COL11A2

Chr 6ADAR

collagen type XI alpha 2 chain

Also known as: DFNA13, DFNB53, FBCG2, HKE5, OSMEDA, OSMEDB, PARP, STL3

NCBI Gene: 1302 ENSG00000204248 UniProt: P13942

This gene encodes one of the two alpha chains of type XI collagen, a minor fibrillar collagen. It is located on chromosome 6 very close to but separate from the gene for retinoid X receptor beta. Type XI collagen is a heterotrimer but the third alpha chain is a post-translationally modified alpha 1 type II chain. Proteolytic processing of this type XI chain produces PARP, a proline/arginine-rich protein that is an amino terminal domain. Mutations in this gene are associated with type III Stickler syndrome, otospondylomegaepiphyseal dysplasia (OSMED syndrome), Weissenbacher-Zweymuller syndrome, autosomal dominant non-syndromic sensorineural type 13 deafness (DFNA13), and autosomal recessive non-syndromic sensorineural type 53 deafness (DFNB53). Alternative splicing results in multiple transcript variants. A related pseudogene is located nearby on chromosome 6. [provided by RefSeq, Jul 2009]

Primary Disease Associations & Inheritance

Deafness, autosomal dominant 13MIM #601868

Deafness, autosomal recessive 53MIM #609706

Fibrochondrogenesis 2MIM #614524

ADAR

Otospondylomegaepiphyseal dysplasia, autosomal dominantMIM #184840

Otospondylomegaepiphyseal dysplasia, autosomal recessiveMIM #215150

775

ClinVar variants

Pathogenic / LP

0.70

pLI score

Active trials

Clinical Summary— COL11A2

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Gene-Disease Validity (ClinGen)

otospondylomegaepiphyseal dysplasia · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

4 total gene-disease associations curated

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Population Constraint (gnomAD)

Moderately constrained gene (pLI 0.70) — some intolerance to loss-of-function variants.

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ClinVar Variants

80 Pathogenic / Likely Pathogenic· 341 VUS of 775 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.

0.31LOEUF

pLI 0.702

Z-score 7.73

OE 0.22 (0.16–0.31)

Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.

2.37Z-score

OE missense 0.79 (0.74–0.83)

755 obs / 961.7 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.

LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.22 (0.16–0.31)

0≤0.351.4

Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.79 (0.74–0.83)

0≤0.61.4

Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.93

0≤1.21.6

LoF obs/exp: 25 / 114.1Missense obs/exp: 755 / 961.7Syn Z: 1.01

ClinVar Variant Classifications

775 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic45

Likely Pathogenic35

VUS341

Likely Benign341

Benign6

Conflicting7

Pathogenic

Likely Pathogenic

341

VUS

341

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	29	0	16	0	45
Likely Pathogenic	24	8	3	0	35
VUS	2	292	42	5	341
Likely Benign	0	32	192	117	341
Benign	0	0	4	2	6
Conflicting	—				7
Total	55	332	257	124	775

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

View in ClinVar →

Protein Context — Lollipop Plot

COL11A2 · protein map & ClinVar variants

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

Gene2Phenotype Curations

COL11A2-related Stickler syndrome

definitive

ADDominant NegativeAltered Gene Product Structure

Dev. DisordersSkeletalEar

G2P ↗

COL11A2-related otospondylomegaepiphyseal dysplasia

definitive

ARDominant NegativeAltered Gene Product Structure

Dev. DisordersSkeletalEar

G2P ↗

COL11A2-related deafness (monoallelic)

definitive

ADUndeterminedAltered Gene Product Structure

Dev. DisordersEar

G2P ↗

missense variantinframe deletioninframe insertion

COL11A2-related deafness (biallelic)

definitive

ARUndeterminedAltered Gene Product Structure

Dev. Disorders

G2P ↗

missense variantinframe deletioninframe insertion

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

COLLAGEN, TYPE XI, ALPHA-2; COL11A2

MIM #120290 · *

Deafness, autosomal dominant 13

MIM #601868