SSH2
Chr 17slingshot protein phosphatase 2
Also known as: SSH-2, SSH-2L
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]
Clinical Summary— SSH2
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Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
Some data sources returned errors (2)
ensembl: Error: Ensembl fetch failed: 500 for https://rest.ensembl.org/lookup/symbol/homo_sapiens/SSH2?content-type=application/json&expand=1
clinvar: Error: NCBI fetch failed: 429 https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esummary.fcgi
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
LoF intolerant — likely haploinsufficient
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.28LOEUF
pLI 0.997
Z-score 6.05
OE 0.16 (0.10–0.28)
Highly LoF-intolerant (top ~10% of genes)
Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
1.95Z-score
OE missense 0.80 (0.75–0.86)
612 obs / 763.9 exp
Mild missense constraint
Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.16 (0.10–0.28)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.80 (0.75–0.86)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.93
0≤1.21.6
LoF obs/exp: 10 / 61.0Missense obs/exp: 612 / 763.9Syn Z: 0.94
ClinVar Variant Classifications
0 submitted variants in ClinVar
Protein Context — Lollipop Plot
SSH2 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
OMIM — Genotype-Phenotype Relationships
1 OMIM entry
SLINGSHOT PROTEIN PHOSPHATASE 2; SSH2
MIM #606779 · *
External Resources
Links to major genomics databases and tools
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
Exome sequencing in 51 early onset non-familial CRC cases.
Thutkawkorapin J et al.·Mol Genet Genomic Med
2019Cohort
Development of novel affinity reagents for detecting protein tyrosine phosphorylation based on superbinder SH2 domain in tumor cells.
Ke AQ et al.·Anal Chim Acta
2018
Unveiling the genetic variation of severe continuous/mixed-type ossification of the posterior longitudinal ligament by whole-exome sequencing and bioinformatic analysis.
Lee CH et al.·Spine J
2021Natural history
Evaluating the effects of archaic protein-altering variants in living human adults.
Molz B et al.·Sci Adv
2025
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Retraction: LINC00174 facilitates cell proliferation, cell migration and tumor growth of osteosarcoma via regulating the TGF-β/SMAD signaling pathway and upregulating SSH2 expression.
Frontiers Editorial Office.·Front Mol Biosci
2023Open Access
Concomitant novel ALK-SSH2, EML4-ALK and ARID2-ALK, EML4-ALK double-fusion variants and confer sensitivity to crizotinib in two lung adenocarcinoma patients, respectively.
Tao H et al.·Diagn Pathol
2022Open AccessCohort
LINC00174 Facilitates Cell Proliferation, Cell Migration and Tumor Growth of Osteosarcoma via Regulating the TGF-β/SMAD Signaling Pathway and Upregulating SSH2 Expression.
Zheng C et al.·Front Mol Biosci
2021Open Access
miR-194 Inhibits the Proliferation of SW620 Colon Cancer Stem Cells Through Downregulation of SSH2 Expression.
Sun B et al.·Cancer Manag Res
2019Open Access
Top 5 resultsSearch Europe PMC ↗
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
SSH2.0: A Better Tool for Predicting the Hydrophobic Interaction Risk of Monoclonal Antibody
Zhou Y et al.·Front Genet
2022
Integrated Mendelian Randomization and Single-Cell Transcriptomics Analysis Identifies Critical Blood Biomarkers and Potential Mechanisms in Epilepsy
Shi J et al.·CNS Neurosci Ther
2025Functional
The Slingshot phosphatase 2 is required for acrosome biogenesis during spermatogenesis in mice
Xu K et al.·Elife
2023
TRPM7 Kinase Domain is Part of the Rac1-SSH2-cofilin Complex Regulating F-actin in the Mouse Nervous System.
Chang J et al.·Neurosci Bull
2023Functional
Genome-Wide Identification of lncRNA and mRNA for Diagnosing Type 2 Diabetes in Saudi Arabia
Albogami S·Pharmgenomics Pers Med
2023
Integrative analysis of single-nucleus RNA sequencing and Mendelian randomization to explore novel risk genes for Alzheimer's disease
Huang C et al.·Medicine (Baltimore)
2024
Top 6 full-text resultsSearch PubTator3 ↗
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools