COL11A1
collagen type XI alpha 1 chain, the group of Collagens
Basic information
Region (hg38): 1:102876467-103108872
Previous symbols: [ "COLL6", "DFNA37" ]
Links
Phenotypes
GenCC
Source:
- Stickler syndrome type 2 (Strong), mode of inheritance: AD
- fibrochondrogenesis 1 (Definitive), mode of inheritance: AR
- Stickler syndrome type 2 (Definitive), mode of inheritance: AD
- Stickler syndrome type 2 (Strong), mode of inheritance: AD
- Marshall syndrome (Strong), mode of inheritance: AD
- Stickler syndrome type 2 (Strong), mode of inheritance: AR
- Marshall syndrome (Strong), mode of inheritance: AR
- Marshall syndrome (Supportive), mode of inheritance: AD
- fibrochondrogenesis (Supportive), mode of inheritance: AD
- Stickler syndrome type 2 (Supportive), mode of inheritance: AD
- autosomal recessive Stickler syndrome (Supportive), mode of inheritance: AR
- autosomal dominant myopia-midfacial retrusion-sensorineural hearing loss-rhizomelic dysplasia syndrome (Supportive), mode of inheritance: AD
- hearing loss, autosomal dominant 37 (Moderate), mode of inheritance: AD
- Marshall syndrome (Definitive), mode of inheritance: AR
- hearing loss, autosomal dominant 37 (Strong), mode of inheritance: AD
- fibrochondrogenesis 1 (Strong), mode of inheritance: AR
- Marshall syndrome (Strong), mode of inheritance: AD
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Stickler syndrome, type II; Deafness, autosomal dominant, 37; Fibrochondrogenesis; Marshall syndrome | AD/AR | Audiologic/Otolaryngologic; Ophthalmologic | Though the conditions may be recognizable, early recognition and treatment of hearing impairment may improve outcomes, including speech and language development; In Stickler syndrome, avoidance of risk factors related to ocular manifestations (eg, contact sports) is indicated | Audiologic/Otolaryngologic; Craniofacial; Musculoskeletal; Ophthalmologic | 13520885; 749746; 6694183; 6507479; 6507478; 8733059; 8872475; 9129742; 10573014; 9529347; 9475607; 10486316; 15286167; 17236192; 21035103; 20301479; 30245514; 33169910; 33605226 |
ClinVar
This is a list of variants' phenotypes submitted to
- not provided (60 variants)
- Stickler syndrome type 2 (7 variants)
- Marshall syndrome (4 variants)
- COL11A1-related disorder (3 variants)
- Fibrochondrogenesis 1 (2 variants)
- Hearing loss, autosomal dominant 37;Marshall syndrome;Stickler syndrome type 2 (1 variants)
- Fibrochondrogenesis (1 variants)
- Inborn genetic diseases (1 variants)
- Stickler syndrome (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the COL11A1 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 | 265 | 24 | 297 | |||
| missense | 17 | 688 | 121 | 67 | 897 | |
| nonsense | 17 | 22 | ||||
| start loss | 0 | |||||
| frameshift | 13 | 23 | ||||
| inframe indel | 11 | 19 | ||||
| splice donor/acceptor (+/-2bp) | 28 | 48 | 82 | |||
| splice region | 3 | 1 | 113 | 123 | 10 | 250 |
| non coding | 61 | 507 | 222 | 790 | ||
| Total | 63 | 85 | 776 | 893 | 313 |
Highest pathogenic variant AF is 0.00000657
Variants in COL11A1
This is a list of pathogenic ClinVar variants found in the COL11A1 region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 1-102876484-T-G | Stickler syndrome type 2 • Fibrochondrogenesis 1 | Uncertain significance (Jan 12, 2018) | ||
| 1-102876531-C-G | Fibrochondrogenesis 1 • Stickler syndrome type 2 | Uncertain significance (Jan 13, 2018) | ||
| 1-102876697-C-T | Fibrochondrogenesis 1 • Stickler syndrome type 2 | Benign/Likely benign (Jun 21, 2021) | ||
| 1-102876718-A-G | Fibrochondrogenesis 1 • Stickler syndrome type 2 | Uncertain significance (Jan 12, 2018) | ||
| 1-102876780-A-G | Fibrochondrogenesis 1 • Stickler syndrome type 2 | Uncertain significance (Jan 13, 2018) | ||
