GJC3

protein-coding

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

Gene summary

This gene encodes a gap junction protein. The encoded protein, also known as a connexin, plays a role in formation of gap junctions, which provide direct connections between neighboring cells. Mutations in this gene have been reported to be associated with nonsyndromic hearing loss.[provided by RefSeq, Feb 2010]

Previous symbols:

GJE1

MANE transcript

NM_181538.3

Inheritance

—

ClinVar variants

U:30B:9

Top phenotype

GJC3-related disorder

gnomAD constraint

pLI —, LoF o/e 0.69

Max pathogenic AF

—

Genomic locus

chr7:99,923,266-99,929,620

External References & Databases

Ensembl (ENSG00000176402)

Transcript & Mutation Effects

hg38 • Region Span ~6.4 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to GJC3 variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 30

GJC3-related disorderTotal: 5

not providedTotal: 2

Variant of unknown significanceTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_181538.3. 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			1 clinvar	1 clinvar	1 clinvar	3
missense			29 clinvar	6 clinvar	1 clinvar	36
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	30	7	2	39

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 3 of 3 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_181538.3	RefSeq	NP_853516.1	2	MANE Select
ENST00000312891.3	Ensembl	ENSP00000325775.2	2	MANE Select
XM_047420329.1	RefSeq	XP_047276285.1	3	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

sensory perception of sound
myelination
AV node cell to bundle of His cell communication by electrical coupling

Molecular Function

protein homodimerization activity
gap junction channel activity involved in AV node cell-bundle of His cell electrical coupling

Cellular Component

connexin complex
integral component of membrane
myelin sheath

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000312891
Coding exons: 2
Length: 6352
Individuals with no LoFs: 125615
Homozygous LoFs: 1
Heterozygous LoFs: 132
Defined: 125748
p: 0.000529

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.102	153	149	1.02	0.00000743	1781
Missense (PolyPhen)		46	42.006	1.0951		533
Synonymous	-0.539	68	62.6	1.09	0.00000300	600
Loss of Function	0.861	6	8.75	0.686	4.65e-7	102

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000063	0.000062	rare
Latino/Admixed American	0.00093	0.00093	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00022	0.00022	rare
Finnish	0.0031	0.0031	notable
European (Non-Finnish)	0.00019	0.00018	rare
South Asian	0.00020	0.00016	rare
Other	0.00049	0.00049	rare

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. {ECO:0000250}.;

Recessive Scores

pRec: 0.107

Intolerance Scores

LoFtool: 0.339
RVIS EVS: 0.19
RVIS percentile EVS: 67.03

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.274

Gene Damage Prediction

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