SSH2
protein-codingslingshot protein phosphatase 2, the group of Slingshot protein phosphatases
Gene summary
This gene encodes a protein tyrosine phosphatase that plays a key role in the regulation of actin filaments. The encoded protein dephosphorylates and activates cofilin, which promotes actin filament depolymerization. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2013]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~304.3 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 SSH2 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001282129.2. 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 | 1 | 2 | 5 | ||
| missense | 155 | 6 | 2 | 163 | ||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 1 | 1 | ||||
| splice donor/acceptor (+/-2bp) | 4 | 4 | ||||
| Total | 0 | 0 | 162 | 7 | 4 | 173 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001269058.1 | 16 | MANE Select | |
| Ensembl | ENSP00000444743.1 | 16 | MANE Select | |
| RefSeq | NP_001269059.1 | 8 | Standard | |
| RefSeq | NP_001269060.1 | 7 | 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
- protein dephosphorylation
- regulation of actin polymerization or depolymerization
- regulation of lamellipodium assembly
- actin cytoskeleton organization
- peptidyl-tyrosine dephosphorylation
Molecular Function
- actin binding
- phosphoprotein phosphatase activity
- protein tyrosine phosphatase activity
- protein tyrosine/serine/threonine phosphatase activity
Cellular Component
- extracellular space
- cytoplasm
- cytoskeleton
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000269033
- Coding exons
- 15
- Length
- 304339
- Individuals with no LoFs
- 125726
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 22
- Defined
- 125748
- p
- 0.0000875
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.95 | 612 | 764 | 0.801 | 0.0000397 | 9366 |
| Missense (PolyPhen) | 135 | 286.86 | 0.47062 | 3397 | ||
| Synonymous | 0.935 | 269 | 289 | 0.930 | 0.0000149 | 2779 |
| Loss of Function | 6.05 | 10 | 61.0 | 0.164 | 0.00000352 | 716 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00012 | 0.00012 | rare |
| Latino/Admixed American | 0.00014 | 0.00014 | rare |
| Ashkenazi Jewish | 0.000099 | 0.000099 | rare |
| East Asian | 0.000054 | 0.000054 | rare |
| Finnish | 0.000092 | 0.000092 | rare |
| European (Non-Finnish) | 0.000053 | 0.000053 | rare |
| South Asian | 0.00016 | 0.00016 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Protein phosphatase which regulates actin filament dynamics. Dephosphorylates and activates the actin binding/depolymerizing factor cofilin, which subsequently binds to actin filaments and stimulates their disassembly. Inhibitory phosphorylation of cofilin is mediated by LIMK1, which may also be dephosphorylated and inactivated by this protein. {ECO:0000269|PubMed:11832213}.;
Recessive Scores
- pRec
- 0.0959
Intolerance Scores
- LoFtool
- 0.379
- RVIS EVS
- -0.1
- RVIS percentile EVS
- 45.68
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- H
- Indispensability pred.
- E
- Indispensability score
- 0.748
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |