COL14A1

Chr 8

collagen type XIV alpha 1 chain

Also known as: UND

NCBI Gene: 7373 ENSG00000187955 UniProt: Q05707 OMIM: 120324

The encoded protein is the alpha chain of type XIV collagen, which plays an adhesive role by integrating collagen bundles and regulating collagen fibril formation in connective tissues. Mutations cause Ehlers-Danlos syndrome, musculocontractural type 2, which follows an autosomal recessive inheritance pattern and presents with joint contractures, skin hyperextensibility, and musculoskeletal abnormalities. The gene shows moderate constraint against loss-of-function variants (LOEUF 0.535).

OMIM ResearchSummary from RefSeq, UniProt

This gene encodes the alpha chain of type XIV collagen, a member of the FACIT (fibril-associated collagens with interrupted triple helices) collagen family. Type XIV collagen interacts with the fibril surface and is involved in the regulation of fibrillogenesis. [provided by RefSeq, Jan 2013]

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.54

LOEUF

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.54LOEUF

pLI 0.000

Z-score 5.47

OE 0.41 (0.32–0.54)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

1.54Z-score

OE missense 0.86 (0.81–0.91)

843 obs / 978.8 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.41 (0.32–0.54)

0≤0.351.4

Missense OE?0.86 (0.81–0.91)

0≤0.61.4

Synonymous OE?1.00

0≤1.21.6

LoF obs/exp: 42 / 101.5Missense obs/exp: 843 / 978.8Syn Z: 0.01

Background carrier burden — how many people carry a rare variant somewhere in COL14A1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 28

2,179 rare PASS variants

Rare truncating (LoF)

1 in 750

277 rare PASS variants

Rare synonymous (reference)

1 in 52

880 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for COL14A1. 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 37	1 in 780
South Asian	~43k	1 in 22	1 in 740
Remaining (unassigned)	~30k	1 in 23	1 in 1,300
European (Finnish)	~27k	1 in 58	1 in 2,700
Admixed American	~22k	1 in 26	1 in 780
African / African American	~21k	1 in 26	1 in 670
East Asian	~20k	1 in 38	1 in 620
Ashkenazi Jewish	~13k	1 in 88	1 in 1,900
Middle Eastern	~2,884	1 in 27	≈ 1 in 1,400

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 43 of 47 coding exons well covered in gnomAD exomes; exons 3, 33, 35, 38 marginal. Genomes: all 47.? see exons ↓