COL6A6

protein-coding

collagen type VI alpha 6 chain, the group of Collagens

Gene summary

This gene encodes a large protein that contains multiple von Willebrand factor domains and forms a component of the basal lamina of epithelial cells. This protein may regulate epithelial cell-fibronectin interactions. Variation in this gene may be implicated in skin diseases. [provided by RefSeq, May 2017]

MANE transcript

NM_001102608.3

Inheritance

ClinVar variants

P:1U:372B:60

Top phenotype

COL6A6-related disorder

gnomAD constraint

pLI —, LoF o/e 0.84

Max pathogenic AF

—

Genomic locus

chr3:130,517,177-130,677,044

External References & Databases

Ensembl (ENSG00000206384)

Transcript & Mutation Effects

hg38 • Region Span ~159.9 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

congenital myopathyLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0019952

Submitter: Broad Center for Mendelian Genomics

myopathyLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0005336

Submitter: Ambry Genetics

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to COL6A6 variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 375

not providedTotal: 49

COL6A6-related disorderTotal: 4

Congenital myopathyTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001102608.3. 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			2 clinvar	9 clinvar	9 clinvar	20
missense			358 clinvar	32 clinvar	7 clinvar	397
nonsense			1 clinvar	1 clinvar		2
start loss						0
frameshift			3 clinvar	1 clinvar		4
splice donor/acceptor (+/-2bp)		1 clinvar	8 clinvar	1 clinvar		10
Total	0	1	372	44	16	433

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 19 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001102608.3	RefSeq	NP_001096078.1	36	MANE Select
ENST00000358511.11	Ensembl	ENSP00000351310.6	36	MANE Select
ENST00000506143.5	Ensembl	ENSP00000426006.1	10	Standard
ENST00000511332.1	Ensembl	ENSP00000422921.1	10	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

PI3K-Akt signaling pathway - Homo sapiens (human)
ECM-receptor interaction - Homo sapiens (human)
Focal adhesion - Homo sapiens (human)
Protein digestion and absorption - Homo sapiens (human)
Human papillomavirus infection - Homo sapiens (human)

Biological Process

cell adhesion

Molecular Function

extracellular matrix structural constituent conferring tensile strength

Cellular Component

extracellular region
collagen trimer
extracellular matrix
collagen-containing extracellular matrix

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000358511
Coding exons: 36
Length: 117822
Individuals with no LoFs: 123102
Homozygous LoFs: 8
Heterozygous LoFs: 1533
Defined: 124643
p: 0.00620

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.419	1201	1.24e+3	0.967	0.0000674	14827
Missense (PolyPhen)		477	520.56	0.91633		6216
Synonymous	1.63	419	464	0.904	0.0000261	4429
Loss of Function	1.44	78	92.9	0.839	0.00000521	1180

Population LoF Frequency

Population	CAF	p-value	Status
African	0.015	0.015	notable
Latino/Admixed American	0.0034	0.0032	notable
Ashkenazi Jewish	0.0042	0.0042	notable
East Asian	0.017	0.017	notable
Finnish	0.0022	0.0021	notable
European (Non-Finnish)	0.0042	0.0041	notable
South Asian	0.010	0.010	notable
Other	0.0057	0.0055	notable

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Collagen VI acts as a cell-binding protein. {ECO:0000250}.;

Intolerance Scores

LoFtool: 0.155
RVIS EVS: -0.67
RVIS percentile EVS: 15.42

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.114

Gene Damage Prediction

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