COL9A1 |
- 0
Haplo
Score - 0
Triplo
Score
Gene Facts External Data Attribution
- HGNC Symbol
- COL9A1 (HGNC:2217) HGNC Entrez Ensembl OMIM UCSC Uniprot GeneReviews LOVD LSDB ClinVar
- HGNC Name
- collagen type IX alpha 1 chain
- Gene type
- protein-coding gene
- Locus type
- gene with protein product
- Previous symbols
- No previous names found
- Alias symbols
- No aliases found
- %HI
- 23.89(Read more about the DECIPHER Haploinsufficiency Index)
- pLI
- 0(Read more about gnomAD pLI score)
- LOEUF
- 0.89(Read more about gnomAD LOEUF score)
- Cytoband
- 6q13
- Genomic Coordinates
-
GRCh37/hg19: chr6:70924764-71012787 NCBI Ensembl UCSC GRCh38/hg38: chr6:70215061-70303084 NCBI Ensembl UCSC - MANE Select Transcript
- NM_001851.6 ENST00000357250.11 (Read more about MANE Select)
- Function
- Structural component of hyaline cartilage and vitreous of the eye. (Source: Uniprot)
Dosage Sensitivity Summary (Gene)
Dosage ID:
ISCA-17698
ClinGen Curation ID:
CCID:006912
Curation Status:
Complete
Issue Type:
Dosage Curation -
Gene
Haploinsufficiency:
No Evidence for Haploinsufficiency
(0)
Triplosensitivity:
No Evidence for Triplosensitivity
(0)
Last Evaluated:
11/06/2013
Haploinsufficiency (HI) Score Details
HI Score:
0
HI Evidence Strength:
No Evidence for Haploinsufficiency
(Disclaimer)
HI Disease:
- epiphyseal dysplasia, multiple, 6 Monarch
HI Evidence Comments:
A single mutation in COL9A1 has been associated with multiple epiphyseal dysplasia (MED), an autosomal dominantly inherited chondrodysplasia that is clinically heterogeneous.
Czarny-Ratajczak et al (2001) (PMID: 11565064) identified a heterozygous insertion of a T at the donor splice site of IVS8+3 in the COL9A1 gene in two patients from a family with multiple epiphyseal dysplasia. Since COL9A1 contains six additional exons coding for the longer NC4 domain compared with the two other collagen IX genes, exon 9 of COL9A1 corresponds to exon 3 in the others. The insertion of a T at the donor splice site of IVS8+3 did not result in skipping of exon 9. It led to a complex splice pattern involving mainly exons 8 and 10 was not in itself surprising, however, since mutations at donor splice sites have been shown to lead to variable splice forms.
From GeneReviews:
"The pathologic effect of mutations in COL9A1, COL9A2, and COL9A3 is not well understood and a number of mechanisms have been proposed for these mutations including the degradation of mRNA from the mutant allele [Holden et al 1999, Spayde et al 2000], an accumulation of abnormal type IX collagen α-chains in the rER of chondrocytes [Bonnemann et al 2000], and/or the degradation of abnormal α-chains [van Mourik et al 1998]. However, the remarkable clustering of all COL9A1, COL9A2, and COL9A3 MED-causing mutations, which result in the in-frame deletion of equivalent regions of the COL3 domain of type IX collagen, led to the hypothesis that the deletion of these specific amino acids was a significant contributing factor to the development of the disease [Briggs & Chapman 2002]. Recent studies have confirmed that a COL9A3 mutation indeed abolishes binding of type IX collagen to matrilin-3 and type II collagen, thus identifying for the first time a molecular consequence of these mutations [Fresquet et al 2007]."
No reported CNV losses in the DGV database.
Mutations in COL9A1 have also been reported in association with an autosomal recessive form of Stickler syndrome.
Triplosensitivity (TS) Score Details
TS Score:
0
TS Evidence Strength:
No Evidence for Triplosensitivity (Disclaimer)
TS Evidence Comments:
Note: DGV database reports CNV gains encompassing COL9A1 (nsv830683 and nssv1445434 (Wong et al., 2007); nsv524328 and nssv700234 (Shaikh et al 2009)).
Genomic View
Select assembly:
(NC_000006.11)
(NC_000006.12)