MCID: SPL034
MIFTS: 41

Split-Hand/foot Malformation 4

Categories: Genetic diseases, Bone diseases, Rare diseases, Fetal diseases

Aliases & Classifications for Split-Hand/foot Malformation 4

MalaCards integrated aliases for Split-Hand/foot Malformation 4:

Name: Split-Hand/foot Malformation 4 54 71 29 13 69
Shfm4 12 24 71 52
Split Hand-Foot Malformation 4 12 14
Split-Hand/foot Malformation, Type 4 24

Characteristics:

OMIM:

54
Inheritance:
autosomal dominant

Miscellaneous:
variable phenotype
reduced penetrance has been reported


HPO:

32
split-hand/foot malformation 4:
Onset and clinical course phenotypic variability
Inheritance autosomal dominant inheritance


Classifications:



External Ids:

OMIM 54 605289
Disease Ontology 12 DOID:0090023
ICD10 33 Q71.6
MedGen 40 C1854442
MeSH 42 D017880
UMLS 69 C0265554

Summaries for Split-Hand/foot Malformation 4

OMIM : 54
Split-hand/split-foot malformation is a limb malformation involving the central rays of the autopod and presenting with syndactyly, median clefts of the hands and feet, and aplasia and/or hypoplasia of the phalanges, metacarpals, and metatarsals. Some patients with SHFM4 have been found to have mental retardation, ectodermal findings, and orofacial clefting (Elliott and Evans, 2006). For additional phenotypic information and a discussion of genetic heterogeneity in this disorder, see SHFM1 (183600). (605289)

MalaCards based summary : Split-Hand/foot Malformation 4, also known as shfm4, is related to split hand-foot malformation and split hand-foot malformation 1, and has symptoms including syndactyly, ectrodactyly and triphalangeal thumb. An important gene associated with Split-Hand/foot Malformation 4 is TP63 (Tumor Protein P63), and among its related pathways/superpathways are TGF-beta Signaling Pathway (WikiPathways) and Signaling by Hedgehog. Affiliated tissues include bone, and related phenotypes are cardiovascular system and digestive/alimentary

UniProtKB/Swiss-Prot : 71 Split-hand/foot malformation 4: A limb malformation involving the central rays of the autopod and presenting with syndactyly, median clefts of the hands and feet, and aplasia and/or hypoplasia of the phalanges, metacarpals, and metatarsals. Some patients have been found to have mental retardation, ectodermal and craniofacial findings, and orofacial clefting.

Disease Ontology : 12 A split-hand/foot malformation that has material basis in heterozygous mutation in the TP63 on chromosome 3q28.

Related Diseases for Split-Hand/foot Malformation 4

Diseases in the Split Hand-Foot Malformation family:

Split-Hand/foot Malformation 5 Split-Hand/foot Malformation 4
Split-Hand/foot Malformation 6 Split-Hand/foot Malformation 3
Split Hand-Foot Malformation 1 Split Hand-Foot Malformation 2

Diseases related to Split-Hand/foot Malformation 4 via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 25)
id Related Disease Score Top Affiliating Genes
1 split hand-foot malformation 10.8
2 split hand-foot malformation 1 10.8
3 split hand split foot malformation autosomal recessive 10.8
4 split hand/foot malformation x-linked 10.8
5 intracranial aneurysm 10.6 DLX5 SEM1
6 hydrops fetalis, nonimmune, and/or atrial septal defect 10.4 DLX5 DLX6 SEM1
7 myelodysplasia and leukemia syndrome with monosomy 7 10.4 DLX5 DLX6
8 hypomyelinating leukodystrophy 10.3 SATB2 TP63 WNT10B
9 tooth agenesis, selective, 8 10.3 DLX5 SEM1 TP63 WNT10B
10 simosa craniofacial syndrome 10.2 FBXW4 SATB2 TP63
11 hair disease 10.1 SUFU TP53
12 congenital absence of both forearm and hand 10.0 DLX5 FBXW4 SEM1 TP63 WNT10B
13 split hand-foot malformation 2 10.0 DLX5 FBXW4 SEM1 TP63 WNT10B
14 lathosterolosis 9.9 NHLH1 SATB2 TP63
15 2-hydroxyglutaric aciduria 9.9 NHLH1 SATB2 TP63
16 myasthenic syndrome, congenital, 2a, slow-channel 9.8 NHLH1 SATB2 TP63
17 breast epithelioid hemangioma 9.6 SATB2 TP53
18 congenital absence of thigh and lower leg with foot present 9.3 BTRC DLX5 DLX6 FBXW4 SEM1 SUFU
19 primary congenital glaucoma 9.3 DLX2 SATB2 WNT10B
20 hypotrichosis 7 9.3 DLX5 DLX6 ITCH SATB2 SEM1 SNCA
21 lower limb deficiency-hypospadias syndrome 9.1 BTRC DLX5 DLX6 FBXW4 SEM1 SUFU
22 cardiomyopathy, familial hypertrophic, 9 7.4 BTRC DLX1 DLX2 DLX5 FBXW4 POLL
23 sonoda syndrome 7.4 BTRC DLX1 DLX2 DLX5 FBXW4 POLL
24 torsion dystonia 13 7.1 BTRC DLX1 DLX2 DLX5 DLX6 FBXW4
25 hay-wells syndrome 4.5 BMP7 BTRC CDKN1C DLX1 DLX2 DLX5

Graphical network of the top 20 diseases related to Split-Hand/foot Malformation 4:



Diseases related to Split-Hand/foot Malformation 4

Symptoms & Phenotypes for Split-Hand/foot Malformation 4

Symptoms via clinical synopsis from OMIM:

54

Skeletal- Feet:
syndactyly
'lobster-claw anomaly
webbing
split foot, unilateral or bilateral
missing metatarsals

Skeletal- Hands:
syndactyly
split hand, unilateral or bilateral
'lobster-claw anomaly
monodactyly
missing phalanges
more

Clinical features from OMIM:

605289

Human phenotypes related to Split-Hand/foot Malformation 4:

32 (show all 8)
id Description HPO Frequency HPO Source Accession
1 syndactyly 32 HP:0001159
2 ectrodactyly 32 HP:0100257
3 triphalangeal thumb 32 HP:0001199
4 split hand 32 HP:0001171
5 aplasia/hypoplasia involving the metacarpal bones 32 HP:0005914
6 aplasia/hypoplasia of the phalanges of the hand 32 HP:0009767
7 aplasia/hypoplasia of the phalanges of the toes 32 HP:0010173
8 aplasia/hypoplasia of metatarsal bones 32 HP:0001964

MGI Mouse Phenotypes related to Split-Hand/foot Malformation 4:

44 (show all 13)
id Description MGI Source Accession Score Top Affiliating Genes
1 cardiovascular system MP:0005385 10.3 BMP7 BTRC DLX1 DLX2 DLX5 ITCH
2 digestive/alimentary MP:0005381 10.24 BMP7 BTRC DLX1 DLX2 DLX5 DLX6
3 growth/size/body region MP:0005378 10.23 TP63 BMP7 BTRC DLX1 DLX2 DLX5
4 craniofacial MP:0005382 10.21 TP53 TP63 BMP7 DLX1 DLX2 DLX5
5 mortality/aging MP:0010768 10.17 DLX6 FBXW4 ITCH NHLH1 SATB2 SNCA
6 embryo MP:0005380 10.08 BMP7 DLX5 DLX6 FBXW4 SATB2 SUFU
7 integument MP:0010771 10.01 BMP7 DLX5 DLX6 ITCH SNCA SUFU
8 limbs/digits/tail MP:0005371 9.97 BMP7 DLX5 DLX6 FBXW4 SATB2 SUFU
9 hearing/vestibular/ear MP:0005377 9.91 BMP7 DLX1 DLX2 DLX5 DLX6 TP53
10 nervous system MP:0003631 9.91 BMP7 DLX1 DLX2 DLX5 DLX6 NHLH1
11 no phenotypic analysis MP:0003012 9.7 DLX1 WNT10B FBXW4 SNCA SUFU TP53
12 respiratory system MP:0005388 9.61 BMP7 DLX2 DLX5 DLX6 ITCH SATB2
13 skeleton MP:0005390 9.44 DLX2 DLX5 DLX6 FBXW4 ITCH SATB2

Drugs & Therapeutics for Split-Hand/foot Malformation 4

Search Clinical Trials , NIH Clinical Center for Split-Hand/foot Malformation 4

Genetic Tests for Split-Hand/foot Malformation 4

Genetic tests related to Split-Hand/foot Malformation 4:

id Genetic test Affiliating Genes
1 Split-Hand/foot Malformation 4 29
2 Split-Hand/foot Malformation, Type 4 24 TP63

Anatomical Context for Split-Hand/foot Malformation 4

MalaCards organs/tissues related to Split-Hand/foot Malformation 4:

39
Bone

Publications for Split-Hand/foot Malformation 4

Variations for Split-Hand/foot Malformation 4

UniProtKB/Swiss-Prot genetic disease variations for Split-Hand/foot Malformation 4:

71
id Symbol AA change Variation ID SNP ID
1 TP63 p.Lys233Glu VAR_020869 rs121908838
2 TP63 p.Lys232Glu VAR_032737
3 TP63 p.Arg319His VAR_032743

ClinVar genetic disease variations for Split-Hand/foot Malformation 4:

6
id Gene Variation Type Significance SNP ID Assembly Location
1 TP63 NM_003722.4(TP63): c.697A> G (p.Lys233Glu) single nucleotide variant Pathogenic rs121908838 GRCh37 Chromosome 3, 189582138: 189582138
2 TP63 NM_003722.4(TP63): c.955C> T (p.Arg319Cys) single nucleotide variant Pathogenic rs121908839 GRCh37 Chromosome 3, 189585694: 189585694
3 TP63 NM_003722.4(TP63): c.289C> T (p.Arg97Cys) single nucleotide variant Pathogenic rs121908848 GRCh37 Chromosome 3, 189456528: 189456528

Expression for Split-Hand/foot Malformation 4

Search GEO for disease gene expression data for Split-Hand/foot Malformation 4.

Pathways for Split-Hand/foot Malformation 4

Pathways related to Split-Hand/foot Malformation 4 according to GeneCards Suite gene sharing:

id Super pathways Score Top Affiliating Genes
1 11.46 BTRC ITCH TP53
2
Show member pathways
11.46 BTRC ITCH SEM1 SUFU
3
Show member pathways
10.3 TP53 TP63

GO Terms for Split-Hand/foot Malformation 4

Cellular components related to Split-Hand/foot Malformation 4 according to GeneCards Suite gene sharing:

id Name GO ID Score Top Affiliating Genes
1 nucleus GO:0005634 9.47 BTRC CDKN1C DLX1 DLX2 DLX5 DLX6

Biological processes related to Split-Hand/foot Malformation 4 according to GeneCards Suite gene sharing:

(show all 37)
id Name GO ID Score Top Affiliating Genes
1 positive regulation of apoptotic process GO:0043065 9.97 BMP7 SNCA TP53 WNT10B
2 negative regulation of transcription from RNA polymerase II promoter GO:0000122 9.97 CDKN1C DLX1 DLX2 SATB2 SNCA SUFU
3 positive regulation of canonical Wnt signaling pathway GO:0090263 9.84 DLX5 SEM1 WNT10B
4 palate development GO:0060021 9.81 DLX5 DLX6 SATB2
5 SCF-dependent proteasomal ubiquitin-dependent protein catabolic process GO:0031146 9.79 BTRC FBXW4 SEM1
6 proteasome-mediated ubiquitin-dependent protein catabolic process GO:0043161 9.79 BTRC SEM1 TP53
7 positive regulation of osteoblast differentiation GO:0045669 9.78 BMP7 TP63 WNT10B
8 positive regulation of cell differentiation GO:0045597 9.76 BMP7 DLX1 DLX2
9 cartilage development GO:0051216 9.76 BMP7 DLX2 FBXW4 SATB2
10 epithelial cell differentiation GO:0030855 9.73 BMP7 DLX5 DLX6 TP63
11 skeletal system development GO:0001501 9.73 BMP7 CDKN1C DLX5 DLX6 SUFU TP63
12 cellular response to BMP stimulus GO:0071773 9.72 BMP7 DLX1 DLX5
13 odontogenesis of dentin-containing tooth GO:0042475 9.71 BMP7 DLX1 DLX2 TP63
14 negative regulation of Notch signaling pathway GO:0045746 9.7 BMP7 DLX1 DLX2
15 negative regulation of smoothened signaling pathway GO:0045879 9.67 BTRC SUFU
16 negative regulation of phosphorylation GO:0042326 9.66 BMP7 CDKN1C
17 DNA damage response, signal transduction by p53 class mediator resulting in transcription of p21 class mediator GO:0006978 9.66 TP53 TP63
18 head development GO:0060322 9.65 DLX5 DLX6
19 proximal/distal pattern formation GO:0009954 9.65 DLX1 DLX2 TP63
20 forebrain neuron differentiation GO:0021879 9.63 DLX1 DLX2
21 negative regulation of oligodendrocyte differentiation GO:0048715 9.63 DLX1 DLX2
22 mitotic G1 DNA damage checkpoint GO:0031571 9.62 TP53 TP63
23 negative regulation of photoreceptor cell differentiation GO:0046533 9.6 DLX1 DLX2
24 subpallium development GO:0021544 9.59 DLX1 DLX2
25 cerebral cortex GABAergic interneuron differentiation GO:0021892 9.58 DLX1 DLX2
26 regulation of transcription from RNA polymerase II promoter involved in forebrain neuron fate commitment GO:0021882 9.54 DLX1 DLX2
27 cerebral cortex GABAergic interneuron fate commitment GO:0021893 9.51 DLX1 DLX2
28 positive regulation of amacrine cell differentiation GO:1902871 9.49 DLX1 DLX2
29 anatomical structure formation involved in morphogenesis GO:0048646 9.46 BMP7 DLX5 DLX6 TP63
30 multicellular organism development GO:0007275 9.4 BMP7 DLX1 DLX2 DLX5 DLX6 FBXW4
31 embryonic limb morphogenesis GO:0030326 9.35 BMP7 DLX5 DLX6 FBXW4 TP63
32 regulation of transcription, DNA-templated GO:0006355 10.3 DLX1 DLX2 DLX5 DLX6 NHLH1 SATB2
33 cell differentiation GO:0030154 10.12 BMP7 DLX1 DLX2 NHLH1 TP53 TP63
34 negative regulation of transcription, DNA-templated GO:0045892 10.04 BMP7 BTRC CDKN1C TP53 TP63
35 positive regulation of transcription, DNA-templated GO:0045893 10.04 BMP7 BTRC CDKN1C DLX5 TP53 TP63
36 transcription from RNA polymerase II promoter GO:0006366 10.03 DLX2 DLX5 NHLH1 SATB2 TP53 TP63
37 positive regulation of transcription from RNA polymerase II promoter GO:0045944 10.02 BMP7 DLX1 DLX2 DLX5 NHLH1 SATB2

Molecular functions related to Split-Hand/foot Malformation 4 according to GeneCards Suite gene sharing:

id Name GO ID Score Top Affiliating Genes
1 DNA binding GO:0003677 9.91 DLX1 DLX2 DLX5 DLX6 NHLH1 POLL
2 transcription regulatory region DNA binding GO:0044212 9.62 DLX5 SNCA TP53 TP63
3 chromatin binding GO:0003682 9.55 DLX1 DLX2 SATB2 TP53 TP63
4 sequence-specific DNA binding GO:0043565 9.43 DLX1 DLX2 DLX5 DLX6 SATB2 TP63
5 RNA polymerase II regulatory region sequence-specific DNA binding GO:0000977 8.92 DLX1 DLX2 NHLH1 TP53

Sources for Split-Hand/foot Malformation 4

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 HPO
66 SNOMED-CT via Orphanet
67 TGDB
68 Tocris
69 UMLS
70 UMLS via Orphanet
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