CHN2

Chr 7

chimerin 2

Also known as: ARHGAP3, BCH, CHN2-3, RHOGAP3

NCBI Gene: 1124ENSG00000106069UniProt: P52757

This gene encodes a guanosine triphosphate (GTP)-metabolizing protein that contains a phorbol-ester/diacylglycerol (DAG)-type zinc finger, a Rho-GAP domain, and an SH2 domain. The encoded protein translocates from the cytosol to the Golgi apparatus membrane upon binding by diacylglycerol (DAG). Activity of this protein is important in cell proliferation and migration, and expression changes in this gene have been detected in cancers. A mutation in this gene has also been associated with schizophrenia in men. Alternative transcript splicing and the use of alternative promoters results in multiple transcript variants. [provided by RefSeq, May 2014]

86
ClinVar variants
24
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— CHN2
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
24 Pathogenic / Likely Pathogenic· 44 VUS of 86 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
Tolerant — LoF & missense variants common in population
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.
0.63LOEUF
pLI 0.002
Z-score 2.97
OE 0.36 (0.22–0.63)
Tolerant

Typical tolerance to LoF variation

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.
1.13Z-score
OE missense 0.80 (0.72–0.90)
214 obs / 265.9 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.0.36 (0.22–0.63)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.80 (0.72–0.90)
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.0.86
0≤1.21.6
LoF obs/exp: 9 / 25.0Missense obs/exp: 214 / 265.9Syn Z: 1.11

ClinVar Variant Classifications

86 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic21
Likely Pathogenic3
VUS44
Likely Benign9
Benign9
21
Pathogenic
3
Likely Pathogenic
44
VUS
9
Likely Benign
9
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
21
0
21
Likely Pathogenic
0
0
3
0
3
VUS
0
36
8
0
44
Likely Benign
0
2
4
3
9
Benign
1
1
5
2
9
Total13941586

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

View in ClinVar →

Protein Context — Lollipop Plot

CHN2 · 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
Discovery of SARS-CoV-2 antiviral drugs through large-scale compound repurposing.
Riva L et al.·Nature
2020
CPVL/CHN2 genetic variant is associated with diabetic retinopathy in Chinese type 2 diabetic patients.
Hu C et al.·Diabetes
2011Meta-analysis
Severe insulin resistance and intrauterine growth deficiency associated with haploinsufficiency for INSR and CHN2: new insights into synergistic pathways involved in growth and metabolism.
Suliman SG et al.·Diabetes
2009
Genetic associations in diabetic nephropathy: a meta-analysis.
Mooyaart AL et al.·Diabetologia
2011Meta-analysis
Genome-wide association study in multiple human prion diseases suggests genetic risk factors additional to PRNP.
Mead S et al.·Hum Mol Genet
2012Meta-analysis
Integrated genome-wide methylation and expression analyses reveal functional predictors of response to antidepressants.
Ju C et al.·Transl Psychiatry
2019Functional
An epigenome-wide DNA methylation study of patients with COVID-19.
Zhou S et al.·Ann Hum Genet
2021Cohort
Identification of a truncated β1-chimaerin variant that inactivates nuclear Rac1.
Casado-Medrano V et al.·J Biol Chem
2020
Genome-wide association study of atypical psychosis.
Kanazawa T et al.·Am J Med Genet B Neuropsychiatr Genet
2013
Chimerin 2 genetic polymorphisms are associated with non-proliferative diabetic retinopathy in Taiwanese type 2 diabetic patients.
Chen M et al.·J Diabetes Complications
2014Cohort
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Discovery of a Novel Integrative Conjugative Element ICEAplChn2 Related to SXT/R391 in Actinobacillus pleuropneumoniae.
Cai J et al.·Microb Drug Resist
2024
Neuroprotective and Antioxidant Properties of CholesteroNitrone ChN2 and QuinolylNitrone QN23 in an Experimental Model of Cerebral Ischemia: Involvement of Necrotic and Apoptotic Cell Death.
Chamorro B et al.·Antioxidants (Basel)
2023🔓 Open AccessFunctional
Identification of Z-Tyr-Ala-CHN2, a Cathepsin L Inhibitor with Broad-Spectrum Cell-Specific Activity against Coronaviruses, including SARS-CoV-2.
Doijen J et al.·Microorganisms
2023🔓 Open Access
Efficacy of Dulaglutide in Chinese Patients with Type 2 Diabetes and Different Glycemic Patterns: a Post-hoc Analysis of the Phase 3 AWARD-CHN2 Trial.
Li Q et al.·Diabetes Ther
2022🔓 Open AccessCohort
Efficacy and Safety of Dulaglutide Versus Insulin Glargine in Chinese T2DM Patients: A Subgroup Analysis of a Randomized Trial (AWARD-CHN2).
Li Y et al.·Diabetes Ther
2019🔓 Open AccessCohort
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