COL4A5

Chr XXLD

collagen type IV alpha 5 chain

Also known as: ASLN, ATS, ATS1, CA54

NCBI Gene: 1287ENSG00000188153UniProt: P29400OMIM: 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.

OMIMResearchSummary from RefSeq, UniProt
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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ClinVar Variants
186 unique Pathogenic / Likely Pathogenic· 51 VUS of 277 total submissions
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Clinical Trials
7 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 OE0.10 (0.05–0.19)
0≤0.351.4
Missense OE0.72 (0.67–0.78)
0≤0.61.4
Synonymous OE1.03
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
DN
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 · 26% of P/LP variants are LoF · LOEUF 0.19

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

ClinVar Variant Classifications

277 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic92
Likely Pathogenic94
VUS51
Likely Benign25
Benign7
Conflicting8
92
Pathogenic
94
Likely Pathogenic
51
VUS
25
Likely Benign
7
Benign
8
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
32
36
24
0
92
Likely Pathogenic
16
75
3
0
94
VUS
0
36
13
2
51
Likely Benign
0
5
15
5
25
Benign
0
2
1
4
7
Conflicting
—8
Total481545611277

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

COL4A5 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
Alport Syndrome

Eurbio-Alport (RaDiCo Cohort) (RaDiCo Eurbio-Alport)

RECRUITING
NCT05927467Institut National de la Santé Et de la Recherche Médicale, FranceStarted 2017-05-09
Alport SyndromeThin Basement Membrane DiseaseAlport Nephropathy

Albuminuria Lowering Effect of Dapagliflozin, Spironolactone and Their Combination in Adult Patients With Alport Syndrome (COMBINE-ALPORT)

ACTIVE NOT RECRUITING
NCT06499948Phase PHASE4Stefan LujinschiStarted 2024-02-26
Treatment with Spironolactone followed by Dapagliflozin followed by their combinationTreatment with Dapagliflozin followed by Spironolactone followed by their combination
Alport Syndrome

Safety and Efficacy of ACEI in Alport Syndrome Patients With COL4A3/COL4A4/COL4A5 Variants

NOT YET RECRUITING
NCT05133050Phase NAXinhua Hospital, Shanghai Jiao Tong University School of MedicineStarted 2022-01-01
Ramipril
Alport Syndrome

BAY3401016; Biomarker Study Alport

RECRUITING
NCT07211685Phase PHASE2BayerStarted 2025-11-19
BAY 3401016Placebo
Alport Syndrome

Genotype-Phenotype Correlations in Patients With Alport Syndrome

RECRUITING
NCT04947813Xinhua Hospital, Shanghai Jiao Tong University School of MedicineStarted 2021-01-01
Alport Syndrome, X-LinkedAlport Syndrome, Autosomal Recessive

EXACT Study: A Blinded Study in Patients With Alport Syndrome to Evaluate Exaluren Efficacy and Safety

NOT YET RECRUITING
NCT07523581Phase PHASE2Eloxx Pharmaceuticals, Inc.Started 2026-05-30
Exaluren
Adenine Phosphoribosyltransferase DeficiencyAH AmyloidosisAHL Amyloidosis

National Registry of Rare Kidney Diseases

RECRUITING
NCT06065852UK Kidney AssociationStarted 2009-11-06
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Guidelines for Genetic Testing and Management of Alport Syndrome.
Savige J et al.·Clin J Am Soc Nephrol
2022
Digenic Alport Syndrome.
Savige J et al.·Clin J Am Soc Nephrol
2022Review
Clinical utility of genetic testing in early-onset kidney disease: seven genes are the main players.
Domingo-Gallego A et al.·Nephrol Dial Transplant
2022
Alport Syndrome: Achieving Early Diagnosis and Treatment.
Kashtan CE·Am J Kidney Dis
2021Review
Alport syndrome and Alport kidney diseases - elucidating the disease spectrum.
Puapatanakul P et al.·Curr Opin Nephrol Hypertens
2024Review
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients