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
• 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
• otospondylomegaepiphyseal dysplasia, autosomal recessive (Strong), 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 (2662 variants)
• not_specified (245 variants)
• Otospondylomegaepiphyseal_dysplasia,_autosomal_recessive (174 variants)
• Otospondylomegaepiphyseal_dysplasia,_autosomal_dominant (174 variants)
• Fibrochondrogenesis_2 (159 variants)
• Inborn_genetic_diseases (152 variants)
• COL11A2-related_disorder (134 variants)
• Autosomal_dominant_nonsyndromic_hearing_loss_13 (73 variants)
• Stickler_Syndrome,_Dominant (69 variants)
• Autosomal_recessive_nonsyndromic_hearing_loss_53 (69 variants)
• Connective_tissue_disorder (57 variants)
• Hearing_impairment (12 variants)
• Fibrochondrogenesis_1 (4 variants)
• Rare_genetic_deafness (3 variants)
• Nonsyndromic_genetic_hearing_loss (3 variants)
• Nonsyndromic_Hearing_Loss,_Dominant (3 variants)
• See_cases (3 variants)
• Short_long_bone (2 variants)
• Thickened_nuchal_skin_fold (2 variants)
• Cystic_hygroma (2 variants)
• Retinal_dystrophy (2 variants)
• Heart,_malformation_of (2 variants)
• Short_lingual_frenulum (1 variants)
• Intellectual_disability (1 variants)
• Infantile_hypophosphatasia (1 variants)
• Conductive_hearing_impairment (1 variants)
• Larsen-like_syndrome,_B3GAT3_type (1 variants)
• Ear_malformation (1 variants)
• Oculodentodigital_dysplasia,_autosomal_recessive (1 variants)
• Deafness (1 variants)
• Nonsyndromic_Deafness (1 variants)
• Short_chin (1 variants)
• Long_philtrum (1 variants)
• Autosomal_dominant_nonsyndromic_hearing_loss_33 (1 variants)
• Down_syndrome (1 variants)
• Reduced_bone_mineral_density (1 variants)
• Disproportionate_short-limb_short_stature (1 variants)
• Single_transverse_palmar_crease (1 variants)
• Abnormal_eyebrow_morphology (1 variants)
• Sensorineural_hearing_loss_disorder (1 variants)
• Macrocephaly (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. These statistics are base on transcript: NM_000080680.3. Only rare variants are included in the table.

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.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous		1	33	580	8	622
missense	7	25	749	297	19	1097
nonsense	32	19	2			53
start loss			1			1
frameshift	56	14	3			73
splice donor/acceptor (+/-2bp)	6	35	2			43
Total	101	94	790	877	27

Highest pathogenic variant AF is 0.0000888372

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