• 3
    Haplo
    Score
  • 0
    Triplo
    Score

Gene Facts External Data Attribution

HGNC Symbol
COL4A5 (HGNC:2207) HGNC Entrez Ensembl OMIM UCSC Uniprot GeneReviews LOVD LSDB ClinVar
HGNC Name
collagen type IV alpha 5 chain
Gene type
protein-coding gene
Locus type
gene with protein product
Previous symbols
ASLN, ATS
Alias symbols
No aliases found
%HI
8.97(Read more about the DECIPHER Haploinsufficiency Index)
pLI
1(Read more about gnomAD pLI score)
LOEUF
0.19(Read more about gnomAD LOEUF score)
Cytoband
Xq22.3
Genomic Coordinates
GRCh37/hg19: chrX:107683068-107940775 NCBI Ensembl UCSC
GRCh38/hg38: chrX:108439838-108697545 NCBI Ensembl UCSC
MANE Select Transcript
NM_033380.3 ENST00000328300.11 (Read more about MANE Select)
Function
Type IV collagen is the major structural component of glomerular basement membranes (GBM), forming a 'chicken-wire' meshwork together with laminins, proteoglycans and entactin/nidogen. (Source: Uniprot)

Dosage Sensitivity Summary (Gene)

Dosage ID:
ISCA-11460
Curation Status:
Complete
Issue Type:
Dosage Curation - Gene
Haploinsufficiency:
Sufficient Evidence for Haploinsufficiency (3)
Triplosensitivity:
No Evidence for Triplosensitivity (0)
Last Evaluated:
09/08/2020

Haploinsufficiency (HI) Score Details

HI Score:
3
HI Evidence Strength:
Sufficient Evidence for Haploinsufficiency (Disclaimer)
HI Disease:
HI Evidence:
  • PUBMED: 16941480
    King et al (2006) sequenced the COL4A5 gene in 25 unrelated patients with clear Alport syndrome and identified 21 mutations including 4 exon level deletions (del exons 2-37; del exons 31-36; del exons 35-36; del exons 46-51), 3 frameshifts (c.2510delG, c.2_3delTG, c.2846delC), 2 canonical splice site mutations (c.1780-1G>A, c.2244+2T>C). Therefore, a total of 9 LOF variants identified in 9 patients with Alport syndrome.
  • PUBMED: 10752524
    Jais et al (2000) 401 male patients with Alport syndrome in 195 families with COL4A5 mutation were reported. Among those, 37 frameshift mutations, 14 nonsense mutations were identified.
  • PUBMED: 30577881
    Zhang et al (2018) All 87 patients with Alport syndrome were tested for COL4A5/6 genotype, where 60 different COL4A5 pathogenic variants were identified in 63 patients, including 10 frameshifts, 5 nonsense (p.Arg373*, p.Lys1284*; p.Arg1680*, p.Ser36*, p.G1360*).
HI Evidence Comments:
About 85% of Alport syndrome is caused by mutations in the collagen gene, COL4A5. The loss-of-function and triplosensitivity ratings for genes on the X chromosome are made in the context of a male genome to account for the effects of hemizygous duplications or nullizygous deletions. In contrast, disruption of some genes on the X chromosome causes male lethality and the ratings of dosage sensitivity instead take into account the phenotype in female individuals. Factors that may affect the severity of phenotypes associated with X-linked disorders include the presence of variable copies of the X chromosome (i.e. 47,XXY or 45,X) and skewed X-inactivation in females.
NOTE:

The loss-of-function and triplosensitivity ratings for genes on the X chromosome are made in the context of a male genome to account for the effects of hemizygous duplications or nullizygous deletions. In contrast, disruption of some genes on the X chromosome causes male lethality and the ratings of dosage sensitivity instead take into account the phenotype in female individuals. Factors that may affect the severity of phenotypes associated with X-linked disorders include the presence of variable copies of the X chromosome (i.e. 47,XXY or 45,X) and skewed X-inactivation in females.

Triplosensitivity (TS) Score Details

TS Score:
0
TS Evidence Strength:
No Evidence for Triplosensitivity (Disclaimer)
NOTE:

The loss-of-function and triplosensitivity ratings for genes on the X chromosome are made in the context of a male genome to account for the effects of hemizygous duplications or nullizygous deletions. In contrast, disruption of some genes on the X chromosome causes male lethality and the ratings of dosage sensitivity instead take into account the phenotype in female individuals. Factors that may affect the severity of phenotypes associated with X-linked disorders include the presence of variable copies of the X chromosome (i.e. 47,XXY or 45,X) and skewed X-inactivation in females.

Genomic View

Select assembly: (NC_000023.10) (NC_000023.11)