HPE
MCID: HLP001
MIFTS: 66

Holoprosencephaly (HPE)

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

Aliases & Classifications for Holoprosencephaly

MalaCards integrated aliases for Holoprosencephaly:

Name: Holoprosencephaly 38 12 76 24 53 54 59 37 55 44 15 40
Holoprosencephaly Sequence 12 29 6
Hpe 53 59

Characteristics:

Orphanet epidemiological data:

59
holoprosencephaly
Inheritance: Multigenic/multifactorial,Not applicable; Prevalence: 1-5/10000 (Europe); Age of onset: Antenatal,Neonatal; Age of death: any age;

Classifications:



Summaries for Holoprosencephaly

NINDS : 54 Holoprosencephaly is a disorder caused by the failure of the prosencephalon (the embryonic forebrain) to sufficiently divide into the double lobes of the cerebral hemispheres. The result is a single-lobed brain structure and severe skull and facial defects. In most cases of holoprosencephaly, the malformations are so severe that babies die before birth. In less severe cases, babies are born with normal or near-normal brain development and facial deformities that may affect the eyes, nose, and upper lip. There are three classifications of holoprosencephaly. Alobar, in which the brain has not divided at all, is usually associated with severe facial deformities. Semilobar, in which the brain's hemispheres have somewhat divided, causes an intermediate form of the disorder. Lobar, in which there is considerable evidence of separate brain hemispheres, is the least severe form. In some cases of lobar holoprosencephaly the baby's brain may be nearly normal. The least severe of the facial anomalies is the median cleft lip (premaxillary agenesis). The most severe is cyclopia, an abnormality characterized by a single eye located in the area normally occupied by the root of the nose, and a missing nose or a proboscis (a tubular-shaped nose) located above the eye. The least common facial anomaly is ethmocephaly, in which a proboscis separates closely-set eyes. Cebocephaly, another facial anomaly, is characterized by a small, flattened nose with a single nostril situated below incomplete or underdeveloped closely-set eyes.

MalaCards based summary : Holoprosencephaly, also known as holoprosencephaly sequence, is related to holoprosencephaly 1 and holoprosencephaly 7. An important gene associated with Holoprosencephaly is FGFR1 (Fibroblast Growth Factor Receptor 1), and among its related pathways/superpathways are Hedgehog signaling pathway and Pathways in cancer. Affiliated tissues include Primitive Streak, brain and eye, and related phenotypes are macrocephaly and hypertelorism

Disease Ontology : 12 A congenital nervous system abnormality characterized by failed or incomplete separation of the forebrain early in gestation; it is accompanied by a spectrum of characteristic craniofacial anomalies.

NIH Rare Diseases : 53 Holoprosencephaly is an abnormality of brain development in which the brain doesn't properly divide into the right and left hemispheres. The condition can also affect development of the head and face. There are 4 types of holoprosencephaly, distinguished by severity. From most to least severe, the 4 types are alobar, semi-lobar, lobar, and middle interhemispheric variant (MIHV). In general, the severity of any facial defects corresponds to the severity of the brain defect. The most severely affected people have one central eye (cyclopia) and a tubular nasal structure (proboscis) located above the eye. In the less severe forms, the brain is only partially divided, and the eyes usually are set close together. Other signs and symptoms often include intellectual disability and pituitary gland problems. Holoprosencephaly can be caused by mutations in any of at least 14 different genes; chromosome abnormalities; or agents that can cause birth defects (teratogens). It may also be a feature of several unique genetic syndromes. In many cases, the exact cause is unknown. Life expectancy for people with this condition varies, and treatment depends on the symptoms and severity in each person.

Wikipedia : 76 Holoprosencephaly (HPE) is a cephalic disorder in which the prosencephalon (the forebrain of the embryo)... more...

GeneReviews: NBK1530

Related Diseases for Holoprosencephaly

Diseases in the Holoprosencephaly family:

Holoprosencephaly 3 Holoprosencephaly 4
Holoprosencephaly 2 Holoprosencephaly 1
Holoprosencephaly 6 Holoprosencephaly 8
Holoprosencephaly 5 Holoprosencephaly 7
Holoprosencephaly 9 Holoprosencephaly 11
Nonsyndromic Holoprosencephaly

Diseases related to Holoprosencephaly via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 173)
# Related Disease Score Top Affiliating Genes
1 holoprosencephaly 1 34.0 GAS1 HPE1 LSS SHH SIX3
2 holoprosencephaly 7 34.0 NODAL PTCH1
3 holoprosencephaly 5 33.9 TGIF1 ZIC1 ZIC2
4 holoprosencephaly 4 33.9 SHH TGIF1 ZIC1 ZIC2
5 holoprosencephaly 8 33.8 DISP1 HPE8 TGIF1
6 holoprosencephaly, recurrent infections, and monocytosis 33.6 GLI2 PTCH1 SIX3
7 agnathia-otocephaly complex 33.5 FGF8 GLI2 NODAL SHH
8 hartsfield syndrome 33.5 FGF8 FGFR1
9 semilobar holoprosencephaly 33.3 CDON DISP1 FGF8 FGFR1 FOXH1 GAS1
10 alobar holoprosencephaly 33.2 CDON DISP1 FGF8 FOXH1 GAS1 GLI2
11 lobar holoprosencephaly 33.2 CDON DISP1 FGF8 FGFR1 FOXH1 GAS1
12 midline interhemispheric variant of holoprosencephaly 33.2 CDON DISP1 FGF8 FOXH1 GAS1 GLI2
13 microform holoprosencephaly 33.2 CDON DISP1 FGF8 FGFR1 FOXH1 GAS1
14 septopreoptic holoprosencephaly 33.1 CDON DISP1 FGF8 FOXH1 GAS1 GLI2
15 patau syndrome 30.3 NODAL SIX3 ZIC2
16 pituitary stalk interruption syndrome 30.1 CDON SHH TGIF1
17 chromosome 18p deletion syndrome 30.0 NODAL SHH SIX3 ZIC2
18 neural tube defects 29.5 MNX1 PTCH1 ZIC1 ZIC2
19 holoprosencephaly 3 12.5
20 holoprosencephaly 2 12.5
21 nonsyndromic holoprosencephaly 12.4
22 holoprosencephaly 9 12.4
23 holoprosencephaly, semilobar, with craniosynostosis 12.4
24 holoprosencephaly 11 12.4
25 holoprosencephaly 6 12.3
26 brachial amelia, cleft lip, and holoprosencephaly 12.2
27 holoprosencephaly with fetal akinesia/hypokinesia sequence 12.1
28 holoprosencephaly caudal dysgenesis 12.1
29 holoprosencephaly ectrodactyly cleft lip palate 11.9
30 pseudotrisomy 13 syndrome 11.9
31 steinfeld syndrome 11.8
32 morse-rawnsley-sargent syndrome 11.5
33 dysgnathia complex 11.4
34 lambotte syndrome 11.4
35 schizencephaly 11.3
36 solitary median maxillary central incisor 11.3
37 chromosome 1q41-q42 deletion syndrome 11.2
38 corpus callosum, agenesis of 11.1
39 heterotaxy, visceral, 1, x-linked 10.9
40 hypoglossia with situs inversus 10.9
41 hydrocephalus, congenital, 3, with brain anomalies 10.9
42 syndromic x-linked intellectual disability turner type 10.9
43 cerebellar agenesis 10.9
44 ring chromosome 18 10.9
45 x-linked intellectual disability, turner type 10.9
46 cleft lip 10.4
47 polydactyly 10.4
48 acquired schizencephaly 10.3 SHH SIX3
49 greig cephalopolysyndactyly syndrome 10.3 GLI2 PTCH1 SHH
50 bardet-biedl syndrome 17 10.3 GLI2 PTCH1 SHH

Graphical network of the top 20 diseases related to Holoprosencephaly:



Diseases related to Holoprosencephaly

Symptoms & Phenotypes for Holoprosencephaly

Human phenotypes related to Holoprosencephaly:

59 32 (show top 50) (show all 95)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 macrocephaly 59 32 occasional (7.5%) Occasional (29-5%) HP:0000256
2 hypertelorism 59 32 occasional (7.5%) Occasional (29-5%) HP:0000316
3 short neck 59 32 occasional (7.5%) Occasional (29-5%) HP:0000470
4 frontal bossing 59 32 occasional (7.5%) Occasional (29-5%) HP:0002007
5 hydrocephalus 59 32 occasional (7.5%) Occasional (29-5%) HP:0000238
6 ptosis 59 32 occasional (7.5%) Occasional (29-5%) HP:0000508
7 diabetes mellitus 59 32 frequent (33%) Frequent (79-30%) HP:0000819
8 seizures 59 32 frequent (33%) Frequent (79-30%) HP:0001250
9 muscular hypotonia 59 32 frequent (33%) Frequent (79-30%) HP:0001252
10 spasticity 59 32 frequent (33%) Frequent (79-30%) HP:0001257
11 muscle weakness 59 32 frequent (33%) Frequent (79-30%) HP:0001324
12 constipation 59 32 occasional (7.5%) Occasional (29-5%) HP:0002019
13 chorea 59 32 occasional (7.5%) Occasional (29-5%) HP:0002072
14 respiratory insufficiency 59 32 occasional (7.5%) Occasional (29-5%) HP:0002093
15 scoliosis 59 32 occasional (7.5%) Occasional (29-5%) HP:0002650
16 macrotia 59 32 occasional (7.5%) Occasional (29-5%) HP:0000400
17 global developmental delay 59 32 frequent (33%) Frequent (79-30%) HP:0001263
18 abnormal facial shape 59 32 hallmark (90%) Very frequent (99-80%) HP:0001999
19 microcephaly 59 32 frequent (33%) Frequent (79-30%) HP:0000252
20 anteverted nares 59 32 occasional (7.5%) Occasional (29-5%) HP:0000463
21 thick eyebrow 59 32 occasional (7.5%) Occasional (29-5%) HP:0000574
22 optic atrophy 59 32 occasional (7.5%) Occasional (29-5%) HP:0000648
23 gastroesophageal reflux 59 32 frequent (33%) Frequent (79-30%) HP:0002020
24 feeding difficulties in infancy 59 32 occasional (7.5%) Occasional (29-5%) HP:0008872
25 cognitive impairment 59 32 frequent (33%) Frequent (79-30%) HP:0100543
26 proteinuria 59 32 occasional (7.5%) Occasional (29-5%) HP:0000093
27 retinopathy 59 32 occasional (7.5%) Occasional (29-5%) HP:0000488
28 arrhythmia 59 32 occasional (7.5%) Occasional (29-5%) HP:0011675
29 hypoglycemia 59 32 frequent (33%) Frequent (79-30%) HP:0001943
30 joint hyperflexibility 59 32 occasional (7.5%) Occasional (29-5%) HP:0005692
31 epicanthus 59 32 occasional (7.5%) Occasional (29-5%) HP:0000286
32 abnormal form of the vertebral bodies 59 32 occasional (7.5%) Occasional (29-5%) HP:0003312
33 cryptorchidism 59 32 occasional (7.5%) Occasional (29-5%) HP:0000028
34 failure to thrive in infancy 59 32 occasional (7.5%) Occasional (29-5%) HP:0001531
35 external ear malformation 59 32 occasional (7.5%) Occasional (29-5%) HP:0008572
36 dystonia 59 32 frequent (33%) Frequent (79-30%) HP:0001332
37 abnormality of neuronal migration 59 32 occasional (7.5%) Occasional (29-5%) HP:0002269
38 aplasia/hypoplasia of the cerebellum 59 32 occasional (7.5%) Occasional (29-5%) HP:0007360
39 chorioretinal coloboma 59 32 occasional (7.5%) Occasional (29-5%) HP:0000567
40 depressed nasal ridge 59 32 frequent (33%) Frequent (79-30%) HP:0000457
41 microphthalmia 59 32 frequent (33%) Frequent (79-30%) HP:0000568
42 deeply set eye 59 32 occasional (7.5%) Occasional (29-5%) HP:0000490
43 diabetes insipidus 59 32 occasional (7.5%) Occasional (29-5%) HP:0000873
44 abnormality of the antihelix 59 32 occasional (7.5%) Occasional (29-5%) HP:0009738
45 upslanted palpebral fissure 59 32 occasional (7.5%) Occasional (29-5%) HP:0000582
46 brachydactyly 59 32 occasional (7.5%) Occasional (29-5%) HP:0001156
47 tetralogy of fallot 59 32 occasional (7.5%) Occasional (29-5%) HP:0001636
48 choanal atresia 59 32 frequent (33%) Frequent (79-30%) HP:0000453
49 hand polydactyly 59 32 occasional (7.5%) Occasional (29-5%) HP:0001161
50 ventricular septal defect 59 32 occasional (7.5%) Occasional (29-5%) HP:0001629

MGI Mouse Phenotypes related to Holoprosencephaly:

46 (show all 18)
# Description MGI Source Accession Score Top Affiliating Genes
1 growth/size/body region MP:0005378 10.41 CDON DHCR7 DISP1 FGF8 FGFR1 FOXH1
2 craniofacial MP:0005382 10.39 CDON DHCR7 DISP1 FGF8 FGFR1 FOXH1
3 cardiovascular system MP:0005385 10.38 CDON DHCR7 DISP1 FGF8 FGFR1 FOXH1
4 mortality/aging MP:0010768 10.36 CDON DHCR7 DISP1 FGF8 FGFR1 FOXH1
5 behavior/neurological MP:0005386 10.35 CDON DHCR7 FGF8 FGFR1 GAS1 GLI2
6 digestive/alimentary MP:0005381 10.35 CDON DHCR7 DISP1 FGF8 FGFR1 FOXH1
7 cellular MP:0005384 10.34 CDON DISP1 FGF8 FGFR1 GAS1 GLI2
8 embryo MP:0005380 10.34 CDON DISP1 FGF8 FGFR1 FOXH1 GAS1
9 nervous system MP:0003631 10.27 CDON DHCR7 DISP1 FGF8 FGFR1 FOXH1
10 homeostasis/metabolism MP:0005376 10.26 DHCR7 DISP1 FGF8 FGFR1 FOXH1 GAS1
11 limbs/digits/tail MP:0005371 10.2 CDON DHCR7 DISP1 FGF8 FGFR1 GAS1
12 muscle MP:0005369 10.14 DHCR7 DISP1 FGF8 FGFR1 FOXH1 GLI2
13 hearing/vestibular/ear MP:0005377 10.1 FGF8 FGFR1 FOXH1 GAS1 GLI2 PTCH1
14 respiratory system MP:0005388 10.07 CDON DHCR7 DISP1 FGF8 FOXH1 GAS1
15 normal MP:0002873 10.06 DISP1 FGF8 FGFR1 FOXH1 GLI2 MNX1
16 skeleton MP:0005390 10.03 CDON DISP1 FGF8 FGFR1 FOXH1 GAS1
17 vision/eye MP:0005391 9.47 CDON DISP1 FGF8 FGFR1 FOXH1 GAS1
18 taste/olfaction MP:0005394 9.35 NODAL PTCH1 SHH SIX3 TGIF1

