COL22A1

Chr 8

collagen type XXII alpha 1 chain

This gene encodes member of the collagen family which is thought to contribute to the stabilization of myotendinous junctions and strengthen skeletal muscle attachments during contractile activity. It belongs to the fibril-associated collagens with interrupted triple helix (FACIT) subset of the collagen superfamily, which associate with collagen fibers through their C-terminal collagenous domains and mediate protein-protein interactions through their N-terminal noncollagenous domains. The encoded protein is deposited in the basement membrane zone of the myotendinous junction which is present only at the tissue junctions of muscles, tendons, the heart, articular cartilage, and skin. A knockdown of the orthologous zebrafish gene induces a muscular dystrophy by disruption of the myotendinous junction. [provided by RefSeq, May 2017]

0
Active trials
19
Pubs (1 yr)
53
P/LP submissions
0%
P/LP missense
0.92
LOEUF
DN
Mechanism· predicted
Clinical SummaryCOL22A1
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
53 unique Pathogenic / Likely Pathogenic· 299 VUS of 430 total submissions

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

430 submitted variants in ClinVar

Classification Summary

Pathogenic52
Likely Pathogenic1
VUS299
Likely Benign20
Benign3
Conflicting2
52
Pathogenic
1
Likely Pathogenic
299
VUS
20
Likely Benign
3
Benign
2
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
52
0
52
Likely Pathogenic
0
0
1
0
1
VUS
1
288
9
1
299
Likely Benign
0
13
3
4
20
Benign
0
2
0
1
3
Conflicting
2
Total1303656377

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

View 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.

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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