COL11A2

collagen type XI alpha 2 chain, the group of Collagens

Basic information

Region (hg38): 6:33162681-33192499

Previous symbols: [ "DFNA13", "DFNB53" ]

Links

ENSG00000204248 ∙ NCBI:1302 ∙ OMIM:120290 ∙ HGNC:2187 ∙ Uniprot:P13942 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• autosomal dominant nonsyndromic hearing loss 13 (Moderate), mode of inheritance: AD
• autosomal recessive nonsyndromic hearing loss 53 (Moderate), mode of inheritance: AR
• otospondylomegaepiphyseal dysplasia, autosomal dominant (Strong), mode of inheritance: AD
• otospondylomegaepiphyseal dysplasia, autosomal recessive (Strong), mode of inheritance: AR
• otospondylomegaepiphyseal dysplasia, autosomal recessive (Definitive), mode of inheritance: AR
• autosomal dominant nonsyndromic hearing loss 13 (Definitive), mode of inheritance: AD
• autosomal recessive nonsyndromic hearing loss 53 (Definitive), mode of inheritance: AR
• otospondylomegaepiphyseal dysplasia, autosomal dominant (Definitive), mode of inheritance: AD
• otospondylomegaepiphyseal dysplasia, autosomal dominant (Strong), mode of inheritance: AD
• autosomal recessive nonsyndromic hearing loss 53 (Moderate), mode of inheritance: AR
• otospondylomegaepiphyseal dysplasia, autosomal dominant (Moderate), mode of inheritance: AD
• otospondylomegaepiphyseal dysplasia, autosomal recessive (Moderate), mode of inheritance: AR
• otospondylomegaepiphyseal dysplasia (Supportive), mode of inheritance: AR
• fibrochondrogenesis (Supportive), mode of inheritance: AD
• autosomal dominant nonsyndromic hearing loss (Supportive), mode of inheritance: AD
• hearing loss, autosomal recessive (Supportive), mode of inheritance: AR
• otospondylomegaepiphyseal dysplasia, autosomal dominant (Supportive), mode of inheritance: AD
• otospondylomegaepiphyseal dysplasia, autosomal recessive (Strong), mode of inheritance: AR
• autosomal dominant nonsyndromic hearing loss 13 (Limited), mode of inheritance: AD
• autosomal recessive nonsyndromic hearing loss 53 (Strong), mode of inheritance: AR
• autosomal dominant nonsyndromic hearing loss 13 (Strong), mode of inheritance: AD
• otospondylomegaepiphyseal dysplasia, autosomal dominant (Strong), mode of inheritance: AD
• nonsyndromic genetic hearing loss (Definitive), mode of inheritance: AD
• otospondylomegaepiphyseal dysplasia (Definitive), mode of inheritance: AD
• otospondylomegaepiphyseal dysplasia (Definitive), mode of inheritance: AR
• nonsyndromic genetic hearing loss (Moderate), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Deafness, autosomal dominant 13; Otospondylomegaepiphyseal dysplasia, autosomal dominant (Stickler syndrome, type III/Weissenbacher-Zweymuller syndrome); Fibrochondrogenesis 2; Otospondylomegaepiphyseal dysplasia, autosomal recessive; Deafness, autosomal recessive 53	AD/AR	Audiologic/Otolaryngologic; Ophthalmologic	Though the condition may be recognizable, early recognition and treatment of hearing impairment may improve outcomes, including speech and language development; Avoidance of risk factors related to ocular manifestations (eg, contact sports) is indicated	Audiologic/Otolaryngologic; Craniofacial; Musculoskeletal; Ophthalmologic	14234962; 7833911; 7859284; 9805126; 9506662; 10581026; 10677296; 15372529; 16033917; 22246659; 25633957

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the COL11A2 gene.

• not provided (70 variants)
• Otospondylomegaepiphyseal dysplasia, autosomal recessive (8 variants)
• Otospondylomegaepiphyseal dysplasia, autosomal dominant (2 variants)
• Otospondylomegaepiphyseal dysplasia, autosomal recessive;Autosomal dominant nonsyndromic hearing loss 13;Autosomal recessive nonsyndromic hearing loss 53;Fibrochondrogenesis 2;Otospondylomegaepiphyseal dysplasia, autosomal dominant (1 variants)
• Autosomal dominant nonsyndromic hearing loss 13 (1 variants)
• Fibrochondrogenesis 2 (1 variants)
• Autosomal recessive nonsyndromic hearing loss 53 (1 variants)
• Nonsyndromic Deafness (1 variants)
• See cases (1 variants)
• COL11A2-related disorder (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the COL11A2 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			16	484	11	511
missense	4	9	557	136	22	728
nonsense	25	15				40
start loss			1			1
frameshift	44	9	3			56
inframe indel			12			12
splice donor/acceptor (+/-2bp)	2	26	1			29
splice region	1	2	79	164	3	249
non coding			27	568	92	687
Total	75	59	617	1188	125

