HPE3
MCID: HLP012
MIFTS: 39

Holoprosencephaly-3 (HPE3) malady

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

Aliases & Classifications for Holoprosencephaly-3

Aliases & Descriptions for Holoprosencephaly-3:

Name: Holoprosencephaly-3 54 66 13
Holoprosencephaly 3 12 66 14 69
Hpe3 12 66
Holoprosencephaly Type Iii 29
Hlp3 12

Characteristics:

HPO:

32
holoprosencephaly-3:
Inheritance autosomal dominant inheritance
Onset and clinical course incomplete penetrance


Classifications:



External Ids:

OMIM 54 142945
Disease Ontology 12 DOID:0110875
MedGen 40 C1840529
MeSH 42 D016142

Summaries for Holoprosencephaly-3

UniProtKB/Swiss-Prot : 66 Holoprosencephaly 3: A structural anomaly of the brain, in which the developing forebrain fails to correctly separate into right and left hemispheres. Holoprosencephaly is genetically heterogeneous and associated with several distinct facies and phenotypic variability. The majority of holoprosencephaly type 3 cases are apparently sporadic, although clear examples of autosomal dominant inheritance have been described.

MalaCards based summary : Holoprosencephaly-3, also known as holoprosencephaly 3, is related to shh-related holoprosencephaly and orofaciodigital syndrome, and has symptoms including malar flattening, midface retrusion and holoprosencephaly. An important gene associated with Holoprosencephaly-3 is SHH (Sonic Hedgehog), and among its related pathways/superpathways are Sudden Infant Death Syndrome (SIDS) Susceptibility Pathways and G alpha (s) signalling events. Affiliated tissues include brain, and related phenotypes are behavior/neurological and growth/size/body region

Disease Ontology : 12 A holoprosencephaly that has material basis in heterozygous mutation in the SHH gene on chromosome 7q36.

Description from OMIM: 142945

Related Diseases for Holoprosencephaly-3

Graphical network of the top 20 diseases related to Holoprosencephaly-3:



Diseases related to Holoprosencephaly-3

Symptoms & Phenotypes for Holoprosencephaly-3

Symptoms by clinical synopsis from OMIM:

142945

Clinical features from OMIM:

142945

Human phenotypes related to Holoprosencephaly-3:

32 (show all 8)
id Description HPO Frequency HPO Source Accession
1 malar flattening 32 HP:0000272
2 midface retrusion 32 HP:0011800
3 holoprosencephaly 32 HP:0001360
4 hypotelorism 32 HP:0000601
5 hydronephrosis 32 HP:0000126
6 abnormality of the nose 32 HP:0000366
7 cyclopia 32 HP:0009914
8 proboscis 32 HP:0012806

MGI Mouse Phenotypes related to Holoprosencephaly-3:

44
id Description MGI Source Accession Score Top Affiliating Genes
1 behavior/neurological MP:0005386 10.07 VIPR2 ADCYAP1 EN2 HSPD1 HTR5A KMT2A
2 growth/size/body region MP:0005378 10 ADCYAP1 EN2 HLX HSPD1 KMT2A KMT2C
3 endocrine/exocrine gland MP:0005379 9.92 FNDC3A HLX MNX1 RUNX2 SHH VIP
4 homeostasis/metabolism MP:0005376 9.9 ADCYAP1 CYB5A EN2 HLX KMT2A MNX1
5 muscle MP:0005369 9.5 ADCYAP1 HLX HSPD1 KMT2A MNX1 RUNX2
6 reproductive system MP:0005389 9.32 VIP VIPR2 ADCYAP1 EN2 FNDC3A HSPD1

Drugs & Therapeutics for Holoprosencephaly-3

Search Clinical Trials , NIH Clinical Center for Holoprosencephaly-3

Genetic Tests for Holoprosencephaly-3

Genetic tests related to Holoprosencephaly-3:

id Genetic test Affiliating Genes
1 Holoprosencephaly 3 29

Anatomical Context for Holoprosencephaly-3

MalaCards organs/tissues related to Holoprosencephaly-3:

