HSAN3
MCID: NRP054
MIFTS: 67

Neuropathy, Hereditary Sensory and Autonomic, Type Iii (HSAN3)

Categories: Bone diseases, Cardiovascular diseases, Ear diseases, Eye diseases, Gastrointestinal diseases, Genetic diseases, Mental diseases, Metabolic diseases, Nephrological diseases, Neuronal diseases, Rare diseases, Skin diseases

Aliases & Classifications for Neuropathy, Hereditary Sensory and Autonomic, Type Iii

MalaCards integrated aliases for Neuropathy, Hereditary Sensory and Autonomic, Type Iii:

Name: Neuropathy, Hereditary Sensory and Autonomic, Type Iii 56 37
Familial Dysautonomia 12 74 24 52 25 53 58 73 36 29 6
Riley-Day Syndrome 56 12 74 24 25 53 58 73 15
Dysautonomia, Familial 56 52 13 43 71
Hsan Iii 56 12 24 73
Hsan3 56 25 58 73
Fd 52 25 73
Hereditary Sensory and Autonomic Neuropathy Type Iii 58 73
Hereditary Sensory and Autonomic Neuropathy 3 74 52
Dys 56 74
Neuropathy, Sensory and Autonomic, Hereditary, Type Iii 39
Hereditary Sensory and Autonomic Neuropathy Type 3 58
Hereditary Sensory Autonomic Neuropathy, Type Iii 24
Neuropathy, Hereditary Sensory and Autonomic, 3 73
Familial Autonomic Nervous Dysfunction 12
Hereditary Sensory Neuropathy Type 3 52
Dysautonomia, Familial; Dys; Fd 56
Dysautonomia Familial 54
Riley Day Syndrome 52
Hsan Type Iii 25
Hsn-Iii 25
Hsn Iii 73
Hsan 3 52
Hsn 3 52

Characteristics:

Orphanet epidemiological data:

58
familial dysautonomia
Inheritance: Autosomal recessive; Prevalence: 1-5/10000; Age of onset: Infancy,Neonatal;

OMIM:

56
Inheritance:
autosomal recessive

Miscellaneous:
progressive disorder
onset at birth
increased prevalence in persons of ashkenazi jewish descent


HPO:

31
neuropathy, hereditary sensory and autonomic, type iii:
Inheritance autosomal recessive inheritance
Onset and clinical course progressive congenital onset


Classifications:

Orphanet: 58  
Rare neurological diseases
Rare eye diseases
Rare skin diseases


Summaries for Neuropathy, Hereditary Sensory and Autonomic, Type Iii

Genetics Home Reference : 25 Familial dysautonomia is a genetic disorder that affects the development and survival of certain nerve cells. The disorder disturbs cells in the autonomic nervous system, which controls involuntary actions such as digestion, breathing, production of tears, and the regulation of blood pressure and body temperature. It also affects the sensory nervous system, which controls activities related to the senses, such as taste and the perception of pain, heat, and cold. Familial dysautonomia is also called hereditary sensory and autonomic neuropathy, type III. Problems related to this disorder first appear during infancy. Early signs and symptoms include poor muscle tone (hypotonia), feeding difficulties, poor growth, lack of tears, frequent lung infections, and difficulty maintaining body temperature. Older infants and young children with familial dysautonomia may hold their breath for prolonged periods of time, which may cause a bluish appearance of the skin or lips (cyanosis) or fainting. This breath-holding behavior usually stops by age 6. Developmental milestones, such as walking and speech, are usually delayed, although some affected individuals show no signs of developmental delay. Additional signs and symptoms in school-age children include bed wetting, episodes of vomiting, reduced sensitivity to temperature changes and pain, poor balance, abnormal curvature of the spine (scoliosis), poor bone quality and increased risk of bone fractures, and kidney and heart problems. Affected individuals also have poor regulation of blood pressure. They may experience a sharp drop in blood pressure upon standing (orthostatic hypotension), which can cause dizziness, blurred vision, or fainting. They can also have episodes of high blood pressure when nervous or excited, or during vomiting incidents. About one-third of children with familial dysautonomia have learning disabilities, such as a short attention span, that require special education classes. By adulthood, affected individuals often have increasing difficulties with balance and walking unaided. Other problems that may appear in adolescence or early adulthood include lung damage due to repeated infections, impaired kidney function, and worsening vision due to the shrinking size (atrophy) of optic nerves, which carry information from the eyes to the brain.

MalaCards based summary : Neuropathy, Hereditary Sensory and Autonomic, Type Iii, also known as familial dysautonomia, is related to insensitivity to pain, congenital, with anhidrosis and neuropathy, hereditary sensory and autonomic, type iia, and has symptoms including constipation and diarrhea. An important gene associated with Neuropathy, Hereditary Sensory and Autonomic, Type Iii is ELP1 (Elongator Complex Protein 1), and among its related pathways/superpathways are Cytoskeleton remodeling Regulation of actin cytoskeleton by Rho GTPases and Sudden Infant Death Syndrome (SIDS) Susceptibility Pathways. The drugs Dopamine and Carbidopa have been mentioned in the context of this disorder. Affiliated tissues include skin, tongue and eye, and related phenotypes are feeding difficulties in infancy and hyperhidrosis

NIH Rare Diseases : 52 Familial dysautonomia , also called hereditary sensory and autonomic neuropathy type III, is a genetic disorder that affects the development and survival of certain nerve cells . The disorder disturbs cells in the autonomic nervous system , which controls involuntary actions such as digestion, breathing, production of tears, and the regulation of blood pressure and body temperature. It also affects the sensory nervous system, which controls activities related to the senses, such as taste and the perception of pain, heat, and cold. Familial dysautonomia is caused by mutations in the IKBKAP gene . It is inherited in an autosomal recessive pattern.

OMIM : 56 Hereditary sensory and autonomic neuropathy type III (HSAN3) is an autosomal recessive neurodegenerative disorder with onset soon after birth. Affected individuals show progressive symptoms resulting from depletion of sensory proprioceptive and autonomic neurons. Features include gastrointestinal dysfunction, gastroesophageal reflux, vomiting crises, recurrent pneumonia, seizures, gait abnormalities with loss of ambulation, kyphoscoliosis, postural hypotension, hypertension crises, absence of fungiform papillae on the tongue, decreased deep tendon reflexes, defective lacrimation, and impaired pain and temperature perception. The disorder is inevitably fatal, with only 50% of patients reaching 40 years of age. HSAN3 has a high carrier frequency in the Ashkenazi Jewish population (summary by Morini et al., 2016). For a discussion of genetic heterogeneity of hereditary sensory and autonomic neuropathy, see HSAN1 (162400). (223900)

NINDS : 53 Dysautonomia refers to a disorder of autonomic nervous system (ANS) function that generally involves failure of the sympathetic or parasympathetic components of the ANS, but dysautonomia involving excessive or overactive ANS actions also can occur. Dysautonomia can be local, as in reflex sympathetic dystrophy, or generalized, as in pure autonomic failure. It can be acute and reversible, as in Guillain-Barre syndrome, or chronic and progressive. Several common conditions such as diabetes and alcoholism can include dysautonomia. Dysautonomia also can occur as a primary condition or in association with degenerative neurological diseases such as Parkinson's disease. Other diseases with generalized, primary dysautonomia include multiple system atrophy and familial dysautonomia. Hallmarks of generalized dysautonomia due to sympathetic failure are impotence (in men) and a fall in blood pressure during standing (orthostatic hypotension). Excessive sympathetic activity can present as hypertension or a rapid pulse rate.

KEGG : 36 Familial dysautonomia (FD), also known as Riley day syndrome, is an autosomal recessive disorder characterized by developmental arrest in the sensory and autonomic nervous systems. Symptoms include decreased sensitivity to pain and temperature, cardiovascular instability, recurrent pneumonias, and gastrointestinal dysfunction. This disorder is primarily confined to individuals of Ashkenazi Jewish descent, and caused by mutations of the IKAP gene that encodes a scaffolding unit ELP1 for a elongator complex.

UniProtKB/Swiss-Prot : 73 Neuropathy, hereditary sensory and autonomic, 3: A form of hereditary sensory and autonomic neuropathy, a genetically and clinically heterogeneous group of disorders characterized by degeneration of dorsal root and autonomic ganglion cells, and by sensory and/or autonomic abnormalities. HSAN3 patients manifest a variety of symptoms such as alacrima, decreased taste, decreased sensitivity to pain and temperature, vasomotor instability, hypoactive or absent deep tendon reflexes, vomiting crises, and gastrointestinal dysfunction.

Wikipedia : 74 Familial dysautonomia (FD) is a rare, progressive, recessive genetic disorder of the autonomic nervous... more...

GeneReviews: NBK1180

Related Diseases for Neuropathy, Hereditary Sensory and Autonomic, Type Iii

Diseases in the Autosomal Dominant Hereditary Sensory and Autonomic Neuropathy family:

Neuropathy, Hereditary Sensory and Autonomic, Type Ia Neuropathy, Hereditary Sensory and Autonomic, Type Iia
Neuropathy, Hereditary Sensory and Autonomic, Type Iii Neuropathy, Hereditary Sensory and Autonomic, Type V
Neuropathy, Hereditary Sensory and Autonomic, Type Iib Neuropathy, Hereditary Sensory and Autonomic, Type Ic
Neuropathy, Hereditary Sensory and Autonomic, Type Vi Neuropathy, Hereditary Sensory and Autonomic, Type Vii
Neuropathy, Hereditary Sensory and Autonomic, Type Viii Hereditary Sensory and Autonomic Neuropathy Type 1
Autosomal Recessive Hereditary Sensory and Autonomic Neuropathy

Diseases related to Neuropathy, Hereditary Sensory and Autonomic, Type Iii via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 791)
# Related Disease Score Top Affiliating Genes
1 insensitivity to pain, congenital, with anhidrosis 33.9 NTRK1 NAA50 BDNF
2 neuropathy, hereditary sensory and autonomic, type iia 32.6 NTRK1 NGF NAA50 ELP1
3 autonomic neuropathy 30.5 NTRK1 NGF ELP1 DBH
4 adrenal gland pheochromocytoma 30.0 NGF BDNF
5 differentiating neuroblastoma 29.9 SMN1 ELP1 ASCL1
6 sensory peripheral neuropathy 29.7 NTRK1 NGF NAA50 BDNF
7 amyotrophic lateral sclerosis 1 29.7 SMN2 SMN1 NTRK2 NTRK1 NGF ELP3
8 hereditary sensory neuropathy 29.7 PRICKLE4 NTRK2 NTRK1 NGF NAA50 ELP3
9 neuroblastoma 29.2 NTRK2 NTRK1 NGF DBH BDNF ASCL1
10 benign epilepsy with centrotemporal spikes 29.2 MCM5 ELP6 ELP4 ELP3 ELP2 ELP1
11 charcot-marie-tooth disease 29.0 SMN2 SMN1 NTRK1 NGF NAA50 ELP1
12 peripheral nervous system disease 28.7 SMN2 SMN1 POU4F1 NTRK1 NGF NAA50
13 retinitis pigmentosa 28.0 SMN2 SMN1 POU4F1 NTRK1 NGF KLF4
14 auditory neuropathy spectrum disorder 11.6
15 fibrous dysplasia/mccune-albright syndrome 11.6
16 depression 11.4
17 cardiac arrest 11.4
18 traumatic brain injury 11.4
19 wallerian degeneration 11.4
20 alexander disease 11.4
21 leukodystrophy 11.4
22 bipolar disorder 11.4
23 neuropathy, hereditary sensory and autonomic, type vi 11.3
24 primary orthostatic hypotension 11.2
25 macroglossia 11.1
26 panic disorder 1 11.1
27 microcephalic osteodysplastic primordial dwarfism, type i 11.1
28 bowen-conradi syndrome 11.1
29 gastrointestinal defects and immunodeficiency syndrome 11.1
30 pycnodysostosis 11.1
31 charcot-marie-tooth disease, axonal, type 2k 11.1
32 spinocerebellar ataxia, autosomal recessive 7 11.1
33 loeys-dietz syndrome 2 11.1
34 deafness, autosomal recessive 59 11.1
35 multiple mitochondrial dysfunctions syndrome 5 11.1
36 loeys-dietz syndrome 11.1
37 walker-warburg syndrome 11.1
38 autosomal recessive cutis laxa type i 11.1
39 hydranencephaly 11.1
40 schizoaffective disorder 11.1
41 congenital intrauterine infection-like syndrome 11.1
42 neonatal adrenoleukodystrophy 11.1
43 x-linked cerebral adrenoleukodystrophy 11.1
44 yusho disease 11.1
45 dysautonomia 10.6
46 muscular dystrophy 10.6
47 dementia 10.5
48 malignant giant cell tumor of the tendon sheath 10.4 NTRK2 NTRK1
49 neurotrophic keratoconjunctivitis 10.4 NGF BDNF
50 muscular dystrophy, congenital, lmna-related 10.4

Graphical network of the top 20 diseases related to Neuropathy, Hereditary Sensory and Autonomic, Type Iii:



Diseases related to Neuropathy, Hereditary Sensory and Autonomic, Type Iii

Symptoms & Phenotypes for Neuropathy, Hereditary Sensory and Autonomic, Type Iii

Human phenotypes related to Neuropathy, Hereditary Sensory and Autonomic, Type Iii:

58 31 (show top 50) (show all 59)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 feeding difficulties in infancy 58 31 hallmark (90%) Very frequent (99-80%) HP:0008872
2 hyperhidrosis 58 31 hallmark (90%) Very frequent (99-80%) HP:0000975
3 emg abnormality 58 31 hallmark (90%) Very frequent (99-80%) HP:0003457
4 hypohidrosis 58 31 hallmark (90%) Very frequent (99-80%) HP:0000966
5 growth delay 58 31 hallmark (90%) Very frequent (99-80%) HP:0001510
6 malignant hyperthermia 58 31 hallmark (90%) Very frequent (99-80%) HP:0002047
7 impaired pain sensation 58 31 hallmark (90%) Very frequent (99-80%) HP:0007328
8 abnormal pupil morphology 58 31 hallmark (90%) Very frequent (99-80%) HP:0000615
9 hyporeflexia 58 31 hallmark (90%) Very frequent (99-80%) HP:0001265
10 alacrima 58 31 hallmark (90%) Very frequent (99-80%) HP:0000522
11 orthostatic hypotension 58 31 hallmark (90%) Very frequent (99-80%) HP:0001278
12 behavioral abnormality 58 31 frequent (33%) Frequent (79-30%) HP:0000708
13 muscular hypotonia 58 31 frequent (33%) Frequent (79-30%) HP:0001252
14 scoliosis 58 31 frequent (33%) Frequent (79-30%) HP:0002650
15 recurrent respiratory infections 58 31 frequent (33%) Frequent (79-30%) HP:0002205
16 gait disturbance 58 31 frequent (33%) Frequent (79-30%) HP:0001288
17 ataxia 58 31 frequent (33%) Frequent (79-30%) HP:0001251
18 hypertension 58 31 frequent (33%) Frequent (79-30%) HP:0000822
19 corneal erosion 58 31 frequent (33%) Frequent (79-30%) HP:0200020
20 corneal opacity 58 31 occasional (7.5%) Occasional (29-5%) HP:0007957
21 avascular necrosis 58 31 occasional (7.5%) Occasional (29-5%) HP:0010885
22 optic atrophy 58 31 occasional (7.5%) Occasional (29-5%) HP:0000648
23 gastroesophageal reflux 58 31 occasional (7.5%) Occasional (29-5%) HP:0002020
24 renal insufficiency 58 31 occasional (7.5%) Occasional (29-5%) HP:0000083
25 acrocyanosis 58 31 occasional (7.5%) Occasional (29-5%) HP:0001063
26 osteolysis 58 31 occasional (7.5%) Occasional (29-5%) HP:0002797
27 myopia 58 31 occasional (7.5%) Occasional (29-5%) HP:0000545
28 glomerulopathy 58 31 occasional (7.5%) Occasional (29-5%) HP:0100820
29 recurrent fractures 58 31 occasional (7.5%) Occasional (29-5%) HP:0002757
30 hyponatremia 58 31 occasional (7.5%) Occasional (29-5%) HP:0002902
31 heterochromia iridis 58 31 occasional (7.5%) Occasional (29-5%) HP:0001100
32 tachycardia 58 31 occasional (7.5%) Occasional (29-5%) HP:0001649
33 abnormality of the peritoneum 58 31 occasional (7.5%) Occasional (29-5%) HP:0002585
34 seizure 31 occasional (7.5%) HP:0001250
35 abnormal pleura morphology 31 occasional (7.5%) HP:0002103
36 seizures 58 Occasional (29-5%)
37 vomiting 31 HP:0002013
38 peripheral neuropathy 58 Very frequent (99-80%)
39 abnormality of the pleura 58 Occasional (29-5%)
40 constipation 31 HP:0002019
41 abnormality of the kidney 58 Occasional (29-5%)
42 corneal ulceration 31 HP:0012804
43 emotional lability 31 HP:0000712
44 diarrhea 31 HP:0002014
45 generalized hypotonia 31 HP:0001290
46 recurrent fever 31 HP:0001954
47 neuropathic arthropathy 31 HP:0002821
48 decreased corneal reflex 31 HP:0008000
49 decreased taste sensation 31 HP:0000224
50 recurrent corneal erosions 31 HP:0000495

Symptoms via clinical synopsis from OMIM:

56
Skeletal Spine:
scoliosis

Skin Nails Hair Skin:
acrocyanosis
hyperhidrosis, episodic
erythematous skin blotching

Head And Neck Eyes:
corneal ulceration
alacrima
decreased corneal reflex
pupillary contraction in response to methacholine

Skeletal:
neuropathic arthropathy

Laboratory Abnormalities:
azotemia
increased serum creatinine
increased blood urea nitrogen (bun)
absent axonal flare response after intradermal histamine injection
increased sensitivity to adrenergic and cholinergic agents

Metabolic Features:
fever, episodic

Head And Neck Mouth:
decreased or absent lingual fungiform papillae
decreased taste

Abdomen Gastrointestinal:
gastroesophageal reflux
feeding difficulties
constipation
diarrhea
poor oral coordination
more
Neurologic Peripheral Nervous System:
hyporeflexia
incoordination
hypotonia
decreased taste
decreased pain and temperature perception
more
Neurologic Behavioral Psychiatric Manifestations:
emotional lability

Genitourinary Kidneys:
glomerulosclerosis
impaired renal function

Respiratory:
recurrent infections due to aspiration
decreased sensitivity to hypoxemia
breath-holding episodes

Growth Other:
poor growth

Cardiovascular Vascular:
hypertension, episodic
postural hypotension without compensatory tachycardia

Clinical features from OMIM:

223900

UMLS symptoms related to Neuropathy, Hereditary Sensory and Autonomic, Type Iii:


constipation, diarrhea

MGI Mouse Phenotypes related to Neuropathy, Hereditary Sensory and Autonomic, Type Iii:

45
# Description MGI Source Accession Score Top Affiliating Genes
1 mortality/aging MP:0010768 10.07 ASCL1 BDNF DBH ELP1 ELP3 KLF4
2 behavior/neurological MP:0005386 10.06 ASCL1 BDNF DBH ELP1 ELP6 KLF4
3 no phenotypic analysis MP:0003012 9.7 ASCL1 BDNF ELP1 NGF NTRK1 POU4F1
4 normal MP:0002873 9.61 ASCL1 BDNF DBH KLF4 NGF NTRK1
5 vision/eye MP:0005391 9.32 ASCL1 BDNF DBH ELP1 KLF4 NAA50

Drugs & Therapeutics for Neuropathy, Hereditary Sensory and Autonomic, Type Iii

Drugs for Neuropathy, Hereditary Sensory and Autonomic, Type Iii (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 22)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Dopamine Approved Phase 3 51-61-6, 62-31-7 681
2
Carbidopa Approved Phase 3 28860-95-9 34359
3
Ipratropium Approved, Experimental Phase 3 60205-81-4, 22254-24-6 43232 657309
4 Antiparkinson Agents Phase 3
5 Aromatic Amino Acid Decarboxylase Inhibitors Phase 3
6 Neurotransmitter Agents Phase 3
7 Dopamine Agents Phase 3
8 Adrenergic beta-Agonists Phase 3
9 Respiratory System Agents Phase 3
10 Cholinergic Agents Phase 3
11 Adrenergic Agents Phase 3
12 Pharmaceutical Solutions Phase 3
13 Albuterol Phase 3
14 Adrenergic Agonists Phase 3
15 Cholinergic Antagonists Phase 3
16 Bronchodilator Agents Phase 3
17 Anti-Asthmatic Agents Phase 3
18 Anticonvulsants Phase 3
19 Bromides Phase 3
20 Tocolytic Agents Phase 3
21
Norepinephrine Approved Phase 2 51-41-2 439260
22
Kinetin Approved Phase 1 525-79-1 3830

Interventional clinical trials:

(show all 12)
# Name Status NCT ID Phase Drugs
1 Carbidopa for the Treatment of Nausea and Vomiting in Familial Dysautonomia Completed NCT01212484 Phase 3 Carbidopa;Placebo
2 The Effects of Bronchodilator Therapy On Respiratory and Autonomic Function in Patients With Familial Dysautonomia Completed NCT01987219 Phase 3 Albuterol-sulphate;Ipratropium-bromide
3 Carbidopa in Familial Dysautonomia: Phase-II Study, Investigational New Drug (IND) 117435, Date: 01/07/13 Completed NCT02553265 Phase 2 Carbidopa Low Dose;Carbidopa High Dose
4 The Nutritional Supplement Phosphatidylserine in Patients With Familial Recruiting NCT02276716 Phase 2 Phosphatidylserine
5 The Safety , Tolerability and Efficacy of Dronabinol, a Synthetic Endocannabinoid Receptor Agonist, for the Treatment of Nausea and Vomiting in Patients With Familial Dysautonomia Withdrawn NCT02608931 Phase 2 Dronabinol
6 The Safety and Tolerability of Kinetin, a Nutritional Supplement That Corrects the Splicing Defect, in Patients With Familial Dysautonomia Completed NCT02274051 Phase 1
7 An Open-Label Pilot Trial of Cognitive Behavioral Therapy in Familial Dysautonomia Completed NCT03013777
8 Assessing the Outcomes of Web-based Pre-test Educational Module for Carrier Genetic Screening in Individuals of Ashkenazi Jewish Descent Completed NCT01999257
9 Natural History of Familial Dysautonomia Recruiting NCT03920774
10 Derivation of Induced Pluripotent Stem Cells From Somatic Cells Donated by Patients With Neurological Diseases for the Study of the Pathogenesis of the Disorders and Development of Novel Therapies Recruiting NCT00874783
11 Proprioception and Sensorimotor Control in Hereditary Sensory and Autonomic Neuropathy Enrolling by invitation NCT02876939
12 A Single-Blind Placebo-Controlled Telemedicine Clinical Trial for Cognitive Behavioral Therapy in Familial Dysautonomia Withdrawn NCT03911063

Search NIH Clinical Center for Neuropathy, Hereditary Sensory and Autonomic, Type Iii

Cochrane evidence based reviews: dysautonomia, familial

Genetic Tests for Neuropathy, Hereditary Sensory and Autonomic, Type Iii

Genetic tests related to Neuropathy, Hereditary Sensory and Autonomic, Type Iii:

# Genetic test Affiliating Genes
1 Familial Dysautonomia 29 ELP1

Anatomical Context for Neuropathy, Hereditary Sensory and Autonomic, Type Iii

MalaCards organs/tissues related to Neuropathy, Hereditary Sensory and Autonomic, Type Iii:

40
Skin, Tongue, Eye, Kidney, Lung, Bone, Brain

Publications for Neuropathy, Hereditary Sensory and Autonomic, Type Iii

Articles related to Neuropathy, Hereditary Sensory and Autonomic, Type Iii:

(show top 50) (show all 607)
# Title Authors PMID Year
1
Tissue-specific expression of a splicing mutation in the IKBKAP gene causes familial dysautonomia. 24 56 6 61 54
11179008 2001
2
Familial dysautonomia is caused by mutations of the IKAP gene. 61 24 56 6 54
11179021 2001
3
Identification of the first non-Jewish mutation in familial Dysautonomia. 24 6 56 61
12687659 2003
4
Precise genetic mapping and haplotype analysis of the familial dysautonomia gene on human chromosome 9q31. 56 6 24 61
10090896 1999
5
Modelling pathogenesis and treatment of familial dysautonomia using patient-specific iPSCs. 54 24 56 61
19693009 2009
6
Weak definition of IKBKAP exon 20 leads to aberrant splicing in familial dysautonomia. 61 24 54 6
16964593 2007
7
Rescue of a human mRNA splicing defect by the plant cytokinin kinetin. 61 54 24 56
14709595 2004
8
Familial dysautonomia: detection of the IKBKAP IVS20(+6T --> C) and R696P mutations and frequencies among Ashkenazi Jews. 61 24 6
12116234 2002
9
A humanized IKBKAP transgenic mouse models a tissue-specific human splicing defect. 54 56 61
17644305 2007
10
EGCG corrects aberrant splicing of IKAP mRNA in cells from patients with familial dysautonomia. 54 61 56
14521957 2003
11
ELP1 Splicing Correction Reverses Proprioceptive Sensory Loss in Familial Dysautonomia. 61 56
30905397 2019
12
Sensory and autonomic deficits in a new humanized mouse model of familial dysautonomia. 56 61
26769677 2016
13
ACOG Committee Opinion No. 442: Preconception and prenatal carrier screening for genetic diseases in individuals of Eastern European Jewish descent. 6 61
19888064 2009
14
Kinetin in familial dysautonomia carriers: implications for a new therapeutic strategy targeting mRNA splicing. 24 61 54
19033881 2009
15
Therapeutic potential and mechanism of kinetin as a treatment for the human splicing disease familial dysautonomia. 61 54 24
17206408 2007
16
Tocotrienols reverse IKAP and monoamine oxidase deficiencies in familial dysautonomia. 24 61 54
16125677 2005
17
Episodic somnolence in an infant with Riley-Day syndrome. 61 24 54
15797185 2005
18
Inherited autonomic neuropathies. 61 56
15088259 2003
19
Familial Dysautonomia 6 61
20301359 2003
20
Familial dysautonomia: a 47-year perspective. How technology confirms clinical acumen. 61 56
9546030 1998
21
Prenatal diagnosis of familial dysautonomia by analysis of linked CA-repeat polymorphisms on chromosome 9q31-q33. 61 56
8599360 1995
22
Prenatal diagnostic testing for familial dysautonomia using linked genetic markers. 56 61
8559751 1995
23
Localization of the gene for familial dysautonomia on chromosome 9 and definition of DNA markers for genetic diagnosis. 61 56
8102296 1993
24
Incidence of familial dysautonomia in Israel 1977-1981. 61 56
3652488 1987
25
Neonatal recognition of familial dysautonomia. 61 56
3585611 1987
26
DNA polymorphisms for the nerve growth factor receptor gene exclude its role in familial dysautonomia. 56 61
2886891 1986
27
Pulmonary manifestations of familial dysautonomia in an adult. 56 61
3963047 1986
28
Diagnosis of familial dysautonomia in the neonatal period. 61 56
3984717 1985
29
Structural gene for beta-nerve growth factor not defective in familial dysautonomia. 56 61
6330750 1984
30
The pupil cycle time in familial dysautonomia. Further evidence for denervation hypersensitivity. 61 56
6656621 1983
31
Familial dysautonomia: a prospective study of survival. 61 56
7097419 1982
32
Aseptic necrosis in familial dysautonomia. 61 56
7053554 1982
33
Progressive sensory loss in familial dysautonomia. 56 61
7254974 1981
34
Altered nerve growth factor in fibroblasts from patients with familial dysautonomia. 56 61
6244581 1980
35
Renal disease in familial dysautonomia. 61 56
7374014 1980
36
Quantitative studies of sympathetic ganglia and spinal cord intermedio-lateral gray columns in familial dysautonomia. 56 61
731273 1978
37
Pregnancy in familial dysautonomia. 56 61
717449 1978
38
Quantitative studies of dorsal root ganglia and neuropathologic observations on spinal cords in familial dysautonomia. 61 56
624961 1978
39
Familial dysautonomia in a non-Jewish child. 56 61
920171 1977
40
Increased nerve-growth-factor beta-chain cross-reacting material in familial dysautonomia. 56 61
987530 1976
41
Deficient sympathetic nervous response in familial dysautonomia. 56 61
1246255 1976
42
The sural nerve in familial dysautonomia. 56 61
1176995 1975
43
The "chest-abdomen sign" in familial dysautonomia. 56 61
1109623 1975
44
Decreased noradrenaline (norepinephrine) synthesis in familial dysautonomia. 61 56
5129321 1971
45
Reduced plasma dopamine-beta-hydroxylase activity in familial dysautonomia. 61 56
5096225 1971
46
Excretion of catecholamine metabolites by children with familial dysautonomia. 56 61
5503687 1970
47
Familial dysautonomia. A report of genetic and clinical studies, with a review of the literature. 61 56
4322121 1970
48
The tongue and taste in familial dysautonomia. 61 56
5444397 1970
49
Riley-Day syndrome (familial dysautonomia). Survey of 27 cases. 56 61
5953423 1966
50
ABSENCE OF TASTE-BUD PAPILLAE IN FAMILIAL DYSAUTONOMIA. 61 56
14245781 1965

Variations for Neuropathy, Hereditary Sensory and Autonomic, Type Iii

ClinVar genetic disease variations for Neuropathy, Hereditary Sensory and Autonomic, Type Iii:

6 (show top 50) (show all 310) ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 ELP1 NM_003640.5(ELP1):c.2505C>A (p.Tyr835Ter)SNV Pathogenic 568263 rs1564084140 9:111659315-111659315 9:108897035-108897035
2 ELP1 NM_003640.5(ELP1):c.2006C>A (p.Ser669Ter)SNV Pathogenic 664647 9:111663713-111663713 9:108901433-108901433
3 ELP1 NM_003640.5(ELP1):c.349del (p.Trp117fs)deletion Pathogenic 648167 9:111689688-111689688 9:108927408-108927408
4 ELP1 NM_003640.5(ELP1):c.2204+6T>CSNV Pathogenic 6085 rs111033171 9:111662096-111662096 9:108899816-108899816
5 ELP1 NM_003640.5(ELP1):c.2087G>C (p.Arg696Pro)SNV Pathogenic/Likely pathogenic 6086 rs137853022 9:111662583-111662583 9:108900303-108900303
6 ELP1 NM_003640.5(ELP1):c.641del (p.Pro214fs)deletion Pathogenic/Likely pathogenic 553108 rs759412460 9:111681541-111681541 9:108919261-108919261
7 ELP1 NM_003640.5(ELP1):c.2499dup (p.Lys834Ter)duplication Pathogenic/Likely pathogenic 423215 rs767527819 9:111659429-111659430 9:108897149-108897150
8 ELP1 NM_003640.5(ELP1):c.3592C>T (p.Arg1198Ter)SNV Pathogenic/Likely pathogenic 553107 rs376078668 9:111641011-111641011 9:108878731-108878731
9 ELP1 NM_003640.5(ELP1):c.2587+2T>GSNV Likely pathogenic 552276 rs1554695299 9:111659231-111659231 9:108896951-108896951
10 ELP1 NM_003640.5(ELP1):c.2958+1G>CSNV Likely pathogenic 552277 rs1239081703 9:111655265-111655265 9:108892985-108892985
11 ELP1 NM_003640.5(ELP1):c.151-1G>TSNV Likely pathogenic 558396 rs1554703613 9:111692202-111692202 9:108929922-108929922
12 ELP1 NM_003640.5(ELP1):c.1908+2T>ASNV Likely pathogenic 552274 rs1554696648 9:111663906-111663906 9:108901626-108901626
13 ELP1 NM_003640.5(ELP1):c.1854+1G>ASNV Likely pathogenic 558407 rs1554696934 9:111665118-111665118 9:108902838-108902838
14 ELP1 NM_003640.5(ELP1):c.1189+1G>ASNV Likely pathogenic 552244 rs1554699327 9:111674543-111674543 9:108912263-108912263
15 ELP1 NM_003640.5(ELP1):c.151-1G>ASNV Likely pathogenic 552705 rs1554703613 9:111692202-111692202 9:108929922-108929922
16 ELP1 NM_003640.5(ELP1):c.3931+1G>TSNV Likely pathogenic 551259 rs143674809 9:111637174-111637174 9:108874894-108874894
17 ELP1 NM_003640.5(ELP1):c.2014+1G>ASNV Likely pathogenic 556440 rs1554696574 9:111663704-111663704 9:108901424-108901424
18 ELP1 NM_003640.5(ELP1):c.1461-1G>TSNV Likely pathogenic 552194 rs539544212 9:111668766-111668766 9:108906486-108906486
19 ELP1 NM_003640.5(ELP1):c.1461-1G>ASNV Likely pathogenic 556902 rs539544212 9:111668766-111668766 9:108906486-108906486
20 ELP1 NM_003640.5(ELP1):c.1360+1G>TSNV Likely pathogenic 553041 rs1201626345 9:111673289-111673289 9:108911009-108911009
21 ELP1 NM_003640.5(ELP1):c.1154del (p.Asn384_Ser385insTer)deletion Likely pathogenic 552243 rs774890086 9:111674579-111674579 9:108912299-108912299
22 ELP1 NM_003640.5(ELP1):c.385+1G>ASNV Likely pathogenic 558252 rs1554703061 9:111689651-111689651 9:108927371-108927371
23 ELP1 NM_003640.5(ELP1):c.147_150+1dupduplication Likely pathogenic 557337 rs1319053366 9:111693275-111693276 9:108930995-108930996
24 ELP1 NM_003640.5(ELP1):c.97del (p.Val33fs)deletion Likely pathogenic 555432 rs1554703851 9:111693330-111693330 9:108931050-108931050
25 ELP1 NM_003640.5(ELP1):c.79C>T (p.Arg27Ter)SNV Likely pathogenic 552197 rs868073099 9:111693348-111693348 9:108931068-108931068
26 ELP1 NM_003640.5(ELP1):c.4C>T (p.Arg2Ter)SNV Likely pathogenic 552235 rs926177767 9:111693423-111693423 9:108931143-108931143
27 ELP1 NM_003640.5(ELP1):c.3643dup (p.Asp1215fs)duplication Likely pathogenic 496211 rs781333644 9:111640959-111640960 9:108878679-108878680
28 ELP1 NM_003640.5(ELP1):c.3285+2T>CSNV Likely pathogenic 526195 rs1554692181 9:111644403-111644403 9:108882123-108882123
29 ELP1 NM_003640.5(ELP1):c.552+2T>ASNV Likely pathogenic 552684 rs1554702142 9:111685120-111685120 9:108922840-108922840
30 ELP1 NM_003640.5(ELP1):c.552+1G>TSNV Likely pathogenic 557099 rs765572951 9:111685121-111685121 9:108922841-108922841
31 ELP1 NM_003640.5(ELP1):c.386-2A>CSNV Likely pathogenic 552783 rs1554702880 9:111688885-111688885 9:108926605-108926605
32 ELP1 NM_003640.5(ELP1):c.150+1G>ASNV Likely pathogenic 553976 rs1554703831 9:111693276-111693276 9:108930996-108930996
33 ELP1 NM_003640.5(ELP1):c.1902_1903del (p.Asp634_Ile635insTer)deletion Likely pathogenic 552275 rs1554696650 9:111663913-111663914 9:108901633-108901634
34 ELP1 NM_003640.5(ELP1):c.304-2A>GSNV Likely pathogenic 552242 rs757972943 9:111689735-111689735 9:108927455-108927455
35 ELP1 NM_003640.5(ELP1):c.54del (p.Asn20fs)deletion Likely pathogenic 552308 rs1554703874 9:111693373-111693373 9:108931093-108931093
36 ELP1 NM_003640.5(ELP1):c.1A>T (p.Met1Leu)SNV Likely pathogenic 552267 rs1554703907 9:111693426-111693426 9:108931146-108931146
37 ELP1 NM_003640.5(ELP1):c.3701-1G>ASNV Likely pathogenic 552298 rs1554691572 9:111640430-111640430 9:108878150-108878150
38 ELP1 NM_003640.5(ELP1):c.2205-1G>CSNV Likely pathogenic 552270 rs1554695846 9:111661030-111661030 9:108898750-108898750
39 ELP1 NM_003640.5(ELP1):c.1751-2A>TSNV Likely pathogenic 558541 rs1554697001 9:111665224-111665224 9:108902944-108902944
40 ELP1 NM_003640.5(ELP1):c.1750+1G>TSNV Likely pathogenic 557775 rs770668926 9:111665842-111665842 9:108903562-108903562
41 ELP1 NM_003640.5(ELP1):c.1469_1470del (p.Gln489_Phe490insTer)deletion Likely pathogenic 552191 rs1554698037 9:111668756-111668757 9:108906476-108906477
42 ELP1 NM_003640.5(ELP1):c.3346+1G>ASNV Likely pathogenic 553813 rs760774999 9:111643984-111643984 9:108881704-108881704
43 ELP1 NC_000009.12:g.(?_108869105)_(108903679_?)deldeletion Likely pathogenic 656290 9:111631385-111665959 9:108869105-108903679
44 ELP1 NM_003640.5(ELP1):c.3572+1G>ASNV Likely pathogenic 651159 9:111641725-111641725 9:108879445-108879445
45 ELP1 NC_000009.12:g.(?_108869115)_(108901681_?)deldeletion Likely pathogenic 583918 9:111631395-111663961 9:108869115-108901681
46 ELP1 NM_003640.5(ELP1):c.2860+2T>CSNV Likely pathogenic 370227 rs754348901 9:111656221-111656221 9:108893941-108893941
47 ELP1 NM_003640.5(ELP1):c.2817C>A (p.Tyr939Ter)SNV Likely pathogenic 370257 rs749052963 9:111656266-111656266 9:108893986-108893986
48 ELP1 NM_003640.5(ELP1):c.2204+1G>ASNV Likely pathogenic 371309 rs1057517169 9:111662101-111662101 9:108899821-108899821
49 ELP1 NM_003640.5(ELP1):c.2158del (p.His720fs)deletion Likely pathogenic 370915 rs1057516865 9:111662148-111662148 9:108899868-108899868
50 ELP1 NM_003640.5(ELP1):c.2076dup (p.Arg693fs)duplication Likely pathogenic 370735 rs763445509 9:111662593-111662594 9:108900313-108900314

UniProtKB/Swiss-Prot genetic disease variations for Neuropathy, Hereditary Sensory and Autonomic, Type Iii:

73
# Symbol AA change Variation ID SNP ID
1 ELP1 p.Arg696Pro VAR_011327 rs137853022

Expression for Neuropathy, Hereditary Sensory and Autonomic, Type Iii

Search GEO for disease gene expression data for Neuropathy, Hereditary Sensory and Autonomic, Type Iii.

Pathways for Neuropathy, Hereditary Sensory and Autonomic, Type Iii

Pathways related to Neuropathy, Hereditary Sensory and Autonomic, Type Iii according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1
Show member pathways
12.26 NTRK2 NTRK1 NGF BDNF
2 11.83 NTRK2 NGF BDNF ASCL1
3 11.72 NTRK2 NTRK1 NGF BDNF
4 11.52 NTRK2 NTRK1 NGF BDNF
5 11.45 NTRK2 NTRK1 NGF BDNF
6 11.44 NGF BDNF ASCL1
7
Show member pathways
11.04 NTRK2 NTRK1 NGF BDNF
8 10.58 NTRK2 BDNF
9
Show member pathways
9.84 NTRK2 NTRK1 NGF

GO Terms for Neuropathy, Hereditary Sensory and Autonomic, Type Iii

Cellular components related to Neuropathy, Hereditary Sensory and Autonomic, Type Iii according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 cytoplasm GO:0005737 10.03 SMN2 SMN1 POU4F1 NTRK2 NTRK1 NAA50
2 axon GO:0030424 9.43 SMN2 SMN1 NTRK2 NTRK1 NGF BDNF
3 SMN-Sm protein complex GO:0034719 9.37 SMN2 SMN1
4 Gemini of coiled bodies GO:0097504 9.32 SMN2 SMN1
5 SMN complex GO:0032797 9.26 SMN2 SMN1
6 Elongator holoenzyme complex GO:0033588 9.02 ELP6 ELP4 ELP3 ELP2 ELP1

Biological processes related to Neuropathy, Hereditary Sensory and Autonomic, Type Iii according to GeneCards Suite gene sharing:

(show all 28)
# Name GO ID Score Top Affiliating Genes
1 negative regulation of apoptotic process GO:0043066 9.99 POU4F1 NTRK1 NGF BDNF ASCL1
2 nervous system development GO:0007399 9.86 SMN2 SMN1 POU4F1 NTRK2 NTRK1 ELP3
3 neuron migration GO:0001764 9.81 NTRK2 ELP3 ASCL1
4 positive regulation of neuron differentiation GO:0045666 9.78 NGF BDNF ASCL1
5 transmembrane receptor protein tyrosine kinase signaling pathway GO:0007169 9.78 NTRK2 NTRK1 NGF BDNF
6 circadian rhythm GO:0007623 9.77 NTRK2 NTRK1 BDNF
7 negative regulation of neuron apoptotic process GO:0043524 9.77 POU4F1 NTRK2 NTRK1 NGF BDNF
8 positive regulation of peptidyl-serine phosphorylation GO:0033138 9.76 NTRK2 NGF BDNF
9 memory GO:0007613 9.75 NGF DBH BDNF
10 positive regulation of synapse assembly GO:0051965 9.71 NTRK2 NTRK1 BDNF
11 regulation of protein kinase B signaling GO:0051896 9.64 NTRK2 NTRK1
12 neuron fate specification GO:0048665 9.63 POU4F1 ASCL1
13 central nervous system neuron development GO:0021954 9.62 NTRK2 ASCL1
14 sympathetic nervous system development GO:0048485 9.62 NTRK1 ASCL1
15 nerve development GO:0021675 9.61 NGF BDNF
16 nerve growth factor signaling pathway GO:0038180 9.58 NTRK1 NGF BDNF
17 peripheral nervous system neuron development GO:0048935 9.57 POU4F1 NTRK2
18 DNA-templated transcription, termination GO:0006353 9.56 SMN2 SMN1
19 positive regulation of collateral sprouting GO:0048672 9.55 NGF BDNF
20 positive regulation of non-membrane spanning protein tyrosine kinase activity GO:1903997 9.52 NTRK2 BDNF
21 brain-derived neurotrophic factor receptor signaling pathway GO:0031547 9.51 NTRK2 BDNF
22 mechanoreceptor differentiation GO:0042490 9.5 NTRK2 NTRK1 BDNF
23 fear response GO:0042596 9.49 DBH BDNF
24 neurotrophin signaling pathway GO:0038179 9.46 NTRK2 NTRK1
25 neurotrophin TRK receptor signaling pathway GO:0048011 9.46 NTRK2 NTRK1 NGF BDNF
26 tRNA wobble base 5-methoxycarbonylmethyl-2-thiouridinylation GO:0002926 9.43 ELP3 ELP1
27 tRNA processing GO:0008033 9.43 ELP6 ELP4 ELP3 ELP2 ELP1 CTU1
28 tRNA wobble uridine modification GO:0002098 9.02 ELP6 ELP4 ELP2 ELP1 CTU1

Molecular functions related to Neuropathy, Hereditary Sensory and Autonomic, Type Iii according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 tRNA binding GO:0000049 9.5 ELP3 ELP1 CTU1
2 nerve growth factor receptor binding GO:0005163 9.26 NGF BDNF
3 neurotrophin binding GO:0043121 9.16 NTRK2 NTRK1
4 phosphorylase kinase regulator activity GO:0008607 8.96 ELP4 ELP3
5 neurotrophin receptor activity GO:0005030 8.62 NTRK2 NTRK1

Sources for Neuropathy, Hereditary Sensory and Autonomic, Type Iii

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
43 MeSH
44 MESH via Orphanet
45 MGI
48 NCI
49 NCIt
50 NDF-RT
53 NINDS
54 Novoseek
56 OMIM
57 OMIM via Orphanet
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
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