MCID: SPL034
MIFTS: 41

Split-Hand/foot Malformation 4

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

Aliases & Classifications for Split-Hand/foot Malformation 4

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

Name: Split-Hand/foot Malformation 4 53 71 28 13 69
Shfm4 53 12 71 51
Split Hand-Foot Malformation 4 12 14

Characteristics:

OMIM:

53
Inheritance:
autosomal dominant

Miscellaneous:
variable phenotype
reduced penetrance has been reported


HPO:

31
split-hand/foot malformation 4:
Onset and clinical course phenotypic variability
Inheritance autosomal dominant inheritance


Classifications:



External Ids:

OMIM 53 605289
Disease Ontology 12 DOID:0090023
ICD10 32 Q71.6
MedGen 39 C1854442
MeSH 41 D017880

Summaries for Split-Hand/foot Malformation 4

OMIM : 53 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 1 and split hand-foot malformation, and has symptoms including split hand, triphalangeal thumb and ectrodactyly. 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 1 Split-Hand/foot Malformation 6
Split-Hand/foot Malformation 3 Split-Hand/foot Malformation 2
Split-Hand/foot Malformation 4 Split-Hand/foot Malformation 5

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

(show all 24)
# Related Disease Score Top Affiliating Genes
1 split-hand/foot malformation 1 31.7 DLX5 SEM1 TP63
2 split hand-foot malformation 31.3 DLX5 FBXW4 SEM1 TP63 WNT10B
3 split hand split foot malformation autosomal recessive 10.9
4 split hand/foot malformation x-linked 10.9
5 paranoid personality disorder 10.4 DLX5 SEM1
6 split-hand/foot malformation 1 with sensorineural hearing loss, autosomal recessive 10.3 DLX5 DLX6 SEM1
7 ectrodactyly, ectodermal dysplasia, and cleft lip/palate syndrome 1 10.2 SATB2 TP63 WNT10B
8 chromosome 2q35 duplication syndrome 10.1 FBXW4 SATB2 TP63
9 cerebellum cancer 10.0 SUFU TP53
10 split hand 10.0 DLX5 FBXW4 SEM1 TP63 WNT10B
11 cleft lip/palate-ectodermal dysplasia syndrome 9.9 NHLH1 SATB2 TP63
12 ectrodactyly, ectodermal dysplasia, and cleft lip/palate syndrome 3 9.9 SATB2 TP53 TP63
13 aging 9.8 SNCA TP53 TP63
14 cleft palate, isolated 9.8 NHLH1 SATB2 TP63
15 periosteal osteogenic sarcoma 9.8 SATB2 TP53
16 split-hand/foot malformation 6 9.7 BTRC DLX5 FBXW4 SEM1 TP63 WNT10B
17 split foot 9.5 BTRC DLX5 DLX6 FBXW4 SEM1 SUFU
18 rapp-hodgkin syndrome 9.4 DLX5 DLX6 ITCH SATB2 SEM1 SNCA
19 split hand-split foot malformation 9.3 BTRC DLX5 DLX6 FBXW4 SEM1 SUFU
20 tooth agenesis 9.3 DLX2 SATB2 WNT10B
21 orofacial cleft 9.0 DLX2 DLX5 DLX6 NHLH1 SATB2 TP63
22 split-hand/foot malformation 3 8.0 BTRC DLX1 DLX2 DLX5 FBXW4 POLL
23 split-hand/foot malformation 5 8.0 BTRC DLX1 DLX2 DLX5 FBXW4 POLL
24 split-hand/foot malformation 2 7.8 BTRC DLX1 DLX2 DLX5 DLX6 FBXW4

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:

53
Skeletal Hands:
triphalangeal thumb
syndactyly
monodactyly
split hand, unilateral or bilateral
'lobster-claw anomaly
more
Skeletal Feet:
syndactyly
'lobster-claw anomaly
webbing
split foot, unilateral or bilateral
missing metatarsals


Clinical features from OMIM:

605289

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

31 (show all 8)
# Description HPO Frequency HPO Source Accession
1 split hand 31 HP:0001171
2 triphalangeal thumb 31 HP:0001199
3 ectrodactyly 31 HP:0100257
4 aplasia/hypoplasia involving the metacarpal bones 31 HP:0005914
5 syndactyly 31 HP:0001159
6 aplasia/hypoplasia of the phalanges of the hand 31 HP:0009767
7 aplasia/hypoplasia of the phalanges of the toes 31 HP:0010173
8 aplasia/hypoplasia of metatarsal bones 31 HP:0001964

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

43 (show all 13)
# 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 TP53 TP63 BMP7 BTRC DLX1 DLX2
4 craniofacial MP:0005382 10.21 SUFU TP53 TP63 BMP7 DLX1 DLX2
5 mortality/aging MP:0010768 10.17 BMP7 DLX5 DLX6 FBXW4 ITCH NHLH1
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 nervous system MP:0003631 9.96 BMP7 DLX1 DLX2 DLX5 DLX6 NHLH1
10 hearing/vestibular/ear MP:0005377 9.91 BMP7 DLX1 DLX2 DLX5 DLX6 TP53
11 no phenotypic analysis MP:0003012 9.7 DLX1 TP53 TP63 WNT10B FBXW4 SNCA
12 respiratory system MP:0005388 9.61 BMP7 DLX2 DLX5 DLX6 ITCH SATB2
13 skeleton MP:0005390 9.44 DLX1 DLX2 DLX5 DLX6 FBXW4 ITCH

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:

# Genetic test Affiliating Genes
1 Split-Hand/foot Malformation 4 28 TP63

Anatomical Context for Split-Hand/foot Malformation 4

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

38
Bone

Publications for Split-Hand/foot Malformation 4

Articles related to Split-Hand/foot Malformation 4:

# Title Authors Year
1
Analysis of large phenotypic variability of EEC and SHFM4 syndromes caused by K193E mutation of the TP63 gene. ( 22574117 )
2012

Variations for Split-Hand/foot Malformation 4

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

71
# 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 rs886039442

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

6
# 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:

# 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:

# 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)
# 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 by RNA polymerase II GO:0000122 9.92 DLX1 DLX2 SATB2 SNCA SUFU TP53
3 proteasome-mediated ubiquitin-dependent protein catabolic process GO:0043161 9.91 BTRC ITCH SEM1 TP53
4 positive regulation of transcription by RNA polymerase II GO:0045944 9.91 BMP7 DLX1 DLX2 DLX5 NHLH1 SATB2
5 positive regulation of canonical Wnt signaling pathway GO:0090263 9.85 DLX5 SEM1 WNT10B
6 palate development GO:0060021 9.81 DLX5 DLX6 SATB2
7 SCF-dependent proteasomal ubiquitin-dependent protein catabolic process GO:0031146 9.79 BTRC FBXW4 SEM1
8 positive regulation of osteoblast differentiation GO:0045669 9.78 BMP7 TP63 WNT10B
9 skeletal system development GO:0001501 9.77 BMP7 DLX5 DLX6 SUFU TP63
10 positive regulation of cell differentiation GO:0045597 9.76 BMP7 DLX1 DLX2
11 cartilage development GO:0051216 9.76 BMP7 DLX2 FBXW4 SATB2
12 epithelial cell differentiation GO:0030855 9.73 BMP7 DLX5 DLX6 TP63
13 cellular response to BMP stimulus GO:0071773 9.72 BMP7 DLX1 DLX5
14 odontogenesis of dentin-containing tooth GO:0042475 9.71 BMP7 DLX1 DLX2 TP63
15 negative regulation of Notch signaling pathway GO:0045746 9.7 BMP7 DLX1 DLX2
16 negative regulation of smoothened signaling pathway GO:0045879 9.67 BTRC SUFU
17 negative regulation of phosphorylation GO:0042326 9.66 BMP7 CDKN1C
18 DNA damage response, signal transduction by p53 class mediator resulting in transcription of p21 class mediator GO:0006978 9.66 TP53 TP63
19 head development GO:0060322 9.65 DLX5 DLX6
20 proximal/distal pattern formation GO:0009954 9.65 DLX1 DLX2 TP63
21 negative regulation of oligodendrocyte differentiation GO:0048715 9.63 DLX1 DLX2
22 forebrain neuron differentiation GO:0021879 9.63 DLX1 DLX2
23 mitotic G1 DNA damage checkpoint GO:0031571 9.62 TP53 TP63
24 negative regulation of photoreceptor cell differentiation GO:0046533 9.6 DLX1 DLX2
25 subpallium development GO:0021544 9.59 DLX1 DLX2
26 cerebral cortex GABAergic interneuron differentiation GO:0021892 9.57 DLX1 DLX2
27 regulation of transcription from RNA polymerase II promoter involved in forebrain neuron fate commitment GO:0021882 9.54 DLX1 DLX2
28 cerebral cortex GABAergic interneuron fate commitment GO:0021893 9.51 DLX1 DLX2
29 positive regulation of amacrine cell differentiation GO:1902871 9.49 DLX1 DLX2
30 anatomical structure formation involved in morphogenesis GO:0048646 9.46 BMP7 DLX5 DLX6 TP63
31 multicellular organism development GO:0007275 9.4 BMP7 DLX1 DLX2 DLX5 DLX6 FBXW4
32 embryonic limb morphogenesis GO:0030326 9.35 BMP7 DLX5 DLX6 FBXW4 TP63
33 regulation of transcription, DNA-templated GO:0006355 10.3 DLX1 DLX2 DLX5 DLX6 NHLH1 SATB2
34 cell differentiation GO:0030154 10.12 BMP7 DLX1 DLX2 NHLH1 TP53 TP63
35 transcription by RNA polymerase II GO:0006366 10.05 DLX2 DLX5 NHLH1 SATB2 TP53 TP63
36 negative regulation of transcription, DNA-templated GO:0045892 10.04 BMP7 BTRC CDKN1C TP53 TP63
37 positive regulation of transcription, DNA-templated GO:0045893 10.03 BMP7 BTRC CDKN1C DLX5 TP53 TP63

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

# 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 9.67 DLX5 SNCA TP53 TP63
3 chromatin binding GO:0003682 9.55 DLX1 DLX2 SATB2 TP53 TP63
4 RNA polymerase II regulatory region sequence-specific DNA binding GO:0000977 9.35 DLX1 DLX2 NHLH1 SATB2 TP53
5 MDM2/MDM4 family protein binding GO:0097371 9.32 TP53 TP63
6 sequence-specific DNA binding GO:0043565 9.17 DLX1 DLX2 DLX5 DLX6 SATB2 TP53

Sources for Split-Hand/foot Malformation 4

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
16 ExPASy
18 FMA
27 GO
28 GTR
29 HGMD
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 MedGen
41 MeSH
42 MESH via Orphanet
43 MGI
45 NCI
46 NCIt
47 NDF-RT
50 NINDS
51 Novoseek
53 OMIM
54 OMIM via Orphanet
58 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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