COL4A5

Chr XXLD

collagen type IV alpha 5 chain

Also known as: ASLN, ATS, ATS1, CA54

NCBI Gene: 1287 ENSG00000188153 UniProt: P29400 OMIM: 303630

The COL4A5 protein is one of six subunits of type IV collagen, the major structural component of basement membranes including the glomerular basement membrane where it forms a meshwork with other proteins. Mutations cause X-linked Alport syndrome (hereditary nephritis), which primarily affects the kidneys but can also involve hearing loss and ocular abnormalities. This gene follows X-linked inheritance and is highly constrained against loss-of-function variants.

OMIM ResearchSummary from RefSeq, UniProt

This gene encodes one of the six subunits of type IV collagen, the major structural component of basement membranes. Mutations in this gene are associated with X-linked Alport syndrome, also known as hereditary nephritis. Like the other members of the type IV collagen gene family, this gene is organized in a head-to-head conformation with another type IV collagen gene so that each gene pair shares a common promoter. Alternatively spliced transcript variants have been identified for this gene. [provided by RefSeq, Aug 2010]

OMIM ResearchGenerating clinical summary…

LOFmechanismXLDLOEUF 0.191 OMIM phenotype

Clinical Summary— COL4A5

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Gene-Disease Validity (ClinGen)

Alport syndrome · XLDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)

Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.

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Clinical Trials

6 active or recruiting trials — potential therapeutic options may be available

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.19LOEUF

pLI 1.000

Z-score 6.59

OE 0.10 (0.05–0.19)

Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?

2.50Z-score

OE missense 0.72 (0.67–0.78)

474 obs / 653.9 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.10 (0.05–0.19)

0≤0.351.4

Missense OE?0.72 (0.67–0.78)

0≤0.61.4

Synonymous OE?1.03

0≤1.21.6

LoF obs/exp: 6 / 61.9Missense obs/exp: 474 / 653.9Syn Z: -0.36

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

definitiveCOL4A5-related Alport syndromeLOFmonoallelic_X_heterozygous

This gene — mechanism propensity

0.5477th %ile

GOF

0.3888th %ile

LOF

0.68top 10%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.19 · ClinGen HI: Sufficient evidence for dosage pathogenicity

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.