COL4A4

Chr 2ARAD

collagen type IV alpha 4 chain

Also known as: ATS2, BFH, BFH1, CA44

The protein forms part of type IV collagen, the major structural component of glomerular basement membranes where it creates a meshwork with other proteins. Mutations cause autosomal recessive Alport syndrome type 2 (hereditary glomerulonephropathy) and autosomal dominant familial benign hematuria (thin basement membrane disease), both primarily affecting kidney function. This gene is highly constrained against loss-of-function variants, indicating its critical importance for normal development and function.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismAR/ADLOEUF 0.622 OMIM phenotypes
Clinical SummaryCOL4A4
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Gene-Disease Validity (ClinGen)
Alport syndrome · SDDefinitive

Definitive — sufficient evidence for diagnostic panels

Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
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Clinical Trials
4 active or recruiting trials — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.62LOEUF
pLI 0.000
Z-score 4.49
OE 0.47 (0.370.62)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
1.02Z-score
OE missense 0.91 (0.860.96)
874 obs / 962.6 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.47 (0.370.62)
00.351.4
Missense OE0.91 (0.860.96)
00.61.4
Synonymous OE1.08
01.21.6
LoF obs/exp: 40 / 84.5Missense obs/exp: 874 / 962.6Syn Z: -1.18
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveCOL4A4-related Alport syndromeLOFAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.75top 25%
GOF
0.5759th %ile
LOF
0.3356th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

COL4A4 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold
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
Digenic Alport Syndrome.
Savige J et al.·Clin J Am Soc Nephrol
2022Review
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 ↗