RAC1

Chr 7AD

Rac family small GTPase 1

Also known as: MIG5, MRD48, Rac-1, TC-25, p21-Rac1

NCBI Gene: 5879ENSG00000136238UniProt: P63000

The protein encoded by this gene is a GTPase which belongs to the RAS superfamily of small GTP-binding proteins. Members of this superfamily appear to regulate a diverse array of cellular events, including the control of cell growth, cytoskeletal reorganization, and the activation of protein kinases. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2009]

Primary Disease Associations & Inheritance

Intellectual developmental disorder, autosomal dominant 48MIM #617751
AD
164
ClinVar variants
60
Pathogenic / LP
0.76
pLI score
1
Active trials
Clinical Summary— RAC1
⚡
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.76) — some intolerance to loss-of-function variants.
📋
ClinVar Variants
60 Pathogenic / Likely Pathogenic· 71 VUS of 164 total submissions
💊
Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available
Some data sources returned errors (1)

pubmed: 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

gnomAD
Missense constrained — critical functional residues
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.
0.47LOEUF
pLI 0.762
Z-score 2.90
OE 0.15 (0.06–0.47)
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.
3.13Z-score
OE missense 0.20 (0.14–0.28)
24 obs / 121.1 exp
Constrained

Highly missense-constrained (top ~0.1%)

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.0.15 (0.06–0.47)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.20 (0.14–0.28)
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.0.83
0≤1.21.6
LoF obs/exp: 2 / 13.5Missense obs/exp: 24 / 121.1Syn Z: 0.96

ClinVar Variant Classifications

164 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic40
Likely Pathogenic20
VUS71
Likely Benign15
Benign4
Conflicting2
40
Pathogenic
20
Likely Pathogenic
71
VUS
15
Likely Benign
4
Benign
2
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
7
33
0
40
Likely Pathogenic
0
18
2
0
20
VUS
9
31
31
0
71
Likely Benign
1
1
5
8
15
Benign
0
0
2
2
4
Conflicting
—2
Total10577310152

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

View in ClinVar →

Protein Context — Lollipop Plot

RAC1 · protein map & ClinVar variants

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

Gene2Phenotype Curations

RAC1-related neurodevelopmental disorder

strong
ADUndeterminedAltered Gene Product Structure
Dev. Disorders
G2P ↗
missense variantinframe deletioninframe insertion

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Intellectual developmental disorder, autosomal dominant 48

MIM #617751

Molecular basis of disorder known

Autosomal dominant
Clinical Literature
Landmark / reviewRecent case evidence
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
Castration-Resistant Prostate CarcinomaMetastatic Castration-Resistant Prostate CarcinomaRefractory Prostate Carcinoma

Testing the Effect of M1774 on Hard-to-Treat Refractory SPOP-mutant Prostate Cancer

ACTIVE NOT RECRUITING
NCT05828082Phase PHASE2National Cancer Institute (NCI)Started 2023-10-16
Biopsy ProcedureBiospecimen CollectionComputed Tomography

External Resources

Links to major genomics databases and tools