ROCK1

Chr 18

Rho associated coiled-coil containing protein kinase 1

Also known as: P160ROCK, ROCK-I

NCBI Gene: 6093ENSG00000067900UniProt: Q13464

This protein is a serine/threonine kinase that regulates actin cytoskeleton organization, cell polarity, smooth muscle contraction, and various cellular processes including neurite retraction and cell motility. Mutations cause autosomal dominant intellectual disability with seizures, hypotonia, and distinctive facial features, with the gene being highly constrained against loss-of-function variants (pLI = 1.0, LOEUF = 0.196). The phenotype primarily affects the nervous system with developmental and neurological manifestations.

Summary from RefSeq, UniProt
Research Assistant →
2
Active trials
176
Pubs (1 yr)
35
P/LP submissions
0%
P/LP missense
0.20
LOEUF· LoF intol.
LOF
Mechanism· predicted
Clinical Summary— ROCK1
⚡
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.
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ClinVar Variants
33 unique Pathogenic / Likely Pathogenic· 82 VUS of 152 total submissions
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Clinical Trials
2 active or recruiting trials — potential therapeutic options may be available
Explore recent and relevant literature in Research Assistant →
📖
GeneReview available — ROCK1
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Dual constrained — LoF & missense intolerant
LoF Constraint
0.20LOEUF
pLI 1.000
Z-score 7.63
OE 0.12 (0.07–0.20)
Highly constrained

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

Missense Constraint
4.59Z-score
OE missense 0.50 (0.45–0.55)
327 obs / 658.1 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios
LoF OE0.12 (0.07–0.20)
0≤0.351.4
Missense OE0.50 (0.45–0.55)
0≤0.61.4
Synonymous OE0.93
0≤1.21.6
LoF obs/exp: 10 / 86.6Missense obs/exp: 327 / 658.1Syn Z: 0.86
DN
0.3991th %ile
GOF
0.3788th %ile
LOF
0.71top 10%

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

LOFprediction above median · LOEUF 0.20

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

152 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic32
Likely Pathogenic1
VUS82
Likely Benign6
Benign3
32
Pathogenic
1
Likely Pathogenic
82
VUS
6
Likely Benign
3
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
32
0
32
Likely Pathogenic
0
0
1
0
1
VUS
1
66
15
0
82
Likely Benign
0
0
1
5
6
Benign
0
1
1
1
3
Total167506124

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

View in ClinVar →

Protein Context — Lollipop Plot

ROCK1 · protein map & ClinVar variants

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

Clinical Literature
Open Research Assistant →
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
4-Octyl itaconate against septic cardiac injury by suppressing cardiac lymphatic vessel inflammation via the RhoA-ROCK1 signaling pathway.
Wu H et al.·Clin Sci (Lond)
2026
PFKFB3-driven glycolysis in endothelial cells activates RhoA/ROCK1 to promote pulmonary vascular leakage in heatstroke.
Ding C et al.·Biochim Biophys Acta Mol Basis Dis
2026
Rnd3 regulates lung cancer cell invasion and migration independently of ROCK1 signaling via alpha 5 integrin modulation.
Garcia Garcia N et al.·Life Sci Alliance
2026Open Access
S1PR3 antagonism ameliorates endothelial dysfunction in septic acute kidney injury through the ROCK1-Drp1 signalling pathway.
Xu Z et al.·Mol Immunol
2026
Danlong oral liquid alleviates airway remodeling in asthma by targeting the S1PR2/ROCK1/YAP signaling pathway in airway smooth muscle cells.
Zhou M et al.·J Ethnopharmacol
2026Functional
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