COL4A6

collagen type IV alpha 6 chain, the group of Collagens

Basic information

Region (hg38): X:108155606-108439497

Links

ENSG00000197565 ∙ NCBI:1288 ∙ OMIM:303631 ∙ HGNC:2208 ∙ Uniprot:Q14031 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• hearing loss, X-linked 6 (Limited), mode of inheritance: XL
• hearing loss, X-linked 6 (Limited), mode of inheritance: XL
• X-linked nonsyndromic hearing loss (Supportive), mode of inheritance: XL
• premature ovarian failure 1 (Limited), mode of inheritance: XL
• hearing loss, X-linked 6 (Strong), mode of inheritance: XL
• hearing loss, X-linked 6 (Limited), mode of inheritance: XL

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Deafness, X-linked 6	XL	Audiologic/Otolaryngologic	Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development	Audiologic/Otolaryngologic	23714752

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the COL4A6 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the COL4A6 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			1	80	24	105
missense			161	26	11	198
nonsense			2			2
start loss						0
frameshift			4			4
inframe indel			3	2		5
splice donor/acceptor (+/-2bp)			1			1
splice region			12	15	3	30
non coding			1	81	50	132
Total	0	0	173	189	85

Variants in COL4A6

This is a list of pathogenic ClinVar variants found in the COL4A6 region.

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

Position	Type	Phenotype	Significance	ClinVar
X-108156930-C-T			Benign (Jul 01, 2018)
X-108157002-A-C		COL4A6-related disorder	Conflicting classifications of pathogenicity (May 02, 2023)
X-108157014-T-C		not specified	Uncertain significance (Feb 07, 2023)
X-108157028-C-T		not specified	Uncertain significance (Dec 13, 2023)
X-108157029-G-A			Likely benign (Sep 20, 2022)
X-108157031-C-T			Uncertain significance (Nov 03, 2022)
X-108157080-A-G			Likely benign (Oct 06, 2020)
X-108157099-C-T			Likely benign (Jun 15, 2021)
X-108157124-C-T		not specified	Uncertain significance (Apr 18, 2023)
X-108157173-C-T			Uncertain significance (Sep 11, 2023)
X-108157174-G-C			Uncertain significance (Jul 13, 2021)
X-108157191-G-GA			Uncertain significance (Oct 13, 2023)
X-108157242-C-G		not specified	Uncertain significance (Dec 14, 2023)
X-108157263-G-A			Uncertain significance (May 25, 2022)
X-108157265-AACAG-A			Likely benign (Jul 08, 2022)
X-108157413-G-T			Benign (Jul 10, 2018)
X-108159446-C-G			Likely benign (Mar 10, 2022)
X-108159454-G-A		not specified • Hearing loss, X-linked 6	Benign (Jan 29, 2024)
X-108159457-C-A			Uncertain significance (Apr 17, 2021)
X-108159464-T-G			Uncertain significance (Jun 28, 2021)
X-108159465-G-A			Likely benign (Jan 05, 2024)
X-108159494-G-A		not specified	Uncertain significance (Dec 17, 2023)
X-108159506-G-A		Hearing loss, X-linked 6	Uncertain significance (Jun 24, 2022)
X-108159513-C-T			Likely benign (Sep 24, 2021)
X-108159516-G-A			Benign (Aug 27, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
COL4A6	protein_coding	protein_coding	ENST00000372216	45	295948

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.899	0.101	125717	7	17	125741	0.0000954

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.48	538	644	0.836	0.0000477	10531
Missense in Polyphen		141	207.79	0.67857		3327
Synonymous	-0.230	246	241	1.02	0.0000188	3812
Loss of Function	5.76	12	60.3	0.199	0.00000452	1087

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000870	0.0000615
Ashkenazi Jewish	0.000134	0.0000992
East Asian	0.000495	0.000326
Finnish	0.00	0.00
European (Non-Finnish)	0.000178	0.000105
Middle Eastern	0.000495	0.000326
South Asian	0.000182	0.0000980
Other	0.000265	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Type IV collagen is the major structural component of glomerular basement membranes (GBM), forming a 'chicken-wire' meshwork together with laminins, proteoglycans and entactin/nidogen.
• Disease: DISEASE: Note=Deletions covering the N-terminal regions of COL4A5 and COL4A6, which are localized in a head-to-head manner, are found in the chromosome Xq22.3 centromeric deletion syndrome. This results in a phenotype with features of diffuse leiomyomatosis and Alport syndrome (DL-ATS).; DISEASE: Deafness, X-linked, 6 (DFNX6) [MIM:300914]: A non- syndromic form of sensorineural hearing loss with prelingual onset. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information. {ECO:0000269|PubMed:23714752}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: PI3K-Akt signaling pathway - Homo sapiens (human);ECM-receptor interaction - Homo sapiens (human);Focal adhesion - Homo sapiens (human);Relaxin signaling pathway - Homo sapiens (human);AGE-RAGE signaling pathway in diabetic complications - Homo sapiens (human);Small cell lung cancer - Homo sapiens (human);Protein digestion and absorption - Homo sapiens (human);Amoebiasis - Homo sapiens (human);Pathways in cancer - Homo sapiens (human);Human papillomavirus infection - Homo sapiens (human);Platelet Aggregation Inhibitor Pathway, Pharmacodynamics;Focal Adhesion;Cellular response to heat stress;Focal Adhesion-PI3K-Akt-mTOR-signaling pathway;Protein alkylation leading to liver fibrosis;PI3K-Akt Signaling Pathway;EMT transition in Colorectal Cancer;Assembly of collagen fibrils and other multimeric structures;HSF1 activation;Attenuation phase;HSF1-dependent transactivation;regulators of bone mineralization;intrinsic prothrombin activation pathway;Regulation of HSF1-mediated heat shock response;Collagen chain trimerization;Collagen biosynthesis and modifying enzymes;Cellular responses to stress;Collagen formation;Extracellular matrix organization;Cellular responses to external stimuli;Beta3 integrin cell surface interactions;Integrin;Cellular response to heat stress;Beta1 integrin cell surface interactions;Syndecan-1-mediated signaling events;Integrins in angiogenesis (Consensus)

Recessive Scores

• pRec: 0.0746

Intolerance Scores

• loftool: 0.0282
• rvis_EVS: 0.37
• rvis_percentile_EVS: 74.73

Haploinsufficiency Scores

• pHI: 0.147
• hipred: N
• hipred_score: 0.429
• ghis: 0.388

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.0121

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Col4a6
• Phenotype: normal phenotype

Zebrafish Information Network

• Gene name: col4a6
• Affected structure: retinal ganglion cell
• Phenotype tag: abnormal
• Phenotype quality: decreased process quality

Gene ontology

• Biological process: cell adhesion;extracellular matrix organization;collagen-activated tyrosine kinase receptor signaling pathway
• Cellular component: extracellular region;collagen type IV trimer;extracellular space;endoplasmic reticulum lumen;extracellular matrix;collagen-containing extracellular matrix
• Molecular function: extracellular matrix structural constituent;extracellular matrix structural constituent conferring tensile strength