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…

DNmechanismLOEUF 0.54

Clinical Summary— COL14A1

⚡

Population Constraint (gnomAD)

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

📋

ClinVar Variants

198 VUS of 378 total submissions

💊

Clinical Trials

2 active or recruiting trials — potential therapeutic options may be available

Explore recent and relevant literature in Research Assistant →

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

This gene — mechanism propensity

0.6938th %ile

GOF

0.6249th %ile

LOF

0.3355th %ile

The highest-scoring mechanism for this gene is dominant-negative.

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

378 submitted variants in ClinVar

ClinVar

Classification Summary

VUS198

Likely Benign34

Benign98

Conflicting1

198

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	0	0	0	0	0
VUS	1	197	0	0	198
Likely Benign	0	19	2	13	34
Benign	0	7	75	16	98
Conflicting	—				1
Total	1	223	77	29	331

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

View in ClinVar →

52 pathogenic / likely-pathogenic (of 54) ClinVar copy-number / structural variants overlap COL14A1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →