MCID: HLP001
MIFTS: 66

Holoprosencephaly

Categories: Rare diseases, Neuronal diseases, Endocrine diseases, Fetal diseases, Genetic 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 7 and holoprosencephaly 5. 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 cryptorchidism and proteinuria

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 7 34.6 NODAL PTCH1
2 holoprosencephaly 5 34.4 TGIF1 ZIC1 ZIC2
3 holoprosencephaly, recurrent infections, and monocytosis 34.4 GLI2 PTCH1 SIX3
4 holoprosencephaly 1 34.4 GAS1 HPE1 LSS SHH SIX3
5 holoprosencephaly 8 34.4 DISP1 HPE8 TGIF1
6 holoprosencephaly 4 34.4 SHH TGIF1 ZIC1 ZIC2
7 hartsfield syndrome 34.0 FGF8 FGFR1
8 agnathia-otocephaly complex 33.8 FGF8 GLI2 NODAL SHH
9 alobar holoprosencephaly 32.7 CDON DISP1 FGF8 FOXH1 GAS1 GLI2
10 midline interhemispheric variant of holoprosencephaly 32.7 CDON DISP1 FGF8 FOXH1 GAS1 GLI2
11 semilobar holoprosencephaly 32.6 CDON DISP1 FGF8 FGFR1 FOXH1 GAS1
12 septopreoptic holoprosencephaly 32.6 CDON DISP1 FGF8 FOXH1 GAS1 GLI2
13 lobar holoprosencephaly 32.5 CDON DISP1 FGF8 FGFR1 FOXH1 GAS1
14 microform holoprosencephaly 32.5 CDON DISP1 FGF8 FGFR1 FOXH1 GAS1
15 pituitary stalk interruption syndrome 30.8 CDON SHH TGIF1
16 chromosome 18p deletion syndrome 30.7 NODAL SHH SIX3 ZIC2
17 orofacial cleft 30.4 FGF8 FGFR1 NODAL SHH
18 neural tube defects 29.3 MNX1 PTCH1 ZIC1 ZIC2
19 holoprosencephaly 3 12.3
20 holoprosencephaly 2 12.3
21 nonsyndromic holoprosencephaly 12.3
22 holoprosencephaly 9 12.3
23 holoprosencephaly, semilobar, with craniosynostosis 12.3
24 holoprosencephaly 11 12.2
25 holoprosencephaly 6 12.1
26 brachial amelia, cleft lip, and holoprosencephaly 12.1
27 holoprosencephaly with fetal akinesia/hypokinesia sequence 12.0
28 holoprosencephaly caudal dysgenesis 11.9
29 congenital nasal pyriform aperture stenosis with holoprosencephaly 11.8
30 holoprosencephaly ectrodactyly cleft lip palate 11.8
31 pseudotrisomy 13 syndrome 11.7
32 steinfeld syndrome 11.7
33 morse-rawnsley-sargent syndrome 11.4
34 lambotte syndrome 11.2
35 dysgnathia complex 11.2
36 schizencephaly 11.1
37 solitary median maxillary central incisor 11.1
38 acquired schizencephaly 11.1 SHH SIX3
39 chromosome 1q41-q42 deletion syndrome 11.0
40 corpus callosum, agenesis of 10.9
41 bardet-biedl syndrome 17 10.9 GLI2 PTCH1 SHH
42 calcifying epithelial odontogenic tumor 10.9 GLI2 PTCH1
43 infratentorial cancer 10.9 GLI2 PTCH1 SHH
44 integumentary system cancer 10.9 GLI2 PTCH1 SHH
45 tooth size 10.9 FGF8 SHH
46 congenital nervous system abnormality 10.9 NODAL SHH SIX3 ZIC2
47 basal cell nevus syndrome 10.8 GAS1 GLI2 PTCH1 SHH
48 heterotaxy, visceral, 1, x-linked 10.8
49 hypoglossia with situs inversus 10.8
50 syndromic x-linked intellectual disability turner type 10.8

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 cryptorchidism 59 32 occasional (7.5%) Occasional (29-5%) HP:0000028
2 proteinuria 59 32 occasional (7.5%) Occasional (29-5%) HP:0000093
3 hydrocephalus 59 32 occasional (7.5%) Occasional (29-5%) HP:0000238
4 microcephaly 59 32 frequent (33%) Frequent (79-30%) HP:0000252
5 macrocephaly 59 32 occasional (7.5%) Occasional (29-5%) HP:0000256
6 epicanthus 59 32 occasional (7.5%) Occasional (29-5%) HP:0000286
7 broad philtrum 59 32 occasional (7.5%) Occasional (29-5%) HP:0000289
8 hypertelorism 59 32 occasional (7.5%) Occasional (29-5%) HP:0000316
9 macrotia 59 32 occasional (7.5%) Occasional (29-5%) HP:0000400
10 depressed nasal tip 59 32 occasional (7.5%) Occasional (29-5%) HP:0000437
11 choanal atresia 59 32 frequent (33%) Frequent (79-30%) HP:0000453
12 depressed nasal ridge 59 32 frequent (33%) Frequent (79-30%) HP:0000457
13 anosmia 59 32 frequent (33%) Frequent (79-30%) HP:0000458
14 anteverted nares 59 32 occasional (7.5%) Occasional (29-5%) HP:0000463
15 short neck 59 32 occasional (7.5%) Occasional (29-5%) HP:0000470
16 retinopathy 59 32 occasional (7.5%) Occasional (29-5%) HP:0000488
17 deeply set eye 59 32 occasional (7.5%) Occasional (29-5%) HP:0000490
18 ptosis 59 32 occasional (7.5%) Occasional (29-5%) HP:0000508
19 anophthalmia 59 32 frequent (33%) Frequent (79-30%) HP:0000528
20 chorioretinal coloboma 59 32 occasional (7.5%) Occasional (29-5%) HP:0000567
21 microphthalmia 59 32 frequent (33%) Frequent (79-30%) HP:0000568
22 thick eyebrow 59 32 occasional (7.5%) Occasional (29-5%) HP:0000574
23 blepharophimosis 59 32 occasional (7.5%) Occasional (29-5%) HP:0000581
24 upslanted palpebral fissure 59 32 occasional (7.5%) Occasional (29-5%) HP:0000582
25 hypotelorism 59 32 frequent (33%) Frequent (79-30%) HP:0000601
26 iris coloboma 59 32 frequent (33%) Frequent (79-30%) HP:0000612
27 optic atrophy 59 32 occasional (7.5%) Occasional (29-5%) HP:0000648
28 synophrys 59 32 occasional (7.5%) Occasional (29-5%) HP:0000664
29 congenital diaphragmatic hernia 59 32 occasional (7.5%) Occasional (29-5%) HP:0000776
30 diabetes mellitus 59 32 frequent (33%) Frequent (79-30%) HP:0000819
31 panhypopituitarism 59 32 occasional (7.5%) Occasional (29-5%) HP:0000871
32 diabetes insipidus 59 32 occasional (7.5%) Occasional (29-5%) HP:0000873
33 brachydactyly 59 32 occasional (7.5%) Occasional (29-5%) HP:0001156
34 hand polydactyly 59 32 occasional (7.5%) Occasional (29-5%) HP:0001161
35 seizures 59 32 frequent (33%) Frequent (79-30%) HP:0001250
36 muscular hypotonia 59 32 frequent (33%) Frequent (79-30%) HP:0001252
37 spasticity 59 32 frequent (33%) Frequent (79-30%) HP:0001257
38 global developmental delay 59 32 frequent (33%) Frequent (79-30%) HP:0001263
39 dandy-walker malformation 59 32 occasional (7.5%) Occasional (29-5%) HP:0001305
40 muscle weakness 59 32 frequent (33%) Frequent (79-30%) HP:0001324
41 dystonia 59 32 frequent (33%) Frequent (79-30%) HP:0001332
42 holoprosencephaly 59 32 hallmark (90%) Very frequent (99-80%) HP:0001360
43 failure to thrive in infancy 59 32 occasional (7.5%) Occasional (29-5%) HP:0001531
44 omphalocele 59 32 occasional (7.5%) Occasional (29-5%) HP:0001539
45 ventricular septal defect 59 32 occasional (7.5%) Occasional (29-5%) HP:0001629
46 tetralogy of fallot 59 32 occasional (7.5%) Occasional (29-5%) HP:0001636
47 abnormal aortic morphology 59 32 occasional (7.5%) Occasional (29-5%) HP:0001679
48 abnormality of the spleen 59 32 occasional (7.5%) Occasional (29-5%) HP:0001743
49 talipes 59 32 occasional (7.5%) Occasional (29-5%) HP:0001883
50 hypoglycemia 59 32 frequent (33%) Frequent (79-30%) HP:0001943

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 PTCH1 SHH SIX3 TGIF1 ZIC1 ZIC2
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 FGFR1 GAS1 GLI2 MNX1 NODAL PTCH1
8 embryo MP:0005380 10.34 FOXH1 GAS1 GLI2 NODAL PTCH1 SHH
9 nervous system MP:0003631 10.27 FGF8 FGFR1 FOXH1 GAS1 GLI2 MNX1
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 NODAL PTCH1 SHH ZIC1 DHCR7 DISP1
13 hearing/vestibular/ear MP:0005377 10.1 FGF8 FGFR1 FOXH1 GAS1 GLI2 PTCH1
14 respiratory system MP:0005388 10.07 DHCR7 DISP1 FGF8 FOXH1 GAS1 GLI2
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 DISP1 FGF8 FGFR1 FOXH1 GAS1 GLI2
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, Cerebellum, Heart, Lung
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 681)
# 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
SIX3 deletions and incomplete penetrance in families affected by holoprosencephaly. ( 28670735 )
2017
22
Facial Evaluation in Holoprosencephaly. ( 27875510 )
2017
23
Endocytic receptor LRP2/megalin-of holoprosencephaly and renal Fanconi syndrome. ( 28497274 )
2017
24
Prenatal diagnosis of monosomy 18p associated with holoprosencephaly: case report. ( 28513240 )
2017
25
Ethanol itself is a holoprosencephaly-inducing teratogen. ( 28441416 )
2017
26
Trisomy 18 and holoprosencephaly. ( 28449414 )
2017
27
Pancreas and gallbladder agenesis in a newborn with semilobar holoprosencephaly, a case report. ( 28525974 )
2017
28
7q Deletion/12q Duplication Is the Possible Cause of an Alobar Holoprosencephaly Case. ( 29456484 )
2017
29
Semi Lobar Holoprosencephaly with Vertebral Segmentation Defects. ( 28883880 )
2017
30
Expanding the FANCO/RAD51C associated phenotype: Cleft lip and palate and lobar holoprosencephaly, two rare findings in Fanconi anemia. ( 29278735 )
2017
31
"Minimal" holoprosencephaly in a 14q deletion syndrome patient. ( 29136354 )
2017
32
Holoprosencephaly. ( 29259929 )
2017
33
BOC is a modifier gene in holoprosencephaly. ( 28677295 )
2017
34
In-depth investigations of adolescents and adults with holoprosencephaly identify unique characteristics. ( 28640243 )
2017
35
Prenatal diagnosis of holoprosencephaly associated with Smith-Lemli-Opitz syndrome (SLOS) in a 46,XX fetus. ( 28805615 )
2017
36
Complex mode of inheritance in holoprosencephaly revealed by whole exome sequencing. ( 26748417 )
2016
37
The middle interhemispheric variant of holoprosencephaly: magnetic resonance and diffusion tensor imaging findings. ( 27089898 )
2016
38
Holoprosencephaly and Pure Red Cell Aplasia in a Feline Leukaemia Virus-Positive Kitten. ( 26897097 )
2016
39
Mutational Spectrum in Holoprosencephaly Shows That FGF is a New Major Signaling Pathway. ( 27363716 )
2016
40
Holoprosencephaly: antenatal and postnatal diagnosis and outcome. ( 26767839 )
2016
41
Impact of holoprosencephaly, exomphalos, megacystis and high NT in first trimester screening for chromosomal abnormalities. ( 27558969 )
2016
42
Microform holoprosencephaly with bilateral congenital elbow dislocation; increasing the phenotypic spectrum of Steinfeld syndrome. ( 26728615 )
2016
43
Alobar Holoprosencephaly Associated with Meningomyelocoele and Omphalocoele: An Unusual Coexistence. ( 28050387 )
2016
44
Six3 dosage mediates the pathogenesis of holoprosencephaly. ( 27770010 )
2016
45
Adult with Middle Interhemispheric Variant of Holoprosencephaly: Neuropsychological, Clinical, and Radiological Findings. ( 27235161 )
2016
46
Zic2 mutation causes holoprosencephaly via disruption of NODAL signalling. ( 27466203 )
2016
47
Gli2 gene dosage and gene-environment interaction illuminate the etiological complexity of holoprosencephaly. ( 27585885 )
2016
48
Case 236: Middle Interhemispheric Variant of Holoprosencephaly. ( 27870630 )
2016
49
Monozygotic twins with de novo ZIC2 gene mutations discordant for the type of holoprosencephaly. ( 26962069 )
2016
50
Semilobar holoprosencephaly in a 12-month-old baby boy born to a primigravida patient with type 1 diabetes mellitus: a case report. ( 27998308 )
2016

Variations for Holoprosencephaly

ClinVar genetic disease variations for Holoprosencephaly:

6
(show top 50) (show all 922)
# Gene Variation Type Significance SNP ID Assembly Location
1 MATN4 NM_030590.3(MATN4): c.515G> C (p.Gly172Ala) single nucleotide variant Likely pathogenic rs730882210 GRCh38 Chromosome 20, 45304356: 45304356
2 MATN4 NM_030590.3(MATN4): c.515G> C (p.Gly172Ala) single nucleotide variant Likely pathogenic rs730882210 GRCh37 Chromosome 20, 43932996: 43932996
3 PTCH1 NM_000264.4(PTCH1): c.37C> G (p.Arg13Gly) single nucleotide variant Uncertain significance rs779791579 GRCh37 Chromosome 9, 98270607: 98270607
4 PTCH1 NM_000264.4(PTCH1): c.37C> G (p.Arg13Gly) single nucleotide variant Uncertain significance rs779791579 GRCh38 Chromosome 9, 95508325: 95508325
5 CDON NM_016952.4(CDON): c.1855G> C (p.Asp619His) single nucleotide variant Uncertain significance rs141081456 GRCh37 Chromosome 11, 125873968: 125873968
6 CDON NM_016952.4(CDON): c.1855G> C (p.Asp619His) single nucleotide variant Uncertain significance rs141081456 GRCh38 Chromosome 11, 126004073: 126004073
7 GLI2 NM_005270.4(GLI2): c.1986G> A (p.Ser662=) single nucleotide variant Benign/Likely benign rs114259687 GRCh37 Chromosome 2, 121743883: 121743883
8 GLI2 NM_005270.4(GLI2): c.1986G> A (p.Ser662=) single nucleotide variant Benign/Likely benign rs114259687 GRCh38 Chromosome 2, 120986307: 120986307
9 GLI2 NM_005270.4(GLI2): c.3048C> T (p.Asp1016=) single nucleotide variant Benign/Likely benign rs140479803 GRCh37 Chromosome 2, 121746538: 121746538
10 GLI2 NM_005270.4(GLI2): c.3048C> T (p.Asp1016=) single nucleotide variant Benign/Likely benign rs140479803 GRCh38 Chromosome 2, 120988962: 120988962
11 GLI2 NM_005270.4(GLI2): c.3590G> A (p.Gly1197Asp) single nucleotide variant Benign/Likely benign rs114823319 GRCh37 Chromosome 2, 121747080: 121747080
12 GLI2 NM_005270.4(GLI2): c.3590G> A (p.Gly1197Asp) single nucleotide variant Benign/Likely benign rs114823319 GRCh38 Chromosome 2, 120989504: 120989504
13 GLI2 NM_005270.4(GLI2): c.3469C> T (p.Leu1157=) single nucleotide variant Uncertain significance rs141988240 GRCh37 Chromosome 2, 121746959: 121746959
14 GLI2 NM_005270.4(GLI2): c.3469C> T (p.Leu1157=) single nucleotide variant Uncertain significance rs141988240 GRCh38 Chromosome 2, 120989383: 120989383
15 GLI2 NM_005270.4(GLI2): c.3018C> T (p.Gly1006=) single nucleotide variant Benign/Likely benign rs373880077 GRCh37 Chromosome 2, 121746508: 121746508
16 GLI2 NM_005270.4(GLI2): c.3018C> T (p.Gly1006=) single nucleotide variant Benign/Likely benign rs373880077 GRCh38 Chromosome 2, 120988932: 120988932
17 GLI2 NM_005270.4(GLI2): c.2940C> T (p.Ser980=) single nucleotide variant Benign/Likely benign rs146811565 GRCh37 Chromosome 2, 121746430: 121746430
18 GLI2 NM_005270.4(GLI2): c.2940C> T (p.Ser980=) single nucleotide variant Benign/Likely benign rs146811565 GRCh38 Chromosome 2, 120988854: 120988854
19 GLI2 NM_005270.4(GLI2): c.4333C> T (p.Leu1445Phe) single nucleotide variant Benign/Likely benign rs146207623 GRCh37 Chromosome 2, 121747823: 121747823
20 GLI2 NM_005270.4(GLI2): c.4333C> T (p.Leu1445Phe) single nucleotide variant Benign/Likely benign rs146207623 GRCh38 Chromosome 2, 120990247: 120990247
21 GLI2 NM_005270.4(GLI2): c.4332G> A (p.Met1444Ile) single nucleotide variant Benign/Likely benign rs146467786 GRCh37 Chromosome 2, 121747822: 121747822
22 GLI2 NM_005270.4(GLI2): c.4332G> A (p.Met1444Ile) single nucleotide variant Benign/Likely benign rs146467786 GRCh38 Chromosome 2, 120990246: 120990246
23 GLI2 NM_005270.4(GLI2): c.4054A> G (p.Met1352Val) single nucleotide variant Benign/Likely benign rs149140724 GRCh37 Chromosome 2, 121747544: 121747544
24 GLI2 NM_005270.4(GLI2): c.4054A> G (p.Met1352Val) single nucleotide variant Benign/Likely benign rs149140724 GRCh38 Chromosome 2, 120989968: 120989968
25 FOXH1 NM_003923.2(FOXH1): c.373A> T (p.Thr125Ser) single nucleotide variant Benign/Likely benign rs112028242 GRCh37 Chromosome 8, 145700346: 145700346
26 FOXH1 NM_003923.2(FOXH1): c.373A> T (p.Thr125Ser) single nucleotide variant Benign/Likely benign rs112028242 GRCh38 Chromosome 8, 144474963: 144474963
27 FOXH1 NM_003923.2(FOXH1): c.783T> C (p.Pro261=) single nucleotide variant Benign/Likely benign rs151147114 GRCh37 Chromosome 8, 145699936: 145699936
28 FOXH1 NM_003923.2(FOXH1): c.783T> C (p.Pro261=) single nucleotide variant Benign/Likely benign rs151147114 GRCh38 Chromosome 8, 144474553: 144474553
29 GLI2 NM_005270.4(GLI2): c.1294G> A (p.Val432Met) single nucleotide variant Benign/Likely benign rs142296407 GRCh37 Chromosome 2, 121732611: 121732611
30 GLI2 NM_005270.4(GLI2): c.1294G> A (p.Val432Met) single nucleotide variant Benign/Likely benign rs142296407 GRCh38 Chromosome 2, 120975035: 120975035
31 FOXH1 NM_003923.2(FOXH1): c.15C> T (p.Ser5=) single nucleotide variant Conflicting interpretations of pathogenicity rs374587860 GRCh38 Chromosome 8, 144475742: 144475742
32 FOXH1 NM_003923.2(FOXH1): c.15C> T (p.Ser5=) single nucleotide variant Conflicting interpretations of pathogenicity rs374587860 GRCh37 Chromosome 8, 145701125: 145701125
33 PTCH1 NM_000264.4(PTCH1): c.3423G> A (p.Ala1141=) single nucleotide variant Conflicting interpretations of pathogenicity rs745948150 GRCh37 Chromosome 9, 98215786: 98215786
34 PTCH1 NM_000264.4(PTCH1): c.3423G> A (p.Ala1141=) single nucleotide variant Conflicting interpretations of pathogenicity rs745948150 GRCh38 Chromosome 9, 95453504: 95453504
35 PTCH1 NM_000264.4(PTCH1): c.2692G> A (p.Asp898Asn) single nucleotide variant Conflicting interpretations of pathogenicity rs531947455 GRCh37 Chromosome 9, 98224149: 98224149
36 PTCH1 NM_000264.4(PTCH1): c.2692G> A (p.Asp898Asn) single nucleotide variant Conflicting interpretations of pathogenicity rs531947455 GRCh38 Chromosome 9, 95461867: 95461867
37 PTCH1 NM_000264.4(PTCH1): c.1216-6C> A single nucleotide variant Conflicting interpretations of pathogenicity rs186008764 GRCh37 Chromosome 9, 98240474: 98240474
38 PTCH1 NM_000264.4(PTCH1): c.1216-6C> A single nucleotide variant Conflicting interpretations of pathogenicity rs186008764 GRCh38 Chromosome 9, 95478192: 95478192
39 FOXH1 NM_003923.2(FOXH1): c.771C> A (p.Gly257=) single nucleotide variant Benign/Likely benign rs115750264 GRCh37 Chromosome 8, 145699948: 145699948
40 FOXH1 NM_003923.2(FOXH1): c.771C> A (p.Gly257=) single nucleotide variant Benign/Likely benign rs115750264 GRCh38 Chromosome 8, 144474565: 144474565
41 PTCH1 NM_000264.4(PTCH1): c.3606C> T (p.Pro1202=) single nucleotide variant Benign/Likely benign rs138240178 GRCh37 Chromosome 9, 98211549: 98211549
42 PTCH1 NM_000264.4(PTCH1): c.3606C> T (p.Pro1202=) single nucleotide variant Benign/Likely benign rs138240178 GRCh38 Chromosome 9, 95449267: 95449267
43 PTCH1 NM_000264.4(PTCH1): c.3567C> T (p.Gly1189=) single nucleotide variant Benign/Likely benign rs62637630 GRCh37 Chromosome 9, 98211588: 98211588
44 PTCH1 NM_000264.4(PTCH1): c.3567C> T (p.Gly1189=) single nucleotide variant Benign/Likely benign rs62637630 GRCh38 Chromosome 9, 95449306: 95449306
45 PTCH1 NM_000264.4(PTCH1): c.2937C> T (p.Asn979=) single nucleotide variant Benign/Likely benign rs58629309 GRCh37 Chromosome 9, 98220526: 98220526
46 PTCH1 NM_000264.4(PTCH1): c.2937C> T (p.Asn979=) single nucleotide variant Benign/Likely benign rs58629309 GRCh38 Chromosome 9, 95458244: 95458244
47 PTCH1 NM_000264.4(PTCH1): c.2913T> C (p.Tyr971=) single nucleotide variant Benign/Likely benign rs2229062 GRCh37 Chromosome 9, 98220550: 98220550
48 PTCH1 NM_000264.4(PTCH1): c.2913T> C (p.Tyr971=) single nucleotide variant Benign/Likely benign rs2229062 GRCh38 Chromosome 9, 95458268: 95458268
49 PTCH1 NM_000264.4(PTCH1): c.1854C> T (p.Cys618=) single nucleotide variant Benign/Likely benign rs62637628 GRCh37 Chromosome 9, 98231429: 98231429
50 PTCH1 NM_000264.4(PTCH1): c.1854C> T (p.Cys618=) single nucleotide variant Benign/Likely benign rs62637628 GRCh38 Chromosome 9, 95469147: 95469147

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 60)
# Name GO ID Score Top Affiliating Genes
1 heart development GO:0007507 9.99 FGF8 GLI2 NODAL SHH
2 in utero embryonic development GO:0001701 9.97 FGFR1 GLI2 NODAL PTCH1
3 regulation of cell proliferation GO:0042127 9.97 DHCR7 FGFR1 PTCH1 SHH SIX3
4 kidney development GO:0001822 9.89 FGF8 GLI2 SHH
5 brain development GO:0007420 9.88 FGFR1 NODAL PTCH1 SIX3 ZIC1 ZIC2
6 positive regulation of neuron differentiation GO:0045666 9.87 CDON FGFR1 GLI2
7 inner ear morphogenesis GO:0042472 9.85 FGF8 FGFR1 ZIC1
8 embryonic limb morphogenesis GO:0030326 9.83 FGFR1 PTCH1 SHH
9 cell fate commitment GO:0045165 9.83 FGF8 GAS1 NODAL SHH
10 branching involved in ureteric bud morphogenesis GO:0001658 9.8 FGF8 PTCH1 SHH
11 heart looping GO:0001947 9.8 FGF8 FOXH1 NODAL SHH
12 pattern specification process GO:0007389 9.78 GLI2 PTCH1 SHH ZIC1
13 developmental growth GO:0048589 9.77 GAS1 GLI2 SHH
14 anterior/posterior pattern specification GO:0009952 9.77 CDON FOXH1 GLI2 NODAL SHH
15 embryonic pattern specification GO:0009880 9.74 DISP1 NODAL SHH
16 embryonic heart tube development GO:0035050 9.73 FGF8 NODAL
17 lung morphogenesis GO:0060425 9.73 FGF8 SHH
18 anatomical structure formation involved in morphogenesis GO:0048646 9.73 GLI2 NODAL SHH
19 dorsal/ventral pattern formation GO:0009953 9.73 DISP1 GLI2 PTCH1 SHH
20 cell fate specification GO:0001708 9.72 CDON SHH
21 male genitalia development GO:0030539 9.72 FGF8 SHH
22 osteoblast development GO:0002076 9.72 GLI2 SHH
23 pharyngeal system development GO:0060037 9.72 FGF8 PTCH1
24 striated muscle cell differentiation GO:0051146 9.72 CDON SHH
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 generation of neurons GO:0048699 9.71 FGF8 FGFR1
29 prostate gland development GO:0030850 9.71 GLI2 PTCH1 SHH
30 aorta morphogenesis GO:0035909 9.7 FGF8 FOXH1
31 digestive tract morphogenesis GO:0048546 9.7 NODAL SHH
32 negative regulation of androgen receptor signaling pathway GO:0060766 9.69 FOXH1 NODAL
33 cell proliferation in forebrain GO:0021846 9.69 FGF8 SIX3
34 dorsal/ventral neural tube patterning GO:0021904 9.69 GLI2 PTCH1 SHH
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 forebrain dorsal/ventral pattern formation GO:0021798 9.67 FGF8 SIX3
40 smoothened signaling pathway involved in dorsal/ventral neural tube patterning GO:0060831 9.66 GLI2 PTCH1
41 telencephalon regionalization GO:0021978 9.66 SHH SIX3
42 mammary gland duct morphogenesis GO:0060603 9.65 GLI2 PTCH1
43 determination of left/right symmetry GO:0007368 9.65 DISP1 FGF8 FOXH1 NODAL SHH
44 spinal cord dorsal/ventral patterning GO:0021513 9.64 GLI2 SHH
45 branching involved in salivary gland morphogenesis GO:0060445 9.63 FGF8 FGFR1 SHH
46 hindgut morphogenesis GO:0007442 9.62 GLI2 SHH
47 smoothened signaling pathway involved in regulation of cerebellar granule cell precursor cell proliferation GO:0021938 9.62 GLI2 SHH
48 formation of anatomical boundary GO:0048859 9.61 NODAL SHH
49 ventral midline development GO:0007418 9.61 GLI2 SHH
50 nodal signaling pathway involved in determination of lateral mesoderm left/right asymmetry GO:1900164 9.6 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 GO:0003700 9.7 FOXH1 GLI2 MNX1 SIX3 TGIF1 ZIC1
2 co-SMAD binding GO:0070410 9.26 FOXH1 TGIF1
3 patched binding GO:0005113 8.96 PTCH1 SHH
4 morphogen activity GO:0016015 8.62 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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