HPE
MCID: HLP001
MIFTS: 66

Holoprosencephaly (HPE)

Categories: Endocrine diseases, Eye diseases, Fetal diseases, Genetic diseases, Neuronal diseases, Rare diseases
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Aliases & Classifications for Holoprosencephaly

MalaCards integrated aliases for Holoprosencephaly:

Name: Holoprosencephaly 11 24 19 52 58 75 53 43 14 38 31 33
Holoprosencephaly Sequence 11 28 5
Hpe 19 58
Hpe - [holoprosencephaly] 33

Characteristics:


Inheritance:

Autosomal recessive,Multigenic/multifactorial,Oligogenic,X-linked dominant 58

Prevelance:

1-5/10000 (Europe, Latin America, Specific population) 6-9/10000 (Taiwan, Province of China) >1/1000 (Japan) 58

Age Of Onset:

Antenatal,Neonatal 58

Classifications:

Orphanet: 58  
Rare neurological diseases
Rare endocrine diseases
Developmental anomalies during embryogenesis


Summaries for Holoprosencephaly

NINDS: 52 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 9 and holoprosencephaly 7. An important gene associated with Holoprosencephaly is FGFR1 (Fibroblast Growth Factor Receptor 1), and among its related pathways/superpathways are Signal Transduction and Signaling by Hedgehog. Affiliated tissues include Primitive Streak, brain and eye, and related phenotypes are abnormal facial shape and holoprosencephaly

GARD: 19 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 genetic changes 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.

Orphanet: 58 A rare complex brain malformation characterized by incomplete cleavage of the prosencephalon, and affecting both the forebrain and face and resulting in neurological manifestations and facial anomalies of variable severity.

Disease Ontology: 11 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.

Wikipedia: 75 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
Holoprosencephaly 14 Nonsyndromic Holoprosencephaly

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

(show top 50) (show all 475)
# Related Disease Score Top Affiliating Genes
1 holoprosencephaly 9 33.3 ZIC2 SIX3 SHH GLI2
2 holoprosencephaly 7 33.2 ZIC2 STAG2 SIX3 PTCH1 GLI2
3 hartsfield syndrome 33.2 FGFR1 FGF8
4 holoprosencephaly 3 33.2 ZIC2 SIX3 SHH PTCH1 GLI2 FOXH1
5 holoprosencephaly 4 33.1 ZIC2 TGIF1 SIX3 SHH FOXH1 FGF8
6 holoprosencephaly 11 33.1 ZIC2 TGIF1 SIX3 SHH PTCH1 GLI2
7 holoprosencephaly 8 33.0 ZIC2 SIX3 HPE8
8 holoprosencephaly 6 33.0 ZIC2 SIX3 SHH PTCH1 HPE6
9 holoprosencephaly 1 32.9 ZRSR2 ZIC2 SIX3 SHH MATN4 HPE1
10 alobar holoprosencephaly 32.8 ZIC2 TGIF1 STAG2 SIX3 SHH PTCH1
11 semilobar holoprosencephaly 32.8 ZIC2 TGIF1 STAG2 SIX3 SHH PTCH1
12 microform holoprosencephaly 32.8 ZIC2 TGIF1 SIX3 SHH PTCH1 NODAL
13 lobar holoprosencephaly 32.8 ZIC2 TGIF1 SIX3 SHH PTCH1 NODAL
14 midline interhemispheric variant of holoprosencephaly 32.8 ZIC2 TGIF1 SIX3 SHH PTCH1 NODAL
15 septopreoptic holoprosencephaly 32.5 ZIC2 TGIF1 SIX3 SHH PTCH1 NODAL
16 holoprosencephaly, recurrent infections, and monocytosis 32.4 SIX3 PTCH1 GLI2
17 patau syndrome 32.3 ZIC2 SIX3 SHH NODAL GLI2 FOXH1
18 culler-jones syndrome 32.1 TGIF1 SIX3 SHH GLI2 CDON
19 cleft lip 31.7 SHH PTCH1 FGFR1 FGF8
20 polydactyly 31.5 ZIC2 SIX3 SHH PTCH1 GLI2 DHCR7
21 cleft palate, isolated 31.4 SHH PTCH1 GLI2 FGFR1 FGF8
22 microcephaly 31.4 ZIC2 ZIC1 TGIF1 STAG2 SHH PTCH1
23 chromosome 18p deletion syndrome 31.3 ZIC2 TGIF1 SIX3
24 solitary median maxillary central incisor 31.3 ZIC2 TGIF1 SIX3 SHH PTCH1 NODAL
25 anencephaly 31.1 ZIC2 SIX3 SHH
26 orofaciodigital syndrome viii 31.1 ZIC2 SIX3 SHH
27 smith-lemli-opitz syndrome 31.1 ZIC2 SIX3 SHH DHCR7
28 neural tube defects 31.1 ZIC2 ZIC1 SHH PTCH1 FGF8
29 septooptic dysplasia 31.0 ZIC2 STAG2 SIX3 SHH GLI2 FGFR1
30 coloboma of macula 31.0 ZIC2 SIX3 SHH PTCH1 FGFR1 FGF8
31 craniosynostosis 30.9 ZIC1 SHH GLI2 FGFR1 FGF8
32 choanal atresia, posterior 30.9 SHH FGFR1 FGF8
33 hypopituitarism 30.8 SIX3 SHH GLI2
34 pallister-hall syndrome 30.8 ZIC2 SIX3 SHH PTCH1 GLI2 FGF8
35 basal cell nevus syndrome 30.8 SHH PTCH1 GLI2 CDON
36 ventricular septal defect 30.7 NODAL FOXH1 FGF8
37 orofacial cleft 30.7 ZIC2 SIX3 SHH PTCH1 GLI2 FGFR1
38 anus, imperforate 30.6 SHH GLI2 FGF8
39 exencephaly 30.6 TGIF1 HPE6
40 kallmann syndrome 30.6 SIX3 PTCH1 FGFR1 FGF8
41 chromosome 2q35 duplication syndrome 30.5 SHH PTCH1 GLI2 FGFR1 FGF8 DHCR7
42 colobomatous microphthalmia 30.5 SIX3 SHH PTCH1
43 synostosis 30.5 ZIC1 SHH FGFR1 FGF8 DHCR7
44 tetralogy of fallot 30.4 SHH NODAL FOXH1 FGF8
45 vacterl association 30.3 ZIC2 SHH GLI2 FGF8
46 double outlet right ventricle 30.2 SHH NODAL FOXH1 FGF8
47 hypospadias 30.2 SHH FGF8 DHCR7
48 dysostosis 29.9 SHH FGFR1 FGF8
49 nonsyndromic holoprosencephaly 11.7
50 agnathia-otocephaly complex 11.6

Graphical network of the top 20 diseases related to Holoprosencephaly:



Diseases related to Holoprosencephaly

Symptoms & Phenotypes for Holoprosencephaly

Human phenotypes related to Holoprosencephaly:

58 30 (show top 50) (show all 96)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 abnormal facial shape 58 30 Hallmark (90%) Very frequent (99-80%)
HP:0001999
2 holoprosencephaly 58 30 Hallmark (90%) Very frequent (99-80%)
HP:0001360
3 median cleft lip and palate 58 30 Hallmark (90%) Very frequent (99-80%)
HP:0008501
4 bilateral cleft lip 58 30 Hallmark (90%) Very frequent (99-80%)
HP:0100336
5 solitary median maxillary central incisor 30 Hallmark (90%) HP:0006315
6 seizure 58 30 Frequent (33%) Frequent (79-30%)
HP:0001250
7 spasticity 58 30 Frequent (33%) Frequent (79-30%)
HP:0001257
8 diabetes mellitus 58 30 Frequent (33%) Frequent (79-30%)
HP:0000819
9 hypotonia 58 30 Frequent (33%) Frequent (79-30%)
HP:0001252
10 muscle weakness 58 30 Frequent (33%) Frequent (79-30%)
HP:0001324
11 global developmental delay 58 30 Frequent (33%) Frequent (79-30%)
HP:0001263
12 microcephaly 58 30 Frequent (33%) Frequent (79-30%)
HP:0000252
13 gastroesophageal reflux 58 30 Frequent (33%) Frequent (79-30%)
HP:0002020
14 cognitive impairment 58 30 Frequent (33%) Frequent (79-30%)
HP:0100543
15 hypoglycemia 58 30 Frequent (33%) Frequent (79-30%)
HP:0001943
16 depressed nasal ridge 58 30 Frequent (33%) Frequent (79-30%)
HP:0000457
17 anosmia 58 30 Frequent (33%) Frequent (79-30%)
HP:0000458
18 iris coloboma 58 30 Frequent (33%) Frequent (79-30%)
HP:0000612
19 choanal atresia 58 30 Frequent (33%) Frequent (79-30%)
HP:0000453
20 anophthalmia 58 30 Frequent (33%) Frequent (79-30%)
HP:0000528
21 microphthalmia 58 30 Frequent (33%) Frequent (79-30%)
HP:0000568
22 dystonia 58 30 Frequent (33%) Frequent (79-30%)
HP:0001332
23 hypotelorism 58 30 Frequent (33%) Frequent (79-30%)
HP:0000601
24 aplasia/hypoplasia of the corpus callosum 58 30 Frequent (33%) Frequent (79-30%)
HP:0007370
25 hyposmia 58 30 Frequent (33%) Frequent (79-30%)
HP:0004409
26 cyclopia 58 30 Frequent (33%) Frequent (79-30%)
HP:0009914
27 tooth agenesis 30 Frequent (33%) HP:0009804
28 macrocephaly 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0000256
29 frontal bossing 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0002007
30 scoliosis 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0002650
31 ptosis 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0000508
32 constipation 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0002019
33 hydrocephalus 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0000238
34 short neck 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0000470
35 chorea 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0002072
36 respiratory insufficiency 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0002093
37 hypertelorism 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0000316
38 macrotia 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0000400
39 anteverted nares 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0000463
40 thick eyebrow 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0000574
41 optic atrophy 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0000648
42 feeding difficulties in infancy 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0008872
43 proteinuria 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0000093
44 retinopathy 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0000488
45 abnormal form of the vertebral bodies 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0003312
46 cryptorchidism 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0000028
47 failure to thrive in infancy 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0001531
48 epicanthus 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0000286
49 external ear malformation 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0008572
50 diabetes insipidus 58 30 Occasional (7.5%) Occasional (29-5%)
HP:0000873

MGI Mouse Phenotypes related to Holoprosencephaly:

45 (show all 17)
# Description MGI Source Accession Score Top Affiliating Genes
1 growth/size/body region MP:0005378 10.39 CDON DHCR7 FGF8 FGFR1 FOXH1 GLI2
2 nervous system MP:0003631 10.37 CDON DHCR7 FGF8 FGFR1 FOXH1 GLI2
3 embryo MP:0005380 10.31 CDON DHCR7 FGF8 FGFR1 FOXH1 GLI2
4 normal MP:0002873 10.27 FGF8 FGFR1 FOXH1 GLI2 NODAL PTCH1
5 digestive/alimentary MP:0005381 10.26 CDON DHCR7 FGF8 FGFR1 FOXH1 GLI2
6 muscle MP:0005369 10.25 CNOT1 DHCR7 FGF8 FGFR1 FOXH1 GLI2
7 craniofacial MP:0005382 10.23 CDON DHCR7 FGF8 FGFR1 FOXH1 GLI2
8 cardiovascular system MP:0005385 10.22 CDON CNOT1 DHCR7 FGF8 FGFR1 FOXH1
9 limbs/digits/tail MP:0005371 10.19 CDON DHCR7 FGF8 FGFR1 GLI2 PTCH1
10 cellular MP:0005384 10.17 CDON FGF8 FGFR1 GLI2 MATN4 NODAL
11 immune system MP:0005387 10.15 DHCR7 FGF8 FGFR1 FOXH1 MATN4 NODAL
12 hearing/vestibular/ear MP:0005377 10.07 FGF8 FGFR1 FOXH1 GLI2 PTCH1 SHH
13 respiratory system MP:0005388 10.06 CDON DHCR7 FGF8 FOXH1 GLI2 NODAL
14 skeleton MP:0005390 10.03 CDON FGF8 FGFR1 FOXH1 GLI2 NODAL
15 vision/eye MP:0005391 9.93 CDON DHCR7 FGF8 FGFR1 FOXH1 GLI2
16 mortality/aging MP:0010768 9.53 CDON CNOT1 DHCR7 FGF8 FGFR1 FOXH1
17 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 Clinical and Genetic Studies on Holoprosencephaly Completed NCT00088426
2 The Experiences and Needs of Parents Continuing a Pregnancy Following Abnormal Prenatal Results: The Case of Holoprosencephaly Completed NCT00005016
3 Genetic Analysis of Brain Disorders Completed NCT00645645
4 EXOMEDIANE - Retrospective Study Using High Throughput Sequencing (HTS) on Biological Samples to Improve Genetic Counseling for Patients With Previously Explored Craniofacial Midline Defects. Completed NCT04691414

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 28 FOXH1 NODAL

Anatomical Context for Holoprosencephaly

Organs/tissues related to Holoprosencephaly:

MalaCards : Brain, Eye, Pituitary, Spinal Cord, Spleen, Cerebellum, Bone
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 2011)
# Title Authors PMID Year
1
A CCR4-NOT Transcription Complex, Subunit 1, CNOT1, Variant Associated with Holoprosencephaly. 62 24 5
31006510 2019
2
A Specific CNOT1 Mutation Results in a Novel Syndrome of Pancreatic Agenesis and Holoprosencephaly through Impaired Pancreatic and Neurological Development. 62 5
31006513 2019
3
A novel SIX3 mutation segregates with holoprosencephaly in a large family. 53 62 24
19353631 2009
4
Holoprosencephaly due to mutations in ZIC2: alanine tract expansion mutations may be caused by parental somatic recombination. 53 62 24
11285244 2001
5
The mutational spectrum of the sonic hedgehog gene in holoprosencephaly: SHH mutations cause a significant proportion of autosomal dominant holoprosencephaly. 53 62 24
10556296 1999
6
Expanding the phenotype and the genotype of Stromme syndrome: A novel variant of the CENPF gene and literature review. 62 24
31953238 2020
7
Loss-of-Function Variants in PPP1R12A: From Isolated Sex Reversal to Holoprosencephaly Spectrum and Urogenital Malformations. 62 24
31883643 2020
8
Radiologic, genetic, and endocrine findings in isolated congenital nasal pyriform aperture stenosis patients. 62 24
31606685 2020
9
Novel heterozygous variants in KMT2D associated with holoprosencephaly. 62 24
31282990 2019
10
Cohesin complex-associated holoprosencephaly. 62 24
31334757 2019
11
Disorders of Ventral Induction/Spectrum of Holoprosencephaly. 62 24
31256862 2019
12
A forebrain undivided: Unleashing model organisms to solve the mysteries of holoprosencephaly. 62 24
30993762 2019
13
A novel dominant-negative FGFR1 variant causes Hartsfield syndrome by deregulating RAS/ERK1/2 pathway. 62 24
30787447 2019
14
Nonsense variants in STAG2 result in distinct sex-dependent phenotypes. 62 24
30765867 2019
15
Extracephalic manifestations of nonchromosomal, nonsyndromic holoprosencephaly. 62 24
29761634 2018
16
Loss-of-function mutations in FGF8 can be independent risk factors for holoprosencephaly. 62 24
29584859 2018
17
Cytogenetics and holoprosencephaly: A chromosomal microarray study of 222 individuals with holoprosencephaly. 62 24
30182442 2018
18
Holoprosencephaly from conception to adulthood. 62 24
30182446 2018
19
Molecular testing in holoprosencephaly. 62 24
29771000 2018
20
Syndromes associated with holoprosencephaly. 62 24
29770994 2018
21
Challenging issues arising in counseling families experiencing holoprosencephaly. 62 24
30182441 2018
22
Prenatal diagnosis of holoprosencephaly. 62 24
29770996 2018
23
Recent advances in understanding inheritance of holoprosencephaly. 62 24
29785796 2018
24
First and second trimester screening for fetal structural anomalies. 62 24
29233624 2018
25
In-depth investigations of adolescents and adults with holoprosencephaly identify unique characteristics. 62 24
28640243 2018
26
SIX3 deletions and incomplete penetrance in families affected by holoprosencephaly. 62 24
28670735 2018
27
Trisomy 18 and holoprosencephaly. 62 24
28449414 2017
28
Mutational Spectrum in Holoprosencephaly Shows That FGF is a New Major Signaling Pathway. 62 24
27363716 2016
29
Dominant-negative kinase domain mutations in FGFR1 can explain the clinical severity of Hartsfield syndrome. 62 24
26931467 2016
30
In Utero MR Imaging of Fetal Holoprosencephaly: A Structured Approach to Diagnosis and Classification. 62 24
26564444 2016
31
Microform holoprosencephaly with bilateral congenital elbow dislocation; increasing the phenotypic spectrum of Steinfeld syndrome. 62 24
26728615 2016
32
Agenesis of the corpus callosum. An autopsy study in fetuses. 62 24
26573426 2016
33
Triploidy: Variation of Phenotype. 62 24
26712875 2016
34
Affected kindred analysis of human X chromosome exomes to identify novel X-linked intellectual disability genes. 5
25679214 2015
35
Homozygous STIL mutation causes holoprosencephaly and microcephaly in two siblings. 62 24
25658757 2015
36
STIL mutation causes autosomal recessive microcephalic lobar holoprosencephaly. 62 24
25218063 2015
37
Pathogenic mutations in GLI2 cause a specific phenotype that is distinct from holoprosencephaly. 62 24
24744436 2014
38
FGFR1 mutations cause Hartsfield syndrome, the unique association of holoprosencephaly and ectrodactyly. 62 24
23812909 2013
39
High Intellectual Function in Individuals with Mutation-Positive Microform Holoprosencephaly. 62 24
23112757 2012
40
Genotypic and phenotypic analysis of 396 individuals with mutations in Sonic Hedgehog. 62 24
22791840 2012
41
Utilizing prospective sequence analysis of SHH, ZIC2, SIX3 and TGIF in holoprosencephaly probands to describe the parameters limiting the observed frequency of mutant gene×gene interactions. 62 24
22310223 2012
42
A broad range of ophthalmologic anomalies is part of the holoprosencephaly spectrum. 62 24
21976454 2011
43
New findings for phenotype-genotype correlations in a large European series of holoprosencephaly cases. 62 24
21940735 2011
44
Holoprosencephaly at prenatal diagnosis: analysis of 28 cases regarding etiopathogenic diagnoses. 62 24
21706511 2011
45
Mutations in CDON, encoding a hedgehog receptor, result in holoprosencephaly and defective interactions with other hedgehog receptors. 62 24
21802063 2011
46
NOTCH, a new signaling pathway implicated in holoprosencephaly. 62 24
21196490 2011
47
Septopreoptic holoprosencephaly: a mild subtype associated with midline craniofacial anomalies. 62 24
20488907 2010
48
Mutations in ZIC2 in human holoprosencephaly: description of a novel ZIC2 specific phenotype and comprehensive analysis of 157 individuals. 62 24
19955556 2010
49
The 11-13-week scan: diagnosis and outcome of holoprosencephaly, exomphalos and megacystis. 62 24
20564304 2010
50
Holoprosencephaly and holoprosencephaly-like phenotypes: Review of facial and molecular findings in patients from a craniofacial hospital in Brazil. 62 24
20104612 2010

