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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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ABCC5
ATP binding cassette subfamily C member 5
Chromosome 3 · 3q27.1
NCBI Gene: 10057Ensembl: ENSG00000114770.18HGNC: HGNC:56UniProt: O15440
101PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Transporter
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
hyaluronan biosynthetic processABC-type transporter activitypurine nucleotide transportglutathione transmembrane transportneurodegenerative diseasetype 2 diabetes mellitusclonal hematopoiesishepatocellular carcinoma
✦AI Summary

ABCC5 (ATP-binding cassette subfamily C member 5) is an ATP-dependent organic anion transporter that mediates cellular efflux of diverse substrates. Functionally, ABCC5 exports endogenous metabolites including cyclic nucleotides (cAMP and cGMP), glutamate conjugates, folic acid, and heme 1. The transporter also confers resistance to antiviral nucleotide analogs and can transport anticancer drugs with low affinity, though its precise role in chemoresistance remains unclear 2. Structurally, ABCC5 contains a positive electrostatic substrate translocation chamber compatible with organic anion transport 3. Beyond drug resistance, emerging evidence reveals broader physiological roles for ABCC5. Knockout studies in animal models demonstrate its involvement in gut formation, brain development, eye development, and iron metabolism, with effects on adipocyte differentiation, insulin sensitivity, and glutamatergic signaling 1. In humans, ABCC5 genetic variants associate with anterior chamber depth and primary angle closure glaucoma susceptibility 4. Clinical relevance extends to doxorubicin-induced cardiotoxicity; ABCC5 knockout increased susceptibility of cardiomyocytes to doxorubicin, suggesting efflux transporter function protects against anthracycline cardiotoxicity 5. However, ABCC5's underappreciated physiological functions in the brain and reproductive system warrant caution against therapeutic targeting 1.

Sources cited
1
ABCC5 exports cyclic nucleotides, glutamate conjugates, and heme; knockout models reveal roles in development, metabolism, neurobiology, male fertility, adipose tissue mass, insulin sensitivity, and schizophrenia-like behaviors
PMID: 41009771
2
ABCC5 transports nucleotides, nucleotide analogs (PMEA, ganciclovir), and cyclic nucleotides; expressed in smooth muscle, nervous tissue, and capillary endothelium with roles in signaling
PMID: 15747503
3
ABCC5 substrate translocation chamber has positive electrostatic potential compatible with organic anion transport
PMID: 17803828
4
ABCC5 SNP rs4148568 and haplotype TCGGAG associated with primary angle closure glaucoma and ocular biometric parameters in northern Chinese population
PMID: 32906129
5
ABCC5 knockout increased susceptibility of induced pluripotent stem cell-derived cardiomyocytes to doxorubicin-induced cardiotoxicity
PMID: 38510289
Disease Associationsⓘ20
neurodegenerative diseaseOpen Targets
0.29Weak
type 2 diabetes mellitusOpen Targets
0.25Weak
clonal hematopoiesisOpen Targets
0.16Weak
hepatocellular carcinomaOpen Targets
0.11Weak
pituitary gland diseaseOpen Targets
0.10Weak
posterior cortical atrophyOpen Targets
0.09Suggestive
neoplasmOpen Targets
0.09Suggestive
breast cancerOpen Targets
0.09Suggestive
prostate cancerOpen Targets
0.08Suggestive
bone remodeling diseaseOpen Targets
0.07Suggestive
non-alcoholic fatty liver diseaseOpen Targets
0.06Suggestive
cancerOpen Targets
0.05Suggestive
malignant pleural mesotheliomaOpen Targets
0.05Suggestive
Miyoshi myopathyOpen Targets
0.05Suggestive
22q11.2 deletion syndromeOpen Targets
0.04Suggestive
lung cancerOpen Targets
0.04Suggestive
hyperinsulinism due to glucokinase deficiencyOpen Targets
0.03Suggestive
acute lymphoblastic leukemiaOpen Targets
0.03Suggestive
cervical cancerOpen Targets
0.03Suggestive
esophageal adenocarcinomaOpen Targets
0.03Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
ABCC3Shared pathway33%ABCC4Shared pathway33%ABCB1Shared pathway27%ABCG2Shared pathway24%SLC15A2Shared pathway23%ABCC1Shared pathway22%
Tissue Expression6 tissues
Heart
100%
Bone Marrow
82%
Ovary
81%
Lung
50%
Brain
46%
Liver
26%
Gene Interaction Network
Click a node to explore
ABCC5ABCC3ABCC4ABCB1ABCG2SLC15A2ABCC1
PROTEIN STRUCTURE
Preparing viewer…
PDB8WI0 · 2.93 Å · EM
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.46Moderately Constrained
pLIⓘ
1.00Intolerant
Observed/Expected LoF0.37 [0.29–0.46]
RankingsWhere ABCC5 stands among ~20K protein-coding genes
  • #4,702of 20,598
    Most Researched101 · top quartile
  • #2,553of 17,882
    Most Constrained (LOEUF)0.46 · top quartile
Genes detectedABCC5
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Functional Validation of Doxorubicin-Induced Cardiotoxicity-Related Genes.
PMID: 38510289
JACC CardioOncol · 2024
1.00
2
An Emerging Paradigm for ABCC5/MRP5 Function in Human Physiology.
PMID: 41009771
Int J Mol Sci · 2025
0.90
3
Three novel ABCC5 splice variants in human retina and their role as regulators of ABCC5 gene expression.
PMID: 17521428
BMC Mol Biol · 2007
0.80
4
Association of Single-Nucleotide Polymorphisms in ABCC5 Gene with Primary Angle Closure Glaucoma and the Ocular Biometric Parameters in a Northern Chinese Population.
PMID: 32906129
Ophthalmic Res · 2021
0.70
5
Cellular export of drugs and signaling molecules by the ATP-binding cassette transporters MRP4 (ABCC4) and MRP5 (ABCC5).
PMID: 15747503
Drug Metab Rev · 2005
0.60