SASH1

Chr 6ARAD

SAM and SH3 domain containing 1

Also known as: CAPOK, DUH, DUH1, SH3D6A, dJ323M4.1

NCBI Gene: 23328ENSG00000111961UniProt: O94885

This gene encodes a scaffold protein involved in the TLR4 signaling pathway that may stimulate cytokine production and endothelial cell migration in response to invading pathogens. The encoded protein has also been described as a potential tumor suppressor that may negatively regulate proliferation, apoptosis, and invasion of cancer cells, and reduced expression of this gene has been observed in multiple human cancers. Mutations in this gene may be associated with abnormal skin pigmentation in human patients. [provided by RefSeq, Oct 2016]

Primary Disease Associations & Inheritance

?Cancer, alopecia, pigment dyscrasia, onychodystrophy, and keratodermaMIM #618373
AR
Dyschromatosis universalis hereditaria 1MIM #127500
AD
0
ClinVar variants
0
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— SASH1
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.29) despite low pLI — interpret in context.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
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.
0.44LOEUF
pLI 0.002
Z-score 4.89
OE 0.29 (0.20–0.44)
Moderately constrained

More LoF-intolerant than ~75% 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.
0.60Z-score
OE missense 0.94 (0.88–1.00)
701 obs / 747.5 exp
Tolerant

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.0.29 (0.20–0.44)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.94 (0.88–1.00)
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.1.04
0≤1.21.6
LoF obs/exp: 16 / 55.2Missense obs/exp: 701 / 747.5Syn Z: -0.50

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

SASH1 · 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

OMIM

?Cancer, alopecia, pigment dyscrasia, onychodystrophy, and keratoderma

MIM #618373

Molecular basis of disorder known

Autosomal recessive

Dyschromatosis universalis hereditaria 1

MIM #127500

Molecular basis of disorder known

Autosomal dominant
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
A multi-omics pipeline integrating machine learning and spatial-cellular analysis identifies SASH1 as a prognostic biomarker and therapeutic target in head and neck squamous cell carcinoma.
Dai Z et al.·Int J Surg
2025
SASH1 Mutations and Hereditary Disorders of Pigmentation: Review of Literature.
Bishnoi A et al.·Pigment Cell Melanoma Res
2025Review
Single-cell RNA sequencing reveals the transcriptomic landscape of kidneys in patients with ischemic acute kidney injury.
Tang R et al.·Chin Med J (Engl)
2023Cohort
SASH1 suppresses triple-negative breast cancer cell invasion through YAP-ARHGAP42-actin axis.
Jiang K et al.·Oncogene
2020
Downregulated SASH1 expression indicates poor clinical prognosis in gastric cancer.
Zhou N et al.·Hum Pathol
2018
The PER3(rs772027021) SNP induces pigmentation phenotypes of dyschromatosis universalis hereditaria.
Chen H et al.·J Mol Med (Berl)
2023
Involvement of SASH1 in the Maintenance of Stable Cell-Cell Adhesion.
Ilnitskaya AS et al.·Biochemistry (Mosc)
2020
Clinical Significance of SASH1 Expression in Glioma.
Yang L et al.·Dis Markers
2015
SASH1 S519N Variant Links Skin Hyperpigmentation and Premature Hair Graying to Dysfunction of Melanocyte Lineage.
Lambert KA et al.·J Invest Dermatol
2025
HMGB1/SET/HAT1 complex-mediated SASH1 repression drives glycolysis and metastasis in lung adenocarcinoma.
Kou F et al.·Oncogene
2023
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools