COL9A1

collagen type IX alpha 1 chain, the group of Collagen proteoglycans|Collagens

Basic information

Region (hg38): 6:70216040-70303084

Links

ENSG00000112280 ∙ NCBI:1297 ∙ OMIM:120210 ∙ HGNC:2217 ∙ Uniprot:P20849 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Stickler syndrome, type 4 (Strong), mode of inheritance: AR
• Stickler syndrome, type 4 (Definitive), mode of inheritance: AR
• epiphyseal dysplasia, multiple, 6 (Definitive), mode of inheritance: AD
• Stickler syndrome, type 4 (Strong), mode of inheritance: AR
• epiphyseal dysplasia, multiple, 6 (Limited), mode of inheritance: AR
• Stickler syndrome, type 4 (Moderate), mode of inheritance: AR
• multiple epiphyseal dysplasia due to collagen 9 anomaly (Supportive), mode of inheritance: AD
• autosomal recessive Stickler syndrome (Supportive), mode of inheritance: AR
• Stickler syndrome, type 4 (Strong), mode of inheritance: AR
• epiphyseal dysplasia, multiple, 6 (Limited), mode of inheritance: Unknown
• Stickler syndrome (Limited), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Stickler syndrome, type IV	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	11565064; 16909383; 20301479

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the COL9A1 gene.

• not provided (38 variants)
• Stickler syndrome, type 4 (2 variants)
• Connective tissue disorder (1 variants)
• Stickler syndrome, type 4;Epiphyseal dysplasia, multiple, 6 (1 variants)
• Sensorineural hearing loss disorder (1 variants)
• See cases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the COL9A1 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			4	184	4	192
missense			401	10	3	414
nonsense	18	5	4			27
start loss						0
frameshift	22	8				30
inframe indel			7			7
splice donor/acceptor (+/-2bp)		19	4			23
splice region			36	54	3	93
non coding		1	9	250	146	406
Total	40	33	429	444	153

Highest pathogenic variant AF is 0.0000394

Variants in COL9A1

This is a list of pathogenic ClinVar variants found in the COL9A1 region.

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

Position	Type	Phenotype	Significance	ClinVar
6-70216631-A-G			Benign (Jun 19, 2018)
6-70216649-G-GT		Multiple Epiphyseal Dysplasia, Dominant • Stickler Syndrome, Recessive	Uncertain significance (Jun 14, 2016)
6-70216654-CT-C			Likely benign (Aug 10, 2019)
6-70216654-C-CT		Multiple Epiphyseal Dysplasia, Dominant • Stickler Syndrome, Recessive	Benign (Aug 18, 2019)
6-70216654-C-CTT			Benign (Aug 06, 2019)
6-70216668-A-G			Benign (Jun 14, 2018)
6-70216723-A-G		Stickler Syndrome, Recessive • Multiple Epiphyseal Dysplasia, Dominant	Uncertain significance (Jun 14, 2016)
6-70216902-G-A			Uncertain significance (Jul 12, 2022)
6-70216909-C-T		COL9A1-related disorder	Likely benign (Nov 13, 2023)
6-70216912-T-C			Likely benign (Jun 17, 2023)
6-70216924-T-C			Likely benign (Jul 07, 2023)
6-70216926-G-A			Uncertain significance (Jul 24, 2020)
6-70216939-C-T			Uncertain significance (Feb 11, 2022)
6-70216940-A-G			Uncertain significance (Jul 10, 2023)
6-70216942-G-A			Likely benign (Oct 17, 2023)
6-70216952-G-C			Uncertain significance (Jun 05, 2022)
6-70216961-C-T			Uncertain significance (Jul 30, 2022)
6-70216968-C-T		Inborn genetic diseases	Uncertain significance (Dec 17, 2023)
6-70216969-G-A			Likely benign (Jan 18, 2024)
6-70216979-G-A			Uncertain significance (Apr 20, 2017)
6-70216979-G-C			Uncertain significance (Jul 06, 2022)
6-70216987-C-T			Likely benign (Jan 25, 2024)
6-70216988-G-A		Inborn genetic diseases	Uncertain significance (May 13, 2024)
6-70216992-G-A			Uncertain significance (Oct 09, 2023)
6-70217008-A-C			Uncertain significance (Jun 13, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
COL9A1	protein_coding	protein_coding	ENST00000357250	38	88023

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
3.07e-19	0.988	125646	0	102	125748	0.000406

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.186	514	526	0.977	0.0000283	5773
Missense in Polyphen		189	231.24	0.81734		2307
Synonymous	-2.58	221	177	1.25	0.00000962	1946
Loss of Function	2.78	40	64.0	0.625	0.00000340	749

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000825	0.000811
Ashkenazi Jewish	0.000199	0.000198
East Asian	0.000435	0.000435
Finnish	0.0000465	0.0000462
European (Non-Finnish)	0.000542	0.000536
Middle Eastern	0.000435	0.000435
South Asian	0.000327	0.000327
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Structural component of hyaline cartilage and vitreous of the eye.
• Disease: DISEASE: Multiple epiphyseal dysplasia 6 (EDM6) [MIM:614135]: A generalized skeletal dysplasia associated with significant morbidity. Joint pain, joint deformity, waddling gait, and short stature are the main clinical signs and symptoms. Radiological examination of the skeleton shows delayed, irregular mineralization of the epiphyseal ossification centers and of the centers of the carpal and tarsal bones. Multiple epiphyseal dysplasia is broadly categorized into the more severe Fairbank and the milder Ribbing types. The Fairbank type is characterized by shortness of stature, short and stubby fingers, small epiphyses in several joints, including the knee, ankle, hand, and hip. The Ribbing type is confined predominantly to the hip joints and is characterized by hands that are normal and stature that is normal or near-normal. {ECO:0000269|PubMed:11565064}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Stickler syndrome 4 (STL4) [MIM:614134]: An autosomal recessive 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:16909383}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: PI3K-Akt signaling pathway - Homo sapiens (human);ECM-receptor interaction - Homo sapiens (human);Focal adhesion - Homo sapiens (human);Protein digestion and absorption - Homo sapiens (human);Human papillomavirus infection - Homo sapiens (human);Gastric Cancer Network 2;PI3K-Akt Signaling Pathway;Developmental Biology;Assembly of collagen fibrils and other multimeric structures;Signal Transduction;Collagen chain trimerization;Collagen biosynthesis and modifying enzymes;Integrin cell surface interactions;Collagen degradation;Signaling by PDGF;Collagen formation;Extracellular matrix organization;Integrin;Degradation of the extracellular matrix;NCAM signaling for neurite out-growth;NCAM1 interactions;Axon guidance;ECM proteoglycans;Signaling by Receptor Tyrosine Kinases (Consensus)

Recessive Scores

• pRec: 0.175

Intolerance Scores

• loftool: 0.0671
• rvis_EVS: -0.86
• rvis_percentile_EVS: 10.96

Haploinsufficiency Scores

• pHI: 0.498
• hipred: Y
• hipred_score: 0.591
• ghis: 0.511

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.598

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Col9a1
• Phenotype: skeleton phenotype; immune system phenotype; hearing/vestibular/ear phenotype; limbs/digits/tail phenotype; cellular phenotype; homeostasis/metabolism phenotype

Gene ontology

• Biological process: animal organ morphogenesis;extracellular matrix organization
• Cellular component: extracellular region;collagen type IX trimer;extracellular space;endoplasmic reticulum lumen;extracellular matrix
• Molecular function: extracellular matrix structural constituent;extracellular matrix structural constituent conferring tensile strength;metal ion binding