ABCB1

Chr 7AR

ATP binding cassette subfamily B member 1

Also known as: ABC20, CD243, CLCS, ENPAT, GP170, MDR1, P-GP, PGY1

NCBI Gene: 5243 ENSG00000085563 UniProt: P08183

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]

Primary Disease Associations & Inheritance

{Colchicine resistance}MIM #120080

{Inflammatory bowel disease 13}MIM #612244

Encephalopathy, acute transientMIM #620950

ClinVar variants

Pathogenic / LP

0.00

pLI score

Active trials

Clinical Summary— ABCB1

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Population Constraint (gnomAD)

Constrained for loss-of-function variants (OE-LoF 0.33) despite low pLI — interpret in context.

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Clinical Trials

12 active or recruiting trials — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.

0.47LOEUF

pLI 0.000

Z-score 4.98

OE 0.33 (0.23–0.47)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.

1.44Z-score

OE missense 0.85 (0.79–0.91)

579 obs / 685.1 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.

LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.33 (0.23–0.47)

0≤0.351.4

Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.85 (0.79–0.91)

0≤0.61.4

Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.02

ABCB1

Primary Disease Associations & Inheritance

Population Genetics & Constraint

ClinVar Variant Classifications

Protein Context — Lollipop Plot

OMIM — Genotype-Phenotype Relationships

Gene Overview

ClinGen Curation

Disease Associations

External Resources

Variant Interpretation

Population Databases

Gene Resources