SMARCA5

Chr 4

SNF2 related chromatin remodeling ATPase 5

Also known as: ISWI, SNF2H, WCRF135, hISWI, hSNF2H

NCBI Gene: 8467ENSG00000153147UniProt: O60264

The protein encoded by this gene is a member of the SWI/SNF family of proteins. Members of this family have helicase and ATPase activities and are thought to regulate transcription of certain genes by altering the chromatin structure around those genes. The protein encoded by this gene is a component of the chromatin remodeling and spacing factor RSF, a facilitator of the transcription of class II genes by RNA polymerase II. The encoded protein is similar in sequence to the Drosophila ISWI chromatin remodeling protein. [provided by RefSeq, Jul 2008]

155
ClinVar variants
36
Pathogenic / LP
1.00
pLI score· haploinsufficient
0
Active trials
Clinical Summary— SMARCA5
🧬
Gene-Disease Validity (ClinGen)
complex neurodevelopmental disorder · ADModerate

Moderate evidence — consider for supplementary testing

⚡
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.
📋
ClinVar Variants
36 Pathogenic / Likely Pathogenic· 108 VUS of 155 total submissions
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Dual constrained — LoF & missense intolerant
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.
0.07LOEUF
pLI 1.000
Z-score 7.28
OE 0.02 (0.01–0.07)
Highly constrained

Among the most LoF-intolerant genes (~top 3%)

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.
5.42Z-score
OE missense 0.35 (0.32–0.40)
198 obs / 558.2 exp
Constrained

Extremely missense-constrained (top ~0.01%)

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.0.02 (0.01–0.07)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.35 (0.32–0.40)
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.0.89
0≤1.21.6
LoF obs/exp: 1 / 63.7Missense obs/exp: 198 / 558.2Syn Z: 1.18

ClinVar Variant Classifications

155 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic30
Likely Pathogenic6
VUS108
Likely Benign8
Benign1
Conflicting2
30
Pathogenic
6
Likely Pathogenic
108
VUS
8
Likely Benign
1
Benign
2
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
1
1
28
0
30
Likely Pathogenic
1
5
0
0
6
VUS
2
97
9
0
108
Likely Benign
0
1
2
5
8
Benign
0
0
1
0
1
Conflicting
—2
Total4104405155

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

SMARCA5 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype

OMIM

No OMIM entries found.

Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
CircRNA inhibits DNA damage repair by interacting with host gene.
Xu X et al.·Mol Cancer
2020
Off-pore Nucleoporin sPOM121 Transcriptionally Propels β-Catenin-driven Tumor Progression and Immune Escape in Prostate Cancer.
Kirthika P et al.·Cancer Discov
2025
Circular RNA SMARCA5 correlates with favorable clinical tumor features and prognosis, and increases chemotherapy sensitivity in intrahepatic cholangiocarcinoma.
Lu Q et al.·J Clin Lab Anal
2020
Pathogenic variants in SMARCA1 cause an X-linked neurodevelopmental disorder modulated by NURF complex composition.
Mirzaa GM et al.·Nat Commun
2025
The Emerging Roles and Clinical Potential of circSMARCA5 in Cancer.
Xue C et al.·Cells
2022Review
SMARCA5 interacts with NUP98-NSD1 oncofusion protein and sustains hematopoietic cells transformation.
Jevtic Z et al.·J Exp Clin Cancer Res
2022
A Novel miR-146a-POU3F2/SMARCA5 Pathway Regulates Stemness and Therapeutic Response in Glioblastoma.
Cui T et al.·Mol Cancer Res
2021
Circular RNA SMARCA5 may serve as a tumor suppressor in non-small cell lung cancer.
Tong S·J Clin Lab Anal
2020
Evaluation of Circular RNA SMARCA5 as a Novel Biomarker for Hepatocellular Carcinoma.
Bedair HM et al.·Asian Pac J Cancer Prev
2024
Negative Correlation Between Circular RNA SMARC5 and MicroRNA 432, and Their Clinical Implications in Bladder Cancer Patients.
Zhang Z et al.·Technol Cancer Res Treat
2021Cohort
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
SMARCA5 Cooperates With RSF1 to Promote Pathological Glycolysis and Chondrocyte Dysfunction in Osteoarthritis Through ATPase-Dependent Chromatin Regulation.
Xu J et al.·FASEB J
2025
Spatiotemporal control of SMARCA5 by a MAPK-RUNX1 axis distinguishes mutant KRAS-driven pancreatic malignancy from tissue regeneration.
Han J et al.·Nat Cancer
2026
SMARCA5 restricts chromatin accessibility to promote male meiosis and fertility in mammals.
Kataruka S et al.·Proc Natl Acad Sci U S A
2025🔓 Open Access
SMARCA5 is required for the development of granule cell neuron precursors and Sonic Hedgehog Medulloblastoma growth.
Tsiami F et al.·Sci Rep
2025🔓 Open Access
SND1-SMARCA5 interaction strengthened by PIM promotes the proliferation, metastasis, and chemoresistance of esophageal squamous cell carcinoma.
Yan Q et al.·Int J Biol Macromol
2025
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