ABCC1

ATP binding cassette subfamily C member 1, the group of ATP binding cassette subfamily C

Basic information

Region (hg38): 16:15949137-16143257

Previous symbols: [ "MRP", "MRP1" ]

Links

ENSG00000103222 ∙ NCBI:4363 ∙ OMIM:158343 ∙ HGNC:51 ∙ Uniprot:P33527 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• hearing loss, autosomal dominant 77 (Moderate), mode of inheritance: AD
• autosomal dominant nonsyndromic hearing loss (Supportive), mode of inheritance: AD
• hearing loss, autosomal dominant 77 (Limited), mode of inheritance: Unknown

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Deafness, autosomal dominant 77	AD	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	Audiologic/Otolaryngologic	31273342

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ABCC1 gene.

• Inborn genetic diseases (42 variants)
• not provided (41 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ABCC1 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				15	8	23
missense			40	3	2	45
nonsense						0
start loss						0
frameshift						0
inframe indel			1			1
splice donor/acceptor (+/-2bp)						0
splice region				3	2	5
non coding				1		1
Total	0	0	41	19	10

Variants in ABCC1

This is a list of pathogenic ClinVar variants found in the ABCC1 region.

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

Position	Type	Phenotype	Significance	ClinVar
16-16007816-G-T		not specified	Uncertain significance (Apr 07, 2022)
16-16007817-A-T		not specified	Uncertain significance (Apr 07, 2022)
16-16007859-A-T		not specified	Uncertain significance (Nov 07, 2023)
16-16007925-A-G		not specified	Uncertain significance (Oct 21, 2021)
16-16007937-T-C		not specified	Uncertain significance (Dec 13, 2023)
16-16007952-G-A		ABCC1-related disorder	Benign (Sep 16, 2020)
16-16009796-G-T		not specified	Uncertain significance (Dec 13, 2022)
16-16009800-G-T		not specified	Uncertain significance (Nov 23, 2022)
16-16009812-G-C		not specified	Uncertain significance (Oct 25, 2022)
16-16009825-C-T		ABCC1-related disorder	Benign (Nov 16, 2020)
16-16009828-T-A		not specified	Uncertain significance (Jan 03, 2024)
16-16009829-C-A		not specified	Uncertain significance (Jan 26, 2022)
16-16009845-G-A		not specified	Uncertain significance (Dec 27, 2023)
16-16014412-G-A			not provided (-)
16-16016542-T-C		not specified	Uncertain significance (Jan 30, 2024)
16-16016556-A-G		not specified	Likely benign (Dec 21, 2023)
16-16016563-T-G		not specified	Uncertain significance (Aug 01, 2023)
16-16016583-G-C		not specified	Uncertain significance (Feb 16, 2023)
16-16016602-C-T			not provided (-)
16-16033130-G-T		not specified	Uncertain significance (Oct 12, 2022)
16-16033152-C-G		not specified	Uncertain significance (Jun 05, 2023)
16-16033158-G-C		not specified	Uncertain significance (May 09, 2023)
16-16036476-A-G		not specified	Uncertain significance (Dec 20, 2022)
16-16036477-T-C		not specified	Uncertain significance (Feb 27, 2024)
16-16036503-G-A		not specified	Uncertain significance (Jan 22, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ABCC1	protein_coding	protein_coding	ENST00000399410	31	193498

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00117	0.999	124854	0	56	124910	0.000224

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.77	782	935	0.837	0.0000594	9995
Missense in Polyphen		230	371.43	0.61923		3873
Synonymous	-1.93	457	407	1.12	0.0000290	3053
Loss of Function	5.85	21	76.1	0.276	0.00000392	854

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000504	0.000500
Ashkenazi Jewish	0.0000996	0.0000993
East Asian	0.0000556	0.0000556
Finnish	0.000326	0.000325
European (Non-Finnish)	0.000293	0.000291
Middle Eastern	0.0000556	0.0000556
South Asian	0.0000982	0.0000980
Other	0.000165	0.000164

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Mediates export of organic anions and drugs from the cytoplasm. Mediates ATP-dependent transport of glutathione and glutathione conjugates, leukotriene C4, estradiol-17-beta-o- glucuronide, methotrexate, antiviral drugs and other xenobiotics. Confers resistance to anticancer drugs. Hydrolyzes ATP with low efficiency. {ECO:0000269|PubMed:10064732, ECO:0000269|PubMed:11114332, ECO:0000269|PubMed:16230346}.
• Pathway: Methotrexate Pathway (Brain Cell), Pharmacokinetics;Methotrexate Pathway, Pharmacokinetics;Doxorubicin Pathway (Cancer Cell), Pharmacodynamics;Vitamin digestion and absorption - Homo sapiens (human);ABC transporters - Homo sapiens (human);Doxorubicin Pathway, Pharmacokinetics;Sphingolipid signaling pathway - Homo sapiens (human);MicroRNAs in cancer - Homo sapiens (human);Vinka Alkaloid Pathway, Pharmacokinetics;Taxane Pathway, Pharmacokinetics;Lamivudine Pathway, Pharmacokinetics/Pharmacodynamics;Pathway_PA165986194 -need delete;Acetaminophen Pathway, Pharmacokinetics;Irinotecan Pathway, Pharmacokinetics;Etoposide Pathway, Pharmacokinetics/Pharmacodynamics;Doxorubicin Metabolism Pathway;Irinotecan Action Pathway;Docetaxel Action Pathway;Paclitaxel Action Pathway;Vincristine Action Pathway;Vinblastine Action Pathway;Vinorelbine Action Pathway;Vindesine Action Pathway;Lamivudine Metabolism Pathway;Acetaminophen Metabolism Pathway;Irinotecan Metabolism Pathway;Irinotecan Pathway;multi-drug resistance factors;Metabolism of lipids;Synthesis of Leukotrienes (LT) and Eoxins (EX);Arachidonic acid metabolism;Androgen and estrogen biosynthesis and metabolism;Cobalamin (Cbl, vitamin B12) transport and metabolism;Metabolism;Fatty acid metabolism;Transport of small molecules;Metabolism of water-soluble vitamins and cofactors;Metabolism of vitamins and cofactors;ABC-family proteins mediated transport;Porphyrin metabolism;S1P1 pathway;Sphingosine 1-phosphate (S1P) pathway (Consensus)

Intolerance Scores

• loftool: 0.0802
• rvis_EVS: -0.84
• rvis_percentile_EVS: 11.29

Haploinsufficiency Scores

• pHI: 0.234
• hipred: Y
• hipred_score: 0.639
• ghis: 0.483

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.291

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Abcc1
• Phenotype: homeostasis/metabolism phenotype; immune system phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); hematopoietic system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span)

Gene ontology

• Biological process: leukotriene metabolic process;drug transmembrane transport;cobalamin metabolic process;cobalamin transport;glutathione transmembrane transport;response to drug;xenobiotic transport;phospholipid translocation;transmembrane transport;cell chemotaxis;sphingolipid translocation;ATP hydrolysis coupled anion transmembrane transport
• Cellular component: vacuolar membrane;plasma membrane;integral component of plasma membrane;membrane;basolateral plasma membrane;extracellular exosome
• Molecular function: phospholipid-translocating ATPase activity;transporter activity;ATP binding;xenobiotic transmembrane transporting ATPase activity;cobalamin-transporting ATPase activity;ATPase activity;glutathione transmembrane transporter activity;ATPase activity, coupled to transmembrane movement of substances;ATPase-coupled anion transmembrane transporter activity;sphingolipid-translocating ATPase activity