ABCC12

Summary

ABCC12 (ATP binding cassette subfamily C member 12, HGNC:14640) is a protein-coding gene on chromosome 16q12.1, encoding ATP-binding cassette sub-family C member 12 (Q96J65). Probable transporter, its substrate specificity is unknown.

This gene is a member of the superfamily of ATP-binding cassette (ABC) transporters and the encoded protein contains two ATP-binding domains and 12 transmembrane regions. ABC proteins transport various molecules across extra- and intracellular membranes. ABC genes are divided into seven distinct subfamilies: ABC1, MDR/TAP, MRP, ALD, OABP, GCN20, and White. This gene is a member of the MRP subfamily which is involved in multi-drug resistance. This gene and another subfamily member are arranged head-to-tail on chromosome 16q12.1. Increased expression of this gene is associated with breast cancer.

Source: NCBI Gene 94160 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 214 total
• MANE Select transcript: NM_001393797

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:14640
Approved symbol	ABCC12
Name	ATP binding cassette subfamily C member 12
Location	16q12.1
Locus type	gene with protein product
Status	Approved
Aliases	MRP9
Ensembl gene	ENSG00000140798
Ensembl biotype	protein_coding
OMIM	607041
Entrez	94160

Gene structure

Transcript identifiers

Ensembl transcripts: 14 — 5 nonsense_mediated_decay, 4 protein_coding, 4 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000311303, ENST00000497206, ENST00000526251, ENST00000527640, ENST00000528693, ENST00000529084, ENST00000529504, ENST00000532355, ENST00000532494, ENST00000533185, ENST00000533639, ENST00000534418, ENST00000649885, ENST00000689320

RefSeq mRNA: 5 — MANE Select: NM_001393797 NM_001392028, NM_001393797, NM_001393798, NM_001393799, NM_033226

CCDS: CCDS92153, CCDS92154, CCDS92155

Canonical transcript exons

ENST00000311303 — 31 exons

Exon	Start	End
ENSE00000945092	48121716	48121840
ENSE00000945093	48117261	48117333
ENSE00000945096	48111578	48111662
ENSE00000945103	48096746	48096902
ENSE00002174309	48153616	48153884
ENSE00002197693	48155841	48155993
ENSE00003466791	48088545	48088734
ENSE00003485107	48104142	48104368
ENSE00003493015	48083909	48084073
ENSE00003496492	48107322	48107425
ENSE00003496798	48111436	48111507
ENSE00003500716	48128459	48128737
ENSE00003509988	48100872	48101009
ENSE00003522080	48105139	48105336
ENSE00003543654	48087926	48088085
ENSE00003545245	48139163	48139336
ENSE00003578299	48133687	48133835
ENSE00003595549	48138228	48138375
ENSE00003599944	48140687	48140920
ENSE00003608468	48091120	48091209
ENSE00003618747	48115415	48115618
ENSE00003623849	48108440	48108529
ENSE00003640654	48086741	48086819
ENSE00003645277	48124213	48124284
ENSE00003648211	48130788	48130895
ENSE00003662894	48085593	48085706
ENSE00003672974	48111776	48111910
ENSE00003681904	48143910	48144065
ENSE00003686500	48141206	48141353
ENSE00003927689	48080882	48083801
ENSE00003928517	48146306	48146474

Expression profiles

Bgee: expression breadth broad, 78 present calls, max score 83.13.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.1558 / max 21.1889, expressed in 53 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
157252	0.0989	41
207868	0.0506	30
157254	0.0063	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	83.13	gold quality
left testis	UBERON:0004533	79.42	gold quality
right testis	UBERON:0004534	78.55	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	78.46	gold quality
testis	UBERON:0000473	76.80	gold quality
right frontal lobe	UBERON:0002810	73.57	gold quality
prefrontal cortex	UBERON:0000451	71.78	gold quality
Brodmann (1909) area 9	UBERON:0013540	70.83	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	69.37	gold quality
frontal cortex	UBERON:0001870	68.48	gold quality
neocortex	UBERON:0001950	66.31	gold quality
anterior cingulate cortex	UBERON:0009835	64.37	gold quality
cerebral cortex	UBERON:0000956	62.90	gold quality
buccal mucosa cell	CL:0002336	62.01	silver quality
hindlimb stylopod muscle	UBERON:0004252	60.68	gold quality
primary visual cortex	UBERON:0002436	55.36	gold quality
muscle of leg	UBERON:0001383	55.17	gold quality
superior frontal gyrus	UBERON:0002661	53.92	gold quality
gastrocnemius	UBERON:0001388	53.73	gold quality
Ammon’s horn	UBERON:0001954	52.82	gold quality
middle temporal gyrus	UBERON:0002771	51.70	gold quality
right hemisphere of cerebellum	UBERON:0014890	51.69	gold quality
occipital lobe	UBERON:0002021	51.46	gold quality
forebrain	UBERON:0001890	50.90	gold quality
biceps brachii	UBERON:0001507	50.52	gold quality
brain	UBERON:0000955	49.82	gold quality
amygdala	UBERON:0001876	49.72	gold quality
skeletal muscle tissue	UBERON:0001134	48.77	gold quality
cortical plate	UBERON:0005343	47.77	silver quality
cerebellar cortex	UBERON:0002129	47.69	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.72

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

68 targeting ABCC12, 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-5193	100.00	67.26	1744
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-4481	100.00	66.42	1669
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-552-5P	99.93	68.56	1583
HSA-MIR-338-5P	99.92	72.34	2951
HSA-MIR-6780A-5P	99.88	66.69	2776
HSA-MIR-6857-5P	99.87	65.32	985
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-548AZ-5P	99.83	69.94	3230
HSA-MIR-548T-5P	99.83	69.91	3220
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-3133	99.81	70.92	3506
HSA-MIR-1273H-5P	99.77	66.32	2471
HSA-MIR-4517	99.76	69.19	1867
HSA-MIR-11181-3P	99.75	66.38	2205
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-1296-3P	99.72	64.04	636
HSA-MIR-494-3P	99.70	71.45	2795
HSA-MIR-30B-3P	99.70	65.76	2325
HSA-MIR-3689A-3P	99.70	65.73	2306
HSA-MIR-3689B-3P	99.70	65.71	2311
HSA-MIR-3689C	99.70	65.71	2311
HSA-MIR-6779-5P	99.70	65.76	2363
HSA-MIR-548AU-3P	99.70	68.22	1373
HSA-MIR-4729	99.69	72.18	4233

Literature-anchored findings (GeneRIF, showing 2)

• alternative splice variants and gene expression (PMID:11688999)
• Deleterious Variants in ABCC12 are Detected in Idiopathic Chronic Cholestasis and Cause Intrahepatic Bile Duct Loss in Model Organisms. (PMID:33771553)

Cross-species orthologs

14 orthologs

Organism	Symbol	Gene ID
danio_rerio	abcc12	ENSDARG00000013050
mus_musculus	Abcc12	ENSMUSG00000036872
rattus_norvegicus	Abcc12	ENSRNOG00000015666
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	Mrp4	FBGN0263316
caenorhabditis_elegans		WBGENE00000477

Paralogs (11): CFTR (ENSG00000001626), ABCC8 (ENSG00000006071), ABCC2 (ENSG00000023839), ABCC9 (ENSG00000069431), ABCC6 (ENSG00000091262), ABCC1 (ENSG00000103222), ABCC3 (ENSG00000108846), ABCC5 (ENSG00000114770), ABCC11 (ENSG00000121270), ABCC10 (ENSG00000124574), ABCC4 (ENSG00000125257)

Protein

Protein identifiers

ATP-binding cassette sub-family C member 12 — Q96J65 (reviewed: Q96J65)

Alternative names: Multidrug resistance-associated protein 9

All UniProt accessions (7): Q96J65, A0A3B3ITL4, A0A8I5KPE2, A0A8I5QJT3, A0A8J8YUR7, B4DYN2, E9PHY2

UniProt curated annotations — full annotation on UniProt →

Function. Probable transporter, its substrate specificity is unknown.

Subcellular location. Endoplasmic reticulum membrane.

Tissue specificity. Expressed in testis (at protein level). Widely expressed at low level. Isoform 5 is specifically expressed in brain, testis and breast cancer cells.

Miscellaneous. May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay. May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay. May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay. May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.

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

Isoforms (5)

UniProt ID	Names	Canonical?
Q96J65-1	1	yes
Q96J65-2	2, A, C, D
Q96J65-3	3, B
Q96J65-4	4
Q96J65-5	5

RefSeq proteins (5): NP_001378957, NP_001380726, NP_001380727, NP_001380728, NP_150229 (=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

UniProt features (46 total): sequence variant 11, transmembrane region 10, splice variant 8, domain 4, glycosylation site 4, sequence conflict 4, binding site 2, chain 1, region of interest 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96J65-F1	78.09	0.21

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): 513–520; 1154–1161

Glycosylation sites (4): 405, 438, 540, 981

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 58 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_MCMV_INFECTION_DN, GSE45365_NK_CELL_VS_CD8A_DC_MCMV_INFECTION_UP, TTTGTAG_MIR520D, KEGG_ABC_TRANSPORTERS, GOBP_TRANSMEMBRANE_TRANSPORT, GOCC_NUCLEAR_OUTER_MEMBRANE_ENDOPLASMIC_RETICULUM_MEMBRANE_NETWORK, GOCC_ORGANELLE_SUBCOMPARTMENT, GOMF_HYDROLASE_ACTIVITY_ACTING_ON_ACID_ANHYDRIDES, GOMF_ACTIVE_TRANSMEMBRANE_TRANSPORTER_ACTIVITY, GOMF_ATP_HYDROLYSIS_ACTIVITY, GOMF_ADENYL_NUCLEOTIDE_BINDING, GOMF_TRANSPORTER_ACTIVITY, GOMF_PRIMARY_ACTIVE_TRANSMEMBRANE_TRANSPORTER_ACTIVITY, IGLV5_37_TARGET_GENES, TOP2B_TARGET_GENES

GO Biological Process (1): transmembrane transport (GO:0055085)

GO Molecular Function (4): ATP binding (GO:0005524), ATP hydrolysis activity (GO:0016887), ABC-type transporter activity (GO:0140359), nucleotide binding (GO:0000166)

GO Cellular Component (3): endoplasmic reticulum (GO:0005783), endoplasmic reticulum membrane (GO:0005789), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
transport	1
cellular process	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
ribonucleoside triphosphate phosphatase activity	1
ATP-dependent activity	1
ATPase-coupled transmembrane transporter activity	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1122 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ABCC12	MRPS7	Q9Y2R9	618
ABCC12	OR10AG1	Q8NH19	551
ABCC12	ABCF2	Q9UG63	524
ABCC12	TSGA10IP	Q3SY00	522
ABCC12	ABCE1	P61221	501
ABCC12	ALDH18A1	P54886	451
ABCC12	ABCF3	Q9NUQ8	450
ABCC12	PIGZ	Q86VD9	438
ABCC12	OR5M9	Q8NGP3	416
ABCC12	FSIP2	Q5CZC0	416
ABCC12	GPANK1	O95872	411
ABCC12	LRRFIP1	Q32MZ4	405
ABCC12	TARS2	Q9BW92	400
ABCC12	TMED2	Q15363	398
ABCC12	ZMIZ1	Q9ULJ6	387

IntAct

6 interactions, top by confidence:

A	B	Type	Score
VCPIP1	VCP	psi-mi:“MI:0914”(association)	0.530
ABCC12	NCL	psi-mi:“MI:0915”(physical association)	0.400
ABCC12	TPR	psi-mi:“MI:0915”(physical association)	0.400
ABCC12	SHTN1	psi-mi:“MI:0914”(association)	0.350
NPAS3	ARNT	psi-mi:“MI:0914”(association)	0.350

BioGRID (15): ABCC12 (Proximity Label-MS), ABCC12 (Proximity Label-MS), KIAA1598 (Affinity Capture-MS), ABCC11 (Affinity Capture-MS), CLUH (Affinity Capture-MS), ABCC12 (Affinity Capture-MS), ABCC12 (Co-localization), FKBP4 (Cross-Linking-MS (XL-MS)), GAPDH (Cross-Linking-MS (XL-MS)), NEFM (Cross-Linking-MS (XL-MS)), ABCC12 (Cross-Linking-MS (XL-MS)), EIF3A (Cross-Linking-MS (XL-MS)), ABCC12 (Affinity Capture-MS), ABCC12 (Co-fractionation), ABCC12 (Affinity Capture-MS)

ESM2 similar proteins: A0A125QXJ1, D3ZHR2, E7F6F7, G5EFD4, H2LNR5, O15440, O70595, O75027, P21441, P21958, P33897, P36370, P48410, P70170, P82451, P9WEL8, Q02592, Q08D64, Q09427, Q09428, Q09429, Q10185, Q2UPC0, Q42093, Q4WA92, Q4WPP6, Q61102, Q63120, Q63563, Q704E8, Q751N2, Q7DM58, Q8LPQ6, Q8RY46, Q92887, Q96J65, Q9C8G9, Q9C8H0, Q9C8H1, Q9DC29

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

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	188
Likely benign	12
Benign	5

Top pathogenic / likely-pathogenic (0)

SpliceAI

4334 predictions. Top by Δscore:

Variant	Effect	Δscore
16:48083901:T:TA	donor_gain	1.0000
16:48083903:CTATA:C	donor_loss	1.0000
16:48083904:TATA:T	donor_loss	1.0000
16:48083905:ATACC:A	donor_loss	1.0000
16:48083906:TACC:T	donor_loss	1.0000
16:48083907:A:AG	donor_loss	1.0000
16:48083911:T:A	donor_gain	1.0000
16:48083912:C:A	donor_gain	1.0000
16:48084069:ATGAT:A	acceptor_gain	1.0000
16:48084070:TGAT:T	acceptor_gain	1.0000
16:48084071:GAT:G	acceptor_gain	1.0000
16:48084072:AT:A	acceptor_gain	1.0000
16:48084072:ATCTG:A	acceptor_loss	1.0000
16:48084073:TC:T	acceptor_loss	1.0000
16:48084074:C:CA	acceptor_loss	1.0000
16:48084074:C:CC	acceptor_gain	1.0000
16:48084075:T:A	acceptor_loss	1.0000
16:48085587:TCTTA:T	donor_loss	1.0000
16:48085588:CTTAC:C	donor_loss	1.0000
16:48085589:TTACC:T	donor_loss	1.0000
16:48085590:TA:T	donor_loss	1.0000
16:48085591:A:T	donor_loss	1.0000
16:48085592:C:A	donor_loss	1.0000
16:48085702:ATTAT:A	acceptor_gain	1.0000
16:48085703:TTAT:T	acceptor_gain	1.0000
16:48085704:TAT:T	acceptor_gain	1.0000
16:48085705:AT:A	acceptor_gain	1.0000
16:48085707:C:CC	acceptor_gain	1.0000
16:48085708:T:G	acceptor_loss	1.0000
16:48086739:A:AC	donor_gain	1.0000

AlphaMissense

8926 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:48140794:A:G	W184R	0.996
16:48140794:A:T	W184R	0.996
16:48144010:A:G	W59R	0.994
16:48144010:A:T	W59R	0.994
16:48085636:C:G	R1262P	0.993
16:48096871:A:G	W1024R	0.993
16:48096871:A:T	W1024R	0.993
16:48121746:A:T	I561K	0.993
16:48124240:G:C	S520R	0.993
16:48124240:G:T	S520R	0.993
16:48124242:T:G	S520R	0.993
16:48124268:A:T	I511K	0.991
16:48115524:T:A	D627V	0.990
16:48115560:C:G	R615P	0.990
16:48140766:C:G	R193P	0.989
16:48115561:G:T	R615S	0.988
16:48115563:G:T	A614D	0.988
16:48124244:T:A	K519M	0.988
16:48140772:G:T	A191D	0.988
16:48140778:C:G	R189P	0.988
16:48141275:G:C	F118L	0.988
16:48141275:G:T	F118L	0.988
16:48141277:A:G	F118L	0.988
16:48141340:A:G	W97R	0.988
16:48141340:A:T	W97R	0.988
16:48115525:C:G	D627H	0.987
16:48117304:A:G	L581P	0.987
16:48115558:C:G	A616P	0.986
16:48115566:A:G	L613P	0.986
16:48121746:A:C	I561R	0.986

dbSNP variants (sampled 300 via entrez): RS1000029876 (16:48106571 GCTCT>G), RS1000092602 (16:48096988 G>A), RS1000126342 (16:48140097 G>C), RS1000219637 (16:48156369 C>T), RS1000245431 (16:48089845 G>T), RS1000269246 (16:48134067 G>C,T), RS1000323950 (16:48127286 C>T), RS1000443174 (16:48096712 T>C), RS1000466104 (16:48082296 G>T), RS1000481734 (16:48118514 A>G), RS1000519601 (16:48135139 G>A,T), RS1000586678 (16:48084149 A>C,G), RS1000629002 (16:48132800 T>C,G), RS1000633803 (16:48155360 T>A), RS1000639351 (16:48133852 A>G)

Disease associations

OMIM: gene MIM:607041 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST002337_15	Amyotrophic lateral sclerosis (sporadic)	9.000000e-06

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: transporter — ABCC subfamily

CTD chemical–gene interactions

8 total (human), top 8 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
benzo(e)pyrene	increases methylation	1
CGP 52608	affects binding, increases reaction	1
Methapyrilene	increases methylation	1
Phthalic Acids	affects methylation	1
Smoke	decreases expression	1
Dronabinol	increases expression	1
Tretinoin	increases expression	1
Aflatoxin B1	decreases methylation	1

Clinical trials (associated diseases)

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