Variations for Holoprosencephaly

ClinVar genetic disease variations for Holoprosencephaly:

5 (show top 50) (show all 274)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 FGF8 NM_033163.5(FGF8):c.559_573del (p.Arg187_Gly191del) DEL Pathogenic
545457 rs1554834321 GRCh37: 10:103530248-103530262
GRCh38: 10:101770491-101770505
2 FGFR1 NM_023110.3(FGFR1):c.880G>A (p.Glu294Lys) SNV Pathogenic
517665 rs528376963 GRCh37: 8:38282083-38282083
GRCh38: 8:38424565-38424565
3 FGF8 NM_033163.5(FGF8):c.469G>T (p.Val157Phe) SNV Likely Pathogenic
545456 rs139565972 GRCh37: 10:103530352-103530352
GRCh38: 10:101770595-101770595
4 FGF8 NM_033163.5(FGF8):c.157-1G>A SNV Likely Pathogenic
545413 rs1554834892 GRCh37: 10:103534670-103534670
GRCh38: 10:101774913-101774913
5 FGF8 NM_033163.5(FGF8):c.356C>T (p.Thr119Met) SNV Likely Pathogenic
235081 rs876661329 GRCh37: 10:103531308-103531308
GRCh38: 10:101771551-101771551
6 FGF8 NM_033163.5(FGF8):c.444+1G>A SNV Likely Pathogenic
545517 rs1490604080 GRCh37: 10:103531219-103531219
GRCh38: 10:101771462-101771462
7 FGF8 NM_033163.5(FGF8):c.157G>C (p.Val53Leu) SNV Likely Pathogenic
545459 rs1554834889 GRCh37: 10:103534669-103534669
GRCh38: 10:101774912-101774912
8 FGF8 NM_033163.5(FGF8):c.398C>T (p.Thr133Met) SNV Likely Pathogenic
545458 rs61730334 GRCh37: 10:103531266-103531266
GRCh38: 10:101771509-101771509
9 ZIC2 NM_007129.5(ZIC2):c.1225C>T (p.Arg409Trp) SNV Likely Pathogenic
635857 rs1594291868 GRCh37: 13:100637349-100637349
GRCh38: 13:99985095-99985095
10 MATN4 NM_001393530.1(MATN4):c.515G>C (p.Gly172Ala) SNV Likely Pathogenic
183295 rs730882210 GRCh37: 20:43932996-43932996
GRCh38: 20:45304356-45304356
11 FGFR1 NM_023110.3(FGFR1):c.2074G>A (p.Glu692Lys) SNV Likely Pathogenic
235088 rs876661335 GRCh37: 8:38271782-38271782
GRCh38: 8:38414264-38414264
12 FGF8 NM_033163.5(FGF8):c.617G>A (p.Arg206Gln) SNV Likely Pathogenic
235083 rs876661331 GRCh37: 10:103530204-103530204
GRCh38: 10:101770447-101770447
13 ZRSR2 NM_005089.4(ZRSR2):c.1207_1208del (p.Arg403fs) DEL Likely Pathogenic
978620 rs1933151965 GRCh37: X:15841123-15841124
GRCh38: X:15823000-15823001
14 FGF8 NM_033163.5(FGF8):c.385C>T (p.Arg129Ter) SNV Likely Pathogenic
235082 rs876661330 GRCh37: 10:103531279-103531279
GRCh38: 10:101771522-101771522
15 CNOT1 NM_016284.5(CNOT1):c.1603C>T (p.Arg535Cys) SNV Conflicting Interpretations Of Pathogenicity
619606 rs1567417422 GRCh37: 16:58610468-58610468
GRCh38: 16:58576564-58576564
16 FOXH1 NM_003923.3(FOXH1):c.386G>A (p.Arg129Gln) SNV Uncertain Significance
577331 rs149905713 GRCh37: 8:145700333-145700333
GRCh38: 8:144474950-144474950
17 FOXH1 NM_003923.3(FOXH1):c.974G>A (p.Cys325Tyr) SNV Uncertain Significance
572194 rs770253235 GRCh37: 8:145699745-145699745
GRCh38: 8:144474362-144474362
18 FOXH1 NM_003923.3(FOXH1):c.746C>T (p.Ala249Val) SNV Uncertain Significance
571322 rs1564751833 GRCh37: 8:145699973-145699973
GRCh38: 8:144474590-144474590
19 FOXH1, KIFC2 NM_003923.3(FOXH1):c.*88A>G SNV Uncertain Significance
909984 rs1024459830 GRCh37: 8:145699533-145699533
GRCh38: 8:144474150-144474150
20 SHH NM_000193.4(SHH):c.468C>A (p.Ser156Arg) SNV Uncertain Significance
545462 rs1554494372 GRCh37: 7:155599084-155599084
GRCh38: 7:155806390-155806390
21 FOXH1 NM_003923.3(FOXH1):c.58C>T (p.Pro20Ser) SNV Uncertain Significance
528229 rs778783647 GRCh37: 8:145701082-145701082
GRCh38: 8:144475699-144475699
22 BOC NM_001378074.1(BOC):c.1670G>A (p.Gly557Glu) SNV Uncertain Significance
523664 rs1553745274 GRCh37: 3:112997069-112997069
GRCh38: 3:113278222-113278222
23 FOXH1 NM_003923.3(FOXH1):c.794C>A (p.Ser265Tyr) SNV Uncertain Significance
409649 rs769660425 GRCh37: 8:145699925-145699925
GRCh38: 8:144474542-144474542
24 FOXH1 NM_003923.3(FOXH1):c.1024G>A (p.Asp342Asn) SNV Uncertain Significance
409646 rs536501327 GRCh37: 8:145699695-145699695
GRCh38: 8:144474312-144474312
25 FOXH1 NM_003923.3(FOXH1):c.653C>T (p.Pro218Leu) SNV Uncertain Significance
409648 rs770944195 GRCh37: 8:145700066-145700066
GRCh38: 8:144474683-144474683
26 DISP1 NM_001377229.1(DISP1):c.743C>T (p.Ala248Val) SNV Uncertain Significance
397657 rs1029577112 GRCh37: 1:223164941-223164941
GRCh38: 1:222991599-222991599
27 CDON NM_001378964.1(CDON):c.*2351CA[17] MICROSAT Uncertain Significance
303436 rs35654681 GRCh37: 11:125828460-125828461
GRCh38: 11:125958565-125958566
28 CDON NM_001378964.1(CDON):c.*2377_*2379delinsCACACACACACACAC INDEL Uncertain Significance
303417 rs886047956 GRCh37: 11:125828458-125828460
GRCh38: 11:125958563-125958565
29 FOXH1, KIFC2 NM_003923.3(FOXH1):c.*74G>A SNV Uncertain Significance
362275 rs562738425 GRCh37: 8:145699547-145699547
GRCh38: 8:144474164-144474164
30 CDON NM_001378964.1(CDON):c.*2376AC[4]ATA[1] INSERT Uncertain Significance
303433 rs371911236 GRCh37: 11:125828460-125828461
GRCh38: 11:125958565-125958566
31 TGIF1 NM_003244.4(TGIF1):c.*133A>G SNV Uncertain Significance
326712 rs886053783 GRCh37: 18:3458071-3458071
GRCh38: 18:3458073-3458073
32 GLI2 NM_001374353.1(GLI2):c.*1837_*1840dup DUP Uncertain Significance
331029 rs558203417 GRCh37: 2:121750084-121750085
GRCh38: 2:120992508-120992509
33 FOXH1 NM_003923.3(FOXH1):c.933G>C (p.Trp311Cys) SNV Uncertain Significance
362278 rs140090667 GRCh37: 8:145699786-145699786
GRCh38: 8:144474403-144474403
34 CDON NM_001378964.1(CDON):c.*1310dup DUP Uncertain Significance
303466 rs886047972 GRCh37: 11:125829526-125829527
GRCh38: 11:125959631-125959632
35 GLI2 NM_001374353.1(GLI2):c.*1376_*1377insACACCCC INSERT Uncertain Significance
331020 rs1553480327 GRCh37: 2:121749626-121749627
GRCh38: 2:120992050-120992051
36 CDON NM_001378964.1(CDON):c.-61-15del DEL Uncertain Significance
303530 rs886047980 GRCh37: 11:125893447-125893447
GRCh38: 11:126023552-126023552
37 GLI2 NM_001374353.1(GLI2):c.*1333AC[19] MICROSAT Uncertain Significance
331019 rs59277032 GRCh37: 2:121749584-121749589
GRCh38: 2:120992008-120992013
38 GLI2 NM_001374353.1(GLI2):c.*1376_*1379dup DUP Uncertain Significance
331023 rs1553480328 GRCh37: 2:121749626-121749627
GRCh38: 2:120992050-120992051
39 GLI2 NM_001374353.1(GLI2):c.*1333AC[26] MICROSAT Uncertain Significance
331016 rs59277032 GRCh37: 2:121749583-121749584
GRCh38: 2:120992007-120992008
40 CDON NM_001378964.1(CDON):c.*2376AC[8]AT[2]A[1] MICROSAT Uncertain Significance
303430 rs371911236 GRCh37: 11:125828460-125828461
GRCh38: 11:125958565-125958566
41 CDON NM_001378964.1(CDON):c.2429C>G (p.Ser810Cys) SNV Uncertain Significance
303498 rs746038393 GRCh37: 11:125864881-125864881
GRCh38: 11:125994986-125994986
42 CDON NM_001378964.1(CDON):c.-61-9_-61-7del DEL Uncertain Significance
303529 rs557544550 GRCh37: 11:125893439-125893441
GRCh38: 11:126023544-126023546
43 GLI2 NM_001374353.1(GLI2):c.*1333AC[20] MICROSAT Uncertain Significance
331018 rs59277032 GRCh37: 2:121749584-121749587
GRCh38: 2:120992008-120992011
44 CDON NM_001378964.1(CDON):c.*3522_*3523del DEL Uncertain Significance
303384 rs886047944 GRCh37: 11:125827314-125827315
GRCh38: 11:125957419-125957420
45 CDON NM_001378964.1(CDON):c.*2345_*2349delinsAACACACACAC INDEL Uncertain Significance
303442 rs886047960 GRCh37: 11:125828488-125828492
GRCh38: 11:125958593-125958597
46 FOXH1 NM_003923.3(FOXH1):c.389G>A (p.Arg130His) SNV Uncertain Significance
362282 rs886062754 GRCh37: 8:145700330-145700330
GRCh38: 8:144474947-144474947
47 CDON NM_001378964.1(CDON):c.*2376_*2377insCATATA MICROSAT Uncertain Significance
303427 rs371911236 GRCh37: 11:125828460-125828461
GRCh38: 11:125958565-125958566
48 FOXH1, KIFC2 NM_003923.3(FOXH1):c.*451C>T SNV Uncertain Significance
362271 rs886062751 GRCh37: 8:145699170-145699170
GRCh38: 8:144473787-144473787
49 CDON NM_001378964.1(CDON):c.*2377delinsCACACACACACACACAC INDEL Uncertain Significance
303424 rs886047958 GRCh37: 11:125828460-125828460
GRCh38: 11:125958565-125958565
50 FOXH1 NM_003923.3(FOXH1):c.785G>T (p.Gly262Val) SNV Uncertain Significance
362279 rs886062752 GRCh37: 8:145699934-145699934
GRCh38: 8:144474551-144474551

Copy number variations for Holoprosencephaly from CNVD:

6 (show all 17)
# CNVD ID Chromosome 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 Holoprosencephaly
5 27746 7 155285496 155297728 Deletion SHH Holoprosencephaly
6 27747 1 212100000 222100000 Deletion PMEL Holoprosencephaly
7 27748 2 45022540 45025894 Deletion SIX3 Holoprosencephaly
8 27749 1 212100000 222100000 Deletion Holoprosencephaly
9 27750 1 212100000 222100000 Deletion TGIF1 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 TGIF1 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 directly related to Holoprosencephaly:

# Pathway Source
1 Hh mutants are degraded by ERAD Reactome 66
2 Hh mutants abrogate ligand secretion Reactome 66

Pathways related to Holoprosencephaly according to GeneCards Suite gene sharing:

(show all 20)
# Super pathways Score Top Affiliating Genes
1 13.6 TGIF1 STAG2 SHH PTCH1 GLI2 FOXH1
2
Show member pathways
12.28 SHH PTCH1 GLI2 CDON
3 11.89 SHH FGFR1 FGF8
4 11.82 ZIC2 NODAL FOXH1 FGFR1 FGF8
5
Show member pathways
11.79 SHH FOXH1 FGFR1
6 11.75 ZIC1 FGFR1 FGF8
7 11.6 SHH FGFR1 FGF8
9 11.33 FGF8 NODAL SHH
10 11.3 SHH FOXH1 FGF8
11 11.2 SHH PTCH1 GLI2
12 11.16 SHH PTCH1 GLI2
13 11.08 SHH PTCH1 GLI2 CDON
14 11.02 SHH GLI2 FGF8
15 10.91 FGFR1 FGF8
16 10.9 SHH PTCH1 GLI2
17
Show member pathways
10.81 SHH PTCH1 GLI2 CDON
18 10.59 SHH PTCH1
19 10.41 SHH PTCH1
20
Show member pathways
9.92 TGIF1 SHH NODAL FGF8

GO Terms for Holoprosencephaly

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

(show all 29)
# Name GO ID Score Top Affiliating Genes
1 brain development GO:0007420 10.27 ZIC2 ZIC1 SIX3 PTCH1 NODAL
2 smoothened signaling pathway GO:0007224 10.08 SHH PTCH1 GLI2 CDON
3 branching involved in ureteric bud morphogenesis GO:0001658 10.06 SHH PTCH1 FGF8
4 heart looping GO:0001947 10.01 SHH NODAL FOXH1 FGF8
5 lung development GO:0030324 9.97 SHH NODAL GLI2 FGF8
6 positive regulation of T cell differentiation in thymus GO:0033089 9.94 SHH GLI2
7 branching involved in salivary gland morphogenesis GO:0060445 9.94 SHH FGF8
8 cell fate commitment GO:0045165 9.93 SHH NODAL FGF8
9 metanephric collecting duct development GO:0072205 9.93 SHH PTCH1
10 cell proliferation in forebrain GO:0021846 9.92 SIX3 FGF8
11 positive regulation of skeletal muscle tissue development GO:0048643 9.91 SHH CDON
12 forebrain dorsal/ventral pattern formation GO:0021798 9.91 SIX3 FGF8
13 telencephalon regionalization GO:0021978 9.9 SIX3 SHH
14 formation of anatomical boundary GO:0048859 9.87 SHH NODAL
15 stem cell proliferation GO:0072089 9.87 SHH PTCH1 GLI2 FGF8
16 spinal cord dorsal/ventral patterning GO:0021513 9.85 SHH GLI2
17 hindgut morphogenesis GO:0007442 9.84 SHH GLI2
18 ventral midline development GO:0007418 9.83 GLI2 SHH
19 spinal cord motor neuron differentiation GO:0021522 9.83 SHH PTCH1 GLI2
20 nodal signaling pathway involved in determination of lateral mesoderm left/right asymmetry GO:1900164 9.81 FOXH1 NODAL
21 epithelial cell proliferation GO:0050673 9.79 SHH PTCH1 GLI2
22 mammary gland duct morphogenesis GO:0060603 9.77 GLI2 PTCH1
23 determination of left/right symmetry GO:0007368 9.76 SHH NODAL FOXH1 FGF8
24 smoothened signaling pathway involved in regulation of cerebellar granule cell precursor cell proliferation GO:0021938 9.73 SHH GLI2
25 pattern specification process GO:0007389 9.7 ZIC1 SHH PTCH1 GLI2
26 dorsal/ventral neural tube patterning GO:0021904 9.65 SHH PTCH1 GLI2
27 anatomical structure formation involved in morphogenesis GO:0048646 9.54 GLI2 NODAL SHH
28 dorsal/ventral pattern formation GO:0009953 9.5 SHH PTCH1 GLI2 FGF8
29 anterior/posterior pattern specification GO:0009952 9.1 SHH NODAL GLI2 FOXH1 CDON

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

# Name GO ID Score Top Affiliating Genes
1 patched binding GO:0005113 9.26 SHH PTCH1
2 morphogen activity GO:0016015 8.92 SHH NODAL

Sources for Holoprosencephaly

2 CDC
6 CNVD
8 Cosmic
9 dbSNP
10 DGIdb
16 EFO
17 ExPASy
18 FMA
19 GARD
27 GO
28 GTR
29 HMDB
30 HPO
31 ICD10
32 ICD10 via Orphanet
33 ICD11
34 ICD9CM
35 IUPHAR
36 LifeMap
38 LOVD
40 MedGen
43 MeSH
44 MESH via Orphanet
45 MGI
48 NCI
49 NCIt
50 NDF-RT
52 NINDS
53 Novoseek
55 ODiseA
56 OMIM via Orphanet
57 OMIM® (Updated 08-Dec-2022)
61 PubChem
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 Tocris
71 UMLS
72 UMLS via Orphanet
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