SHFM4
MCID: SPL034
MIFTS: 40

Split-Hand/foot Malformation 4 (SHFM4)

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

Aliases & Classifications for Split-Hand/foot Malformation 4

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

Name: Split-Hand/foot Malformation 4 57 75 29 13 6 73
Shfm4 57 12 75 55
Split Hand-Foot Malformation 4 12 15
Split-Hand/foot Malformation, Type 4 40

Characteristics:

OMIM:

57
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 57 605289
Disease Ontology 12 DOID:0090023
ICD10 33 Q71.6 Q71.60
ICD9CM 35 755.58
SNOMED-CT 68 13624003 81208006
MedGen 42 C1854442

Summaries for Split-Hand/foot Malformation 4

OMIM : 57 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. An important gene associated with Split-Hand/foot Malformation 4 is TP63 (Tumor Protein P63), and among its related pathways/superpathways are Hippo signaling pathway and Signaling by Hedgehog. Affiliated tissues include bone, and related phenotypes are split hand and triphalangeal thumb

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

UniProtKB/Swiss-Prot : 75 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.

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 22)
# Related Disease Score Top Affiliating Genes
1 split-hand/foot malformation 1 31.8 DLX5 SEM1 TP63
2 split hand-foot malformation 31.5 DLX5 FBXW4 SEM1 TP63 WNT10B
3 split hand split foot malformation autosomal recessive 11.0
4 split hand/foot malformation x-linked 11.0
5 paranoid personality disorder 10.2 DLX5 SEM1
6 split-hand/foot malformation 1 with sensorineural hearing loss, autosomal recessive 10.1 DLX5 DLX6 SEM1
7 ectrodactyly, ectodermal dysplasia, and cleft lip/palate syndrome 1 10.1 SATB2 TP63
8 ankyloblepharon-ectodermal defects-cleft lip/palate 10.1 SATB2 TP63
9 ectrodactyly, ectodermal dysplasia, and cleft lip/palate syndrome 3 10.0 SATB2 TP63
10 chromosome 2q35 duplication syndrome 10.0 FBXW4 SATB2 TP63
11 split-hand/foot malformation 3 10.0 BTRC FBXW4 SEM1 WNT10B
12 trophoblastic neoplasm 9.9 CDKN1C TP63
13 cleft lip/palate-ectodermal dysplasia syndrome 9.9 NHLH1 SATB2 TP63
14 syngnathia 9.9 DLX2 SATB2
15 split-hand/foot malformation 6 9.8 BTRC DLX5 FBXW4 SEM1 TP63 WNT10B
16 isolated split hand-split foot malformation 9.8 BTRC DLX5 DLX6 SEM1 TP63 WNT10B
17 cleft palate, isolated 9.8 NHLH1 SATB2 TP63
18 tooth agenesis 9.8 DLX2 SATB2 WNT10B
19 rapp-hodgkin syndrome 9.7 DLX5 DLX6 ITCH SATB2 SEM1 SNCA
20 orofacial cleft 9.5 DLX2 DLX5 DLX6 NHLH1 SATB2 TP63
21 split-hand/foot malformation 5 9.0 BTRC DLX1 DLX2 DLX5 FBXW4 POLL
22 split-hand/foot malformation 2 8.9 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:

57
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:

32 (show all 9)
# Description HPO Frequency HPO Source Accession
1 split hand 32 HP:0001171
2 triphalangeal thumb 32 HP:0001199
3 ectrodactyly 32 HP:0100257
4 aplasia/hypoplasia involving the metacarpal bones 32 HP:0005914
5 syndactyly 32 HP:0001159
6 split foot 32 HP:0001839
7 aplasia/hypoplasia of the phalanges of the hand 32 HP:0009767
8 aplasia/hypoplasia of the phalanges of the toes 32 HP:0010173
9 aplasia/hypoplasia of metatarsal bones 32 HP:0001964

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

46 (show all 13)
# Description MGI Source Accession Score Top Affiliating Genes
1 cardiovascular system MP:0005385 10.26 BMP7 BTRC DLX1 DLX2 DLX5 ITCH
2 growth/size/body region MP:0005378 10.2 BMP7 BTRC DLX1 DLX2 DLX5 DLX6
3 digestive/alimentary MP:0005381 10.19 BMP7 BTRC DLX1 DLX2 DLX5 DLX6
4 craniofacial MP:0005382 10.16 BMP7 DLX1 DLX2 DLX5 DLX6 ITCH
5 mortality/aging MP:0010768 10.13 BMP7 BTRC DLX1 DLX2 DLX5 DLX6
6 embryo MP:0005380 10.02 BMP7 DLX5 DLX6 FBXW4 SATB2 SUFU
7 integument MP:0010771 9.95 BMP7 DLX5 DLX6 ITCH SNCA SUFU
8 limbs/digits/tail MP:0005371 9.91 BMP7 DLX5 DLX6 FBXW4 SATB2 SUFU
9 nervous system MP:0003631 9.91 BMP7 DLX1 DLX2 DLX5 DLX6 NHLH1
10 hearing/vestibular/ear MP:0005377 9.83 BMP7 DLX1 DLX2 DLX5 DLX6
11 no phenotypic analysis MP:0003012 9.63 DLX1 FBXW4 SNCA SUFU TP63 WNT10B
12 respiratory system MP:0005388 9.56 BMP7 DLX2 DLX5 DLX6 ITCH SATB2
13 skeleton MP:0005390 9.4 BMP7 BTRC DLX1 DLX2 DLX5 DLX6

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 29 TP63

Anatomical Context for Split-Hand/foot Malformation 4

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

41
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:

75
# 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.697A> G (p.Lys233Glu) single nucleotide variant Pathogenic rs121908838 GRCh38 Chromosome 3, 189864349: 189864349
3 TP63 NM_003722.4(TP63): c.955C> T (p.Arg319Cys) single nucleotide variant Pathogenic rs121908839 GRCh37 Chromosome 3, 189585694: 189585694
4 TP63 NM_003722.4(TP63): c.955C> T (p.Arg319Cys) single nucleotide variant Pathogenic rs121908839 GRCh38 Chromosome 3, 189867905: 189867905
5 TP63 NM_003722.4(TP63): c.289C> T (p.Arg97Cys) single nucleotide variant Pathogenic rs121908848 GRCh37 Chromosome 3, 189456528: 189456528
6 TP63 NM_003722.4(TP63): c.289C> T (p.Arg97Cys) single nucleotide variant Pathogenic rs121908848 GRCh38 Chromosome 3, 189738739: 189738739

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 11.52 BMP7 BTRC WNT10B
2
Show member pathways
11.46 BTRC ITCH SEM1 SUFU
3
Show member pathways
11.31 BTRC SUFU WNT10B

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 9.44 BTRC CDKN1C DLX1 DLX2 DLX5 DLX6

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

(show all 29)
# Name GO ID Score Top Affiliating Genes
1 negative regulation of transcription by RNA polymerase II GO:0000122 9.92 CDKN1C DLX1 DLX2 SATB2 SNCA SUFU
2 roof of mouth development GO:0060021 9.77 DLX5 DLX6 SATB2
3 positive regulation of osteoblast differentiation GO:0045669 9.77 BMP7 TP63 WNT10B
4 positive regulation of cell differentiation GO:0045597 9.74 BMP7 DLX1 DLX2
5 cartilage development GO:0051216 9.73 BMP7 DLX2 FBXW4 SATB2
6 negative regulation of Notch signaling pathway GO:0045746 9.72 BMP7 DLX1 DLX2
7 cellular response to BMP stimulus GO:0071773 9.71 BMP7 DLX1 DLX5
8 epithelial cell differentiation GO:0030855 9.71 BMP7 DLX5 DLX6 TP63
9 odontogenesis of dentin-containing tooth GO:0042475 9.67 BMP7 DLX1 DLX2 TP63
10 proximal/distal pattern formation GO:0009954 9.65 DLX1 DLX2 TP63
11 negative regulation of smoothened signaling pathway GO:0045879 9.64 BTRC SUFU
12 embryonic pattern specification GO:0009880 9.64 BMP7 SATB2
13 head development GO:0060322 9.63 DLX5 DLX6
14 negative regulation of phosphorylation GO:0042326 9.63 BMP7 CDKN1C
15 skeletal system development GO:0001501 9.63 BMP7 CDKN1C DLX5 DLX6 SUFU TP63
16 negative regulation of oligodendrocyte differentiation GO:0048715 9.61 DLX1 DLX2
17 forebrain neuron differentiation GO:0021879 9.61 DLX1 DLX2
18 negative regulation of photoreceptor cell differentiation GO:0046533 9.58 DLX1 DLX2
19 subpallium development GO:0021544 9.58 DLX1 DLX2
20 cerebral cortex GABAergic interneuron differentiation GO:0021892 9.56 DLX1 DLX2
21 anatomical structure formation involved in morphogenesis GO:0048646 9.56 BMP7 DLX5 DLX6 TP63
22 regulation of transcription from RNA polymerase II promoter involved in forebrain neuron fate commitment GO:0021882 9.52 DLX1 DLX2
23 cerebral cortex GABAergic interneuron fate commitment GO:0021893 9.51 DLX1 DLX2
24 positive regulation of amacrine cell differentiation GO:1902871 9.49 DLX1 DLX2
25 multicellular organism development GO:0007275 9.36 BMP7 DLX1 DLX2 DLX5 DLX6 FBXW4
26 embryonic limb morphogenesis GO:0030326 9.35 BMP7 DLX5 DLX6 FBXW4 TP63
27 positive regulation of transcription by RNA polymerase II GO:0045944 10.06 BMP7 DLX1 DLX2 DLX5 NHLH1 SATB2
28 positive regulation of transcription, DNA-templated GO:0045893 10.02 BMP7 BTRC CDKN1C DLX5 TP63
29 transcription by RNA polymerase II GO:0006366 10.02 DLX2 DLX5 NHLH1 SATB2 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 9.86 DLX1 DLX2 DLX5 DLX6 NHLH1 POLL
2 DNA-binding transcription factor activity, RNA polymerase II-specific GO:0000981 9.7 DLX1 DLX2 DLX5 DLX6 NHLH1 SATB2
3 chromatin binding GO:0003682 9.62 DLX1 DLX2 SATB2 TP63
4 RNA polymerase II regulatory region sequence-specific DNA binding GO:0000977 9.26 DLX1 DLX2 NHLH1 SATB2
5 sequence-specific DNA binding GO:0043565 9.1 DLX1 DLX2 DLX5 DLX6 SATB2 TP63

Sources for Split-Hand/foot Malformation 4

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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