ABCC11

Summary

ABCC11 (ATP binding cassette subfamily C member 11, HGNC:14639) is a protein-coding gene on chromosome 16q12.1, encoding ATP-binding cassette sub-family C member 11 (Q96J66). ATP-dependent transporter of the ATP-binding cassette (ABC) family that actively extrudes physiological compounds and xenobiotics from cells.

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 ABC full transporter is a member of the MRP subfamily which is involved in multi-drug resistance. The product of this gene participates in physiological processes involving bile acids, conjugated steroids, and cyclic nucleotides. In addition, a SNP in this gene is responsible for determination of human earwax type. This gene and family member ABCC12 are determined to be derived by duplication and are both localized to chromosome 16q12.1. Multiple alternatively spliced transcript variants have been described for this gene.

Source: NCBI Gene 85320 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 277 total — 4 pathogenic
• Phenotypes (HPO): 3
• Druggable target: yes
• MANE Select transcript: NM_001370497

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:14639
Approved symbol	ABCC11
Name	ATP binding cassette subfamily C member 11
Location	16q12.1
Locus type	gene with protein product
Status	Approved
Aliases	MRP8
Ensembl gene	ENSG00000121270
Ensembl biotype	protein_coding
OMIM	607040
Entrez	85320

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 5 protein_coding, 3 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000353782, ENST00000356608, ENST00000394747, ENST00000394748, ENST00000565329, ENST00000565487, ENST00000567385, ENST00000569172, ENST00000569991

RefSeq mRNA: 5 — MANE Select: NM_001370497 NM_001370496, NM_001370497, NM_032583, NM_033151, NM_145186

CCDS: CCDS10732, CCDS10733

Canonical transcript exons

ENST00000356608 — 30 exons

Exon	Start	End
ENSE00000821421	48187201	48187427
ENSE00000901652	48198141	48198275
ENSE00000901654	48203228	48203300
ENSE00000901655	48205413	48205537
ENSE00000901656	48208425	48208496
ENSE00000901657	48210948	48211199
ENSE00001408007	48247314	48247539
ENSE00001774793	48200276	48200479
ENSE00003500914	48214881	48215029
ENSE00003506366	48197971	48198067
ENSE00003509803	48222598	48222831
ENSE00003513384	48175258	48175417
ENSE00003516711	48178597	48178686
ENSE00003538938	48196232	48196321
ENSE00003558084	48215197	48215344
ENSE00003559049	48213443	48213550
ENSE00003571278	48192520	48192717
ENSE00003578138	48227806	48227964
ENSE00003579789	48216114	48216287
ENSE00003584050	48230437	48230573
ENSE00003601116	48193879	48193982
ENSE00003624184	48170105	48170218
ENSE00003634513	48176924	48177113
ENSE00003647936	48184440	48184626
ENSE00003654769	48167496	48167660
ENSE00003654805	48231823	48231939
ENSE00003662214	48186953	48187090
ENSE00003679060	48224282	48224429
ENSE00003687851	48170889	48170967
ENSE00003906760	48165773	48167366

Expression profiles

Bgee: expression breadth ubiquitous, 126 present calls, max score 77.64.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0115 / max 10.8596, expressed in 4 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
157256	0.0076	4
157255	0.0039	1

Top tissues by expression

234 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	77.64	gold quality
right lobe of liver	UBERON:0001114	72.94	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	70.14	silver quality
liver	UBERON:0002107	65.41	gold quality
left testis	UBERON:0004533	64.60	gold quality
right uterine tube	UBERON:0001302	64.26	gold quality
right testis	UBERON:0004534	64.08	gold quality
testis	UBERON:0000473	63.99	gold quality
sural nerve	UBERON:0015488	63.73	gold quality
pancreatic ductal cell	CL:0002079	60.74	silver quality
sperm	CL:0000019	60.25	gold quality
bone marrow cell	CL:0002092	59.76	gold quality
prefrontal cortex	UBERON:0000451	58.33	gold quality
epithelium of nasopharynx	UBERON:0001951	58.14	gold quality
epithelium of mammary gland	UBERON:0003244	57.48	silver quality
mammary duct	UBERON:0001765	57.30	silver quality
thoracic mammary gland	UBERON:0005200	57.18	gold quality
mammary gland	UBERON:0001911	56.96	gold quality
putamen	UBERON:0001874	54.85	gold quality
epithelial cell of pancreas	CL:0000083	54.74	gold quality
cardiac muscle of right atrium	UBERON:0003379	54.34	gold quality
left ventricle myocardium	UBERON:0006566	54.23	gold quality
ventricular zone	UBERON:0003053	54.20	silver quality
nucleus accumbens	UBERON:0001882	54.12	gold quality
kidney epithelium	UBERON:0004819	53.93	gold quality
amygdala	UBERON:0001876	53.80	gold quality
upper arm skin	UBERON:0004263	53.52	gold quality
caudate nucleus	UBERON:0001873	53.50	gold quality
stromal cell of endometrium	CL:0002255	52.99	silver quality
frontal cortex	UBERON:0001870	52.77	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.04

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

15 targeting ABCC11, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-515-5P	99.92	69.82	2343
HSA-MIR-519E-5P	99.92	69.62	2358
HSA-MIR-7157-5P	99.66	69.33	1829
HSA-MIR-4310	99.59	68.84	2527
HSA-MIR-182-3P	99.57	67.57	825
HSA-MIR-519D-5P	99.41	69.30	2057
HSA-MIR-2115-3P	99.31	69.68	2026
HSA-MIR-4291	99.20	68.88	2969
HSA-MIR-2115-5P	98.66	68.07	1191
HSA-MIR-665	97.60	65.64	1781
HSA-MIR-4724-3P	97.57	67.31	785
HSA-MIR-383-5P	96.86	67.55	820

Literature-anchored findings (GeneRIF, showing 40)

• alternative splice variants and gene expression (PMID:11688999)
• Impaired 2’,3’-dideoxy-3’-thiacytidine accumulation in T-lymphoblastoid cells as a mechanism of acquired resistance independent of multidrug resistant protein 4 with a possible role for ATP-binding cassette C11. (PMID:12133003)
• Results suggest that MRP8 participates in physiological processes involving bile acids, conjugated steroids, and cyclic nucleotides and indicate that this pump has complex interactions with its substrates. (PMID:15537867)
• Transport function together with the localization of the ABCC11 protein in vicinity to GABA A receptors is consistent with a role of ABCC11 in dehydroepiandrosterone 3-sulfate release from neurons. (PMID:16359813)
• An SNP, 538G –> A (rs17822931), in the ABCC11 gene is responsible for determination of earwax type in several ethnic groups. (PMID:16444273)
• High expression of MRP8 is associated with reduced intracellular levels of cytosine arabinoside and results in acute myeloid leukemia. (PMID:19240178)
• Data suggest that a single-nucleotide polymorphism in the ABCC11 gene has an effect on the N-linked glycosylation of ABCC11, intracellular sorting, and proteasomal degradation of the variant protein. (PMID:19383836)
• The allele frequencies of the ABCC11 locus within ancient populations on the Northern Japanese island of Hokkaido, were investigated. (PMID:19557017)
• The SmartAmp method-based genotyping of the ABCC11 gene would provide an accurate and practical tool for guidance of appropriate treatment (PMID:19625231)
• Wet/dry types of earwax are determined by the c.538G>A single-nucleotide polymorphism in the ABCC11 gene. (PMID:19644513)
• ABCC11 has a role in the biochemical formation of human axillary odor (PMID:19710689)
• Results showed that ABCC11 may be one of the biomarkers for MTA treatment in adenocarcinomas. (PMID:20718756)
• Data show that latitude is associated with allele frequency of ABCC11 rs17822931-A in Asian, Native American, and European populations, implying that the selective advantage of rs17822931-A is related to an adaptation to a cold climate. (PMID:20937735)
• Earwax-associated polymorphism in ABCC11 is not associated with breast cancer. (PMID:21165769)
• overview of the discovery and genetic polymorphisms inABCC11; focus on the impact of ABCC11 538G>A on the apocrine phenotype, patients’ response to nucleoside-based chemotherapy and the potential risk of breast cancer [review] (PMID:21182469)
• Study shows that Japanese women with wet earwax have a higher relative risk of developing breast cancer than those with dry earwax. The ABCC11 SNPs that determine these phenotypes should be further investigated. (PMID:21187511)
• The expression of ABCC11 protein appears to be decreased in most breast cancer (BC). (PMID:21423094)
• High expression of ATP-binding cassette transporter ABCC11 in breast tumors is associated with aggressive subtypes and low disease-free survival. (PMID:23288347)
• Cerumen types, determined by CYP2D6 and the incidence of breast cancer is significantly higher among the moist cerumen type. Further studies on the polymorphism of this gene are scheduled in relation to carcinogenesis and malignancy. (PMID:23350374)
• The rs17822931 SNP in ABCC11 is associated with wet earwax and bromhidrosis in a chinese family. (PMID:23970085)
