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…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.01

LOEUF

Multiple*

Mechanism· predicted

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

Background carrier burden — how many people carry a rare variant somewhere in COL6A6?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 15

3,036 rare PASS variants

Rare truncating (LoF)

1 in 78

500 rare PASS variants

Rare synonymous (reference)

1 in 35

1,049 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for COL6A6. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 24	1 in 170
South Asian	~43k	1 in 15	1 in 74
Remaining (unassigned)	~30k	1 in 13	1 in 72
European (Finnish)	~27k	1 in 58	1 in 310
Admixed American	~22k	1 in 17	1 in 120
African / African American	~21k	1 in 14	1 in 72
East Asian	~20k	1 in 20	1 in 91
Ashkenazi Jewish	~13k	1 in 67	1 in 320
Middle Eastern	~2,884	1 in 14	1 in 93

Each group is summed over the variants that are rare in that group. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 32 of 36 coding exons well covered in gnomAD exomes; exons 10, 19, 23, 29 marginal. Genomes: all 36.? see exons ↓