COL6A6

Chr 3

collagen type VI alpha 6 chain

NCBI Gene: 131873 ENSG00000206384 UniProt: A6NMZ7 OMIM: 616613

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]

OMIM Research

OMIM ResearchGenerating clinical summary…

MultiplemechanismLOEUF 1.01

Clinical Summary— COL6A6

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

1 unique Pathogenic / Likely Pathogenic· 359 VUS of 447 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.01LOEUF

pLI 0.000

Z-score 1.44

OE 0.84 (0.70–1.01)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.42Z-score

OE missense 0.97 (0.92–1.01)

1201 obs / 1242.5 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.84 (0.70–1.01)

0≤0.351.4

Missense OE?0.97 (0.92–1.01)

0≤0.61.4

Synonymous OE?0.90

0≤1.21.6

LoF obs/exp: 78 / 92.9Missense obs/exp: 1201 / 1242.5Syn Z: 1.63

This gene — mechanism propensity

0.6647th %ile

GOF

0.6735th %ile

LOF

0.3744th %ile

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

GOFprediction above median

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

447 submitted variants in ClinVar

ClinVar

Classification Summary

Likely Pathogenic1

VUS359

Likely Benign43

Benign21

Conflicting2

Likely Pathogenic

359

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	0	0	0
Likely Pathogenic	1	0	0	0	1
VUS	5	354	0	0	359
Likely Benign	2	30	2	9	43
Benign	0	10	1	10	21
Conflicting	—				2
Total	8	394	3	19	426

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

11 pathogenic / likely-pathogenic (of 17) ClinVar copy-number / structural variants overlap COL6A6 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →