GJA8

gap junction protein alpha 8, the group of Gap junction proteins

Basic information

Region (hg38): 1:147902795-147909269

Previous symbols: [ "CAE1", "CZP1", "CAE" ]

Links

ENSG00000121634 ∙ NCBI:2703 ∙ OMIM:600897 ∙ HGNC:4281 ∙ Uniprot:P48165 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• cataract - microcornea syndrome (Supportive), mode of inheritance: AD
• pulverulent cataract (Supportive), mode of inheritance: AD
• early-onset sutural cataract (Supportive), mode of inheritance: AD
• early-onset nuclear cataract (Supportive), mode of inheritance: AD
• total early-onset cataract (Supportive), mode of inheritance: AD
• cataract 1 multiple types (Definitive), mode of inheritance: AD
• cataract 1 multiple types (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Cataract 1, multiple types	AD/AR	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	14059288; 9497259; 10480374; 11846744; 14627691; 16604058; 18006672; 19756179; 21720542; 20019893; 20597646; 20806042; 21921990

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the GJA8 gene.

• Cataract 1 multiple types (18 variants)
• not provided (5 variants)
• Developmental cataract (2 variants)
• GJA8-related disorder (2 variants)
• Anterior segment dysgenesis (1 variants)
• acorea-microphthalmia-cataract syndrome (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the GJA8 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			4	20	3	27
missense	23	15	67	10	3	118
nonsense			3			3
start loss						0
frameshift			2			2
inframe indel			1			1
splice donor/acceptor (+/-2bp)						0
splice region			1			1
non coding			1	3	3	7
Total	23	15	78	33	9

Highest pathogenic variant AF is 0.00000657

Variants in GJA8

This is a list of pathogenic ClinVar variants found in the GJA8 region.

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

Position	Type	Phenotype	Significance	ClinVar
1-147902830-A-G		Cataract 1 multiple types	Uncertain significance (Jan 13, 2018)
1-147902840-C-T		Cataract 1 multiple types • Zonular Pulverulent Cataract	Likely benign (Jun 14, 2016)
1-147902849-A-G		Cataract 1 multiple types • Zonular Pulverulent Cataract	Likely benign (Jun 14, 2016)
1-147907615-A-G			Benign (Oct 01, 2018)
1-147907814-A-G			Benign (Jul 31, 2018)
1-147907897-G-T			Benign (Oct 09, 2018)
1-147907941-T-G		Cataract 1 multiple types	Uncertain significance (Apr 27, 2017)
1-147907947-G-T		GJA8-related disorder	Likely benign (Jul 05, 2022)
1-147907965-T-A		Cataract 1 multiple types	Uncertain significance (Jan 21, 2023)
1-147907967-G-C		Cataract 1 multiple types	Uncertain significance (Jan 21, 2023)
1-147907974-C-A		Cataract 1 multiple types • GJA8-related disorder	Conflicting classifications of pathogenicity (Jan 21, 2023)
1-147907974-CTGGGGAACATCT-C		Cataract 1 multiple types	Uncertain significance (Jan 21, 2023)
1-147907975-T-C		Cataract 1 multiple types	Conflicting classifications of pathogenicity (Sep 05, 2023)
1-147907977-G-A		Inborn genetic diseases • Cataract 1 multiple types	Uncertain significance (Dec 13, 2023)
1-147907990-A-G		Inborn genetic diseases	Uncertain significance (May 17, 2023)
1-147907994-G-C		Inborn genetic diseases	Uncertain significance (Aug 19, 2023)
1-147907995-G-C		Inborn genetic diseases	Uncertain significance (Nov 12, 2021)
1-147908000-T-G			Uncertain significance (Feb 26, 2023)
1-147908008-C-T		Cataract 1 multiple types	Uncertain significance (Jan 21, 2023)
1-147908013-G-A		Cataract 1 multiple types • Zonular Pulverulent Cataract	Uncertain significance (Jan 21, 2023)
1-147908019-G-A		Developmental cataract • Cataract 1 multiple types • Cataract 46 juvenile-onset	Likely pathogenic (Oct 31, 2023)
1-147908019-G-C		Cataract 1 multiple types	Likely pathogenic (Jan 21, 2023)
1-147908019-G-T		Cataract 1 multiple types	Likely pathogenic (Mar 14, 2023)
1-147908022-A-G		Cataract 1 multiple types	Uncertain significance (Feb 15, 2018)
1-147908023-G-C		Cataract 1 multiple types	Likely pathogenic (Jan 21, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
GJA8	protein_coding	protein_coding	ENST00000240986	1	6448

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00220	0.927	125705	0	43	125748	0.000171

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.199	270	261	1.03	0.0000178	2807
Missense in Polyphen		58	85.717	0.67665		971
Synonymous	-1.57	145	123	1.18	0.00000959	906
Loss of Function	1.58	6	11.9	0.506	5.16e-7	150

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000578	0.0000578
Ashkenazi Jewish	0.00	0.00
East Asian	0.000109	0.000109
Finnish	0.000929	0.000924
European (Non-Finnish)	0.000146	0.000141
Middle Eastern	0.000109	0.000109
South Asian	0.0000660	0.0000653
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.
• Pathway: Calcium Regulation in the Cardiac Cell (Consensus)

Recessive Scores

• pRec: 0.241

Intolerance Scores

• loftool: 0.138
• rvis_EVS: -0.18
• rvis_percentile_EVS: 40.36

Haploinsufficiency Scores

• pHI: 0.331
• hipred: N
• hipred_score: 0.197
• ghis: 0.397

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.651

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Gja8
• Phenotype: cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); vision/eye phenotype

Gene ontology

• Biological process: lens development in camera-type eye;cell-cell signaling;visual perception;protein homooligomerization;transmembrane transport
• Cellular component: integral component of plasma membrane;connexin complex
• Molecular function: gap junction channel activity;channel activity