CHN1

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

Basic information

Region (hg38): 2:174798808-175005381

Previous symbols: [ "CHN", "DURS2" ]

Links

ENSG00000128656 ∙ NCBI:1123 ∙ OMIM:118423 ∙ HGNC:1943 ∙ Uniprot:P15882 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Duane retraction syndrome (Supportive), mode of inheritance: AD
• Duane retraction syndrome 2 (Limited), mode of inheritance: AD
• Duane retraction syndrome 2 (Strong), mode of inheritance: AD
• Duane retraction syndrome 2 (Moderate), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Duane retraction syndrome 2	AD	General	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	Neurologic	18653847; 21555619; 21715346

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CHN1 gene.

• Duane retraction syndrome 2 (50 variants)
• not provided (21 variants)
• Inborn genetic diseases (12 variants)
• Duane retraction syndrome (5 variants)
• CHN1-related condition (1 variants)
• Oromandibular-limb hypogenesis spectrum (1 variants)
• 19 conditions (1 variants)
• Duane syndrome type 1 (1 variants)
• See cases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CHN1 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			5	6	4	15
missense		3	26	1		30
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region			3			3
non coding			25	4	4	33
Total	0	3	56	11	8

Variants in CHN1

This is a list of pathogenic ClinVar variants found in the CHN1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
2-174799360-G-A		Duane retraction syndrome 2	Uncertain significance (Jan 13, 2018)
2-174799378-AAAGT-A		Duane retraction syndrome	Likely benign (Jun 14, 2016)
2-174799424-ATTAAT-A		Duane retraction syndrome	Uncertain significance (Jun 14, 2016)
2-174799439-C-T		Duane retraction syndrome 2	Benign (Jan 12, 2018)
2-174799448-A-G		Duane retraction syndrome 2	Likely benign (Jan 13, 2018)
2-174799473-T-A		Duane retraction syndrome 2	Likely benign (Jan 13, 2018)
2-174799481-T-G		Duane retraction syndrome 2	Uncertain significance (Jan 13, 2018)
2-174799508-T-C		Duane retraction syndrome 2	Uncertain significance (Jan 12, 2018)
2-174799552-C-T		Duane retraction syndrome 2	Uncertain significance (Jan 12, 2018)
2-174799690-G-A		Duane retraction syndrome 2	Uncertain significance (Jan 12, 2018)
2-174799694-G-A		Duane retraction syndrome 2	Uncertain significance (Apr 27, 2017)
2-174799779-C-G		Duane retraction syndrome 2	Uncertain significance (Jan 13, 2018)
2-174799807-C-T		Duane retraction syndrome 2	Uncertain significance (Jan 12, 2018)
2-174799860-G-A		Duane retraction syndrome 2	Uncertain significance (Jan 13, 2018)
2-174799864-G-A		Duane retraction syndrome 2	Uncertain significance (Jan 13, 2018)
2-174799901-T-TA		Duane retraction syndrome	Uncertain significance (Jun 14, 2016)
2-174799918-T-C		Duane retraction syndrome 2	Uncertain significance (Jan 12, 2018)
2-174799962-C-T		Duane retraction syndrome 2	Uncertain significance (Jan 12, 2018)
2-174800064-A-G		Duane retraction syndrome 2	Uncertain significance (Jan 12, 2018)
2-174800088-A-G		Duane retraction syndrome 2	Benign (Jan 13, 2018)
2-174800128-G-A			Benign (Dec 31, 2019)
2-174800154-C-T			Uncertain significance (Aug 13, 2019)
2-174800174-A-G		Duane syndrome type 1	not provided (-)
2-174800177-T-C		Duane retraction syndrome 2	Uncertain significance (Jan 12, 2018)
2-174800181-T-C			Uncertain significance (Feb 07, 2017)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CHN1	protein_coding	protein_coding	ENST00000409900	13	206007

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0305	0.969	124642	0	12	124654	0.0000481

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.27	187	242	0.771	0.0000125	3013
Missense in 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

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000580	0.0000580
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.000186	0.000186
European (Non-Finnish)	0.0000445	0.0000442
Middle Eastern	0.00	0.00
South Asian	0.0000327	0.0000327
Other	0.00	0.00

dbNSFP

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.
• Pathway: Signal Transduction;rho cell motility signaling pathway;t cell receptor signaling pathway;rac1 cell motility signaling pathway;Rho GTPase cycle;adp-ribosylation factor;Signaling by Rho GTPases;Regulation of RAC1 activity (Consensus)

Recessive Scores

• pRec: 0.153

Intolerance Scores

• loftool: 0.478
• rvis_EVS: -0.54
• rvis_percentile_EVS: 20.26

Haploinsufficiency Scores

• pHI: 0.296
• hipred: Y
• hipred_score: 0.853
• ghis: 0.666

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.776

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Chn1
• Phenotype: normal phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); hematopoietic system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); skeleton phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); growth/size/body region phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); cellular phenotype; homeostasis/metabolism phenotype; muscle phenotype

Zebrafish Information Network

• Gene name: chn1
• Affected structure: cranial nerve III
• Phenotype tag: abnormal
• Phenotype quality: process quality

Gene ontology

• Biological process: motor neuron axon guidance;positive regulation of signal transduction;intracellular signal transduction;positive regulation of GTPase activity;ephrin receptor signaling pathway;regulation of axonogenesis;regulation of small GTPase mediated signal transduction
• Cellular component: cytosol
• Molecular function: SH3/SH2 adaptor activity;GTPase activator activity;protein binding;metal ion binding;ephrin receptor binding