39
Brain

Publications for Holoprosencephaly-3

Variations for Holoprosencephaly-3

UniProtKB/Swiss-Prot genetic disease variations for Holoprosencephaly-3:

66 (show top 50) (show all 79)
id Symbol AA change Variation ID SNP ID
1 SHH p.Gly31Arg VAR_003619 rs28936675
2 SHH p.Trp117Gly VAR_003620 rs104894040
3 SHH p.Trp117Arg VAR_003621 rs104894040
4 SHH p.Asp88Val VAR_009163 rs104894050
5 SHH p.Gln100His VAR_009164 rs587778792
6 SHH p.Asn115Lys VAR_009165 rs267607047
7 SHH p.Glu188Gln VAR_009166 rs587778799
8 SHH p.Asp222Asn VAR_009167 rs587778805
9 SHH p.Val224Glu VAR_009168 rs104894042
10 SHH p.Ala226Thr VAR_009169 rs104894043
11 SHH p.Ser236Arg VAR_009170 rs587778806
12 SHH p.Gly290Asp VAR_009172 rs104894047
13 SHH p.Ala383Thr VAR_009174 rs137853341
14 SHH p.Pro424Ala VAR_009176 rs104894048
15 SHH p.Ser436Leu VAR_009177
16 SHH p.Arg6Thr VAR_023804
17 SHH p.Ala110Asp VAR_023806
18 SHH p.Thr150Arg VAR_023807
19 SHH p.Leu271Pro VAR_023809
20 SHH p.Val332Ala VAR_023810 rs104894052
21 SHH p.Pro347Gln VAR_023811
22 SHH p.Ile354Thr VAR_023812
23 SHH p.Arg381Pro VAR_023813
24 SHH p.Gly27Ala VAR_039888
25 SHH p.Ile111Asn VAR_039889
26 SHH p.His140Pro VAR_039890
27 SHH p.His140Gln VAR_039891
28 SHH p.Cys183Phe VAR_039892
29 SHH p.Thr267Ile VAR_039893
30 SHH p.Ala373Thr VAR_039894
31 SHH p.Leu17Pro VAR_062592
32 SHH p.Pro26Leu VAR_062593
33 SHH p.Leu39Pro VAR_062594
34 SHH p.Glu53Lys VAR_062595
35 SHH p.Asp83Val VAR_062596
36 SHH p.Ile84Phe VAR_062597
37 SHH p.Cys102Arg VAR_062598
38 SHH p.Cys102Tyr VAR_062599
39 SHH p.Leu109Phe VAR_062600
40 SHH p.Ala110Thr VAR_062601
41 SHH p.Val124Met VAR_062602
42 SHH p.Glu136Lys VAR_062603
43 SHH p.Gly143Asp VAR_062604
44 SHH p.Arg144Pro VAR_062605
45 SHH p.Asp147Asn VAR_062606
46 SHH p.Thr150Lys VAR_062607
47 SHH p.Ser156Arg VAR_062608
48 SHH p.Phe170Cys VAR_062609
49 SHH p.Asp171His VAR_062610
50 SHH p.Cys183Arg VAR_062611

ClinVar genetic disease variations for Holoprosencephaly-3:

6 (show all 28)
id Gene Variation Type Significance SNP ID Assembly Location
1 SHH NM_000193.3(SHH): c.263A> T (p.Asp88Val) single nucleotide variant Pathogenic rs104894050 GRCh37 Chromosome 7, 155604554: 155604554
2 SHH NM_000193.3(SHH): c.91G> A (p.Gly31Arg) single nucleotide variant Pathogenic rs28936675 GRCh37 Chromosome 7, 155604726: 155604726
3 SHH NM_000193.3(SHH): c.298C> T (p.Gln100Ter) single nucleotide variant Pathogenic rs104894044 GRCh37 Chromosome 7, 155604519: 155604519
4 SHH NM_000193.3(SHH): c.313A> T (p.Lys105Ter) single nucleotide variant Pathogenic rs104894045 GRCh37 Chromosome 7, 155599239: 155599239
5 SHH NM_000193.3(SHH): c.349T> G (p.Trp117Gly) single nucleotide variant Pathogenic rs104894040 GRCh37 Chromosome 7, 155599203: 155599203
6 SHH NM_000193.3(SHH): c.349T> C (p.Trp117Arg) single nucleotide variant Pathogenic rs104894040 GRCh37 Chromosome 7, 155599203: 155599203
7 SHH NM_000193.3(SHH): c.671T> A (p.Val224Glu) single nucleotide variant Pathogenic rs104894042 GRCh37 Chromosome 7, 155596312: 155596312
8 SHH NM_000193.3(SHH): c.676G> A (p.Ala226Thr) single nucleotide variant Pathogenic rs104894043 GRCh37 Chromosome 7, 155596307: 155596307
9 SHH NM_000193.3(SHH): c.788_808del21 (p.Arg263_Ala269del) deletion Pathogenic rs397515375 GRCh37 Chromosome 7, 155596175: 155596195
10 SHH NM_000193.3(SHH): c.850G> T (p.Glu284Ter) single nucleotide variant Pathogenic rs104894046 GRCh37 Chromosome 7, 155596133: 155596133
11 SHH NM_000193.3(SHH): c.1147G> A (p.Ala383Thr) single nucleotide variant Pathogenic rs137853341 GRCh37 Chromosome 7, 155595836: 155595836
12 SHH NM_000193.3(SHH): c.1270C> G (p.Pro424Ala) single nucleotide variant Pathogenic rs104894048 GRCh37 Chromosome 7, 155595713: 155595713
13 SHH NM_000193.3(SHH): c.1132_1140delGCGCCCTTC (p.Ala378_Phe380del) deletion Pathogenic rs397515376 GRCh37 Chromosome 7, 155595843: 155595851
14 SHH NM_000193.3(SHH): c.766G> T (p.Glu256Ter) single nucleotide variant Pathogenic rs104894051 GRCh37 Chromosome 7, 155596217: 155596217
15 SHH NM_000193.3(SHH): c.383G> A (p.Trp128Ter) single nucleotide variant Pathogenic rs104894053 GRCh37 Chromosome 7, 155599169: 155599169
16 SHH NM_000193.3(SHH): c.345C> A (p.Asn115Lys) single nucleotide variant Pathogenic rs267607047 GRCh37 Chromosome 7, 155599207: 155599207
17 NM_000193.2: c.1308C> T single nucleotide variant Pathogenic
18 SHH NM_000193.3(SHH): c.1210_1224delGGGGACCGCGGGGGC (p.Asp405_Gly409del) deletion Pathogenic rs587778786 GRCh37 Chromosome 7, 155595759: 155595773
19 SHH NM_000193.3(SHH): c.9_10insGCTG (p.Leu4Alafs) insertion Pathogenic rs587778788 GRCh37 Chromosome 7, 155604807: 155604808
20 SHH NM_000193.3(SHH): c.38_45delTCTCCTCG (p.Val13Alafs) deletion Pathogenic rs587778789 GRCh37 Chromosome 7, 155604772: 155604779
21 SHH NM_000193.3(SHH): c.300G> C (p.Gln100His) single nucleotide variant Pathogenic rs587778792 GRCh37 Chromosome 7, 155604517: 155604517
22 SHH NM_000193.3(SHH): c.474C> G (p.Tyr158Ter) single nucleotide variant Pathogenic rs146990376 GRCh37 Chromosome 7, 155599078: 155599078
23 SHH NM_000193.3(SHH): c.562G> C (p.Glu188Gln) single nucleotide variant Pathogenic rs587778799 GRCh37 Chromosome 7, 155598990: 155598990
24 SHH NM_000193.3(SHH): c.625C> T (p.Gln209Ter) single nucleotide variant Pathogenic rs587778803 GRCh37 Chromosome 7, 155596358: 155596358
25 SHH NM_000193.3(SHH): c.664G> A (p.Asp222Asn) single nucleotide variant Pathogenic rs587778805 GRCh37 Chromosome 7, 155596319: 155596319
26 SHH NM_000193.3(SHH): c.708C> A (p.Ser236Arg) single nucleotide variant Pathogenic rs587778806 GRCh37 Chromosome 7, 155596275: 155596275
27 SHH NM_000193.3(SHH): c.1040C> G (p.Pro347Arg) single nucleotide variant Likely pathogenic rs886042458 GRCh37 Chromosome 7, 155595943: 155595943
28 SHH NM_000193.3(SHH): c.1284delC (p.Thr429Profs) deletion Pathogenic rs1057518660 GRCh37 Chromosome 7, 155595699: 155595699

Expression for Holoprosencephaly-3

Search GEO for disease gene expression data for Holoprosencephaly-3.

Pathways for Holoprosencephaly-3

Pathways related to Holoprosencephaly-3 according to GeneCards Suite gene sharing:

id Super pathways Score Top Affiliating Genes
1 11.47 ADCYAP1 HSPD1 VIPR1 VIPR2
2 11.19 ADCYAP1 NPS VIP VIPR1 VIPR2
3 10.73 EN2 SHH
4 10.54 VIPR1 VIPR2

GO Terms for Holoprosencephaly-3

Cellular components related to Holoprosencephaly-3 according to GeneCards Suite gene sharing:

id Name GO ID Score Top Affiliating Genes
1 histone methyltransferase complex GO:0035097 8.62 KMT2A KMT2C

Biological processes related to Holoprosencephaly-3 according to GeneCards Suite gene sharing:

id Name GO ID Score Top Affiliating Genes
1 embryonic forelimb morphogenesis GO:0035115 9.46 RUNX2 SHH
2 cAMP-mediated signaling GO:0019933 9.43 ADCYAP1 HTR5A
3 hindbrain development GO:0030902 9.4 EN2 SHH
4 positive regulation of synaptic transmission, glutamatergic GO:0051968 9.37 ADCYAP1 NPS
5 histone H3-K4 methylation GO:0051568 9.32 KMT2A KMT2C
6 embryonic digestive tract morphogenesis GO:0048557 9.26 HLX SHH
7 osteoblast development GO:0002076 9.16 RUNX2 SHH
8 positive regulation of cell proliferation GO:0008284 9.1 ADCYAP1 HLX RUNX2 SHH VIP VIPR1
9 positive regulation of adenylate cyclase activity involved in G-protein coupled receptor signaling pathway GO:0010579 8.96 ADCYAP1 VIP

Molecular functions related to Holoprosencephaly-3 according to GeneCards Suite gene sharing:

id Name GO ID Score Top Affiliating Genes
1 neuropeptide hormone activity GO:0005184 9.16 ADCYAP1 VIP
2 histone methyltransferase activity (H3-K4 specific) GO:0042800 8.96 KMT2A KMT2C
3 vasoactive intestinal polypeptide receptor activity GO:0004999 8.62 VIPR1 VIPR2

Sources for Holoprosencephaly-3

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
16 ExPASy
18 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 MedGen
42 MeSH
43 MESH via Orphanet
44 MGI
46 NCI
47 NCIt
48 NDF-RT
51 NINDS
52 Novoseek
54 OMIM
55 OMIM via Orphanet
59 PubMed
60 QIAGEN
65 SNOMED-CT via Orphanet
67 TGDB
68 Tocris
69 UMLS
70 UMLS via Orphanet
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