CHN1

protein-coding

chimerin 1, the group of Rho GTPase activating proteins|SH2 domain containing

Gene summary

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]

Previous symbols:

CHN
DURS2

MANE transcript

NM_001822.7

Inheritance

ClinVar variants

P:14U:81B:18

Top phenotype

Duane retraction syndrome 2

gnomAD constraint

pLI —, LoF o/e 0.3

Max pathogenic AF

—

Genomic locus

chr2:174,798,809-175,005,381

External References & Databases

Ensembl (ENSG00000128656)

Transcript & Mutation Effects

hg38 • Region Span ~206.6 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

Duane retraction syndrome 2STRONG

Inheritance Pattern: AD

Disease ID:MONDO:0011444

Submitter: G2P

Duane retraction syndrome 2DEFINITIVE

Inheritance Pattern: AD

Disease ID:MONDO:0011444

Submitter: ClinGen

CHN1 was first reported in relation to autosomal dominant Duane retraction syndrome in 2008 (Miyake et al., PMID: 18653847). Duane retraction syndrome is a congenital disorder characterized by restricted horizontal eye movement with globe retraction and palpebral fissure narrowing on attempted adduction. 20 missense variants that have been reported in at least 21 probands in 10 publications (PMIDs: 18653847, 21555619, 21715346, 29031989, 33004823, 33667650, 37853116, 38356699, 38509018, 40212284) and ClinVar (SCV000854481.4) are included in this curation. The mechanism of pathogenicity has been reported to be gain-of-function. This gene-disease relationship is also supported by an animal model (PMID: 28346224). The mouse model reveals that the knock-in mutants have delayed abducens nerve growth and selective trochlear and cervical spinal nerve anomalies. This gene-disease pair was originally evaluated by the Brain Malformations GCEP on 7/26/2022. It was reevaluated on 11/25/2025 (SOP Version 11). As a result of this reevaluation, the classification increased from moderate to definitive with the addition of genetic evidence (PMIDs: 33667650, 37853116, 38356699, 38509018, 40212284; ClinVar: SCV000854481.4). This evidence for this gene-disease relationship has been repeatedly demonstrated in both the research and clinical diagnostic settings, and has been upheld over time.

Duane retraction syndrome 2LIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0011444

Submitter: Labcorp Genetics (formerly Invitae)

Duane retraction syndromeSUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0007473

Submitter: Orphanet

Clinical Genomic Database (CGD)

Duane retraction syndrome 2AD

Manifestation: Neurologic

Intervention: General

Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing

Refs: 18653847; 21555619; 21715346

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to CHN1 variants in ClinVar

8 Conditions Cataloged

Inborn genetic diseasesTotal: 51

Duane retraction syndrome 2Total: 35

not providedTotal: 30

not specifiedTotal: 7

CHN1-related disorderTotal: 4

Autosomal dominant Robinow syndrome 2Total: 1

Oromandibular-limb hypogenesis spectrumTotal: 1

Duane syndrome type 1Total: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001822.7. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			5 clinvar	12 clinvar	3 clinvar	20
missense	10 clinvar	4 clinvar	72 clinvar	3 clinvar		89
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			3 clinvar			3
Total	10	4	81	15	3	113

Highest pathogenic variant AF is 0.000006574795

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 55 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001822.7	RefSeq	NP_001813.1	13	MANE Select
ENST00000409900.9	Ensembl	ENSP00000386741.4	13	MANE Select
NM_001025201.4	RefSeq	NP_001020372.2	12	Standard
NM_001206602.2	RefSeq	NP_001193531.1	7	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
chn1	Danio rerio	Structure: cranial nerve III Quality: process quality abnormal

Gene / Model

Organism

Observed Phenotype

chn1

Danio rerio

Structure: cranial nerve III

Quality: process quality

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Signal Transduction
rho cell motility signaling pathway
t cell receptor signaling pathway
rac1 cell motility signaling pathway
Rho GTPase cycle

Biological Process

motor neuron axon guidance
positive regulation of signal transduction
intracellular signal transduction
positive regulation of GTPase activity
ephrin receptor signaling pathway

Molecular Function

SH3/SH2 adaptor activity
GTPase activator activity
protein binding
metal ion binding
ephrin receptor binding

Cellular Component

cytosol

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000409900
Coding exons: 13
Length: 206007
Individuals with no LoFs: 124642
Homozygous LoFs: 0
Heterozygous LoFs: 12
Defined: 124654
p: 0.0000481

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.27	187	242	0.771	0.0000125	3013
Missense (PolyPhen)		87	128.28	0.67821		1638
Synonymous	0.165	88	90.0	0.978	0.00000523	829
Loss of Function	3.11	7	23.2	0.302	0.00000111	327

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000058	0.000058	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0.00019	0.00019	rare
European (Non-Finnish)	0.000045	0.000044	rare
South Asian	0.000033	0.000033	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: GTPase-activating protein for p21-rac and a phorbol ester receptor. Involved in the assembly of neuronal locomotor circuits as a direct effector of EPHA4 in axon guidance.;
Disease: DISEASE: Duane retraction syndrome 2 (DURS2) [MIM:604356]: A form of Duane retraction syndrome, a congenital eye movement disorder characterized by a failure of cranial nerve VI (the abducens nerve) to develop normally, resulting in restriction or absence of abduction, adduction or both, narrowing of the palpebral fissure, and retraction of the globe on attempted adduction. Undiagnosed in children, it can lead to amblyopia, a permanent uncorrectable loss of vision. {ECO:0000269|PubMed:18653847}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Recessive Scores

pRec: 0.153

Intolerance Scores

LoFtool: 0.478
RVIS EVS: -0.54
RVIS percentile EVS: 20.26

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.776

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium