SSH3
protein-codingslingshot protein phosphatase 3, the group of Slingshot protein phosphatases
Gene summary
The ADF (actin-depolymerizing factor)/cofilin family (see MIM 601442) is composed of stimulus-responsive mediators of actin dynamics. ADF/cofilin proteins are inactivated by kinases such as LIM domain kinase-1 (LIMK1; MIM 601329). The SSH family appears to play a role in actin dynamics by reactivating ADF/cofilin proteins in vivo (Niwa et al., 2002 [PubMed 11832213]).[supplied by OMIM, Mar 2008]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~9.1 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to SSH3 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_017857.4. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 2 | 2 | ||||
| missense | 124 | 4 | 128 | |||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 1 | 1 | ||||
| splice donor/acceptor (+/-2bp) | 4 | 4 | ||||
| Total | 0 | 0 | 132 | 4 | 0 | 136 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_060327.3 | 14 | MANE Select | |
| Ensembl | ENSP00000312081.4 | 14 | MANE Select | |
| Ensembl | ENSP00000310055.7 | 10 | Standard | |
| Ensembl | ENSP00000310055.7 | 10 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Regulation of actin cytoskeleton - Homo sapiens (human)
- Axon guidance - Homo sapiens (human)
- Regulation of Actin Cytoskeleton
Biological Process
- regulation of actin polymerization or depolymerization
- regulation of lamellipodium assembly
- peptidyl-tyrosine dephosphorylation
- regulation of axonogenesis
Molecular Function
- actin binding
- protein tyrosine phosphatase activity
- protein tyrosine/serine/threonine phosphatase activity
Cellular Component
- nucleus
- cytoplasm
- cytoskeleton
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000308127
- Coding exons
- 14
- Length
- 9160
- Individuals with no LoFs
- 125610
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 138
- Defined
- 125748
- p
- 0.000549
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.600 | 371 | 405 | 0.916 | 0.0000251 | 4238 |
| Missense (PolyPhen) | 135 | 151.72 | 0.88978 | 1578 | ||
| Synonymous | 0.461 | 156 | 163 | 0.954 | 0.00000994 | 1349 |
| Loss of Function | 1.47 | 26 | 35.4 | 0.734 | 0.00000180 | 349 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00031 | 0.00031 | rare |
| Latino/Admixed American | 0.00093 | 0.00093 | rare |
| Ashkenazi Jewish | 0.00030 | 0.00030 | rare |
| East Asian | 0.00087 | 0.00087 | rare |
| Finnish | 0.00033 | 0.00032 | rare |
| European (Non-Finnish) | 0.00049 | 0.00048 | rare |
| South Asian | 0.00062 | 0.00062 | rare |
| Other | 0.00016 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Protein phosphatase which may play a role in the regulation of actin filament dynamics. Can dephosphorylate and activate the actin binding/depolymerizing factor cofilin, which subsequently binds to actin filaments and stimulates their disassembly (By similarity). {ECO:0000250}.;
Recessive Scores
- pRec
- 0.0973
Intolerance Scores
- LoFtool
- 0.592
- RVIS EVS
- -0.77
- RVIS percentile EVS
- 13.15
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.507
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |