COL28A1

Chr 7

collagen type XXVIII alpha 1 chain

Also known as: COL28

NCBI Gene: 340267 ENSG00000215018 UniProt: Q2UY09 OMIM: 609996

The protein may function as a cell-binding protein and belongs to a class of collagens containing von Willebrand factor type A domains. Based on the provided information, no specific diseases have been established for COL28A1 mutations, and the inheritance pattern is not determined. The predicted mechanism of pathogenicity is dominant negative.

OMIM ResearchSummary from RefSeq, UniProt, Mechanism

COL28A1 belongs to a class of collagens containing von Willebrand factor (VWF; MIM 613160) type A (VWFA) domains (Veit et al., 2006 [PubMed 16330543]).[supplied by OMIM, Nov 2010]

OMIM ResearchGenerating clinical summary…

DNmechanismLOEUF 1.04

Clinical Summary— COL28A1

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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

179 VUS of 221 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.04LOEUF

pLI 0.000

Z-score 1.29

OE 0.83 (0.67–1.04)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.88Z-score

OE missense 1.10 (1.03–1.17)

678 obs / 616.6 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.83 (0.67–1.04)

0≤0.351.4

Missense OE?1.10 (1.03–1.17)

0≤0.61.4

Synonymous OE?1.16

0≤1.21.6

LoF obs/exp: 55 / 66.3Missense obs/exp: 678 / 616.6Syn Z: -1.79

This gene — mechanism propensity

0.7034th %ile

GOF

0.6150th %ile

LOF

0.4135th %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

221 submitted variants in ClinVar

ClinVar

Classification Summary

VUS179

Likely Benign11

Benign3

179

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	0	0
Likely Pathogenic	0	0	0	0
VUS	179	0	0	179
Likely Benign	8	0	3	11
Benign	1	1	1	3
Total	188	1	4	193

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

View in ClinVar →

28 pathogenic / likely-pathogenic (of 45) ClinVar copy-number / structural variants overlap COL28A1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →