ABCC3

Chr 17

ATP binding cassette subfamily C member 3

Also known as: ABC31, EST90757, MLP2, MOAT-D, MRP3, cMOAT2

NCBI Gene: 8714UniProt: O15438

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. The specific function of this protein has not yet been determined; however, this protein may play a role in the transport of biliary and intestinal excretion of organic anions. Alternatively spliced variants which encode different protein isoforms have been described; however, not all variants have been fully characterized. [provided by RefSeq, Jul 2008]

1
Active trials
223
ClinVar variants
11
Pathogenic / LP
0.6
Missense Z
0.90
LOEUF
9
Pubs (2 yr)
Clinical Summary— ABCC3
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
11 Pathogenic / Likely Pathogenic· 177 VUS of 223 total submissions
💊
Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available
📖
GeneReview available — ABCC3
Authoritative clinical overview · Recommended first read
Open GeneReview ↗
Some data sources returned errors (1)

ensembl: Error: Ensembl fetch failed: 500 for https://rest.ensembl.org/lookup/symbol/homo_sapiens/ABCC3?content-type=application/json&expand=1

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.90LOEUF
pLI 0.000
Z-score 2.29
OE 0.71 (0.57–0.90)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.63Z-score
OE missense 0.94 (0.89–1.00)
848 obs / 901.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.71 (0.57–0.90)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.94 (0.89–1.00)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.90
0≤1.21.6
LoF obs/exp: 52 / 73.1Missense obs/exp: 848 / 901.2Syn Z: 1.59

ClinVar Variant Classifications

223 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic10
Likely Pathogenic1
VUS177
Likely Benign30
Benign5
10
Pathogenic
1
Likely Pathogenic
177
VUS
30
Likely Benign
5
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
10
0
10
Likely Pathogenic
0
0
1
0
1
VUS
0
177
0
0
177
Likely Benign
0
19
1
10
30
Benign
0
3
1
1
5
Total01991311223

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

View in ClinVar →

Protein Context — Lollipop Plot

ABCC3 · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Modulation of Hepatic MRP3/ABCC3 by Xenobiotics and Pathophysiological Conditions: Role in Drug Pharmacokinetics.
Ghanem CI et al.·Curr Med Chem
2019Review
ABCB1, ABCG2, ABCC1, ABCC2, and ABCC3 drug transporter polymorphisms and their impact on drug bioavailability: what is our current understanding?
Bruckmueller H et al.·Expert Opin Drug Metab Toxicol
2021Review
Polymorphisms of the drug transporters ABCB1, ABCG2, ABCC2 and ABCC3 and their impact on drug bioavailability and clinical relevance.
Bruhn O et al.·Expert Opin Drug Metab Toxicol
2014Review
Genetics of perioperative pain management.
Packiasabapathy S et al.·Curr Opin Anaesthesiol
2018Review
Nanobodies targeting ABCC3 for immunotargeted applications in glioblastoma.
Ruiz-López E et al.·Sci Rep
2022
A susceptibility gene signature for ERBB2-driven mammary tumour development and metastasis in collaborative cross mice.
Yang H et al.·EBioMedicine
2024
Pharmacogenomics in pediatric oncology patients with solid tumors related to chemotherapy-induced toxicity: A systematic review.
Hansson P et al.·Crit Rev Oncol Hematol
2025Review
The transmembrane transporter ABCC3 participates in liver cancer progression and is a potential biomarker.
Carrasco-Torres G et al.·Tumour Biol
2016
Overexpression of ABCC3 promotes cell proliferation, drug resistance, and aerobic glycolysis and is associated with poor prognosis in urinary bladder cancer patients.
Liu X et al.·Tumour Biol
2016Cohort
Role of the Drug Transporter ABCC3 in Breast Cancer Chemoresistance.
Balaji SA et al.·PLoS One
2016
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Analysis of ABCC3 in glioma progression: implications for prognosis, immunotherapy, and drug resistance
Shen L et al.·Discov Oncol
2025
Recombinant Expression of ABCC2 Variants Confirms the Importance of Mutations in Extracellular Loop 4 for Cry1F Resistance in Fall Armyworm
Franz L et al.·Toxins (Basel)
2022
Identification of ABCC3 and its isoforms as potential biomarker in hepatocellular carcinoma.
Zertuche-Martínez C et al.·Toxicol Mech Methods
2023
Clinicopathological and Prognostic Significance of ABCC3 in Human Glioma
Fang DD et al.·J Oncol
2021
Folate-Associated Gene Expression in Primary Tumors Is Associated With Tumor Response and Progression-Free Survival of Patients With Metastatic Colorectal Cancer Undergoing 5-FU/Leucovorin-Based Combination Chemotherapy
Odin E et al.·Cancer Med
2025Cohort
Identification of a Five-mRNA Signature as a Novel Potential Prognostic Biomarker for Glioblastoma by Integrative Analysis
Xu H et al.·Front Genet
2022
Association Study of SLCO1B3 and ABCC3 Genetic Variants in Gallstone Disease
Banach B et al.·Genes (Basel)
2022
The implications of ABCC3 in cancer drug resistance: can we use it as a therapeutic target?
Ramírez-Cosmes A et al.·Am J Cancer Res
2021
Top 8 full-text resultsSearch PubTator3 ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
Opioid Use DisorderPregnancy Related

Predicting and Preventing Adverse Maternal and Child Outcomes of Opioid Use Disorder in Pregnancy

RECRUITING
NCT05942313Ilana HullStarted 2023-08-28
Buprenorphine/ Methadone exposure

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