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GeneE
10 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
β“˜GeneE is for informational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment.
CHN1
chimerin 1
Chromosome 2 Β· 2q31.1
NCBI Gene: 1123Ensembl: ENSG00000128656.16HGNC: HGNC:1943UniProt: P15882
63PubMed Papers
21Diseases
0Drugs
13Pathogenic Variants
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
protein bindingephrin receptor bindingGTPase activator activitymotor neuron axon guidanceDuane retraction syndromesmoking initiationautosomal dominant Robinow syndromeRobinow syndrome
✦AI Summary

CHN1 encodes alpha2-chimaerin, a RacGAP (Rac guanosine triphosphatase-activating protein) that regulates small GTPase signaling and functions as a phorbol ester receptor 1. In neuronal development, CHN1 serves as a direct effector of EPHA4 in axon guidance, with critical importance in ocular motor axon pathfinding and the assembly of cranial motor neuron circuits 12. Gain-of-function mutations in CHN1 cause Duane retraction syndrome type 2 (DURS2), a congenital eye movement disorder resulting from aberrant extraocular muscle innervation by brainstem motor neurons 13. Beyond its developmental neurological function, CHN1 exhibits pathological roles in multiple cancers. In gastric and cervical carcinomas, CHN1 is upregulated and promotes cancer progression through distinct mechanisms: in cervical cancer, it activates the Akt/GSK-3Ξ²/Snail pathway to induce epithelial-mesenchymal transition 4, while in esophageal squamous cell carcinoma, the TBX18-CHN1-RhoA axis promotes radioresistance 5. High CHN1 expression correlates with poor survival and immune infiltration patterns in gastric cancer 6. Recent evidence suggests CHN1 may serve as a biomarker for atopic dermatitis-associated depression through immune regulatory networks 7. These findings establish CHN1 as a multifunctional regulator with critical roles in developmental neurobiology and pathological significance in cancer progression and immune-mediated conditions.

Sources cited
1
CHN1 encodes alpha2-chimaerin, a RacGAP protein, and gain-of-function mutations cause Duane retraction syndrome through defective ocular motor axon pathfinding
PMID: 18653847
2
CHN1 is a known CCDD disease gene with potential non-coding regulatory variants affecting cranial motor neuron development
PMID: 39333082
3
CHN1 mutations identified in Duane retraction syndrome patients, including bilateral cases and familial presentations
PMID: 29031989
4
CHN1 is upregulated in gastric cancer and high expression correlates with poor survival and immune cell infiltration
PMID: 34152250
5
CHN1 acts downstream of TBX18 and upstream of RhoA to promote radioresistance in esophageal squamous cell carcinoma
PMID: 37399907
6
CHN1 promotes epithelial-mesenchymal transition in cervical carcinoma via Akt/GSK-3Ξ²/Snail signaling pathway
PMID: 34238315
7
CHN1 is upregulated in atopic dermatitis patients with depression and correlates with Th2/Th17 cytokine signatures and depression severity
PMID: 41333466
Disease Associationsβ“˜21
Duane retraction syndromeOpen Targets
0.78Strong
smoking initiationOpen Targets
0.37Weak
autosomal dominant Robinow syndromeOpen Targets
0.33Weak
Robinow syndromeOpen Targets
0.33Weak
Moebius syndromeOpen Targets
0.27Weak
Mobius syndromeOpen Targets
0.27Weak
multiple sclerosisOpen Targets
0.25Weak
cardiac arrestOpen Targets
0.24Weak
genetic disorderOpen Targets
0.19Weak
hemolytic anemiaOpen Targets
