GJA3

gap junction protein alpha 3, the group of Gap junction proteins

Basic information

Region (hg38): 13:20138254-20161052

Previous symbols: [ "CZP3" ]

Links

ENSG00000121743 ∙ NCBI:2700 ∙ OMIM:121015 ∙ HGNC:4277 ∙ Uniprot:Q9Y6H8 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• cataract 14 multiple types (Definitive), mode of inheritance: AD
• cataract 14 multiple types (Strong), mode of inheritance: AD
• pulverulent cataract (Supportive), mode of inheritance: AD
• early-onset nuclear cataract (Supportive), mode of inheritance: AD
• early-onset posterior polar cataract (Supportive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Cataract 14, multiple types	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	Ophthalmologic	10205266; 10746562; 15286166; 22312188; 22550389; 22876138; 23592915; 23734083

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the GJA3 gene.

• Cataract 14 multiple types (142 variants)
• not provided (27 variants)
• Inborn genetic diseases (15 variants)
• Zonular Pulverulent Cataract (8 variants)
• not specified (3 variants)
• Developmental cataract (3 variants)
• Congenital cataracts-facial dysmorphism-neuropathy syndrome (1 variants)
• GJA3-related condition (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the GJA3 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			8	6	7	21
missense	4	9	52	2	3	70
nonsense			1			1
start loss						0
frameshift		1	1	1		3
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding			46	4	28	78
Total	4	10	108	13	38

Variants in GJA3

This is a list of pathogenic ClinVar variants found in the GJA3 region.

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

Position	Type	Phenotype	Significance	ClinVar
13-20138372-C-T		Cataract 14 multiple types	Uncertain significance (Jan 13, 2018)
13-20138472-G-C		Cataract 14 multiple types	Uncertain significance (Apr 27, 2017)
13-20138587-CT-C		Zonular Pulverulent Cataract	Uncertain significance (Jun 14, 2016)
13-20138592-C-T		Cataract 14 multiple types	Uncertain significance (Jan 13, 2018)
13-20138607-CA-C		Zonular Pulverulent Cataract	Benign (Jun 14, 2016)
13-20138771-T-C		Cataract 14 multiple types	Uncertain significance (Jan 12, 2018)
13-20138799-A-C		Cataract 14 multiple types	Uncertain significance (Jan 12, 2018)
13-20138815-G-A		Cataract 14 multiple types	Benign (Jan 12, 2018)
13-20138873-G-A		Cataract 14 multiple types	Uncertain significance (Jan 13, 2018)
13-20138882-G-T		Cataract 14 multiple types	Uncertain significance (Jan 13, 2018)
13-20139050-T-C		Cataract 14 multiple types	Uncertain significance (Jan 13, 2018)
13-20139058-T-C		Cataract 14 multiple types	Uncertain significance (Jan 12, 2018)
13-20139111-G-A		Cataract 14 multiple types	Benign (Jan 12, 2018)
13-20139117-A-G		Cataract 14 multiple types	Benign (Jan 13, 2018)
13-20139150-T-C		Cataract 14 multiple types	Benign (Jan 12, 2018)
13-20139152-T-A		Cataract 14 multiple types	Uncertain significance (Jan 12, 2018)
13-20139286-G-A		Cataract 14 multiple types	Uncertain significance (Jan 13, 2018)
13-20139379-A-G		Cataract 14 multiple types	Benign (Jan 13, 2018)
13-20139388-T-A		Cataract 14 multiple types	Benign (Jan 13, 2018)
13-20139512-A-G		Cataract 14 multiple types	Benign (Jan 13, 2018)
13-20139555-G-T		Cataract 14 multiple types	Benign (Jan 12, 2018)
13-20139565-T-C		Cataract 14 multiple types	Benign (Jan 13, 2018)
13-20139618-T-C		Cataract 14 multiple types	Uncertain significance (Jan 13, 2018)
13-20139641-T-C		Cataract 14 multiple types	Uncertain significance (Jan 12, 2018)
13-20139670-T-G		Cataract 14 multiple types	Uncertain significance (Jan 13, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
GJA3	protein_coding	protein_coding	ENST00000241125	1	22795

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00131	0.667	125667	0	18	125685	0.0000716

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.71	186	264	0.704	0.0000186	2751
Missense in Polyphen		48	105.69	0.45416		1148
Synonymous	0.866	121	134	0.905	0.0000109	926
Loss of Function	0.682	5	6.94	0.721	3.01e-7	75

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000296	0.0000296
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.0000463	0.0000462
European (Non-Finnish)	0.000128	0.000123
Middle Eastern	0.00	0.00
South Asian	0.0000328	0.0000327
Other	0.000165	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: One gap junction consists of a cluster of closely packed pairs of transmembrane channels, the connexons, through which materials of low MW diffuse from one cell to a neighboring cell.
• Disease: DISEASE: Cataract 14, multiple types (CTRCT14) [MIM:601885]: An opacification of the crystalline lens of the eye that frequently results in visual impairment or blindness. Opacities vary in morphology, are often confined to a portion of the lens, and may be static or progressive. CTRCT14 includes zonular pulverulent cataract, among others. Zonular or lamellar cataracts are opacities, broad or narrow, usually consisting of powdery white dots affecting only certain layers or zones between the cortex and nucleus of an otherwise clear lens. The opacity may be so dense as to render the entire central region of the lens completely opaque, or so translucent that vision is hardly if at all impeded. Usually sharply separated from a clear cortex outside them, they may have projections from their outer edges known as riders or spokes. {ECO:0000269|PubMed:10205266, ECO:0000269|PubMed:10746562, ECO:0000269|PubMed:14627959, ECO:0000269|PubMed:15208569, ECO:0000269|PubMed:15286166, ECO:0000269|PubMed:15448617, ECO:0000269|PubMed:16234473, ECO:0000269|PubMed:16254549, ECO:0000269|PubMed:16885921, ECO:0000269|PubMed:16971895, ECO:0000269|PubMed:17615540, ECO:0000269|PubMed:17893674, ECO:0000269|PubMed:20431721, ECO:0000269|PubMed:21552498, ECO:0000269|PubMed:21647269, ECO:0000269|PubMed:21681855, ECO:0000269|PubMed:21897748, ECO:0000269|PubMed:22312188, ECO:0000269|PubMed:24772942, ECO:0000269|PubMed:25635993, ECO:0000269|PubMed:26683566}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Calcium Regulation in the Cardiac Cell (Consensus)

Recessive Scores

• pRec: 0.128

Haploinsufficiency Scores

• pHI: 0.225
• hipred: N
• hipred_score: 0.421
• ghis: 0.495

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.789

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Gja3
• Phenotype: vision/eye phenotype

Zebrafish Information Network

• Gene name: gja3
• Affected structure: cardiac muscle cell
• Phenotype tag: abnormal
• Phenotype quality: malformed

Gene ontology

• Biological process: cell-cell signaling;visual perception;transmembrane transport
• Cellular component: connexin complex;integral component of membrane
• Molecular function: gap junction channel activity