Drugs & Therapeutics for Holoprosencephaly

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Study of the Experiences and Needs of Parents Continuing a Pregnancy Following a Prenatal Diagnosis of Holopresencephaly Completed NCT00005016
2 Genetic Analysis of Left-Right Axis Formations Completed NCT00341133
3 Clinical and Genetic Studies on Holoprosencephaly Recruiting NCT00088426
4 A Study of the Genetic Analysis of Brain Disorders Recruiting NCT00645645

Search NIH Clinical Center for Holoprosencephaly

Cochrane evidence based reviews: holoprosencephaly

Genetic Tests for Holoprosencephaly

Genetic tests related to Holoprosencephaly:

# Genetic test Affiliating Genes
1 Holoprosencephaly Sequence 29 FOXH1 NODAL

Anatomical Context for Holoprosencephaly

MalaCards organs/tissues related to Holoprosencephaly:

41
Brain, Eye, Pituitary, Bone, Heart, Cerebellum, Kidney
LifeMap Discovery
Data from LifeMap, the Embryonic Development and Stem Cells Database

Cells/anatomical compartments in embryo or adult related to Holoprosencephaly:
# Tissue Anatomical CompartmentCell Relevance
1 Primitive Streak Primitive Streak Affected by disease

Publications for Holoprosencephaly

Articles related to Holoprosencephaly:

(show top 50) (show all 871)
# Title Authors Year
1
Functions of TGIF homeodomain proteins and their roles in normal brain development and holoprosencephaly. ( 29749689 )
2018
2
Clinical and Demographic Evaluation of a Holoprosencephaly Cohort From the Kyoto Collection of Human Embryos. ( 29663664 )
2018
3
Extracephalic manifestations of nonchromosomal, nonsyndromic holoprosencephaly. ( 29761634 )
2018
4
Holoprosencephaly in the genomics era. ( 29770992 )
2018
5
50 Years Ago in The Journal of Pediatrics: Familial Holoprosencephaly with Endocrine Dysgenesis. ( 29246365 )
2018
6
Semilobar holoprosencephaly with cebocephaly associated with maternal early onset preeclampsia: a case report. ( 29980223 )
2018
7
Loss-of-function mutations in FGF8 can be independent risk factors for holoprosencephaly. ( 29584859 )
2018
8
Nongenetic risk factors for holoprosencephaly: An updated review of the epidemiologic literature. ( 29761639 )
2018
9
Genetic and Rare Disease of the CNS. Part II: Holoprosencephaly (HPE). ( 29665691 )
2018
10
Holoprosencephaly: A clinical genomics perspective. ( 29749690 )
2018
11
Recent advances in understanding inheritance of holoprosencephaly. ( 29785796 )
2018
12
Solitary median maxillary central incisor, holoprosencephaly and congenital nasal pyriform aperture stenosis in a premature infant: case report. ( 29333838 )
2018
13
Syndromes associated with holoprosencephaly. ( 29770994 )
2018
14
Link between the causative genes of holoprosencephaly: Zic2 directly regulates Tgif1 expression. ( 29391420 )
2018
15
Modeling the complex etiology of holoprosencephaly in mice. ( 29749693 )
2018
16
Management Strategies for Hydrocephalus in Alobar Holoprosencephaly: A Case Report and Discussion. ( 29902800 )
2018
17
Molecular testing in holoprosencephaly. ( 29771000 )
2018
18
Structural insights into the impact of two holoprosencephaly-related mutations on human TGIF1 homeodomain. ( 29355528 )
2018
19
Prenatal diagnosis of holoprosencephaly. ( 29770996 )
2018
20
ZIC2 in Holoprosencephaly. ( 29442327 )
2018
21
Alobar holoprosencephaly associated with a rare chromosomal abnormality: Case report and literature review. ( 30024536 )
2018
22
Common genetic causes of holoprosencephaly are limited to a small set of evolutionarily conserved driver genes of midline development coordinated by TGF-β, hedgehog, and FGF signaling. ( 29992659 )
2018
23
Neuropathology of holoprosencephaly. ( 30182440 )
2018
24
Challenging issues arising in counseling families experiencing holoprosencephaly. ( 30182441 )
2018
25
Cytogenetics and holoprosencephaly: A chromosomal microarray study of 222 individuals with holoprosencephaly. ( 30182442 )
2018
26
Holoprosencephaly flashcards: An updated summary for the clinician. ( 30182444 )
2018
27
Further evidence for complex inheritance of holoprosencephaly: Lessons learned from pre- and postnatal diagnostic testing in Germany. ( 30182445 )
2018
28
Holoprosencephaly from conception to adulthood. ( 30182446 )
2018
29
Low-level parental mosaicism affects the recurrence risk of holoprosencephaly. ( 30197418 )
2018
30
MRI of lobar holoprosencephaly in a cat with hypodipsic hypernatraemia. ( 30263144 )
2018
31
Integrated clinical and omics approach to rare diseases: novel genes and oligogenic inheritance in holoprosencephaly. ( 30508070 )
2018
32
Digynic triploidy in a fetus presenting with semilobar holoprosencephaly. ( 30545546 )
2018
33
SIX3 deletions and incomplete penetrance in families affected by holoprosencephaly. ( 28670735 )
2017
34
Facial Evaluation in Holoprosencephaly. ( 27875510 )
2017
35
Endocytic receptor LRP2/megalin-of holoprosencephaly and renal Fanconi syndrome. ( 28497274 )
2017
36
Prenatal diagnosis of monosomy 18p associated with holoprosencephaly: case report. ( 28513240 )
2017
37
Ethanol itself is a holoprosencephaly-inducing teratogen. ( 28441416 )
2017
38
Trisomy 18 and holoprosencephaly. ( 28449414 )
2017
39
Pancreas and gallbladder agenesis in a newborn with semilobar holoprosencephaly, a case report. ( 28525974 )
2017
40
7q Deletion/12q Duplication Is the Possible Cause of an Alobar Holoprosencephaly Case. ( 29456484 )
2017
41
Semi Lobar Holoprosencephaly with Vertebral Segmentation Defects. ( 28883880 )
2017
42
Expanding the FANCO/RAD51C associated phenotype: Cleft lip and palate and lobar holoprosencephaly, two rare findings in Fanconi anemia. ( 29278735 )
2017
43
"Minimal" holoprosencephaly in a 14q deletion syndrome patient. ( 29136354 )
2017
44
Holoprosencephaly. ( 29259929 )
2017
45
BOC is a modifier gene in holoprosencephaly. ( 28677295 )
2017
46
In-depth investigations of adolescents and adults with holoprosencephaly identify unique characteristics. ( 28640243 )
2017
47
Prenatal diagnosis of holoprosencephaly associated with Smith-Lemli-Opitz syndrome (SLOS) in a 46,XX fetus. ( 28805615 )
2017
48
Cyclopia and proboscis - the extreme end of holoprosencephaly. ( 29556657 )
2017
49
Complex mode of inheritance in holoprosencephaly revealed by whole exome sequencing. ( 26748417 )
2016
50
The middle interhemispheric variant of holoprosencephaly: magnetic resonance and diffusion tensor imaging findings. ( 27089898 )
2016

Variations for Holoprosencephaly

ClinVar genetic disease variations for Holoprosencephaly:

6 (show top 50) (show all 1014)
# Gene Variation Type Significance SNP ID Assembly Location
1 PTCH1 NM_000264.3(PTCH1): c.2183C> T (p.Thr728Met) single nucleotide variant Conflicting interpretations of pathogenicity rs115556836 GRCh37 Chromosome 9, 98231100: 98231100
2 PTCH1 NM_000264.3(PTCH1): c.2183C> T (p.Thr728Met) single nucleotide variant Conflicting interpretations of pathogenicity rs115556836 GRCh38 Chromosome 9, 95468818: 95468818
3 PTCH1 NM_000264.3(PTCH1): c.3155C> T (p.Thr1052Met) single nucleotide variant Likely benign rs138911275 GRCh37 Chromosome 9, 98220308: 98220308
4 PTCH1 NM_000264.3(PTCH1): c.3155C> T (p.Thr1052Met) single nucleotide variant Likely benign rs138911275 GRCh38 Chromosome 9, 95458026: 95458026
5 GLI2 NM_005270.4(GLI2): c.4663T> C (p.Ser1555Pro) single nucleotide variant Conflicting interpretations of pathogenicity rs144372453 GRCh37 Chromosome 2, 121748153: 121748153
6 GLI2 NM_005270.4(GLI2): c.4663T> C (p.Ser1555Pro) single nucleotide variant Conflicting interpretations of pathogenicity rs144372453 GRCh38 Chromosome 2, 120990577: 120990577
7 GLI2 NM_005270.4(GLI2): c.4558G> A (p.Asp1520Asn) single nucleotide variant Conflicting interpretations of pathogenicity rs114814747 GRCh37 Chromosome 2, 121748048: 121748048
8 GLI2 NM_005270.4(GLI2): c.4558G> A (p.Asp1520Asn) single nucleotide variant Conflicting interpretations of pathogenicity rs114814747 GRCh38 Chromosome 2, 120990472: 120990472
9 PTCH1 NM_000264.4(PTCH1): c.2678G> A (p.Arg893His) single nucleotide variant Conflicting interpretations of pathogenicity rs138154222 GRCh37 Chromosome 9, 98224163: 98224163
10 PTCH1 NM_000264.4(PTCH1): c.2678G> A (p.Arg893His) single nucleotide variant Conflicting interpretations of pathogenicity rs138154222 GRCh38 Chromosome 9, 95461881: 95461881
11 PTCH1 NM_000264.4(PTCH1): c.3845C> T (p.Pro1282Leu) single nucleotide variant Benign/Likely benign rs2227968 GRCh37 Chromosome 9, 98209693: 98209693
12 PTCH1 NM_000264.4(PTCH1): c.3845C> T (p.Pro1282Leu) single nucleotide variant Benign/Likely benign rs2227968 GRCh38 Chromosome 9, 95447411: 95447411
13 PTCH1 NM_000264.3(PTCH1): c.3944C> T (p.Pro1315Leu) single nucleotide variant Benign rs357564 GRCh37 Chromosome 9, 98209594: 98209594
14 PTCH1 NM_000264.3(PTCH1): c.3944C> T (p.Pro1315Leu) single nucleotide variant Benign rs357564 GRCh38 Chromosome 9, 95447312: 95447312
15 PTCH1 NM_000264.4(PTCH1): c.4027G> A (p.Gly1343Arg) single nucleotide variant Conflicting interpretations of pathogenicity rs200100952 GRCh37 Chromosome 9, 98209511: 98209511
16 PTCH1 NM_000264.4(PTCH1): c.4027G> A (p.Gly1343Arg) single nucleotide variant Conflicting interpretations of pathogenicity rs200100952 GRCh38 Chromosome 9, 95447229: 95447229
17 PTCH1 NM_000264.4(PTCH1): c.4324C> T (p.Arg1442Trp) single nucleotide variant Conflicting interpretations of pathogenicity rs143464326 GRCh37 Chromosome 9, 98209214: 98209214
18 PTCH1 NM_000264.4(PTCH1): c.4324C> T (p.Arg1442Trp) single nucleotide variant Conflicting interpretations of pathogenicity rs143464326 GRCh38 Chromosome 9, 95446932: 95446932
19 PTCH1 NM_000264.4(PTCH1): c.4325G> A (p.Arg1442Gln) single nucleotide variant Conflicting interpretations of pathogenicity rs56023271 GRCh37 Chromosome 9, 98209213: 98209213
20 PTCH1 NM_000264.4(PTCH1): c.4325G> A (p.Arg1442Gln) single nucleotide variant Conflicting interpretations of pathogenicity rs56023271 GRCh38 Chromosome 9, 95446931: 95446931
21 PTCH1 NM_000264.4(PTCH1): c.4080C> T (p.Ser1360=) single nucleotide variant Benign/Likely benign rs62637631 GRCh37 Chromosome 9, 98209458: 98209458
22 PTCH1 NM_000264.4(PTCH1): c.4080C> T (p.Ser1360=) single nucleotide variant Benign/Likely benign rs62637631 GRCh38 Chromosome 9, 95447176: 95447176
23 FOXH1 NM_003923.2(FOXH1): c.338G> C (p.Ser113Thr) single nucleotide variant Benign/Likely benign rs144830740 GRCh37 Chromosome 8, 145700381: 145700381
24 FOXH1 NM_003923.2(FOXH1): c.338G> C (p.Ser113Thr) single nucleotide variant Benign/Likely benign rs144830740 GRCh38 Chromosome 8, 144474998: 144474998
25 GLI2 NM_005270.4(GLI2): c.3349G> T (p.Val1117Leu) single nucleotide variant Benign/Likely benign rs147580961 GRCh37 Chromosome 2, 121746839: 121746839
26 GLI2 NM_005270.4(GLI2): c.3349G> T (p.Val1117Leu) single nucleotide variant Benign/Likely benign rs147580961 GRCh38 Chromosome 2, 120989263: 120989263
27 GLI2 NM_005270.4(GLI2): c.3466G> T (p.Ala1156Ser) single nucleotide variant Benign rs3738880 GRCh37 Chromosome 2, 121746956: 121746956
28 GLI2 NM_005270.4(GLI2): c.3466G> T (p.Ala1156Ser) single nucleotide variant Benign rs3738880 GRCh38 Chromosome 2, 120989380: 120989380
29 GLI2 NM_005270.4(GLI2): c.3916G> A (p.Asp1306Asn) single nucleotide variant Benign rs12711538 GRCh37 Chromosome 2, 121747406: 121747406
30 GLI2 NM_005270.4(GLI2): c.3916G> A (p.Asp1306Asn) single nucleotide variant Benign rs12711538 GRCh38 Chromosome 2, 120989830: 120989830
31 GLI2 NM_005270.4(GLI2): c.3939A> G (p.Pro1313=) single nucleotide variant Benign rs10167980 GRCh37 Chromosome 2, 121747429: 121747429
32 GLI2 NM_005270.4(GLI2): c.3939A> G (p.Pro1313=) single nucleotide variant Benign rs10167980 GRCh38 Chromosome 2, 120989853: 120989853
33 GLI2 NM_005270.4(GLI2): c.3943C> T (p.Pro1315Ser) single nucleotide variant Benign/Likely benign rs114376238 GRCh37 Chromosome 2, 121747433: 121747433
34 GLI2 NM_005270.4(GLI2): c.3943C> T (p.Pro1315Ser) single nucleotide variant Benign/Likely benign rs114376238 GRCh38 Chromosome 2, 120989857: 120989857
35 CDON NM_016952.4(CDON): c.223G> A (p.Val75Ile) single nucleotide variant Benign rs3740912 GRCh37 Chromosome 11, 125891269: 125891269
36 CDON NM_016952.4(CDON): c.223G> A (p.Val75Ile) single nucleotide variant Benign rs3740912 GRCh38 Chromosome 11, 126021374: 126021374
37 CDON NM_016952.4(CDON): c.330T> C (p.Pro110=) single nucleotide variant Benign/Likely benign rs35131477 GRCh37 Chromosome 11, 125891162: 125891162
38 CDON NM_016952.4(CDON): c.330T> C (p.Pro110=) single nucleotide variant Benign/Likely benign rs35131477 GRCh38 Chromosome 11, 126021267: 126021267
39 NODAL NM_018055.4(NODAL): c.193+12C> T single nucleotide variant Benign rs10999338 GRCh37 Chromosome 10, 72201219: 72201219
40 NODAL NM_018055.4(NODAL): c.193+12C> T single nucleotide variant Benign rs10999338 GRCh38 Chromosome 10, 70441463: 70441463
41 NODAL NM_018055.4(NODAL): c.494A> G (p.His165Arg) single nucleotide variant Benign rs1904589 GRCh37 Chromosome 10, 72195439: 72195439
42 NODAL NM_018055.4(NODAL): c.494A> G (p.His165Arg) single nucleotide variant Benign rs1904589 GRCh38 Chromosome 10, 70435683: 70435683
43 PTCH1 NM_000264.4(PTCH1): c.2199A> G (p.Ser733=) single nucleotide variant Benign/Likely benign rs2227970 GRCh37 Chromosome 9, 98231084: 98231084
44 PTCH1 NM_000264.4(PTCH1): c.2199A> G (p.Ser733=) single nucleotide variant Benign/Likely benign rs2227970 GRCh38 Chromosome 9, 95468802: 95468802
45 PTCH1 NM_000264.4(PTCH1): c.1641C> T (p.Ser547=) single nucleotide variant Benign/Likely benign rs2066830 GRCh37 Chromosome 9, 98238403: 98238403
46 PTCH1 NM_000264.4(PTCH1): c.1641C> T (p.Ser547=) single nucleotide variant Benign/Likely benign rs2066830 GRCh38 Chromosome 9, 95476121: 95476121
47 PTCH1 NM_000264.4(PTCH1): c.318C> T (p.Leu106=) single nucleotide variant Benign/Likely benign rs1805153 GRCh37 Chromosome 9, 98268765: 98268765
48 PTCH1 NM_000264.4(PTCH1): c.318C> T (p.Leu106=) single nucleotide variant Benign/Likely benign rs1805153 GRCh38 Chromosome 9, 95506483: 95506483
49 PTCH1 NM_000264.4(PTCH1): c.735A> G (p.Thr245=) single nucleotide variant Benign/Likely benign rs1805154 GRCh37 Chromosome 9, 98244242: 98244242
50 PTCH1 NM_000264.4(PTCH1): c.735A> G (p.Thr245=) single nucleotide variant Benign/Likely benign rs1805154 GRCh38 Chromosome 9, 95481960: 95481960

Copy number variations for Holoprosencephaly from CNVD:

7 (show all 17)
# CNVD ID Chromosom Start End Type Gene Symbol CNVD Disease
1 27741 1 212100000 222100000 Deletion DISP1 Holoprosencephaly
2 27742 10 53744046 53747423 Deletion DKK1 Holoprosencephaly
3 27743 2 121271336 121449155 Deletion GLI2 Holoprosencephaly
4 27745 1 212100000 222100000 Deletion PATCHED Holoprosencephaly
5 27746 7 155285496 155297728 Deletion SHH Holoprosencephaly
6 27747 1 212100000 222100000 Deletion SIL Holoprosencephaly
7 27748 2 45022540 45025894 Deletion SIX3 Holoprosencephaly
8 27749 1 212100000 222100000 Deletion SMOOTHENED Holoprosencephaly
9 27750 1 212100000 222100000 Deletion TGIF Holoprosencephaly
10 27751 13 99432319 99437020 Deletion ZIC2 Holoprosencephaly
11 80937 13 99432319 99437020 Microdeletion ZIC2 Holoprosencephaly
12 91539 15 31400000 37900000 Deletion Holoprosencephaly
13 93580 15 55800000 65300000 Deletion Holoprosencephaly
14 120908 18 3402071 3448406 Microdeletion TGIF Holoprosencephaly
15 146030 2 45022540 45025894 Microdeletion SIX3 Holoprosencephaly
16 210238 6 29900000 45200000 Gain Holoprosencephaly
17 222729 7 155285496 155297728 Microdeletion SHH Holoprosencephaly

Expression for Holoprosencephaly

Search GEO for disease gene expression data for Holoprosencephaly.

Pathways for Holoprosencephaly

Pathways related to Holoprosencephaly according to KEGG:

37
# Name Kegg Source Accession
1 Hedgehog signaling pathway hsa04340

GO Terms for Holoprosencephaly

Biological processes related to Holoprosencephaly according to GeneCards Suite gene sharing:

(show top 50) (show all 62)
# Name GO ID Score Top Affiliating Genes
1 heart development GO:0007507 9.98 FGF8 GLI2 NODAL SHH
2 in utero embryonic development GO:0001701 9.97 FGFR1 GLI2 NODAL PTCH1
3 regulation of cell proliferation GO:0042127 9.91 DHCR7 FGFR1 PTCH1 SHH SIX3
4 kidney development GO:0001822 9.9 FGF8 GLI2 SHH
5 positive regulation of neuron differentiation GO:0045666 9.87 CDON FGFR1 GLI2
6 inner ear morphogenesis GO:0042472 9.85 FGF8 FGFR1 ZIC1
7 smoothened signaling pathway GO:0007224 9.84 CDON GLI2 PTCH1 SHH
8 embryonic limb morphogenesis GO:0030326 9.83 FGFR1 PTCH1 SHH
9 pattern specification process GO:0007389 9.83 GLI2 PTCH1 SHH ZIC1
10 branching involved in ureteric bud morphogenesis GO:0001658 9.81 FGF8 PTCH1 SHH
11 brain development GO:0007420 9.8 FGFR1 NODAL PTCH1 SIX3 ZIC1 ZIC2
12 cell fate commitment GO:0045165 9.78 FGF8 GAS1 NODAL SHH
13 developmental growth GO:0048589 9.77 GAS1 GLI2 SHH
14 anatomical structure development GO:0048856 9.76 GLI2 SHH SIX3
15 heart looping GO:0001947 9.76 FGF8 FOXH1 NODAL SHH
16 anatomical structure formation involved in morphogenesis GO:0048646 9.74 GLI2 NODAL SHH
17 hindbrain development GO:0030902 9.73 GLI2 SHH
18 lung morphogenesis GO:0060425 9.73 FGF8 SHH
19 embryonic heart tube development GO:0035050 9.73 FGF8 NODAL
20 cell fate specification GO:0001708 9.73 CDON SHH
21 embryonic pattern specification GO:0009880 9.73 DISP1 NODAL SHH
22 male genitalia development GO:0030539 9.72 FGF8 SHH
23 osteoblast development GO:0002076 9.72 GLI2 SHH
24 pharyngeal system development GO:0060037 9.72 FGF8 PTCH1
25 spinal cord motor neuron differentiation GO:0021522 9.72 GLI2 PTCH1 SHH
26 embryonic morphogenesis GO:0048598 9.71 CDON SHH
27 somite development GO:0061053 9.71 PTCH1 SHH
28 aorta morphogenesis GO:0035909 9.71 FGF8 FOXH1
29 digestive tract morphogenesis GO:0048546 9.71 NODAL SHH
30 negative regulation of androgen receptor signaling pathway GO:0060766 9.7 FOXH1 NODAL
31 prostate gland development GO:0030850 9.7 PTCH1 SHH
32 striated muscle cell differentiation GO:0051146 9.7 CDON SHH
33 generation of neurons GO:0048699 9.69 FGF8 FGFR1
34 cell proliferation in forebrain GO:0021846 9.69 FGF8 SIX3
35 organ induction GO:0001759 9.68 FGF8 FGFR1
36 positive regulation of T cell differentiation in thymus GO:0033089 9.68 GLI2 SHH
37 positive regulation of skeletal muscle tissue development GO:0048643 9.68 CDON SHH
38 lung-associated mesenchyme development GO:0060484 9.67 FGFR1 SHH
39 dorsal/ventral neural tube patterning GO:0021904 9.67 GLI2 PTCH1 SHH
40 dorsal/ventral pattern formation GO:0009953 9.67 DISP1 GLI2 PTCH1 SHH
41 forebrain dorsal/ventral pattern formation GO:0021798 9.66 FGF8 SIX3
42 smoothened signaling pathway involved in dorsal/ventral neural tube patterning GO:0060831 9.66 GLI2 PTCH1
43 telencephalon regionalization GO:0021978 9.65 SHH SIX3
44 mammary gland duct morphogenesis GO:0060603 9.65 GLI2 PTCH1
45 anterior/posterior pattern specification GO:0009952 9.65 CDON FOXH1 GLI2 NODAL SHH
46 spinal cord dorsal/ventral patterning GO:0021513 9.64 GLI2 SHH
47 formation of anatomical boundary GO:0048859 9.63 NODAL SHH
48 hindgut morphogenesis GO:0007442 9.62 GLI2 SHH
49 smoothened signaling pathway involved in regulation of cerebellar granule cell precursor cell proliferation GO:0021938 9.62 GLI2 SHH
50 nodal signaling pathway involved in determination of lateral mesoderm left/right asymmetry GO:1900164 9.61 FOXH1 NODAL

Molecular functions related to Holoprosencephaly according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 DNA-binding transcription factor activity, RNA polymerase II-specific GO:0000981 9.87 FOXH1 GLI2 MNX1 SIX3 TGIF1 ZIC1
2 co-SMAD binding GO:0070410 9.26 FOXH1 TGIF1
3 DNA-binding transcription factor activity GO:0003700 9.17 FOXH1 GLI2 MNX1 SIX3 TGIF1 ZIC1
4 patched binding GO:0005113 9.16 PTCH1 SHH
5 morphogen activity GO:0016015 8.96 NODAL SHH

Sources for Holoprosencephaly

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 ExPASy
19 FMA
28 GO
29 GTR
30 HGMD
31 HMDB
32 HPO
33 ICD10
34 ICD10 via Orphanet
35 ICD9CM
36 IUPHAR
37 KEGG
38 LifeMap
40 LOVD
42 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
54 NINDS
55 Novoseek
57 OMIM
58 OMIM via Orphanet
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 SNOMED-CT via Orphanet
71 TGDB
72 Tocris
73 UMLS
74 UMLS via Orphanet
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