ABCB1

protein-coding

ATP binding cassette subfamily B member 1, the group of ATP binding cassette subfamily B|CD molecules

Gene summary

The membrane-associated 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 MDR/TAP subfamily. Members of the MDR/TAP subfamily are involved in multidrug resistance. The protein encoded by this gene is an ATP-dependent drug efflux pump for xenobiotic compounds with broad substrate specificity. It is responsible for decreased drug accumulation in multidrug-resistant cells and often mediates the development of resistance to anticancer drugs. This protein also functions as a transporter in the blood-brain barrier. Mutations in this gene are associated with colchicine resistance and Inflammatory bowel disease 13. Alternative splicing and the use of alternative promoters results in multiple transcript variants. [provided by RefSeq, Feb 2017]

Previous symbols:

PGY1
MDR1
CLCS

MANE transcript

NM_001348946.2

Inheritance

AD, AR

ClinVar variants

P:4U:248B:24

Top phenotype

Colchicine metabolism, association with; Encephalopathy, acute, transient

gnomAD constraint

pLI —, LoF o/e 0.33

Max pathogenic AF

—

Genomic locus

chr7:87,503,017-87,713,323

External References & Databases

Ensembl (ENSG00000085563)

Transcript & Mutation Effects

hg38 • Region Span ~210.3 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

inflammatory bowel disease 13LIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0012831

Submitter: PanelApp Australia

Clinical Genomic Database (CGD)

Colchicine metabolism, association with; Encephalopathy, acute, transientAD/AR

Manifestation: General

Intervention: Pharmacogenomic

Rationale: Selection and dosing of medications (eg,colchicine) may be affected by the presence of variants; In Encephalopathy, acute, transient, sequelae may be related to the use of certain medications, and awareness may allow appropriate avoidance and management of such episodes

Refs: 7188928; 7129432; 17259950; 18973929; 21851199; 32627353; 32813957

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to ABCB1 variants in ClinVar

9 Conditions Cataloged

Tramadol responseTotal: 499

not specifiedTotal: 86

not providedTotal: 22

ABCB1-related disorderTotal: 16

Inflammatory bowel disease 13Total: 3

Encephalopathy, acute transientTotal: 2

COLCHICINE RESISTANCETotal: 1

Hereditary breast ovarian cancer syndromeTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001348946.2. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			33 clinvar	14 clinvar	2 clinvar	49
missense	1 clinvar	1 clinvar	193 clinvar	5 clinvar	3 clinvar	203
nonsense	1 clinvar		9 clinvar			10
start loss						0
frameshift			7 clinvar			7
splice donor/acceptor (+/-2bp)	1 clinvar		6 clinvar			7
Total	3	1	248	19	5	276

Highest pathogenic variant AF is 0.0000020523205

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 37 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001348946.2	RefSeq	NP_001335875.1	27	MANE Select
ENST00000622132.5	Ensembl	ENSP00000478255.1	27	MANE Select
NM_000927.5	RefSeq	NP_000918.2	27	Standard
NM_001348944.2	RefSeq	NP_001335873.1	27	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
abcb4	Danio rerio	Structure: efflux transmembrane transporter activity Quality: decreased process quality abnormal

Gene / Model

Organism

Observed Phenotype

abcb4

Danio rerio

Structure: efflux transmembrane transporter activity

Quality: decreased process quality

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Citalopram Pathway, Pharmacokinetics
Methotrexate Pathway (Brain Cell), Pharmacokinetics
Methotrexate Pathway, Pharmacokinetics
Gastric cancer - Homo sapiens (human)
Doxorubicin Pathway (Cancer Cell), Pharmacodynamics

Biological Process

G2/M transition of mitotic cell cycle
drug transmembrane transport
response to drug
xenobiotic transport
phospholipid translocation

Molecular Function

transporter activity
protein binding
ATP binding
xenobiotic transmembrane transporting ATPase activity
ATPase activity, coupled to transmembrane movement of substances

Cellular Component

plasma membrane
cell surface
membrane
integral component of membrane
apical plasma membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000265724
Coding exons: 27
Length: 209437
Individuals with no LoFs: 125709
Homozygous LoFs: 0
Heterozygous LoFs: 39
Defined: 125748
p: 0.000155

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.44	579	685	0.845	0.0000367	8394
Missense (PolyPhen)		149	222.02	0.6711		2586
Synonymous	-0.185	245	241	1.02	0.0000125	2522
Loss of Function	4.98	21	64.0	0.328	0.00000365	772

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00025	0.00025	rare
Latino/Admixed American	0.00017	0.00017	rare
Ashkenazi Jewish	0.000099	0.000099	rare
East Asian	0.00011	0.00011	rare
Finnish	0.000093	0.000092	rare
European (Non-Finnish)	0.00018	0.00018	rare
South Asian	0.000065	0.000065	rare
Other	0.00033	0.00033	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.;
Disease: DISEASE: Inflammatory bowel disease 13 (IBD13) [MIM:612244]: A chronic, relapsing inflammation of the gastrointestinal tract with a complex etiology. It is subdivided into Crohn disease and ulcerative colitis phenotypes. Crohn disease may affect any part of the gastrointestinal tract from the mouth to the anus, but most frequently it involves the terminal ileum and colon. Bowel inflammation is transmural and discontinuous; it may contain granulomas or be associated with intestinal or perianal fistulas. In contrast, in ulcerative colitis, the inflammation is continuous and limited to rectal and colonic mucosal layers; fistulas and granulomas are not observed. Both diseases include extraintestinal inflammation of the skin, eyes, or joints. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.;

Recessive Scores

pRec: 0.680

Intolerance Scores

LoFtool: 0.0227
RVIS EVS: 0.1
RVIS percentile EVS: 60.76

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.519

Gene Damage Prediction

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