DLC1

Chr 8

DLC1 Rho GTPase activating protein

Also known as: ARHGAP7, HP, STARD12, p122-RhoGAP

NCBI Gene: 10395ENSG00000164741UniProt: Q96QB1

This gene encodes a GTPase-activating protein (GAP) that is a member of the rhoGAP family of proteins which play a role in the regulation of small GTP-binding proteins. GAP family proteins participate in signaling pathways that regulate cell processes involved in cytoskeletal changes. This gene functions as a tumor suppressor gene in a number of common cancers, including prostate, lung, colorectal, and breast cancers. Multiple transcript variants due to alternative promoters and alternative splicing have been found for this gene.[provided by RefSeq, Apr 2010]

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Primary Disease Associations & Inheritance

Colorectal cancer, somaticMIM #114500
0
Active trials
14
Pubs (1 yr)
40
P/LP submissions
0%
P/LP missense
0.26
LOEUF· LoF intol.
LOF
Mechanism· predicted
Clinical Summary— DLC1
⚡
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
40 unique Pathogenic / Likely Pathogenic· 180 VUS of 398 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint
0.26LOEUF
pLI 0.999
Z-score 6.38
OE 0.15 (0.09–0.26)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint
-2.93Z-score
OE missense 1.28 (1.22–1.34)
1123 obs / 878.5 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.15 (0.09–0.26)
0≤0.351.4
Missense OE1.28 (1.22–1.34)
0≤0.61.4
Synonymous OE1.30
0≤1.21.6
LoF obs/exp: 10 / 65.9Missense obs/exp: 1123 / 878.5Syn Z: -4.52
DN
0.3395th %ile
GOF
0.3987th %ile
LOF
0.77top 5%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.26

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

398 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic35
Likely Pathogenic5
VUS180
Likely Benign79
Benign90
Conflicting8
35
Pathogenic
5
Likely Pathogenic
180
VUS
79
Likely Benign
90
Benign
8
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
35
0
35
Likely Pathogenic
0
0
5
0
5
VUS
1
159
19
1
180
Likely Benign
0
21
23
35
79
Benign
0
15
62
13
90
Conflicting
—8
Total119514449397

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

View in ClinVar →

Protein Context — Lollipop Plot

DLC1 · protein map & ClinVar variants

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Filamin a binds deleted in liver cancer 1 (DLC1) to promote its tumor suppressor activity and inhibit the SRF coactivator MRTF-A.
Sergeev M et al.·Neoplasia
2026Open Access
Mechanosensitive biochemical imprinting of the talin interaction with DLC1 regulates RhoA activity and cardiomyocyte remodeling.
Marhuenda E et al.·Sci Adv
2025Open AccessFunctional
Determination of trunk neural crest cell fate and susceptibility to splicing perturbation by the DLC1-SF3B1-PHF5A splicing complex.
Zheng Z et al.·Nat Commun
2025Open Access
The circDUSP1/miR-429/DLC1 regulatory network affects proliferation, migration, and invasion of triple-negative breast cancer cells.
Jian C et al.·Sci Rep
2025Open Access
Integrated mathematical and experimental modeling uncovers enhanced EMT plasticity upon loss of the DLC1 tumor suppressor.
Höpfl S et al.·PLoS Comput Biol
2025Open AccessFunctional
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients