COL9A3

collagen type IX alpha 3 chain, the group of Collagen proteoglycans|Collagens

Basic information

Region (hg38): 20:62816244-62841159

Links

ENSG00000092758 ∙ NCBI:1299 ∙ OMIM:120270 ∙ HGNC:2219 ∙ Uniprot:Q14050 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• epiphyseal dysplasia, multiple, 3 (Moderate), mode of inheritance: AD
• epiphyseal dysplasia, multiple, 3 (Definitive), mode of inheritance: AD
• Stickler syndrome (Strong), mode of inheritance: AR
• epiphyseal dysplasia, multiple, 3 (Moderate), mode of inheritance: AD
• multiple epiphyseal dysplasia due to collagen 9 anomaly (Supportive), mode of inheritance: AD
• autosomal recessive Stickler syndrome (Supportive), mode of inheritance: AR
• Stickler syndrome (Limited), mode of inheritance: AR
• Stickler syndrome, type 6 (Definitive), mode of inheritance: AR
• epiphyseal dysplasia, multiple, 3 (Strong), mode of inheritance: AD
• Stickler syndrome, type 6 (Strong), mode of inheritance: AR
• Stickler syndrome, type 6 (Limited), mode of inheritance: AR
• Stickler syndrome (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Stickler syndrome, type VI	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	10090888; 10655510; 15551337; 20301302; 24273071; 30450842; 31090205; 33570243; 35241111

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the COL9A3 gene.

• not_provided (1447 variants)
• Inborn_genetic_diseases (132 variants)
• not_specified (75 variants)
• COL9A3-related_disorder (62 variants)
• Epiphyseal_dysplasia,_multiple,_3 (45 variants)
• Connective_tissue_disorder (25 variants)
• Intervertebral_disc_disorder (22 variants)
• Stickler_syndrome,_type_6 (17 variants)
• Stickler_syndrome (5 variants)
• Hearing_impairment (3 variants)
• Multiple_Epiphyseal_Dysplasia,_Dominant (2 variants)
• Lattice_retinal_degeneration (2 variants)
• Retinal_detachment (2 variants)
• Bilateral_sensorineural_hearing_impairment (1 variants)
• Autosomal_recessive_Stickler_syndrome (1 variants)
• Skeletal_dysplasia (1 variants)
• Epiphyseal_dysplasia,_multiple,_3,_with_myopathy (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the COL9A3 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000001853.4. 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		21	259	4	285
missense		2	564	49	5	620
nonsense	11	3	3			17
start loss			1			1
frameshift	17	7	6			30
splice donor/acceptor (+/-2bp)	4	5	21			30
Total	33	17	616	308	9

Highest pathogenic variant AF is 0.0000148936

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
COL9A3	protein_coding	protein_coding	ENST00000343916	32	24916

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
3.28e-12	0.999	125688	0	60	125748	0.000239

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.382	471	448	1.05	0.0000293	4119
Missense in Polyphen		186	192.84	0.96454		1756
Synonymous	-2.33	231	190	1.21	0.0000144	1544
Loss of Function	3.00	27	49.9	0.541	0.00000303	525

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000610	0.000598
Ashkenazi Jewish	0.000100	0.0000992
East Asian	0.000273	0.000272
Finnish	0.00	0.00
European (Non-Finnish)	0.000255	0.000246
Middle Eastern	0.000273	0.000272
South Asian	0.000362	0.000359
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Structural component of hyaline cartilage and vitreous of the eye.
• Disease: DISEASE: Multiple epiphyseal dysplasia 3 (EDM3) [MIM:600969]: 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:10090888, ECO:0000269|PubMed:25381065}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Intervertebral disc disease (IDD) [MIM:603932]: A common musculo-skeletal disorder caused by degeneration of intervertebral disks of the lumbar spine. It results in low-back pain and unilateral leg pain. {ECO:0000269|PubMed:11308397, ECO:0000269|PubMed:25381065}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry. Susceptibility to intervertebral disk disease is conferred by variant p.Arg103Trp (PubMed:11308397). {ECO:0000269|PubMed:11308397}.
• 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)

Intolerance Scores

• loftool: 0.0916
• rvis_EVS: 0.61
• rvis_percentile_EVS: 82.97

Haploinsufficiency Scores

• pHI: 0.498
• hipred: N
• hipred_score: 0.413
• ghis: 0.446

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.808

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Col9a3

Gene ontology

• Biological process: male gonad development;female gonad development;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