM_020975.6(RET):c.191C>T (p.Pro64Leu)SNV risk factor 13924 rs77596424 10:43596024-43596024 10:43100576-43100576
25 RET RET, 1-BP DEL, G1120deletion risk factor 13920
26 RET NM_020975.6(RET):c.2690G>A (p.Arg897Gln)SNV risk factor 13921 rs76087194 10:43615611-43615611 10:43120163-43120163
27 RET NM_020975.6(RET):c.538C>T (p.Arg180Ter)SNV risk factor 13925 rs76449634 10:43597990-43597990 10:43102542-43102542
28 RET NM_020975.6(RET):c.989G>A (p.Arg330Gln)SNV risk factor 13926 rs80236571 10:43601945-43601945 10:43106497-43106497
29 RET NM_020975.6(RET):c.1179C>A (p.Phe393Leu)SNV risk factor 13927 rs78098482 10:43604594-43604594 10:43109146-43109146
30 DPYD NM_000110.3(DPYD):c.1905+1G>ASNV drug response 432 rs3918290 1:97915614-97915614 1:97450058-97450058
31 RET NM_020975.6(RET):c.2293T>C (p.Ser765Pro)SNV risk factor 13907 rs75075748 10:43613829-43613829 10:43118381-43118381
32 ECE1 NM_001397.3(ECE1):c.1879C>T (p.Arg627Trp)SNV Likely pathogenic 599419 rs200894751 1:21551904-21551904 1:21225411-21225411
33 ECE1 NM_001397.3(ECE1):c.1067T>G (p.Phe356Cys)SNV Likely pathogenic 599418 rs765763704 1:21573810-21573810 1:21247317-21247317
34 PROKR1 NM_138964.3(PROKR1):c.1019T>A (p.Leu340Gln)SNV Likely pathogenic 599422 rs144018404 2:68882545-68882545 2:68655413-68655413
35 PHOX2B NM_003924.3(PHOX2B):c.445C>G (p.Arg149Gly)SNV Likely pathogenic 599417 rs1560465785 4:41748324-41748324 4:41746307-41746307
36 IHH NM_002181.4(IHH):c.151C>A (p.Gln51Lys)SNV Likely pathogenic 273383 rs1553540620 2:219925039-219925039 2:219060317-219060317
37 TBATA NM_152710.4(TBATA):c.157C>T (p.Arg53Cys)SNV Likely pathogenic 375275 rs759944122 10:72541677-72541677 10:70781921-70781921
38 NCLN NM_020170.4(NCLN):c.496C>T (p.Gln166Ter)SNV Likely pathogenic 375276 rs1057519322 19:3193402-3193402 19:3193404-3193404
39 NUP98 NM_016320.5(NUP98):c.5207A>G (p.Asn1736Ser)SNV Likely pathogenic 375277 rs1057519323 11:3697585-3697585 11:3676355-3676355
40 DENND3 NM_014957.5(DENND3):c.1959del (p.Lys653fs)deletion Likely pathogenic 375278 rs1057519052 8:142178509-142178509 8:141168410-141168410
41 RET NM_020975.6(RET):c.1753T>C (p.Cys585Arg)SNV Likely pathogenic 695031 10:43608405-43608405 10:43112957-43112957
42 RET NM_020975.6(RET):c.860G>T (p.Arg287Leu)SNV Likely pathogenic 692071 10:43600634-43600634 10:43105186-43105186
43 DSCAM NM_001389.5(DSCAM):c.2363C>T (p.Ala788Val)SNV Likely pathogenic 599423 rs1419539530 21:41561159-41561159 21:40189232-40189232
44 SOX10 NM_001301130.2(POLR2F):c.293+6894T>CSNV Likely pathogenic 599421 rs760539449 22:38370071-38370071 22:37974064-37974064
45 RET NM_020975.6(RET):c.1879+1G>ASNV Likely pathogenic 666595 10:43609124-43609124 10:43113676-43113676
46 EDNRB NM_001122659.3(EDNRB):c.1013C>T (p.Pro338Leu)SNV Likely pathogenic 619135 rs1566304640 13:78474728-78474728 13:77900593-77900593
47 EDNRB NM_001122659.3(EDNRB):c.553G>A (p.Val185Met)SNV Likely pathogenic 619136 rs781214034 13:78477673-78477673 13:77903538-77903538
48 RET NM_020975.6(RET):c.440T>C (p.Phe147Ser)SNV Likely pathogenic 599631 rs1564490097 10:43597892-43597892 10:43102444-43102444
49 RET NM_020975.6(RET):c.604G>C (p.Val202Leu)SNV Likely pathogenic 599632 rs751572082 10:43598056-43598056 10:43102608-43102608
50 RET NM_020975.6(RET):c.2437C>T (p.Arg813Trp)SNV Likely pathogenic 599633 rs779996040 10:43615023-43615023 10:43119575-43119575

UniProtKB/Swiss-Prot genetic disease variations for Hirschsprung Disease 1:

73 (show top 50) (show all 67)
# Symbol AA change Variation ID SNP ID
1 RET p.Ser32Leu VAR_006295 rs76764689
2 RET p.Pro64Leu VAR_006296 rs77596424
3 RET p.Cys142Ser VAR_006298
4 RET p.Arg231His VAR_006299 rs79661516
5 RET p.Glu251Lys VAR_006300 rs562449603
6 RET p.Arg287Gln VAR_006301
7 RET p.Arg330Gln VAR_006302 rs80236571
8 RET p.Phe393Leu VAR_006303 rs78098482
9 RET p.Pro399Leu VAR_006304 rs155481836
10 RET p.Arg475Gln VAR_006305 rs138624658
11 RET p.Cys609Tyr VAR_006306 rs77939446
12 RET p.Cys609Trp VAR_006307 rs377767396
13 RET p.Cys618Arg VAR_006311 rs76262710
14 RET p.Cys618Ser VAR_006313 rs79781594
15 RET p.Cys620Arg VAR_006316 rs77316810
16 RET p.Ser690Pro VAR_006331
17 RET p.Ser767Arg VAR_006334
18 RET p.Arg873Gln VAR_006338 rs145100471
19 RET p.Phe893Leu VAR_006339
20 RET p.Arg897Gln VAR_006340 rs76087194
21 RET p.Lys907Glu VAR_006341 rs377767430
22 RET p.Glu921Lys VAR_006343
23 RET p.Arg972Gly VAR_006346 rs76534745
24 RET p.Pro973Leu VAR_006347
25 RET p.Met980Thr VAR_006348
26 RET p.Pro20Leu VAR_009459
27 RET p.Arg77Cys VAR_009460
28 RET p.Phe174Ser VAR_009462
29 RET p.Arg180Pro VAR_009463
30 RET p.Cys197Tyr VAR_009464
31 RET p.Arg313Gln VAR_009465 rs77702891
32 RET p.Arg360Trp VAR_009467
33 RET p.Asn394Lys VAR_009468
34 RET p.Cys620Trp VAR_009475 rs79890926
35 RET p.Gln626Lys VAR_009476 rs125557516
36 RET p.Glu762Gln VAR_009481
37 RET p.Tyr791Phe VAR_009483 rs77724903
38 RET p.Arg813Gln VAR_009484 rs131873377
39 RET p.Leu1061Pro VAR_009490 rs536486113
40 RET p.Met1064Thr VAR_009491 rs149513065
41 RET p.Leu40Pro VAR_009492
42 RET p.Ser765Pro VAR_009493 rs75075748
43 RET p.Arg114His VAR_018154 rs76397662
44 RET p.Val145Gly VAR_035711
45 RET p.Arg114Cys VAR_067101 rs747483905
46 RET p.Pro155Leu VAR_067102
47 RET p.Arg175Pro VAR_067103
48 RET p.Thr278Ala VAR_067104 rs541929171
49 RET p.Thr278Pro VAR_067105
50 RET p.Asp300Asn VAR_067106

Copy number variations for Hirschsprung Disease 1 from CNVD:

7 (show top 50) (show all 71)
# CNVD ID Chromosome Start End Type Gene Symbol CNVD Disease
1 18951 1 148000000 149600000 Copy number SYT11 Hirschsprung''s Disease
2 20073 1 15300000 153300000 Copy number MLLT11 Hirschsprung''s Disease
3 21744 1 16100000 27800000 Copy number ECE1 Hirschsprung''s Disease
4 27738 1 212100000 222100000 Copy number TGFB2 Hirschsprung''s Disease
5 31489 1 27800000 30000000 Copy number PHACTR4 Hirschsprung''s Disease
6 32195 1 34400000 46500000 Copy number ELAVL4 Hirschsprung''s Disease
7 39756 10 119100000 121700000 Copy number GFRA1 Hirschsprung''s Disease
8 40003 10 123100000 127400000 Copy number HMX3 Hirschsprung''s Disease
9 40580 10 130500000 135374737 Copy number EBF3 Hirschsprung''s Disease
10 42900 10 42100000 53300000 Copy number RET Hirschsprung''s Disease
11 42990 10 42892522 42945803 Copy number RET Hirschsprung''s Disease
12 42991 10 42892522 42945803 Copy number RET Hirschsprung''s Disease
13 45473 10 71300000 74600000 Copy number KIAA1279 Hirschsprung''s Disease
14 46634 10 83625076 84735341 Deletion NRG3 Hirschsprung''s disease
15 50018 11 112800000 115400000 Copy number CADM1 Hirschsprung''s Disease
16 54386 11 43400000 52900000 Copy number GNG3 Hirschsprung''s Disease
17 58336 11 67100000 69200000 Copy number PHOX2A Hirschsprung''s Disease
18 61617 12 100000000 102400000 Copy number ASCL1 Hirschsprung''s Disease
19 62272 12 107500000 112800000 Copy number TBX3 Hirschsprung''s Disease
20 67116 12 36500000 56300000 Copy number PRPH Hirschsprung''s Disease
21 76415 13 31100000 39500000 Copy number MAB21L1 Hirschsprung''s Disease
22 79452 13 72100000 77800000 Copy number EDNRB Hirschsprung''s Disease
23 80534 13 93800000 100500000 Copy number ZIC2 Hirschsprung''s Disease
24 84987 14 36900000 48300000 Copy number GNG2 Hirschsprung''s Disease
25 92697 15 42700000 55800000 Copy number SCG3 Hirschsprung''s Disease
26 106264 16 87200000 88827254 Copy number TUBB3 Hirschsprung''s Disease
27 111276 17 35400000 35600000 Copy number MAPT Hirschsprung''s Disease
28 112061 17 37800000 47600000 Copy number HOXB5 Hirschsprung''s Disease
29 119804 18 17300000 23300000 Copy number CDH2 Hirschsprung''s Disease
30 124157 19 1 6900000 Copy number NRTN Hirschsprung''s Disease
31 137403 2 144700000 148400000 Copy number ZFHX1B Hirschsprung''s Disease
32 138713 2 169500000 177700000 Copy number HOXD4 Hirschsprung''s Disease
33 139529 2 182700000 197100000 Copy number DLX1 Hirschsprung''s Disease
34 140088 2 191600000 197100000 Copy number TMEFF2 Hirschsprung''s Disease
35 154860 20 49200000 62435964 Copy number EDN3 Hirschsprung''s Disease
36 155271 20 54400000 62435964 Copy number STMN3 Hirschsprung''s Disease
37 155663 20 57308893 57334442 Copy number EDN3 Hirschsprung''s Disease
38 158147 21 30500000 34700000 Copy number IFNGR2 Hirschsprung''s Disease
39 158148 21 30500000 34700000 Copy number IL10RB Hirschsprung''s Disease
40 158149 21 30500000 34700000 Copy number SOD1 Hirschsprung''s Disease
41 158150 21 30500000 34700000 Copy number SON Hirschsprung''s Disease
42 158780 21 36700000 38600000 Copy number CBR1 Hirschsprung''s Disease
43 158927 21 38600000 41400000 Copy number TTC3 Hirschsprung''s Disease
44 159193 21 41400000 46944323 Copy number CSTB Hirschsprung''s Disease
45 159196 21 41400000 46944323 Copy number PFKL Hirschsprung''s Disease
46 159198 21 41400000 46944323 Copy number TFF3 Hirschsprung''s Disease
47 164253 22 35900000 39300000 Copy number SOX10 Hirschsprung''s Disease
48 166121 3 1 74200000 Copy number ARHGEF3 Hirschsprung''s Disease
49 167059 3 112800000 115000000 Copy number TAGLN3 Hirschsprung''s Disease
50 170885 3 161200000 169200000 Copy number SERPINI1 Hirschsprung''s Disease

Expression for Hirschsprung Disease 1

Search GEO for disease gene expression data for Hirschsprung Disease 1.

Pathways for Hirschsprung Disease 1

Pathways related to Hirschsprung Disease 1 according to KEGG:

36
# Name Kegg Source Accession
1 Calcium signaling pathway hsa04020
2 Neuroactive ligand-receptor interaction hsa04080

Pathways related to Hirschsprung Disease 1 according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1
Show member pathways
11.78 RET NRTN GFRA1 GDNF
2 10.71 RET GFRA1 GDNF
3 10.37 NRTN GFRA1 GDNF
4 9.81 RET GFRA1 GDNF

GO Terms for Hirschsprung Disease 1

Biological processes related to Hirschsprung Disease 1 according to GeneCards Suite gene sharing:

(show all 14)
# Name GO ID Score Top Affiliating Genes
1 nervous system development GO:0007399 9.88 SEMA3D RET NRTN GFRA1 GDNF EDNRB
2 MAPK cascade GO:0000165 9.8 RET NRTN GFRA1 GDNF
3 axon guidance GO:0007411 9.55 SEMA3D RET NRTN GFRA1 GDNF
4 regulation of vasoconstriction GO:0019229 9.54 EDN3 ECE1
5 peripheral nervous system development GO:0007422 9.54 SOX10 GDNF EDNRB
6 response to pain GO:0048265 9.52 RET EDNRB
7 vasoconstriction GO:0042310 9.51 EDNRB EDN3
8 glial cell-derived neurotrophic factor receptor signaling pathway GO:0035860 9.48 RET GFRA1
9 regulation of systemic arterial blood pressure by endothelin GO:0003100 9.46 EDN3 ECE1
10 vein smooth muscle contraction GO:0014826 9.43 EDNRB EDN3
11 melanocyte differentiation GO:0030318 9.43 SOX10 EDNRB EDN3
12 posterior midgut development GO:0007497 9.32 RET EDNRB
13 enteric nervous system development GO:0048484 9.26 SOX10 RET GDNF EDNRB
14 neural crest cell migration GO:0001755 9.17 SOX10 SEMA3D RET NRTN GDNF EDNRB

Molecular functions related to Hirschsprung Disease 1 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 signaling receptor binding GO:0005102 8.92 NRTN GFRA1 GDNF EDN3

Sources for Hirschsprung Disease 1

3 CDC
7 CNVD
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10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
28 GO
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30 HMDB
31 HPO
32 ICD10
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68 SNOMED-CT via HPO
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72 UMLS via Orphanet
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