| 1-102876789-C-T | Stickler syndrome type 2 • Fibrochondrogenesis 1 | Uncertain significance (Jan 13, 2018) | ||
| 1-102876792-A-T | Fibrochondrogenesis 1 • Stickler syndrome type 2 | Conflicting classifications of pathogenicity (Jan 12, 2018) | ||
| 1-102876816-C-T | Fibrochondrogenesis 1 • Stickler syndrome type 2 | Conflicting classifications of pathogenicity (Apr 01, 2023) | ||
| 1-102876836-T-C | Stickler syndrome type 2 • Fibrochondrogenesis 1 | Benign (May 10, 2021) | ||
| 1-102876914-G-A | Fibrochondrogenesis 1 • Stickler syndrome type 2 | Benign (May 11, 2021) | ||
| 1-102876928-T-A | Fibrochondrogenesis 1 • Stickler syndrome type 2 | Likely benign (Jan 13, 2018) | ||
| 1-102876937-C-T | Fibrochondrogenesis 1 • Stickler syndrome type 2 | Uncertain significance (Mar 02, 2018) | ||
| 1-102877066-C-G | Stickler syndrome type 2 • Fibrochondrogenesis 1 | Uncertain significance (Jan 13, 2018) | ||
| 1-102877118-A-G | Fibrochondrogenesis 1 • Stickler syndrome type 2 | Uncertain significance (Jan 13, 2018) | ||
| 1-102877143-C-T | Stickler syndrome type 2 • Fibrochondrogenesis 1 | Uncertain significance (Mar 02, 2018) | ||
| 1-102877210-G-A | Fibrochondrogenesis 1 • Stickler syndrome type 2 | Conflicting classifications of pathogenicity (Jan 13, 2018) | ||
| 1-102877304-T-C | Stickler syndrome type 2 • Fibrochondrogenesis 1 | Uncertain significance (Jan 13, 2018) | ||
| 1-102877315-A-G | Likely benign (May 11, 2021) | |||
| 1-102877332-G-A | Fibrochondrogenesis 1 • Stickler syndrome type 2 | Likely benign (Jan 13, 2018) | ||
| 1-102877387-C-T | Fibrochondrogenesis 1 • Stickler syndrome type 2 | Benign/Likely benign (May 11, 2021) | ||
| 1-102877390-C-CT | Fibrochondrogenesis 1 • Stickler Syndrome, Dominant • Marshall syndrome | Uncertain significance (Jun 14, 2016) | ||
| 1-102877440-T-C | Stickler syndrome type 2 • Fibrochondrogenesis 1 | Uncertain significance (Jan 13, 2018) | ||
| 1-102877484-T-G | Stickler syndrome type 2 • Fibrochondrogenesis 1 | Uncertain significance (Jan 13, 2018) | ||
| 1-102877511-C-T | Fibrochondrogenesis 1 • Stickler syndrome type 2 | Uncertain significance (Jan 12, 2018) | ||
| 1-102877533-A-G | Fibrochondrogenesis 1 • Stickler syndrome type 2 | Uncertain significance (Jan 13, 2018) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| COL11A1 | protein_coding | protein_coding | ENST00000370096 | 67 | 232030 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 1.00 | 1.85e-7 | 125708 | 0 | 40 | 125748 | 0.000159 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 1.02 | 903 | 994 | 0.909 | 0.0000503 | 11410 |
| Missense in Polyphen | 166 | 183.93 | 0.90251 | 2148 | ||
| Synonymous | -1.26 | 350 | 321 | 1.09 | 0.0000165 | 3744 |
| Loss of Function | 8.61 | 17 | 118 | 0.144 | 0.00000599 | 1433 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.000327 | 0.000327 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.000601 | 0.000598 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.000151 | 0.000149 |
| Middle Eastern | 0.000601 | 0.000598 |
| South Asian | 0.000101 | 0.0000980 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: May play an important role in fibrillogenesis by controlling lateral growth of collagen II fibrils.;
- Disease
- DISEASE: Stickler syndrome 2 (STL2) [MIM:604841]: An autosomal dominant form of Stickler syndrome, an inherited disorder that associates ocular signs with more or less complete forms of Pierre Robin sequence, bone disorders and sensorineural deafness. Ocular disorders may include juvenile cataract, myopia, strabismus, vitreoretinal or chorioretinal degeneration, retinal detachment, and chronic uveitis. Pierre Robin sequence includes an opening in the roof of the mouth (a cleft palate), a large tongue (macroglossia), and a small lower jaw (micrognathia). Bones are affected by slight platyspondylisis and large, often defective epiphyses. Juvenile joint laxity is followed by early signs of arthrosis. The degree of hearing loss varies among affected individuals and may become more severe over time. Syndrome expressivity is variable. {ECO:0000269|PubMed:10486316, ECO:0000269|PubMed:20513134, ECO:0000269|PubMed:8872475}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Marshall syndrome (MRSHS) [MIM:154780]: An autosomal dominant disorder characterized by ocular abnormalities, deafness, craniofacial anomalies, and anhidrotic ectodermal dysplasia. Clinical features include short stature; flat or retruded midface with short, depressed nose, flat nasal bridge and anteverted nares; cleft palate with or without the Pierre Robin sequence; appearance of large eyes with ocular hypertelorism; cataracts, either congenital or juvenile; esotropia; high myopia; sensorineural hearing loss; spondyloepiphyseal abnormalities; calcification of the falx cerebri; ectodermal abnormalities, including defects in sweating and dental structures. {ECO:0000269|PubMed:10486316}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Fibrochondrogenesis 1 (FBCG1) [MIM:228520]: A severe short-limbed skeletal dysplasia characterized by broad long-bone metaphyses, pear-shaped vertebral bodies, and characteristic morphology of the growth plate, in which the chondrocytes have a fibroblastic appearance and there are regions of fibrous cartilage extracellular matrix. Clinical features include a flat midface with a small nose and anteverted nares, significant shortening of all limb segments but relatively normal hands and feet, and a small bell-shaped thorax with a protuberant abdomen. {ECO:0000269|PubMed:21035103}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
- Pathway
- Protein digestion and absorption - Homo sapiens (human);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)
Recessive Scores
- pRec
- 0.347
Intolerance Scores
- loftool
- 0.00944
- rvis_EVS
- -0.36
- rvis_percentile_EVS
- 28.64
Haploinsufficiency Scores
- pHI
- 0.354
- hipred
- Y
- hipred_score
- 0.591
- ghis
- 0.522
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- N
- gene_indispensability_score
- 0.222
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | High | High | High |
| Primary Immunodeficiency | High | High | High |
| Cancer | High | High | High |
Mouse Genome Informatics
- Gene name
- Col11a1
- Phenotype
- craniofacial phenotype; growth/size/body region phenotype; respiratory system phenotype; immune system phenotype; skeleton phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); hearing/vestibular/ear phenotype; limbs/digits/tail phenotype; digestive/alimentary phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span);
Gene ontology
- Biological process
- cartilage condensation;ossification;chondrocyte development;proteoglycan metabolic process;visual perception;sensory perception of sound;extracellular matrix organization;collagen fibril organization;endodermal cell differentiation;tendon development;inner ear morphogenesis;embryonic skeletal system morphogenesis;detection of mechanical stimulus involved in sensory perception of sound;ventricular cardiac muscle tissue morphogenesis
- Cellular component
- extracellular region;collagen type XI trimer;extracellular space;endoplasmic reticulum lumen;extracellular matrix;collagen-containing extracellular matrix
- Molecular function
- extracellular matrix structural constituent;heparin binding;extracellular matrix structural constituent conferring tensile strength;protein binding, bridging;metal ion binding;extracellular matrix binding;heparan sulfate binding