GeneBe

SSH1

protein-coding

slingshot protein phosphatase 1, the group of Slingshot protein phosphatases|MicroRNA protein coding host genes

Gene summary

The protein encoded by this gene belongs to the slingshot homolog (SSH) family of phosphatases, which regulate actin filament dynamics. The SSH proteins dephosphorylate and activate the actin binding/depolymerizing factor cofilin, which subsequently binds to actin filaments and stimulates their disassembly. Cofilin is inactivated by kinases such as LIM domain kinase-1 (LIMK1), which may also be dephosphorylated and inactivated by SSH proteins. The SSH family thus appears to play a role in actin dynamics by reactivating cofilin proteins. Alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Aug 2011]

MANE transcript

NM_018984.4

Inheritance

—

ClinVar variants

U:166B:22

Top phenotype

SSH1-related disorder

gnomAD constraint

pLI —, LoF o/e 0.33

Max pathogenic AF

—

Genomic locus

chr12:108,778,191-108,857,590

External References & Databases

Ensembl (ENSG00000084112)NCBI Gene (54434)OMIM (606778)HGNC:30579GenCCUniProt (Q8WYL5)AlphaFoldClinVar (SSH1)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~79.4 kb
Loading mutation effect viewer...

GenCC 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 SSH1 variants in ClinVar

4 Conditions Cataloged
not specifiedTotal: 170
not providedTotal: 10
SSH1-related disorderTotal: 3
Premature ovarian insufficiencyTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_018984.4. 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.

EffectPLPVUSLBBSum
synonymous
1
clinvar
1
clinvar
2
clinvar
 4
missense
161
clinvar
17
clinvar
2
clinvar
 180
nonsense
0
start loss
0
frameshift
1
clinvar
 1
splice donor/acceptor (+/-2bp)
3
clinvar
 3
Total00166184188
Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 32 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_018984.4RefSeqNP_061857.315MANE Select
ENST00000326495.10EnsemblENSP00000315713.515MANE Select
NM_001161330.2RefSeqNP_001154802.114Standard
NM_001161331.1RefSeqNP_001154803.113Standard

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
  • CXCR4-mediated signaling events
  • FGF signaling pathway

Biological Process

  • cell morphogenesis
  • protein dephosphorylation
  • regulation of actin polymerization or depolymerization
  • regulation of lamellipodium assembly
  • actin cytoskeleton organization

Molecular Function

  • actin binding
  • phosphoprotein phosphatase activity
  • protein tyrosine phosphatase activity
  • protein binding
  • protein tyrosine/serine/threonine phosphatase activity

Cellular Component

  • cytoplasm
  • cytosol
  • cytoskeleton
  • plasma membrane
  • lamellipodium

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000326495
Coding exons
15
Length
74901
Individuals with no LoFs
125699
Homozygous LoFs
0
Heterozygous LoFs
49
Defined
125748
p
0.000195
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense1.025406110.8840.00003796891
Missense (PolyPhen)96168.670.569161880
Synonymous-0.5492662551.040.00001742072
Loss of Function3.991441.80.3350.00000233485

Population LoF Frequency

PopulationCAFp-valueStatus
African0.000660.00062rare
Latino/Admixed American0.000210.00020rare
Ashkenazi Jewish00.0absent
East Asian0.000170.00016rare
Finnish00.0absent
European (Non-Finnish)0.000180.00018rare
South Asian0.000160.00016rare
Other0.000720.00065rare

dbNSFP Gene Annotations

Source: dbNSFP

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, ECO:0000269|PubMed:12684437, ECO:0000269|PubMed:12807904, ECO:0000269|PubMed:14531860, ECO:0000269|PubMed:14645219, ECO:0000269|PubMed:15056216, ECO:0000269|PubMed:15159416, ECO:0000269|PubMed:15660133, ECO:0000269|PubMed:15671020, ECO:0000269|PubMed:16230460}.;

Recessive Scores

pRec
0.115

Intolerance Scores

LoFtool
0.556
RVIS EVS
-0.37
RVIS percentile EVS
28.31

Essentials

Essential (CRISPR)
N
Essential (CRISPR2)
N
Essential (gene trap)
N
Indispensability pred.
E
Indispensability score
0.916

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium
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