GeneBe

GJA3

protein-coding

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

Gene summary

The protein encoded by this gene is a connexin and is a component of lens fiber gap junctions. Defects in this gene are a cause of zonular pulverulent cataract type 3 (CZP3). [provided by RefSeq, Jan 2010]

Previous symbols:
  • CZP3

MANE transcript

NM_021954.4

Inheritance

AD

ClinVar variants

P:47U:143B:36

Top phenotype

Cataract 14, multiple types

gnomAD constraint

pLI —, LoF o/e 0.72

Max pathogenic AF

—

Genomic locus

chr13:20,138,255-20,161,052

External References & Databases

Ensembl (ENSG00000121743)NCBI Gene (2700)OMIM (121015)HGNC:4277GenCCUniProt (Q9Y6H8)AlphaFoldClinVar (GJA3)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~22.8 kb
Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

cataract 14 multiple typesDEFINITIVE

Inheritance Pattern: AD

Disease ID:MONDO:0011162

Submitter: G2P

cataract 14 multiple typesSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0011162

Submitter: Labcorp Genetics (formerly Invitae)

early-onset posterior polar cataractSUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0020378

Submitter: Orphanet

pulverulent cataractSUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0011430

Submitter: Orphanet

early-onset nuclear cataractSUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0020376

Submitter: Orphanet

cataract 14 multiple typesSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0011162

Submitter: PanelApp Australia

Clinical Genomic Database (CGD)

Cataract 14, multiple typesAD

Manifestation: Ophthalmologic

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: 10205266; 10746562; 15286166; 22312188; 22550389; 22876138; 23592915; 23734083Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to GJA3 variants in ClinVar

10 Conditions Cataloged
Cataract 14 multiple typesTotal: 145
Inborn genetic diseasesTotal: 58
not providedTotal: 36
GJA3-related disorderTotal: 23
not specifiedTotal: 7
Developmental cataractTotal: 6
GJA3-related disordersTotal: 5
Bilateral congenital or childhood onset cataractsTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_021954.4. 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.

EffectPLPVUSLBBSum
synonymous
8
clinvar
20
clinvar
3
clinvar
 31
missense
3
clinvar
34
clinvar
125
clinvar
11
clinvar
1
clinvar
 174
nonsense
3
clinvar
 3
start loss
1
clinvar
1
clinvar
 2
frameshift
1
clinvar
8
clinvar
6
clinvar
1
clinvar
 16
splice donor/acceptor (+/-2bp)
0
Total443143324226

Highest pathogenic variant AF is 0.00008154425

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 13 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_021954.4RefSeqNP_068773.21MANE Select
ENST00000241125.4EnsemblENSP00000241125.31MANE Select
ENST00000890229.1EnsemblENSP00000560288.11Standard
ENST00000890230.1EnsemblENSP00000560289.11Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / ModelOrganismObserved Phenotype
gja3Danio rerio

Structure: cardiac muscle cell

Quality: malformed

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

  • Calcium Regulation in the Cardiac Cell

Biological Process

  • cell-cell signaling
  • visual perception
  • transmembrane transport

Molecular Function

  • gap junction channel activity

Cellular Component

  • connexin complex
  • integral component of membrane

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000241125
Coding exons
1
Length
22795
Individuals with no LoFs
125667
Homozygous LoFs
0
Heterozygous LoFs
18
Defined
125685
p
0.0000716
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense1.711862640.7040.00001862751
Missense (PolyPhen)48105.690.454161148
Synonymous0.8661211340.9050.0000109926
Loss of Function0.68256.940.7213.01e-775

Population LoF Frequency

PopulationCAFp-valueStatus
African00.0absent
Latino/Admixed American0.0000300.000029rare
Ashkenazi Jewish00.0absent
East Asian00.0absent
Finnish0.0000460.000046rare
European (Non-Finnish)0.000130.00012rare
South Asian0.0000330.000033rare
Other0.000160.00016rare

dbNSFP Gene Annotations

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.;

Recessive Scores

pRec
0.128

Essentials

Essential (CRISPR)
N
Essential (CRISPR2)
N
Essential (gene trap)
N
Indispensability pred.
E
Indispensability score
0.789

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium
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