HPE
MCID: HLP001
MIFTS: 67

Holoprosencephaly (HPE)

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

Aliases & Classifications for Holoprosencephaly

MalaCards integrated aliases for Holoprosencephaly:

Name: Holoprosencephaly 12 74 24 52 53 58 36 54 43 15 39 32
Holoprosencephaly Sequence 12 29 6
Hpe 52 58

Characteristics:

Orphanet epidemiological data:

58
holoprosencephaly
Inheritance: Multigenic/multifactorial,Not applicable; Prevalence: 1-5/10000 (Europe); Age of onset: Antenatal,Neonatal; Age of death: any age;

Classifications:

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


Summaries for Holoprosencephaly

NINDS : 53 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 1. 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 abnormal facial shape and holoprosencephaly

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 : 52 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.

KEGG : 36 Holoprosencephaly (HPE) is characterized by incomplete separation of forebrain and facial components into left and right sides.

Wikipedia : 74 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 402)
# Related Disease Score Top Affiliating Genes
1 holoprosencephaly 9 35.2 ZIC2 SIX3 SHH PTCH1 GLI2 FOXH1
2 holoprosencephaly 1 35.1 ZIC2 SIX3 SHH HPE1 GLI2 GAS1
3 holoprosencephaly 3 35.1 ZIC2 SIX3 SHH GLI2 DISP1
4 holoprosencephaly 2 35.1 ZIC2 SIX3 SHH GLI2 FOXH1 DISP1
5 holoprosencephaly 7 35.1 ZIC2 SIX3 PTCH1 DISP1
6 holoprosencephaly 5 35.1 ZIC2 SIX3 SHH LOC110008580 GLI2 FOXH1
7 holoprosencephaly 4 35.1 ZIC2 TGIF1 SIX3 SHH GLI2 FOXH1
8 holoprosencephaly 11 35.0 ZIC2 SIX3 SHH PTCH1 GLI2 FOXH1
9 holoprosencephaly 8 34.9 ZIC2 TGIF1 HPE8 DISP1
10 semilobar holoprosencephaly 34.7 ZIC2 TGIF1 SIX3 SHH PTCH1 NODAL
11 lobar holoprosencephaly 34.7 ZIC2 TGIF1 SIX3 SHH PTCH1 NODAL
12 alobar holoprosencephaly 34.7 ZIC2 TGIF1 SIX3 SHH PTCH1 NODAL
13 microform holoprosencephaly 34.7 ZIC2 TGIF1 SIX3 SHH PTCH1 NODAL
14 midline interhemispheric variant of holoprosencephaly 34.6 ZIC2 TGIF1 SIX3 SHH PTCH1 NODAL
15 holoprosencephaly, recurrent infections, and monocytosis 34.5 SIX3 PTCH1 GLI2
16 hartsfield syndrome 34.5 FGFR1 FGF8
17 septopreoptic holoprosencephaly 34.5 ZIC2 TGIF1 SIX3 SHH PTCH1 NODAL
18 patau syndrome 32.0 ZIC2 SIX3 SHH NODAL FOXH1 DISP1
19 cleft palate, isolated 31.8 SHH PTCH1 GLI2 FGFR1 FGF8
20 solitary median maxillary central incisor 31.5 ZIC2 TGIF1 SIX3 SHH PTCH1 NODAL
21 coloboma of macula 31.4 ZIC2 SIX3 SHH PTCH1 GLI2 FGFR1
22 septooptic dysplasia 31.4 TGIF1 SIX3 SHH GLI2 FGFR1 FGF8
23 neural tube defects 31.3 ZIC2 ZIC1 SHH PTCH1 FGF8
24 craniosynostosis 31.3 ZIC1 PTCH1 FGFR1 FGF8
25 chromosome 18p deletion syndrome 31.3 ZIC2 TGIF1
26 culler-jones syndrome 31.2 TGIF1 SIX3 SHH GLI2 CDON
27 pallister-hall syndrome 31.1 ZIC2 SIX3 SHH PTCH1 GLI2 GAS1
28 basal cell nevus syndrome 31.1 SHH PTCH1 GLI2 GAS1 CDON
29 orofacial cleft 31.1 ZIC2 SIX3 SHH PTCH1 GLI2 FGFR1
30 hypopituitarism 31.0 SIX3 SHH GLI2
31 chromosome 2q35 duplication syndrome 31.0 SHH PTCH1 FGFR1 FGF8 DHCR7
32 synostosis 30.9 SHH FGFR1 FGF8
33 tetralogy of fallot 30.8 SHH NODAL FOXH1 FGF8
34 pituitary stalk interruption syndrome 30.8 TGIF1 SHH CDON
35 anus, imperforate 30.7 SHH GLI2 FGF8
36 orofaciodigital syndrome viii 30.7 ZIC2 SIX3 DISP1
37 charge syndrome 30.7 ZIC1 SHH FGFR1 FGF8
38 congenital hypogonadotropic hypogonadism 30.7 FGFR1 FGF8
39 pfeiffer syndrome 30.4 FGFR1 FGF8 DHCR7
40 nonsyndromic holoprosencephaly 12.7
41 holoprosencephaly, semilobar, with craniosynostosis 12.6
42 holoprosencephaly 12 with or without pancreatic agenesis 12.6
43 holoprosencephaly with fetal akinesia/hypokinesia sequence 12.6
44 holoprosencephaly 6 12.5
45 brachial amelia, cleft lip, and holoprosencephaly 12.5
46 holoprosencephaly 13, x-linked 12.5
47 agnathia-otocephaly complex 12.3
48 holoprosencephaly-caudal dysgenesis syndrome 12.2
49 pseudotrisomy 13 syndrome 12.1
50 pancreatic agenesis-holoprosencephaly syndrome 12.1

Graphical network of the top 20 diseases related to Holoprosencephaly:



Diseases related to Holoprosencephaly

Symptoms & Phenotypes for Holoprosencephaly

Human phenotypes related to Holoprosencephaly:

58 31 (show top 50) (show all 94)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 abnormal facial shape 58 31 hallmark (90%) Very frequent (99-80%) HP:0001999
2 holoprosencephaly 58 31 hallmark (90%) Very frequent (99-80%) HP:0001360
3 single median maxillary incisor 58 31 hallmark (90%) Very frequent (99-80%) HP:0006315
4 median cleft lip and palate 58 31 hallmark (90%) Very frequent (99-80%) HP:0008501
5 bilateral cleft lip 58 31 hallmark (90%) Very frequent (99-80%) HP:0100336
6 global developmental delay 58 31 frequent (33%) Frequent (79-30%) HP:0001263
7 muscular hypotonia 58 31 frequent (33%) Frequent (79-30%) HP:0001252
8 microcephaly 58 31 frequent (33%) Frequent (79-30%) HP:0000252
9 gastroesophageal reflux 58 31 frequent (33%) Frequent (79-30%) HP:0002020
10 cognitive impairment 58 31 frequent (33%) Frequent (79-30%) HP:0100543
11 muscle weakness 58 31 frequent (33%) Frequent (79-30%) HP:0001324
12 spasticity 58 31 frequent (33%) Frequent (79-30%) HP:0001257
13 hypoglycemia 58 31 frequent (33%) Frequent (79-30%) HP:0001943
14 diabetes mellitus 58 31 frequent (33%) Frequent (79-30%) HP:0000819
15 depressed nasal ridge 58 31 frequent (33%) Frequent (79-30%) HP:0000457
16 anosmia 58 31 frequent (33%) Frequent (79-30%) HP:0000458
17 iris coloboma 58 31 frequent (33%) Frequent (79-30%) HP:0000612
18 choanal atresia 58 31 frequent (33%) Frequent (79-30%) HP:0000453
19 anophthalmia 58 31 frequent (33%) Frequent (79-30%) HP:0000528
20 microphthalmia 58 31 frequent (33%) Frequent (79-30%) HP:0000568
21 reduced number of teeth 58 31 frequent (33%) Frequent (79-30%) HP:0009804
22 dystonia 58 31 frequent (33%) Frequent (79-30%) HP:0001332
23 hypotelorism 58 31 frequent (33%) Frequent (79-30%) HP:0000601
24 aplasia/hypoplasia of the corpus callosum 58 31 frequent (33%) Frequent (79-30%) HP:0007370
25 hyposmia 58 31 frequent (33%) Frequent (79-30%) HP:0004409
26 cyclopia 58 31 frequent (33%) Frequent (79-30%) HP:0009914
27 seizure 31 frequent (33%) HP:0001250
28 hypertelorism 58 31 occasional (7.5%) Occasional (29-5%) HP:0000316
29 macrotia 58 31 occasional (7.5%) Occasional (29-5%) HP:0000400
30 short neck 58 31 occasional (7.5%) Occasional (29-5%) HP:0000470
31 scoliosis 58 31 occasional (7.5%) Occasional (29-5%) HP:0002650
32 macrocephaly 58 31 occasional (7.5%) Occasional (29-5%) HP:0000256
33 hydrocephalus 58 31 occasional (7.5%) Occasional (29-5%) HP:0000238
34 anteverted nares 58 31 occasional (7.5%) Occasional (29-5%) HP:0000463
35 thick eyebrow 58 31 occasional (7.5%) Occasional (29-5%) HP:0000574
36 optic atrophy 58 31 occasional (7.5%) Occasional (29-5%) HP:0000648
37 feeding difficulties in infancy 58 31 occasional (7.5%) Occasional (29-5%) HP:0008872
38 proteinuria 58 31 occasional (7.5%) Occasional (29-5%) HP:0000093
39 retinopathy 58 31 occasional (7.5%) Occasional (29-5%) HP:0000488
40 arrhythmia 58 31 occasional (7.5%) Occasional (29-5%) HP:0011675
41 frontal bossing 58 31 occasional (7.5%) Occasional (29-5%) HP:0002007
42 abnormal form of the vertebral bodies 58 31 occasional (7.5%) Occasional (29-5%) HP:0003312
43 cryptorchidism 58 31 occasional (7.5%) Occasional (29-5%) HP:0000028
44 failure to thrive in infancy 58 31 occasional (7.5%) Occasional (29-5%) HP:0001531
45 epicanthus 58 31 occasional (7.5%) Occasional (29-5%) HP:0000286
46 ptosis 58 31 occasional (7.5%) Occasional (29-5%) HP:0000508
47 external ear malformation 58 31 occasional (7.5%) Occasional (29-5%) HP:0008572
48 respiratory insufficiency 58 31 occasional (7.5%) Occasional (29-5%) HP:0002093
49 diabetes insipidus 58 31 occasional (7.5%) Occasional (29-5%) HP:0000873
50 upslanted palpebral fissure 58 31 occasional (7.5%) Occasional (29-5%) HP:0000582

MGI Mouse Phenotypes related to Holoprosencephaly:

45 (show all 17)
# Description MGI Source Accession Score Top Affiliating Genes
1 craniofacial MP:0005382 10.38 CDON DHCR7 DISP1 FGF8 FGFR1 FOXH1
2 cardiovascular system MP:0005385 10.37 CDON CNOT1 DHCR7 DISP1 FGF8 FGFR1
3 growth/size/body region MP:0005378 10.37 CDON DHCR7 DISP1 FGF8 FGFR1 FOXH1
4 behavior/neurological MP:0005386 10.35 CDON DHCR7 FGF8 FGFR1 GAS1 GLI2
5 mortality/aging MP:0010768 10.34 CDON CNOT1 DHCR7 DISP1 FGF8 FGFR1
6 embryo MP:0005380 10.32 CDON DISP1 FGF8 FGFR1 FOXH1 GAS1
7 digestive/alimentary MP:0005381 10.3 CDON DHCR7 DISP1 FGF8 FGFR1 FOXH1
8 cellular MP:0005384 10.29 CDON DISP1 FGF8 FGFR1 GAS1 GLI2
9 nervous system MP:0003631 10.24 CDON DHCR7 DISP1 FGF8 FGFR1 FOXH1
10 limbs/digits/tail MP:0005371 10.2 CDON DHCR7 DISP1 FGF8 FGFR1 GAS1
11 muscle MP:0005369 10.14 CNOT1 DHCR7 DISP1 FGF8 FGFR1 FOXH1
12 hearing/vestibular/ear MP:0005377 10.08 FGF8 FGFR1 FOXH1 GAS1 GLI2 PTCH1
13 respiratory system MP:0005388 10.07 CDON DHCR7 DISP1 FGF8 FOXH1 GAS1
14 normal MP:0002873 10.02 DISP1 FGF8 FGFR1 FOXH1 GLI2 NODAL
15 skeleton MP:0005390 10 CDON DISP1 FGF8 FGFR1 FOXH1 GAS1
16 vision/eye MP:0005391 9.44 CDON DISP1 FGF8 FGFR1 FOXH1 GAS1
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 Left-Right Axis Malformations Completed NCT00341133
4 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:

40
Brain, Eye, Pituitary, Heart, Bone, Cerebellum, Cortex
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 1894)
# Title Authors PMID Year
1
A novel SIX3 mutation segregates with holoprosencephaly in a large family. 54 24 6 61
19353631 2009
2
The mutational spectrum of the sonic hedgehog gene in holoprosencephaly: SHH mutations cause a significant proportion of autosomal dominant holoprosencephaly. 24 6 54 61
10556296 1999
3
Mutations in CDON, encoding a hedgehog receptor, result in holoprosencephaly and defective interactions with other hedgehog receptors. 61 6 24
21802063 2011
4
Clinical spectrum of SIX3-associated mutations in holoprosencephaly: correlation between genotype, phenotype and function. 61 24 6
19346217 2009
5
PTCH mutations in four Brazilian patients with holoprosencephaly and in one with holoprosencephaly-like features and normal MRI. 6 61 54
17001668 2006
6
Previously undescribed nonsense mutation in SHH caused autosomal dominant holoprosencephaly with wide intrafamilial variability. 54 6 61
12567406 2003
7
Molecular screening of the TGIF gene in holoprosencephaly: identification of two novel mutations. 6 61 54
12522553 2003
8
Identification of novel mutations in SHH and ZIC2 in a South American (ECLAMC) population with holoprosencephaly. 61 54 6
11479728 2001
9
A new mutation in the six-domain of SIX3 gene causes holoprosencephaly. 6 61 54
11039582 2000
10
Mutations in TGIF cause holoprosencephaly and link NODAL signalling to human neural axis determination. 54 61 6
10835638 2000
11
Missense substitutions in the GAS1 protein present in holoprosencephaly patients reduce the affinity for its ligand, SHH. 6 61
21842183 2012
12
Clinical findings in patients with GLI2 mutations--phenotypic variability. 6 61
21204792 2012
13
ZIC2 mutations are seen in holoprosencephaly and not partial rhombencephalosynapsis. 6 61
21990207 2011
14
Recurrent partial rhombencephalosynapsis and holoprosencephaly in siblings with a mutation of ZIC2. 6 61
21638761 2011
15
Novel heterozygous nonsense GLI2 mutations in patients with hypopituitarism and ectopic posterior pituitary lobe without holoprosencephaly. 6 61
20685856 2010
16
Holoprosencephaly and holoprosencephaly-like phenotype and GAS1 DNA sequence changes: Report of four Brazilian patients. 61 6
20583177 2010
17
Heterozygous mutations in SIX3 and SHH are associated with schizencephaly and further expand the clinical spectrum of holoprosencephaly. 61 6
20157829 2010
18
A sonic hedgehog missense mutation associated with holoprosencephaly causes defective binding to GAS1. 6 61
19478089 2009
19
Mutations in the human SIX3 gene in holoprosencephaly are loss of function. 61 6
18791198 2008
20
Cerebro-oculo-nasal syndrome: 13 new Brazilian cases. 61 6
17985375 2007
21
GLI2 mutations in four Brazilian patients: how wide is the phenotypic spectrum? 61 6
17096318 2006
22
SIX3 mutations with holoprosencephaly. 61 6
17001667 2006
23
Molecular mechanisms of Sonic hedgehog mutant effects in holoprosencephaly. 61 6
16282375 2005
24
Functional characterization of SIX3 homeodomain mutations in holoprosencephaly: interaction with the nuclear receptor NR4A3/NOR1. 61 6
15523651 2004
25
Loss-of-function mutations in the human GLI2 gene are associated with pituitary anomalies and holoprosencephaly-like features. 61 6
14581620 2003
26
SONIC HEDGEHOG mutations causing human holoprosencephaly impair neural patterning activity. 6 61
12709790 2003
27
Extreme variability of expression of a Sonic Hedgehog mutation: attention difficulties and holoprosencephaly. 6 61
11919111 2002
28
Mutations in PATCHED-1, the receptor for SONIC HEDGEHOG, are associated with holoprosencephaly. 6 61
11941477 2002
29
Holoprosencephaly due to mutations in ZIC2: alanine tract expansion mutations may be caused by parental somatic recombination. 24 54 61
11285244 2001
30
Holoprosencephaly Overview 6 61
20301702 2000
31
Mutations in the homeodomain of the human SIX3 gene cause holoprosencephaly. 61 6
10369266 1999
32
Holoprosencephaly due to mutations in ZIC2, a homologue of Drosophila odd-paired. 61 6
9771712 1998
33
Mutations in the C-terminal domain of Sonic Hedgehog cause holoprosencephaly. 6 61
9302262 1997
34
Mutations in the human Sonic Hedgehog gene cause holoprosencephaly. 6 61
8896572 1996
35
Expanding the phenotype and the genotype of Stromme syndrome: A novel variant of the CENPF gene and literature review. 24 61
31953238 2020
36
Loss-of-Function Variants in PPP1R12A: From Isolated Sex Reversal to Holoprosencephaly Spectrum and Urogenital Malformations. 61 24
31883643 2020
37
Radiologic, genetic, and endocrine findings in isolated congenital nasal pyriform aperture stenosis patients. 24 61
31606685 2020
38
Novel heterozygous variants in KMT2D associated with holoprosencephaly. 24 61
31282990 2019
39
Cohesin complex-associated holoprosencephaly. 61 24
31334757 2019
40
A forebrain undivided: Unleashing model organisms to solve the mysteries of holoprosencephaly. 61 24
30993762 2019
41
Disorders of Ventral Induction/Spectrum of Holoprosencephaly. 61 24
31256862 2019
42
A novel dominant-negative FGFR1 variant causes Hartsfield syndrome by deregulating RAS/ERK1/2 pathway. 24 61
30787447 2019
43
A CCR4-NOT Transcription Complex, Subunit 1, CNOT1, Variant Associated with Holoprosencephaly. 61 24
31006510 2019
44
Nonsense variants in STAG2 result in distinct sex-dependent phenotypes. 24 61
30765867 2019
45
Syndromes associated with holoprosencephaly. 24 61
29770994 2018
46
Prenatal diagnosis of holoprosencephaly. 61 24
29770996 2018
47
Molecular testing in holoprosencephaly. 61 24
29771000 2018
48
Recent advances in understanding inheritance of holoprosencephaly. 61 24
29785796 2018
49
Extracephalic manifestations of nonchromosomal, nonsyndromic holoprosencephaly. 24 61
29761634 2018
50
Challenging issues arising in counseling families experiencing holoprosencephaly. 24 61
30182441 2018

Variations for Holoprosencephaly

ClinVar genetic disease variations for Holoprosencephaly:

6 (show top 50) (show all 238) ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 FGFR1 NM_023110.2(FGFR1):c.880G>A (p.Glu294Lys)SNV Pathogenic 517665 rs528376963 8:38282083-38282083 8:38424565-38424565
2 FGF8 NM_033164.4(FGF8):c.526_540del (p.Arg176_Gly180del)deletion Pathogenic 545457 rs1554834321 10:103530248-103530262 10:101770491-101770505
3 FGF8 NM_033164.4(FGF8):c.352C>T (p.Arg118Ter)SNV Pathogenic/Likely pathogenic 235082 rs876661330 10:103531279-103531279 10:101771522-101771522
4 FGF8 NM_033164.4(FGF8):c.323C>T (p.Thr108Met)SNV Likely pathogenic 235081 rs876661329 10:103531308-103531308 10:101771551-101771551
5 MATN4 NM_003833.4(MATN4):c.515G>C (p.Gly172Ala)SNV Likely pathogenic 183295 rs730882210 20:43932996-43932996 20:45304356-45304356
6 FGFR1 NM_023110.2(FGFR1):c.2074G>A (p.Glu692Lys)SNV Likely pathogenic 235088 rs876661335 8:38271782-38271782 8:38414264-38414264
7 FGF8 NM_033164.4(FGF8):c.584G>A (p.Arg195Gln)SNV Likely pathogenic 235083 rs876661331 10:103530204-103530204 10:101770447-101770447
8 FGF8 NM_033164.4(FGF8):c.365C>T (p.Thr122Met)SNV Likely pathogenic 545458 rs61730334 10:103531266-103531266 10:101771509-101771509
9 FGF8 NM_033164.4(FGF8):c.157-33G>CSNV Likely pathogenic 545459 rs1554834889 10:103534669-103534669 10:101774912-101774912
10 FGF8 NM_033164.4(FGF8):c.157-34G>ASNV Likely pathogenic 545413 rs1554834892 10:103534670-103534670 10:101774913-101774913
11 FGF8 NM_033164.4(FGF8):c.436G>T (p.Val146Phe)SNV Likely pathogenic 545456 rs139565972 10:103530352-103530352 10:101770595-101770595
12 FGF8 NM_033164.4(FGF8):c.411+1G>ASNV Likely pathogenic 545517 rs1490604080 10:103531219-103531219 10:101771462-101771462
13 ZIC2 NM_007129.5(ZIC2):c.1225C>T (p.Arg409Trp)SNV Likely pathogenic 635857 13:100637349-100637349 13:99985095-99985095
14 NODAL NM_018055.5(NODAL):c.972G>A (p.Leu324=)SNV Conflicting interpretations of pathogenicity 697481 10:72192764-72192764 10:70433008-70433008
15 FGF8 NM_033164.4(FGF8):c.130C>T (p.Arg44Trp)SNV Conflicting interpretations of pathogenicity 545461 rs781205876 10:103534913-103534913 10:101775156-101775156
16 TGIF1 NM_003244.3(TGIF1):c.123C>T (p.Asn41=)SNV Conflicting interpretations of pathogenicity 259014 rs138292737 18:3456458-3456458 18:3456460-3456460
17 FOXH1 NM_003923.3(FOXH1):c.15C>T (p.Ser5=)SNV Conflicting interpretations of pathogenicity 215825 rs374587860 8:145701125-145701125 8:144475742-144475742
18 PTCH1 NM_000264.5(PTCH1):c.3155C>T (p.Thr1052Met)SNV Conflicting interpretations of pathogenicity 8224 rs138911275 9:98220308-98220308 9:95458026-95458026
19 NODAL NM_018055.5(NODAL):c.904C>T (p.Arg302Cys)SNV Conflicting interpretations of pathogenicity 95883 rs150819707 10:72192832-72192832 10:70433076-70433076
20 FGF8 NM_033164.4(FGF8):c.86_103dup (p.Gly29_Arg34dup)duplication Conflicting interpretations of pathogenicity 545463 rs762175290 10:103534939-103534940 10:101775182-101775183
21 PTCH1 NM_000264.5(PTCH1):c.2460C>T (p.Tyr820=)SNV Conflicting interpretations of pathogenicity 367667 rs766227557 9:98229498-98229498 9:95467216-95467216
22 NODAL NM_018055.5(NODAL):c.*836G>CSNV Uncertain significance 300286 rs886047098 10:72191856-72191856 10:70432100-70432100
23 NODAL NM_018055.5(NODAL):c.*747dupduplication Uncertain significance 300287 rs886047099 10:72191944-72191945 10:70432188-70432189
24 PTCH1 NM_000264.5(PTCH1):c.*2288dupduplication Uncertain significance 367626 rs548096592 9:98206386-98206387 9:95444104-95444105
25 NODAL NM_018055.5(NODAL):c.221C>T (p.Thr74Met)SNV Uncertain significance 300309 rs886047104 10:72195712-72195712 10:70435956-70435956
26 NODAL NM_018055.5(NODAL):c.203T>C (p.Val68Ala)SNV Uncertain significance 300311 rs886047105 10:72195730-72195730 10:70435974-70435974
27 NODAL NM_018055.5(NODAL):c.125C>T (p.Ala42Val)SNV Uncertain significance 300312 rs146471900 10:72201299-72201299 10:70441543-70441543
28 NODAL NM_018055.5(NODAL):c.*480G>ASNV Uncertain significance 300293 rs886047101 10:72192212-72192212 10:70432456-70432456
29 NODAL NM_018055.5(NODAL):c.*121C>ASNV Uncertain significance 300297 rs578069296 10:72192571-72192571 10:70432815-70432815
30 NODAL NM_018055.5(NODAL):c.593C>A (p.Ser198Tyr)SNV Uncertain significance 300300 rs377663429 10:72195340-72195340 10:70435584-70435584
31 NODAL NM_018055.5(NODAL):c.*678G>ASNV Uncertain significance 300290 rs374692279 10:72192014-72192014 10:70432258-70432258
32 NODAL NM_018055.5(NODAL):c.*676C>TSNV Uncertain significance 300292 rs886047100 10:72192016-72192016 10:70432260-70432260
33 NODAL NM_018055.5(NODAL):c.550C>T (p.Pro184Ser)SNV Uncertain significance 300301 rs752979542 10:72195383-72195383 10:70435627-70435627
34 NODAL NM_018055.5(NODAL):c.514C>G (p.Gln172Glu)SNV Uncertain significance 300302 rs886047102 10:72195419-72195419 10:70435663-70435663
35 NODAL NM_018055.5(NODAL):c.393G>C (p.Arg131=)SNV Uncertain significance 300304 rs765235855 10:72195540-72195540 10:70435784-70435784
36 NODAL NM_018055.5(NODAL):c.280C>T (p.Arg94Trp)SNV Uncertain significance 300308 rs778607015 10:72195653-72195653 10:70435897-70435897
37 NODAL NM_018055.5(NODAL):c.-9C>TSNV Uncertain significance 300313 rs756480830 10:72201432-72201432 10:70441676-70441676
38 CDON NM_016952.4(CDON):c.*2380_*2381insCACAinsertion Uncertain significance 303411 rs886047954 11:125828456-125828457 11:125958561-125958562
39 CDON NM_001243597.1(CDON):c.*2379_*2380CA[3]short repeat Uncertain significance 303419 rs886047955 11:125828458-125828459 11:125958563-125958564
40 CDON NM_016952.4(CDON):c.*2373_*2378deldeletion Uncertain significance 303421 rs886047957 11:125828459-125828464 11:125958564-125958569
41 CDON NM_016952.4(CDON):c.*2376_*2377insCACATATATAinsertion Uncertain significance 303425 rs371911236 11:125828460-125828461 11:125958565-125958566
42 CDON NM_016952.4(CDON):c.*2376_*2377insCATATAinsertion Uncertain significance 303427 rs371911236 11:125828460-125828461 11:125958565-125958566
43 CDON NM_016952.4(CDON):c.*2376_*2377insCACACATATAinsertion Uncertain significance 303428 rs371911236 11:125828460-125828461 11:125958565-125958566
44 CDON NM_016952.4(CDON):c.*2376_*2377insCACACACACATATAinsertion Uncertain significance 303429 rs371911236 11:125828460-125828461 11:125958565-125958566
45 CDON NM_016952.4(CDON):c.*2376_*2377insCACACACACACATAinsertion Uncertain significance 303435 rs371911236 11:125828460-125828461 11:125958565-125958566
46 CDON NM_001243597.1(CDON):c.*2351_*2352CA[16]short repeat Uncertain significance 303440 rs35654681 11:125828460-125828461 11:125958565-125958566
47 CDON NM_016952.4(CDON):c.*2345_*2349delinsAACACACACACindel Uncertain significance 303442 rs886047960 11:125828488-125828492 11:125958593-125958597
48 CDON NM_016952.4(CDON):c.*1310dupduplication Uncertain significance 303466 rs886047972 11:125829526-125829527 11:125959631-125959632
49 CDON NM_016952.4(CDON):c.2429C>G (p.Ser810Cys)SNV Uncertain significance 303498 rs746038393 11:125864881-125864881 11:125994986-125994986
50 CDON NM_016952.4(CDON):c.1553-17TC[3]short repeat Uncertain significance 303517 rs762936563 11:125875960-125875963 11:126006065-126006068

Copy number variations for Holoprosencephaly from CNVD:

7 (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 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:

36
# 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 61)
# Name GO ID Score Top Affiliating Genes
1 positive regulation of transcription by RNA polymerase II GO:0045944 10.22 ZIC1 SIX3 SHH NODAL GLI2 FOXH1
2 positive regulation of cell proliferation GO:0008284 10.1 SHH NODAL GLI2 FGFR1 FGF8
3 positive regulation of transcription, DNA-templated GO:0045893 10.1 ZIC2 ZIC1 SHH PTCH1 GLI2 FOXH1
4 negative regulation of transcription by RNA polymerase II GO:0000122 10.06 TGIF1 SHH PTCH1 NODAL GLI2 FOXH1
5 heart development GO:0007507 9.99 SHH NODAL GLI2 FGF8
6 in utero embryonic development GO:0001701 9.98 PTCH1 NODAL GLI2 FGFR1
7 regulation of cell proliferation GO:0042127 9.95 SIX3 SHH PTCH1 FGFR1 DHCR7
8 kidney development GO:0001822 9.9 SHH GLI2 FGF8
9 positive regulation of neuron differentiation GO:0045666 9.89 GLI2 FGFR1 CDON
10 brain development GO:0007420 9.85 ZIC2 ZIC1 SIX3 PTCH1 NODAL FGFR1
11 inner ear morphogenesis GO:0042472 9.84 ZIC1 FGFR1 FGF8
12 anatomical structure development GO:0048856 9.83 SIX3 SHH GLI2
13 cell fate commitment GO:0045165 9.83 SHH NODAL GAS1 FGF8
14 embryonic limb morphogenesis GO:0030326 9.82 SHH PTCH1 FGFR1
15 positive regulation of cell differentiation GO:0045597 9.81 SHH FGFR1 FGF8
16 smoothened signaling pathway GO:0007224 9.81 SHH PTCH1 GLI2 CDON
17 branching involved in ureteric bud morphogenesis GO:0001658 9.8 SHH PTCH1 FGF8
18 heart looping GO:0001947 9.8 SHH NODAL FOXH1 FGF8
19 developmental growth GO:0048589 9.76 SHH GLI2 GAS1
20 embryonic pattern specification GO:0009880 9.75 SHH NODAL DISP1
21 regulation of smoothened signaling pathway GO:0008589 9.74 ZIC1 PTCH1 GAS1
22 striated muscle cell differentiation GO:0051146 9.73 SHH CDON
23 embryonic heart tube development GO:0035050 9.73 NODAL FGF8
24 spinal cord motor neuron differentiation GO:0021522 9.73 SHH PTCH1 GLI2
25 pattern specification process GO:0007389 9.73 ZIC1 SHH PTCH1 GLI2
26 male genitalia development GO:0030539 9.72 SHH FGF8
27 osteoblast development GO:0002076 9.72 SHH GLI2
28 pharyngeal system development GO:0060037 9.72 PTCH1 FGF8
29 somite development GO:0061053 9.72 SHH PTCH1
30 digestive tract morphogenesis GO:0048546 9.72 SHH NODAL
31 negative regulation of androgen receptor signaling pathway GO:0060766 9.71 NODAL FOXH1
32 aorta morphogenesis GO:0035909 9.71 FOXH1 FGF8
33 regulation of stem cell population maintenance GO:2000036 9.71 NODAL CNOT1
34 smooth muscle tissue development GO:0048745 9.71 SHH PTCH1
35 anatomical structure formation involved in morphogenesis GO:0048646 9.71 SHH NODAL GLI2
36 negative regulation of intracellular estrogen receptor signaling pathway GO:0033147 9.7 FOXH1 CNOT1
37 prostate gland development GO:0030850 9.7 SHH PTCH1
38 generation of neurons GO:0048699 9.7 FGFR1 FGF8
39 multicellular organism development GO:0007275 9.7 ZIC2 ZIC1 TGIF1 SIX3 SHH NODAL
40 cell proliferation in forebrain GO:0021846 9.69 SIX3 FGF8
41 organ induction GO:0001759 9.69 FGFR1 FGF8
42 metanephric collecting duct development GO:0072205 9.68 SHH PTCH1
43 positive regulation of T cell differentiation in thymus GO:0033089 9.68 SHH GLI2
44 lung-associated mesenchyme development GO:0060484 9.68 SHH FGFR1
45 positive regulation of skeletal muscle tissue development GO:0048643 9.67 SHH CDON
46 smoothened signaling pathway involved in dorsal/ventral neural tube patterning GO:0060831 9.66 PTCH1 GLI2
47 telencephalon regionalization GO:0021978 9.66 SIX3 SHH
48 forebrain dorsal/ventral pattern formation GO:0021798 9.65 SIX3 FGF8
49 dorsal/ventral neural tube patterning GO:0021904 9.65 SHH PTCH1 GLI2
50 anterior/posterior pattern specification GO:0009952 9.65 SHH NODAL GLI2 FOXH1 CDON

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

# Name GO ID Score Top Affiliating Genes
1 DNA-binding transcription factor activity GO:0003700 9.8 ZIC2 ZIC1 TGIF1 SIX3 GLI2 FOXH1
2 DNA-binding transcription factor activity, RNA polymerase II-specific GO:0000981 9.63 ZIC2 ZIC1 TGIF1 SIX3 GLI2 FOXH1
3 co-SMAD binding GO:0070410 9.26 TGIF1 FOXH1
4 patched binding GO:0005113 8.96 SHH PTCH1
5 morphogen activity GO:0016015 8.62 SHH NODAL

Sources for Holoprosencephaly

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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