ABCC4
Chr 13ATP binding cassette subfamily C member 4 (PEL blood group)
Also known as: MOAT-B, MOATB, MRP4
ABCC4 encodes an ATP-binding cassette transporter that actively pumps cyclic nucleotides (cAMP, cGMP), prostaglandins, bile acids, and other signaling molecules out of cells. Mutations cause autosomal recessive pseudohypoaldosteronism type 1 with salt-wasting, hyperkalemia, and metabolic acidosis typically presenting in infancy. The gene is highly constrained against loss-of-function mutations (LOEUF 0.492), indicating that complete protein loss is likely incompatible with normal development.
Moderate evidence — consider for supplementary testing
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
More LoF-intolerant than ~75% of genes
Mild missense constraint
This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
313 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 0 | 0 | 78 | 0 | 78 |
Likely Pathogenic | 0 | 0 | 0 | 0 | 0 |
VUS | 1 | 135 | 13 | 0 | 149 |
Likely Benign | 0 | 9 | 4 | 10 | 23 |
Benign | 0 | 6 | 8 | 11 | 25 |
| Total | 1 | 150 | 103 | 21 | 275 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
ABCC4 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
External Resources
Links to major genomics databases and tools