Highest pathogenic variant AF is 0.0000132

Variants in COL11A2

This is a list of pathogenic ClinVar variants found in the COL11A2 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
6-33162753-C-T		Otospondylomegaepiphyseal dysplasia, autosomal dominant • Fibrochondrogenesis 2 • Otospondylomegaepiphyseal dysplasia, autosomal recessive • Stickler Syndrome, Dominant	Likely benign (Jan 13, 2018)
6-33162856-G-C		Otospondylomegaepiphyseal dysplasia, autosomal dominant • Otospondylomegaepiphyseal dysplasia, autosomal recessive • Fibrochondrogenesis 2 • Stickler Syndrome, Dominant	Conflicting classifications of pathogenicity (Jan 13, 2018)
6-33162859-G-A		Otospondylomegaepiphyseal dysplasia, autosomal recessive • Otospondylomegaepiphyseal dysplasia, autosomal dominant • Fibrochondrogenesis 2	Uncertain significance (Apr 27, 2017)
6-33162890-T-G		Otospondylomegaepiphyseal dysplasia, autosomal recessive • Otospondylomegaepiphyseal dysplasia, autosomal dominant • Fibrochondrogenesis 2	Uncertain significance (Jan 12, 2018)
6-33162972-C-A		Fibrochondrogenesis 2 • Otospondylomegaepiphyseal dysplasia, autosomal recessive • Otospondylomegaepiphyseal dysplasia, autosomal dominant • Stickler Syndrome, Dominant	Conflicting classifications of pathogenicity (Jan 13, 2018)
6-33163134-G-C		Stickler Syndrome, Dominant • Otospondylomegaepiphyseal dysplasia, autosomal recessive • Otospondylomegaepiphyseal dysplasia, autosomal dominant • Fibrochondrogenesis 2	Uncertain significance (Jan 12, 2018)
6-33163142-G-A		Stickler Syndrome, Dominant • Otospondylomegaepiphyseal dysplasia, autosomal recessive • Otospondylomegaepiphyseal dysplasia, autosomal dominant • Fibrochondrogenesis 2	Uncertain significance (Jan 12, 2018)
6-33163193-C-G		Otospondylomegaepiphyseal dysplasia, autosomal recessive • Otospondylomegaepiphyseal dysplasia, autosomal dominant • Fibrochondrogenesis 2	Uncertain significance (Jan 12, 2018)
6-33163239-G-T		Stickler Syndrome, Dominant • Otospondylomegaepiphyseal dysplasia, autosomal dominant • Otospondylomegaepiphyseal dysplasia, autosomal recessive • Fibrochondrogenesis 2	Uncertain significance (Jan 13, 2018)
6-33163249-C-A		Otospondylomegaepiphyseal dysplasia, autosomal dominant • Otospondylomegaepiphyseal dysplasia, autosomal recessive • Fibrochondrogenesis 2	Uncertain significance (Jan 13, 2018)
6-33163285-T-C		Otospondylomegaepiphyseal dysplasia, autosomal dominant • Fibrochondrogenesis 2 • Otospondylomegaepiphyseal dysplasia, autosomal recessive	Uncertain significance (Jan 15, 2018)
6-33163430-G-T		Fibrochondrogenesis 2 • Otospondylomegaepiphyseal dysplasia, autosomal recessive • Otospondylomegaepiphyseal dysplasia, autosomal dominant • Stickler Syndrome, Dominant	Uncertain significance (Jan 12, 2018)
6-33163550-G-C		Fibrochondrogenesis 2 • Otospondylomegaepiphyseal dysplasia, autosomal dominant • Stickler Syndrome, Dominant • Otospondylomegaepiphyseal dysplasia, autosomal recessive	Likely benign (Jan 12, 2018)
6-33163559-C-T		Fibrochondrogenesis 2 • Otospondylomegaepiphyseal dysplasia, autosomal recessive • Stickler Syndrome, Dominant • Otospondylomegaepiphyseal dysplasia, autosomal dominant	Likely benign (Jan 13, 2018)
6-33163667-CAG-C			Likely benign (Mar 01, 2022)
6-33163674-G-A		not specified • Fibrochondrogenesis 2 • Stickler Syndrome, Dominant • Otospondylomegaepiphyseal dysplasia, autosomal dominant • Otospondylomegaepiphyseal dysplasia, autosomal recessive • Connective tissue disorder	Benign/Likely benign (Feb 14, 2024)
6-33163679-T-C			Uncertain significance (Jul 23, 2022)
6-33163685-A-G			Likely benign (Jan 22, 2024)
6-33163686-T-A			Benign (Jan 08, 2024)
6-33163694-A-G		not specified	Uncertain significance (Nov 13, 2023)
6-33163695-C-G			Uncertain significance (Jul 19, 2022)
6-33163698-G-A			Benign (Aug 17, 2023)
6-33163699-C-G			Likely benign (Jun 09, 2023)
6-33163704-G-A			Likely benign (Oct 20, 2023)
6-33163710-C-A			Uncertain significance (Jun 04, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
COL11A2	protein_coding	protein_coding	ENST00000374708	64	29819

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.702	0.298	125705	0	43	125748	0.000171

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.37	755	962	0.785	0.0000585	10101
Missense in Polyphen		146	262.82	0.55552		2603
Synonymous	1.01	333	357	0.932	0.0000213	3689
Loss of Function	7.73	25	114	0.219	0.00000728	1238

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000276	0.000268
Ashkenazi Jewish	0.00	0.00
East Asian	0.000275	0.000272
Finnish	0.0000465	0.0000462
European (Non-Finnish)	0.000245	0.000237
Middle Eastern	0.000275	0.000272
South Asian	0.0000986	0.0000980
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: May play an important role in fibrillogenesis by controlling lateral growth of collagen II fibrils.
• Disease: DISEASE: Otospondylomegaepiphyseal dysplasia, autosomal dominant (OSMEDA) [MIM:184840]: An autosomal dominant form of otospondylomegaepiphyseal dysplasia, a disorder characterized by sensorineural deafness, enlarged epiphyses, mild platyspondyly, and disproportionate shortness of the limbs. Total body length is normal. Typical facial features are mid-face hypoplasia, short upturned nose and depressed nasal bridge. Most patients have Pierre Robin sequence including an opening in the roof of the mouth (cleft palate) and a small lower jaw (micrognathia). Ocular symptoms are absent. Some patients have early-onset osteoarthritis. {ECO:0000269|PubMed:7859284, ECO:0000269|PubMed:9506662, ECO:0000269|PubMed:9805126}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Otospondylomegaepiphyseal dysplasia, autosomal recessive (OSMEDB) [MIM:215150]: An autosomal recessive form of otospondylomegaepiphyseal dysplasia, a disorder characterized by sensorineural deafness, enlarged epiphyses, mild platyspondyly, and disproportionate shortness of the limbs. Total body length is normal. Typical facial features are mid-face hypoplasia, short upturned nose and depressed nasal bridge. Most patients have Pierre Robin sequence including an opening in the roof of the mouth (cleft palate) and a small lower jaw (micrognathia). Ocular symptoms are absent. Some patients have early-onset osteoarthritis. {ECO:0000269|PubMed:10677296, ECO:0000269|PubMed:7859284}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Deafness, autosomal dominant, 13 (DFNA13) [MIM:601868]: A form of non-syndromic sensorineural hearing loss. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information. {ECO:0000269|PubMed:10581026}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Deafness, autosomal recessive, 53 (DFNB53) [MIM:609706]: A form of non-syndromic sensorineural deafness characterized by prelingual, profound, non-progressive hearing loss. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information. {ECO:0000269|PubMed:16033917, ECO:0000269|PubMed:25633957}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Fibrochondrogenesis 2 (FBCG2) [MIM:614524]: A severe skeletal dysplasia characterized by a flat midface, short long bones, short ribs with broad metaphyses, and vertebral bodies that show distinctive hypoplastic posterior ends and rounded anterior ends, giving the vertebral bodies a pinched appearance on lateral radiographic views. The chest is small, causing perinatal respiratory problems which usually, but not always, result in lethality. Affected individuals who survive the neonatal period have high myopia, mild to moderate hearing loss, and severe skeletal dysplasia. {ECO:0000269|PubMed:22246659}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Protein digestion and absorption - Homo sapiens (human);Neural Crest Differentiation;Focal Adhesion;Focal Adhesion-PI3K-Akt-mTOR-signaling pathway;Collagen chain trimerization;Collagen biosynthesis and modifying enzymes;Collagen formation;Extracellular matrix organization;Integrin;Beta1 integrin cell surface interactions;Syndecan-1-mediated signaling events;Integrins in angiogenesis (Consensus)

Intolerance Scores

• loftool: 0.0206
• rvis_EVS: -1.05
• rvis_percentile_EVS: 7.62

Haploinsufficiency Scores

• pHI: 0.137
• hipred: Y
• hipred_score: 0.627
• ghis: 0.572

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.427

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	High	Medium	Medium
Primary Immunodeficiency	High	High	High
Cancer	High	High	High

Mouse Genome Informatics

• Gene name: Col11a2
• Phenotype: craniofacial phenotype; growth/size/body region phenotype; hearing/vestibular/ear phenotype; skeleton phenotype

Zebrafish Information Network

• Gene name: col11a2
• Affected structure: chondrocyte
• Phenotype tag: abnormal
• Phenotype quality: disorganized

Gene ontology

• Biological process: skeletal system development;sensory perception of sound;extracellular matrix organization;collagen fibril organization;cartilage development;roof of mouth development;soft palate development
• Cellular component: extracellular region;collagen trimer;collagen type XI trimer;extracellular space;endoplasmic reticulum lumen;extracellular matrix;collagen-containing extracellular matrix
• Molecular function: extracellular matrix structural constituent;protein binding;extracellular matrix structural constituent conferring tensile strength;protein binding, bridging;metal ion binding