• Our results suggest that a specific type of toxicity, leukopenia, is associated with a particular variant of ABCC11, which is different from the earwax and eQTL variants. (PMID:24024896)
• ABCC11 gene SNP results in lower levels of axillary odour in the A/A homozygotes, but A/A subjects still produce noticeable amounts of axillary odour. Axillary skin metabolites/bacterial genera/personal hygiene behaviours are also influenced by this SNP. (PMID:24076068)
• role in the generation of axillary malodour (PMID:24533866)
• A single nucleotide polymorphism in ABCC11 affects the cerumen volatile organic compounds profiles of individuals from African, Caucasian, and Asian descent. (PMID:25501636)
• The ABCC11 gene SNP of the 538 G>A allele was associated with a downregulation of the mRNA expression of ApoD in the apocrine glands, which may indicate a role for the ABCC11 gene in the mediation of osmidrosis (PMID:25633187)
• identified c.1637C>T (T546M), previously associated with 5-FU-related toxicity, as a novel functionally damaging ABCC11 variant exhibiting markedly reduced transport function of 5-FdUMP, the active cytotoxic metabolite of 5-FU. Detailed analysis of 14 subpopulations revealed highest allele frequencies of c.1637C>T in Europeans and Americans (up to 11%) compared with Africans and Asians (up to 3%). (PMID:25896536)
• ABCC11 c.1637C>T polymorphisms affects fluoropyrimidine toxicity to leukocytes (PMID:27001120)
• Our results confirmed the association between NAF yield and earwax phenotype through ABCC11 genotype. Combined with the recency of last birth, ABCC11 genotype should be considered in the design of studies utilizing NAF as a biosample. (PMID:27027309)
• Presents a simple isothermal genotyping method capable of detecting single nucleotide polymorphisms in the human ATP-binding cassette transporter ABCC11 gene and its application to the clinical diagnosis of axillary osmidrosis. (PMID:27057547)
• No Association of the rs17822931 Polymorphism in ABCC11 was found with Breast Cancer Risk in Koreans. (PMID:27268641)
• These results suggest that N-linked glycosylation is important for the protein stability of ABCC11, and physiological alteration in glucose may affect the ABCC11 protein level and ABCC11-related phenotypes in humans, such as axillary osmidrosis. (PMID:27281343)
• The present study shows that the protein expression of ABCC10 significantly associates with overall survival and the expression of ABCC11 with disease-free interval of colorectal cancer patients (PMID:27468921)
• Tenofovir disoproxil fumarate is a new substrate of ABCC11. (PMID:28167562)
• ABCC11 protein was detected in the human axillary apocrine glands of the 538GG homozygote or 538GA heterozygote, not in the 538AA homozygote. These findings would contribute to a better understanding of the molecular basis of axillary osmidrosis. (PMID:28212277)
• our study has provided conclusive evidence for the association of rs17822931 in the ABCC11 with the susceptibility of AO in the Chinese Han population (PMID:28485377)
• High MRP8 expression is associated with Rheumatoid Arthritis. (PMID:29530998)
• the differential expression pattern of ABCC11 and ABCB5 genes may serve as outliers, potentially associated with incidence of multifocal/multicentric breast cancer (PMID:29552773)
• Serum levels of MRP8/MRP14 and MRP6 were up-regulated in patients with Graves’ disease (GD) and Hashimoto’s thyroiditis (HT). In addition, mRNA expression of MRP proteins in PBMCs and the thyroid gland was markedly elevated in these patients. (PMID:29656212)
• The previous findings of a previously unreported homozygous genotype for both the Delta27 and A alleles suggest that the Delta27 deletion might have occurred in the A allele of ABCC11 gene with the 538G>A mutation. (PMID:30047321)
• Rs17822931, a functional single nucleotide polymorphism (SNP) in ABCC11, may play a role in the carcinogenesis. (PMID:30883634)

Cross-species orthologs

17 orthologs

Organism	Symbol	Gene ID
danio_rerio	abcc6a	ENSDARG00000016750
danio_rerio	abcc10	ENSDARG00000077988
danio_rerio	abcc6b.2	ENSDARG00000094901
danio_rerio	abcc6b.1	ENSDARG00000105403
drosophila_melanogaster	l(2)03659	FBGN0010549
drosophila_melanogaster	CG7627	FBGN0032026
drosophila_melanogaster	MRP	FBGN0032456
drosophila_melanogaster	CG9270	FBGN0032908
drosophila_melanogaster	CG10505	FBGN0034612
drosophila_melanogaster	Mrp5	FBGN0038740
drosophila_melanogaster	rdog	FBGN0039644
drosophila_melanogaster	CG11898	FBGN0039645
drosophila_melanogaster	CG31792	FBGN0051792
drosophila_melanogaster	CG31793	FBGN0051793
drosophila_melanogaster	Mrp4	FBGN0263316
caenorhabditis_elegans		WBGENE00000477
caenorhabditis_elegans		WBGENE00003413

Paralogs (11): CFTR (ENSG00000001626), ABCC8 (ENSG00000006071), ABCC2 (ENSG00000023839), ABCC9 (ENSG00000069431), ABCC6 (ENSG00000091262), ABCC1 (ENSG00000103222), ABCC3 (ENSG00000108846), ABCC5 (ENSG00000114770), ABCC10 (ENSG00000124574), ABCC4 (ENSG00000125257), ABCC12 (ENSG00000140798)

Protein

Protein identifiers

ATP-binding cassette sub-family C member 11 — Q96J66 (reviewed: Q96J66)

Alternative names: Multidrug resistance-associated protein 8

All UniProt accessions (2): Q96J66, H3BRJ2

UniProt curated annotations — full annotation on UniProt →

Function. ATP-dependent transporter of the ATP-binding cassette (ABC) family that actively extrudes physiological compounds and xenobiotics from cells. Plays a role in physiological processes involving bile acids, conjugated steroids and cyclic nucleotides, including cAMP and cGMP. Mediates the ATP-dependent efflux of a range of physiological lipophilic anions, including the glutathione S-conjugates leukotriene C4 and dinitrophenyl S-glutathione, steroid sulfates, such as dehydroepiandrosterone 3-sulfate (DHEAS) and estrone 3-sulfate, glucuronides such as estradiol 17-beta-D-glucuronide (E(2)17betaG), the monoanionic bile acids glycocholate and taurocholate, and methotrexate. Plays a role in the transport of earwax components. Participates in the secretion of odorants and their precursors from the apocrine sweat glands, including the secretion of glutamine conjugates, as well as the Cys-Gly-(S) conjugates of 3-methyl-3-sulfanyl-hexanol. Involved in the cellular extrusion of nucleotide analogs, hence confering resistance to various drugs, including clinically relevant drugs such as 5-fluorouracil (5-FU) and methotrexate.

Subcellular location. Cell membrane. Vacuole membrane. Cytoplasmic vesicle membrane. Apical cell membrane.

Tissue specificity. Expressed in apocrine glands (at protein level). Expressed at moderate levels in breast and testis and at very low levels in liver, brain and placenta. Localizes to axons of the central and peripheral nervous system (at protein level).

Polymorphism. Variations in ABCC11 gene may affect apocrine gland secretion, which determines earwax type, axillary osmidrosis, and colostrum secretion [MIM:117800]. The wet, cerumen-containing earwax type is a dominant trait, while the dry type, characterized by the lack of oily components, is recessive. The dry type is frequently observed (80-95%) among East Asians, but is uncommon (0-3%) in populations of European and African origins. Intermediate frequencies (30-50%) are seen in populations of Southern Asia, the Pacific Islands, Central Asia and Asia Minor, as well as among the Native North Americans and Inuit. The variant p.Gly180Arg is associated with dry earwax phenotype and lack of axillary odor. It has been suggested that the selective advantage of variant p.Gly180Arg might be related to an adaptation to a cold climate.

Miscellaneous. This protein has no ortholog in rodents.

Similarity. Belongs to the ABC transporter superfamily. ABCC family. Conjugate transporter (TC 3.A.1.208) subfamily.

Isoforms (2)

UniProt ID	Names	Canonical?
Q96J66-1	1	yes
Q96J66-2	2, Isoform A

RefSeq proteins (5): NP_001357425, NP_001357426, NP_115972, NP_149163, NP_660187 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003439	ABC_transporter-like_ATP-bd	Domain
IPR003593	AAA+_ATPase	Domain
IPR011527	ABC1_TM_dom	Domain
IPR017871	ABC_transporter-like_CS	Conserved_site
IPR027417	P-loop_NTPase	Homologous_superfamily
IPR036640	ABC1_TM_sf	Homologous_superfamily
IPR050173	ABC_transporter_C-like	Family

Pfam: PF00005, PF00664

Catalyzed reactions (Rhea), 10 shown:

• an S-substituted glutathione(in) + ATP + H2O = an S-substituted glutathione(out) + ADP + phosphate + H(+) (RHEA:19121)
• leukotriene C4(in) + ATP + H2O = leukotriene C4(out) + ADP + phosphate + H(+) (RHEA:38963)
• taurocholate(in) + ATP + H2O = taurocholate(out) + ADP + phosphate + H(+) (RHEA:50052)
• glycocholate(in) + ATP + H2O = glycocholate(out) + ADP + phosphate + H(+) (RHEA:50056)
• 17beta-estradiol 17-O-(beta-D-glucuronate)(in) + ATP + H2O = 17beta-estradiol 17-O-(beta-D-glucuronate)(out) + ADP + phosphate + H(+) (RHEA:60128)
• estrone 3-sulfate(in) + ATP + H2O = estrone 3-sulfate(out) + ADP + phosphate + H(+) (RHEA:61348)
• dehydroepiandrosterone 3-sulfate(in) + ATP + H2O = dehydroepiandrosterone 3-sulfate(out) + ADP + phosphate + H(+) (RHEA:61364)
• 2,4-dinitrophenyl-S-glutathione(in) + ATP + H2O = 2,4-dinitrophenyl-S-glutathione(out) + ADP + phosphate + H(+) (RHEA:61380)
• 3’,5’-cyclic AMP(in) + ATP + H2O = 3’,5’-cyclic AMP(out) + ADP + phosphate + H(+) (RHEA:66184)
• 3’,5’-cyclic GMP(in) + ATP + H2O = 3’,5’-cyclic GMP(out) + ADP + phosphate + H(+) (RHEA:66188)

UniProt features (59 total): topological domain 12, transmembrane region 12, sequence variant 11, sequence conflict 8, domain 4, mutagenesis site 4, binding site 2, glycosylation site 2, chain 1, region of interest 1, compositionally biased region 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96J66-F1	79.30	0.26

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (2): 544–551; 1175–1182

Glycosylation sites (2): 838, 844

Mutagenesis-validated functional residues (4):

Position	Phenotype
180	does not affect n-glycosylation.
180	loss of n-glycosylation.
838	loss of n-glycosylation.
844	loss of n-glycosylation.

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-382556	ABC-family protein mediated transport
R-HSA-382551	Transport of small molecules

MSigDB gene sets: 73 (showing top): GOCC_VACUOLAR_MEMBRANE, GOBP_NUCLEOTIDE_TRANSPORT, GOBP_ORGANIC_ACID_TRANSPORT, KEGG_ABC_TRANSPORTERS, GOBP_ORGANIC_HYDROXY_COMPOUND_TRANSPORT, GOBP_ORGANOPHOSPHATE_ESTER_TRANSPORT, GOMF_NUCLEOBASE_CONTAINING_COMPOUND_TRANSMEMBRANE_TRANSPORTER_ACTIVITY, GOBP_NUCLEOBASE_CONTAINING_COMPOUND_TRANSPORT, GOBP_ORGANIC_ANION_TRANSPORT, GOBP_BILE_ACID_AND_BILE_SALT_TRANSPORT, GOBP_PURINE_NUCLEOTIDE_TRANSPORT, GOBP_MONOCARBOXYLIC_ACID_TRANSPORT, GOCC_APICAL_PLASMA_MEMBRANE, GOBP_LIPID_LOCALIZATION, GOBP_TRANSMEMBRANE_TRANSPORT

GO Biological Process (8): obsolete organic anion transport (GO:0015711), bile acid and bile salt transport (GO:0015721), purine nucleotide transport (GO:0015865), xenobiotic transport (GO:0042908), transmembrane transport (GO:0055085), leukotriene transport (GO:0071716), lipid transport (GO:0006869), monoatomic anion transmembrane transport (GO:0098656)

