ABCC2

ATP binding cassette subfamily C member 2, the group of ATP binding cassette subfamily C

Basic information

Region (hg38): 10:99782639-99852594

Previous symbols: [ "CMOAT" ]

Links

ENSG00000023839 ∙ NCBI:1244 ∙ OMIM:601107 ∙ HGNC:53 ∙ Uniprot:Q92887 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Dubin-Johnson syndrome (Supportive), mode of inheritance: AR
• Dubin-Johnson syndrome (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Dubin-Johnson syndrome	AD/AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Gastrointestinal	13193360; 5926936; 5532959; 520367; 2035335; 8621134; 9425227; 16952291; 16863439; 16549534; 19881259; 21044052; 22955427; 23007012; 23069858; 23115734
Heterozygotes may display manifestations; The presence of variants may have pharmacogenomic implications

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ABCC2 gene.

• not provided (498 variants)
• Dubin-Johnson syndrome (174 variants)
• Inborn genetic diseases (52 variants)
• ABCC2-related condition (32 variants)
• not specified (20 variants)
• Autosomal recessive inherited pseudoxanthoma elasticum (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ABCC2 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			34	69	8	111
missense	3	4	188	12	8	215
nonsense	27	3	1			31
start loss						0
frameshift	30	6	2			38
inframe indel			3			3
splice donor/acceptor (+/-2bp)	5	11	2			18
splice region			10	12	3	25
non coding			18	42	52	112
Total	65	24	248	123	68

Highest pathogenic variant AF is 0.000716

Variants in ABCC2

This is a list of pathogenic ClinVar variants found in the ABCC2 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
10-99782756-G-A		Dubin-Johnson syndrome	Uncertain significance (Jan 12, 2018)
10-99782802-A-G		Dubin-Johnson syndrome	Uncertain significance (Jan 13, 2018)
10-99782805-T-C		Dubin-Johnson syndrome	Uncertain significance (Jan 12, 2018)
10-99782821-C-T		Dubin-Johnson syndrome • not specified • ABCC2-related disorder	Benign/Likely benign (Oct 11, 2023)
10-99782822-G-A		Dubin-Johnson syndrome	Benign (Apr 27, 2017)
10-99782847-G-A		ABCC2-related disorder	Uncertain significance (Dec 12, 2023)
10-99782848-C-T			Likely benign (Mar 27, 2023)
10-99782850-G-A			Likely benign (Jan 19, 2024)
10-99782867-C-T		Dubin-Johnson syndrome • ABCC2-related disorder	Uncertain significance (Feb 13, 2024)
10-99782871-T-A			Likely benign (Mar 07, 2023)
10-99782879-T-C			Likely pathogenic (Oct 04, 2023)
10-99782884-A-T			Likely benign (Jan 04, 2024)
10-99782890-A-G		Dubin-Johnson syndrome	Conflicting classifications of pathogenicity (Jan 09, 2024)
10-99782895-T-C			Likely benign (Sep 08, 2023)
10-99784600-G-A		Dubin-Johnson syndrome	Conflicting classifications of pathogenicity (Jan 29, 2024)
10-99784602-C-T			Likely benign (Jan 22, 2024)
10-99784610-T-C			Likely benign (Nov 10, 2023)
10-99784630-C-T		Dubin-Johnson syndrome • ABCC2-related disorder	Uncertain significance (Dec 18, 2023)
10-99784631-G-A		Dubin-Johnson syndrome	Conflicting classifications of pathogenicity (Jan 04, 2024)
10-99784640-C-T			Likely benign (Aug 04, 2023)
10-99784641-C-T			Likely benign (Nov 29, 2022)
10-99784643-G-C			Likely benign (Jan 09, 2024)
10-99784662-A-T		Inborn genetic diseases	Uncertain significance (Dec 22, 2023)
10-99784664-T-A			Likely benign (May 16, 2023)
10-99784673-G-A			Conflicting classifications of pathogenicity (Nov 17, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ABCC2	protein_coding	protein_coding	ENST00000370449	32	69461

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
5.20e-47	6.44e-7	125193	2	553	125748	0.00221

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.995	863	785	1.10	0.0000433	10132
Missense in Polyphen		317	301.37	1.0518		3897
Synonymous	-0.406	315	306	1.03	0.0000170	3062
Loss of Function	0.381	73	76.6	0.953	0.00000430	883

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00287	0.00287
Ashkenazi Jewish	0.0000992	0.0000992
East Asian	0.00299	0.00294
Finnish	0.00864	0.00863
European (Non-Finnish)	0.00115	0.00114
Middle Eastern	0.00299	0.00294
South Asian	0.00340	0.00337
Other	0.00147	0.00147

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Mediates hepatobiliary excretion of numerous organic anions. May function as a cellular cisplatin transporter.
• Pathway: Methotrexate Pathway, Pharmacokinetics;Doxorubicin Pathway (Cancer Cell), Pharmacodynamics;Bile secretion - Homo sapiens (human);ABC transporters - Homo sapiens (human);Doxorubicin Pathway, Pharmacokinetics;Carbamazepine Pathway, Pharmacokinetics;Statin Pathway - Generalized, Pharmacokinetics;Atorvastatin/Lovastatin/Simvastatin Pathway, Pharmacokinetics;Pravastatin Pathway, Pharmacokinetics;Codeine and Morphine Pathway, Pharmacokinetics;Platinum Pathway, Pharmacokinetics/Pharmacodynamics;Vinka Alkaloid Pathway, Pharmacokinetics;Taxane Pathway, Pharmacokinetics;Lamivudine Pathway, Pharmacokinetics/Pharmacodynamics;Tramadol Pharmacokinetics;Mycophenolic acid Pathway, Pharmacokinetics;Mycophenolic acid Pathway, Pharmacokinetics/Pharmacodynamics;Ibuprofen Pathway, Pharmacokinetics;Irinotecan Pathway, Pharmacokinetics;Irinotecan Pathway, Pharmacodynamics;Doxorubicin Metabolism Pathway;Mycophenolic Acid Metabolism Pathway;Irinotecan Action Pathway;Docetaxel Action Pathway;Paclitaxel Action Pathway;Vincristine Action Pathway;Vinblastine Action Pathway;Vinorelbine Action Pathway;Vindesine Action Pathway;Tramadol Metabolism Pathway;Lamivudine Metabolism Pathway;Irinotecan Metabolism Pathway;Codeine and Morphine Metabolism;Drug Induction of Bile Acid Pathway;Irinotecan Pathway;Constitutive Androstane Receptor Pathway;Pregnane X Receptor pathway;Nuclear Receptors Meta-Pathway;NRF2 pathway;Nuclear Receptors in Lipid Metabolism and Toxicity;Photodynamic therapy-induced NFE2L2 (NRF2) survival signaling;Liver steatosis AOP;Transport of small molecules;ABC-family proteins mediated transport (Consensus)

Recessive Scores

• pRec: 0.239

Intolerance Scores

• loftool: 0.0978
• rvis_EVS: 0.96
• rvis_percentile_EVS: 90.09

Haploinsufficiency Scores

• pHI: 0.108
• hipred: N
• hipred_score: 0.167
• ghis: 0.403

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.782

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Abcc2
• Phenotype: renal/urinary system phenotype; homeostasis/metabolism phenotype; liver/biliary system phenotype; hematopoietic system phenotype

Gene ontology

• Biological process: bilirubin transport;transmembrane transport;ATP hydrolysis coupled anion transmembrane transport
• Cellular component: plasma membrane;integral component of plasma membrane;cell surface;membrane;apical plasma membrane
• Molecular function: protein binding;ATP binding;organic anion transmembrane transporter activity;bilirubin transmembrane transporter activity;ATPase activity, coupled to transmembrane movement of substances;ATPase-coupled anion transmembrane transporter activity