ABCC4

Chr 13

ATP binding cassette subfamily C member 4 (PEL blood group)

Also known as: MOAT-B, MOATB, MRP4

NCBI Gene: 10257 ENSG00000125257 UniProt: O15439 OMIM: 605250

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.

OMIM ResearchSummary from RefSeq, UniProt

The protein encoded by this gene is a member of the superfamily of ATP-binding cassette (ABC) transporters. ABC proteins transport various molecules across extra- and intra-cellular membranes. ABC genes are divided into seven distinct subfamilies (ABC1, MDR/TAP, MRP, ALD, OABP, GCN20, White). This protein is a member of the MRP subfamily which is involved in multi-drug resistance. This family member plays a role in cellular detoxification as a pump for its substrate, organic anions. It may also function in prostaglandin-mediated cAMP signaling in ciliogenesis. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Sep 2014]

OMIM ResearchGenerating clinical summary…

Clinical highlights

Gene–disease validity (ClinGen)

Moderate · qualitative platelet defect · AR · ClinGen 2024

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.49

LOEUF

Multiple*

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.49LOEUF

pLI 0.000

Z-score 5.12

OE 0.35 (0.26–0.49)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

1.70Z-score

OE missense 0.82 (0.77–0.88)

591 obs / 719.4 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.35 (0.26–0.49)

0≤0.351.4

Missense OE?0.82 (0.77–0.88)

0≤0.61.4

Synonymous OE?1.06

0≤1.21.6

LoF obs/exp: 26 / 73.3Missense obs/exp: 591 / 719.4Syn Z: -0.75

Background carrier burden — how many people carry a rare variant somewhere in ABCC4?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 39

1,545 rare PASS variants

Rare truncating (LoF)

1 in 380

227 rare PASS variants

Rare synonymous (reference)

1 in 63

672 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for ABCC4. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 51	1 in 410
South Asian	~43k	1 in 36	1 in 620
Remaining (unassigned)	~30k	1 in 28	1 in 400
European (Finnish)	~27k	1 in 130	1 in 2,200
Admixed American	~22k	1 in 41	1 in 340
African / African American	~21k	1 in 34	1 in 610
East Asian	~20k	1 in 46	1 in 560
Ashkenazi Jewish	~13k	1 in 310	1 in 710
Middle Eastern	~2,884	1 in 39	≈ 1 in 720

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 29 of 31 coding exons well covered in gnomAD exomes; exons 14, 25 marginal. Genomes: all 31.? see exons ↓