GO Molecular Function (10): ATP binding (GO:0005524), obsolete organic anion transmembrane transporter activity (GO:0008514), ABC-type xenobiotic transporter activity (GO:0008559), purine nucleotide transmembrane transporter activity (GO:0015216), ABC-type glutathione S-conjugate transporter activity (GO:0015431), ABC-type bile acid transporter activity (GO:0015432), ATP hydrolysis activity (GO:0016887), obsolete ATPase-coupled inorganic anion transmembrane transporter activity (GO:0043225), ABC-type transporter activity (GO:0140359), nucleotide binding (GO:0000166)

GO Cellular Component (8): vacuolar membrane (GO:0005774), plasma membrane (GO:0005886), apical plasma membrane (GO:0016324), cytoplasmic vesicle membrane (GO:0030659), extracellular exosome (GO:0070062), vacuole (GO:0005773), membrane (GO:0016020), cytoplasmic vesicle (GO:0031410)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Transport of small molecules	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
transport	3
ABC-type transporter activity	3
cytoplasm	2
lipid transport	1
monocarboxylic acid transport	1
organic hydroxy compound transport	1
nucleotide transport	1
cellular process	1
icosanoid transport	1
lipid localization	1
monoatomic anion transport	1
monoatomic ion transmembrane transport	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
xenobiotic transmembrane transporter activity	1
nucleotide transmembrane transporter activity	1
purine nucleotide transport	1
sulfur compound transmembrane transporter activity	1
bile acid transmembrane transporter activity	1
ATPase-coupled carboxylic acid transmembrane transporter activity	1
ATPase-coupled lipid transmembrane transporter activity	1
ribonucleoside triphosphate phosphatase activity	1
ATP-dependent activity	1
ATPase-coupled transmembrane transporter activity	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
vacuole	1
bounding membrane of organelle	1
membrane	1
cell periphery	1
apical part of cell	1
plasma membrane region	1
vesicle membrane	1
cytoplasmic vesicle	1
extracellular vesicle	1
intracellular membrane-bounded organelle	1
cellular anatomical structure	1
intracellular vesicle	1

Protein interactions and networks

STRING

1080 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ABCC11	ABCF2	Q9UG63	554
ABCC11	MRPS7	Q9Y2R9	520
ABCC11	ABCG4	Q9H172	489
ABCC11	ABCE1	P61221	477
ABCC11	SRARP	Q8NEQ6	465
ABCC11	ABCF3	Q9NUQ8	458
ABCC11	ABCA10	Q8WWZ4	444
ABCC11	ABCG8	Q9H221	419
ABCC11	ABCF1	Q8NE71	419
ABCC11	FSIP2	Q5CZC0	403
ABCC11	EDAR	Q9UNE0	400
ABCC11	GATB	O75879	400
ABCC11	ZMIZ1	Q9ULJ6	391
ABCC11	TMED2	Q15363	387
ABCC11	TPK1	Q9H3S4	387

IntAct

6 interactions, top by confidence:

A	B	Type	Score
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
CFTR	HAX1	psi-mi:“MI:0914”(association)	0.610
ABCC11	H3-4	psi-mi:“MI:0915”(physical association)	0.400
ABCC12	SHTN1	psi-mi:“MI:0914”(association)	0.350
DNAJA2	ENC1	psi-mi:“MI:0914”(association)	0.350

BioGRID (7): ABCC11 (Affinity Capture-MS), ABCC11 (Proximity Label-MS), ABCC11 (Affinity Capture-MS), ABCC11 (Positive Genetic), ABCC11 (PCA), ABCC11 (Co-localization), VTI1A (Cross-Linking-MS (XL-MS))

ESM2 similar proteins: A2XCD4, A7KVC2, B2RX12, O15438, O15440, O35379, O60706, O88563, P33527, P70170, P82451, P91660, Q07DZ6, Q07E16, Q09427, Q09428, Q09429, Q10RX7, Q1LX78, Q28689, Q2QLH0, Q42093, Q5F364, Q63120, Q63563, Q6UR05, Q6Y306, Q7DM58, Q7GB25, Q80WJ6, Q864R9, Q8CG09, Q8HXQ5, Q8LGU1, Q8VI47, Q8VZZ4, Q92887, Q96J65, Q96J66, Q9C8G9

Diamond homologs: A0A0D1CZ63, A0A0U1LQE1, A0A1U8QTJ9, A2XCD4, A7KVC2, B2RX12, E9Q236, F1M3J4, F9X9V4, G4N2B5, J9VQH1, O15438, O15439, O15440, O31708, O35379, O60706, O70127, O88269, O88563, O95255, P0CE69, P14772, P16875, P16877, P21439, P21440, P32386, P33527, P38735, P39109, P53049, P70170, P82451, P91660, P9WEL8, Q07QX6, Q08201, Q09427, Q0VQP5

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

277 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	4
Likely pathogenic	0
Uncertain significance	210
Likely benign	31
Benign	11

Top pathogenic / likely-pathogenic (4)

Variant ID	HGVS	Classification
148087	GRCh38/hg38 16q11.2-12.1(chr16:46466829-52355793)x3	Pathogenic
442863	GRCh37/hg19 16q11.2-12.1(chr16:46737110-51838691)x1	Pathogenic
443550	GRCh37/hg19 16p11.2-q21(chr16:34197492-64509054)x3	Pathogenic
59467	GRCh38/hg38 16q11.2-12.1(chr16:46466829-51939304)x1	Pathogenic

SpliceAI

5113 predictions. Top by Δscore:

Variant	Effect	Δscore
16:48167365:ACC:A	acceptor_loss	1.0000
16:48167367:C:G	acceptor_loss	1.0000
16:48167498:T:TA	donor_gain	1.0000
16:48167499:C:A	donor_gain	1.0000
16:48167657:TGAT:T	acceptor_gain	1.0000
16:48167658:GAT:G	acceptor_gain	1.0000
16:48167658:GATC:G	acceptor_loss	1.0000
16:48167659:AT:A	acceptor_gain	1.0000
16:48167660:TC:T	acceptor_loss	1.0000
16:48167661:C:CC	acceptor_gain	1.0000
16:48167668:A:AC	acceptor_gain	1.0000
16:48170887:A:AC	donor_gain	1.0000
16:48170887:ACGG:A	donor_gain	1.0000
16:48170887:ACGGC:A	donor_gain	1.0000
16:48170888:C:CC	donor_gain	1.0000
16:48170888:CGG:C	donor_gain	1.0000
16:48170888:CGGC:C	donor_gain	1.0000
16:48170888:CGGCC:C	donor_gain	1.0000
16:48170968:C:CC	acceptor_gain	1.0000
16:48170972:CA:C	acceptor_gain	1.0000
16:48170973:A:C	acceptor_gain	1.0000
16:48175254:TCA:T	donor_loss	1.0000
16:48175254:TCAC:T	donor_gain	1.0000
16:48175255:CA:C	donor_loss	1.0000
16:48175255:CACC:C	donor_gain	1.0000
16:48175256:A:AC	donor_gain	1.0000
16:48175257:C:CC	donor_gain	1.0000
16:48175413:CTTCC:C	acceptor_gain	1.0000
16:48175414:TTCC:T	acceptor_gain	1.0000
16:48175415:TCC:T	acceptor_gain	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000005538 (16:48248215 A>G), RS1000018855 (16:48187181 A>G), RS1000097481 (16:48233410 G>C), RS1000151842 (16:48248925 C>A), RS1000175477 (16:48175371 C>T), RS1000177724 (16:48181359 A>C), RS1000228051 (16:48175596 G>A), RS1000255465 (16:48210964 T>A,C), RS1000266390 (16:48193248 A>G), RS1000271741 (16:48240399 T>C), RS1000280406 (16:48175934 A>C,T), RS1000295930 (16:48186265 G>A), RS1000302792 (16:48240166 A>G), RS1000369021 (16:48217412 A>G), RS1000408527 (16:48233157 T>C)

Disease associations

OMIM: gene MIM:607040 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): breast ductal adenocarcinoma (MONDO:0005590)

Orphanet (0):

HPO phenotypes

3 total (3 of 3 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000598	Abnormality of the ear
HP:0003002	Breast carcinoma

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST002586_6	Fasting plasma glucose	2.000000e-36
GCST006090_3	Excessive sweating	7.000000e-10

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D018270	Carcinoma, Ductal, Breast	C04.557.470.200.025.232.500; C04.557.470.615.132.500; C04.588.180.390; C17.800.090.500.390

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2073702 (SINGLE PROTEIN)

PharmGKB: 1 entry (VIP=true, CPIC=false)

PharmGKB clinical annotations

1 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs7194667	Toxicity	3	fluorouracil	Leukopenia;Neoplasms

PharmGKB variants

5 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs7194667	ABCC11	3	3.00	1	fluorouracil
rs8056100	ABCC11		0.00	0
rs11861379	ABCC11		0.00	0
rs17822471	ABCC11		0.00	0
rs17822931	ABCC11		0.00	0

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: transporter — ABCC subfamily

CTD chemical–gene interactions

30 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Aflatoxin B1	decreases expression, decreases methylation, increases methylation	3
Fulvestrant	increases methylation, decreases expression, decreases reaction, affects cotreatment	2
Benzo(a)pyrene	affects methylation, decreases expression	2
Methotrexate	decreases abundance, decreases response to substance	2
Valproic Acid	affects expression, decreases methylation	2
methyleugenol	decreases expression	1
bisphenol A	affects cotreatment, increases methylation	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
CGP 52608	affects binding, increases reaction	1
Pemetrexed	affects response to substance, decreases response to substance	1
Docetaxel	decreases response to substance, increases expression	1
Amiodarone	increases expression	1
Cadmium	decreases expression	1
Chenodeoxycholic Acid	affects cotreatment, increases expression	1
Deoxycholic Acid	affects cotreatment, increases expression	1
Endosulfan	decreases expression	1
Estradiol	decreases expression, decreases reaction	1
Fluorodeoxyuridylate	decreases response to substance, increases export	1
Fluorouracil	decreases response to substance	1
Glycochenodeoxycholic Acid	affects cotreatment, increases expression	1
Glycocholic Acid	affects cotreatment, increases expression	1
Glycodeoxycholic Acid	affects cotreatment, increases expression	1
N-Nitrosopyrrolidine	decreases expression	1
Rifampin	increases expression	1
Tamoxifen	decreases reaction, increases expression, decreases expression	1
Triclosan	affects cotreatment, increases expression	1
Urethane	decreases expression	1
Zidovudine	increases expression	1
Okadaic Acid	decreases expression	1
Genistein	increases expression	1

ChEMBL screening assays

15 unique, capped per target: 15 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL2075321	Functional	TP_TRANSPORTER: efflux in MRP8-1-expressing LLC-PK1 cells	MRP8, ATP-binding cassette C11 (ABCC11), is a cyclic nucleotide efflux pump and a resistance factor for fluoropyrimidines 2’,3’-dideoxycytidine and 9’-(2’-phosphonylmethoxyethyl)adenine. — J Biol Chem

Clinical trials (associated diseases)

11 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT03414970	PHASE3	ACTIVE_NOT_RECRUITING	Hypofractionated Radiation Therapy After Mastectomy in Preventing Recurrence in Patients With Stage IIa-IIIa Breast Cancer
NCT00461344	PHASE2	TERMINATED	Docetaxel + Doxorubicin as Neoadjuvant Chemotherapy in Patients With Breast Cancer
NCT07499999	PHASE2	NOT_YET_RECRUITING	Randomized Double-Blind Phase II Trial of Baby Exemestane Versus Baby Tamoxifen in Post-Menopausal Women at High Risk for Breast Cancer
NCT00637364	PHASE1/PHASE2	SUSPENDED	High Intensity Focused Ultrasound Tumor Treatment for Pancreatic Cancer Pain
NCT02779855	PHASE1/PHASE2	COMPLETED	Talimogene Laherparepvec in Combination With Neoadjuvant Chemotherapy in Triple Negative Breast Cancer
NCT01753908	EARLY_PHASE1	COMPLETED	Broccoli Sprout Extract in Treating Patients With Breast Cancer
NCT01796041	EARLY_PHASE1	COMPLETED	Intraoperative Imaging of Breast Cancer With Indocyanine Green
NCT01208974	Not specified	ACTIVE_NOT_RECRUITING	Nipple-Areola Complex (NAC) Irradiation After Nipple-Sparing Mastectomy and Reconstruction
NCT01875198	Not specified	TERMINATED	Oncologic Impact of Splenectomy-omitting Radical Pancreatectomy in Well-selected Left-sided Pancreatic Cancer
NCT03543397	Not specified	UNKNOWN	MRI in Ductal Carcinoma in Situ (DCIS)
NCT03834532	Not specified	COMPLETED	Living Well After Breast Surgery