0.18Weak
ovarian neoplasmOpen Targets
0.17Weak
Duane anomalyOpen Targets
0.16Weak
ovarian dysfunctionOpen Targets
0.10Weak
cervical cancerOpen Targets
0.09Suggestive
gastric cancerOpen Targets
0.08Suggestive
Alzheimer diseaseOpen Targets
0.07Suggestive
diffuse large B-cell lymphomaOpen Targets
0.06Suggestive
neoplasmOpen Targets
0.06Suggestive
developmental and epileptic encephalopathy, 9Open Targets
0.06Suggestive
familial infantile myoclonic epilepsyOpen Targets
0.05Suggestive
Duane retraction syndrome 2UniProt
Pathogenic Variants13
NM_001822.7(CHN1):c.428A>G (p.Tyr143Cys)Likely pathogenic
Duane retraction syndrome 2
β˜…β˜†β˜†β˜†2024β†’ Residue 143
NM_001822.7(CHN1):c.643G>A (p.Gly215Arg)Likely pathogenic
Oromandibular-limb hypogenesis spectrum
β˜…β˜†β˜†β˜†2022β†’ Residue 215
NM_001822.7(CHN1):c.667G>A (p.Ala223Thr)Likely pathogenic
not provided
β˜…β˜†β˜†β˜†2018β†’ Residue 223
NM_001822.7(CHN1):c.661T>C (p.Tyr221His)Pathogenic
Duane retraction syndrome 2|not provided
β˜…β˜†β˜†β˜†2017β†’ Residue 221
NM_001822.7(CHN1):c.1106T>G (p.Ile369Ser)Pathogenic
Autosomal dominant Robinow syndrome 2
β˜†β˜†β˜†β˜†2019β†’ Residue 369
NM_001822.7(CHN1):c.422C>T (p.Pro141Leu)Pathogenic
Duane retraction syndrome 2
β˜†β˜†β˜†β˜†2011β†’ Residue 141
NM_001822.7(CHN1):c.668C>T (p.Ala223Val)Pathogenic
Duane retraction syndrome 2
β˜†β˜†β˜†β˜†2008β†’ Residue 223
NM_001822.7(CHN1):c.682G>A (p.Gly228Ser)Pathogenic
Duane retraction syndrome 2
β˜†β˜†β˜†β˜†2008β†’ Residue 228
NM_001822.7(CHN1):c.755C>A (p.Pro252Gln)Pathogenic
Duane retraction syndrome 2
β˜†β˜†β˜†β˜†2008β†’ Residue 252
NM_001822.7(CHN1):c.937G>A (p.Glu313Lys)Pathogenic
Duane retraction syndrome 2
β˜†β˜†β˜†β˜†2008β†’ Residue 313
NM_001822.7(CHN1):c.378T>G (p.Ile126Met)Pathogenic
Duane retraction syndrome 2
β˜†β˜†β˜†β˜†2008β†’ Residue 126
NM_001822.7(CHN1):c.427T>C (p.Tyr143His)Pathogenic
Duane retraction syndrome 2
β˜†β˜†β˜†β˜†2008β†’ Residue 143
NM_001822.7(CHN1):c.60A>T (p.Leu20Phe)Pathogenic
Duane retraction syndrome 2
β˜†β˜†β˜†β˜†2008β†’ Residue 20
View on ClinVar β†—
Related Genes
CDC42Protein interaction93%NCK2Protein interaction84%SALL4Protein interaction83%EPHA4Protein interaction78%HOXA1Protein interaction73%ROBO3Protein interaction70%
Tissue Expression6 tissues
Brain
100%
Heart
6%
Lung
3%
Ovary
2%
Bone Marrow
1%
Liver
1%
Gene Interaction Network
Click a node to explore
CHN1CDC42NCK2SALL4EPHA4HOXA1ROBO3
PROTEIN STRUCTURE
Preparing viewer…
PDB2OSA Β· 1.80 Γ… Β· X-ray
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
0.79LoF Tolerant
pLIβ“˜
0.01Tolerant
Observed/Expected LoF0.52 [0.35–0.79]
RankingsWhere CHN1 stands among ~20K protein-coding genes
  • #7,347of 20,598
    Most Researched63
  • #2,604of 5,498
    Most Pathogenic Variants13
  • #6,525of 17,882
    Most Constrained (LOEUF)0.79
Genes detectedCHN1
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
Bioinformatics-based analysis of the association between the A1-chimaerin (
PMID: 34152250
Bioengineered Β· 2021
1.00
2
A cell type-aware framework for nominating non-coding variants in Mendelian regulatory disorders.
PMID: 39333082
Nat Commun Β· 2024
0.90
3
TBX18 knockdown sensitizes esophageal squamous cell carcinoma to radiotherapy by blocking the CHN1/RhoA axis.
PMID: 37399907
Radiother Oncol Β· 2023
0.80
4
CHN1 gene mutation analysis in patients with Duane retraction syndrome.
PMID: 29031989
J AAPOS Β· 2017
0.70
5
Human CHN1 mutations hyperactivate alpha2-chimaerin and cause Duane's retraction syndrome.
PMID: 18653847
Science Β· 2008
0.60