COL22A1

Chr 8

collagen type XXII alpha 1 chain

The protein is a fibril-associated collagen that stabilizes myotendinous junctions and strengthens skeletal muscle attachments during contractile activity, while also functioning as a cell adhesion ligand for skin epithelial cells and fibroblasts. Mutations cause autosomal recessive myopathy with joint contractures. This gene is not highly constrained against loss-of-function variants, and the associated myopathy primarily affects the musculoskeletal system with characteristic joint involvement.

OMIMResearchSummary from RefSeq, UniProt
DNmechanismLOEUF 0.92
Clinical SummaryCOL22A1
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.92LOEUF
pLI 0.000
Z-score 2.23
OE 0.77 (0.640.92)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
-0.37Z-score
OE missense 1.03 (0.981.09)
996 obs / 963.9 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.77 (0.640.92)
00.351.4
Missense OE1.03 (0.981.09)
00.61.4
Synonymous OE1.07
01.21.6
LoF obs/exp: 83 / 108.1Missense obs/exp: 996 / 963.9Syn Z: -1.08
DN
0.6938th %ile
GOF
0.5465th %ile
LOF
0.4627th %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

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

COL22A1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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