CHN1

Chr 2ADAR

chimerin 1

Also known as: ARHGAP2, CHN, DURS2, NC, RHOGAP2

This gene encodes GTPase-activating protein for ras-related p21-rac and a phorbol ester receptor. It is predominantly expressed in neurons, and plays an important role in neuronal signal-transduction mechanisms. Mutations in this gene are associated with Duane's retraction syndrome 2 (DURS2). Alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Apr 2011]

OMIMResearchGenerating clinical summary…
GOFmechanismAD/ARLOEUF 0.572 OMIM phenotypes
Clinical SummaryCHN1
🧬
Gene-Disease Validity (ClinGen)
Duane retraction syndrome 2 · ADModerate

Moderate evidence — consider for supplementary testing

Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.30) despite low pLI — interpret in context.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint?
0.57LOEUF
pLI 0.031
Z-score 3.11
OE 0.30 (0.170.57)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?
1.27Z-score
OE missense 0.77 (0.680.87)
187 obs / 242.5 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?
LoF OE?0.30 (0.170.57)
00.351.4
Missense OE?0.77 (0.680.87)
00.61.4
Synonymous OE?0.98
01.21.6
LoF obs/exp: 7 / 23.2Missense obs/exp: 187 / 242.5Syn Z: 0.16
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
strongCHN1-related Duane retraction syndromeGOFAD

This gene — mechanism propensity

DN
0.6259th %ile
GOF
0.6346th %ile
LOF
0.3453th %ile

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

GOF1 literature citation
DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Literature Evidence

GOFMoreover, amino acid residue P252 was previously reported to be altered to a different residue in a previously reported DRS pedigree; thus, this is the first report of 2 CHN1 mutations altering the same residue, further supporting a gain-of-function etiology.1

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

References

  1. 1.PMID 21555619

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

CHN1 · 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

No active trials found for this gene.

Search ClinicalTrials.gov →