ABCG2 ATP binding cassette subfamily G member 2 (Junior blood group) [Homo sapiens (human)] - Gene

Summary

Official Symbol: ABCG2provided by HGNC
Official Full Name: ATP binding cassette subfamily G member 2 (Junior blood group)provided by HGNC
Primary source: HGNC:HGNC:74
See related: Ensembl:ENSG00000118777 MIM:603756
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: MRX; MXR; ABCP; BCRP; BMDP; MXR1; ABC15; BCRP1; CD338; GOUT1; MXR-1; CDw338; UAQTL1; EST157481
Summary: The membrane-associated protein encoded by this gene is included in 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 White subfamily. Alternatively referred to as a breast cancer resistance protein, this protein functions as a xenobiotic transporter which may play a major role in multi-drug resistance. It likely serves as a cellular defense mechanism in response to mitoxantrone and anthracycline exposure. Significant expression of this protein has been observed in the placenta, which may suggest a potential role for this molecule in placenta tissue. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Apr 2012]
Expression: Biased expression in small intestine (RPKM 33.2), duodenum (RPKM 16.6) and 12 other tissues See more
Orthologs: mouse all

Genomic context

Location:: 4q22.1

Exon count:: 21

Annotation release	Status	Assembly	Chr	Location
109.20200228	current	GRCh38.p13 (GCF_000001405.39)	4	NC_000004.12 (88090264..88231626, complement)
105	previous assembly	GRCh37.p13 (GCF_000001405.25)	4	NC_000004.11 (89011416..89152569, complement)

Chromosome 4 - NC_000004.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

These results provide strong evidence for a role of ABCG2 and BCRP in allopurinol response.
Title: Genome-Wide Association and Functional Studies Reveal Novel Pharmacological Mechanisms for Allopurinol.
The joint effect of the ABCG2 rs2231142 T allele and cardiovascular risk factors (obesity, hypertension and dyslipidemia) was also associated with increased Hyperuricemia (HUA) risk and serum uric acid levels. Each copy of the risk T allele was significantly associated with enhanced HUA risk in patients with hypertriglyceridemia compared to controls.
Title: ABCG2 rs2231142 variant in hyperuricemia is modified by SLC2A9 and SLC22A12 polymorphisms and cardiovascular risk factors in an elderly community-dwelling population.
CCN2 increases ABCG2 expression and promotes drug resistance through the alpha6beta1 integrin receptor, whereas CCN2 downregulates miR-519d.
Title: CCN2 promotes drug resistance in osteosarcoma by enhancing ABCG2 expression.
Hepatocellular Carcinoma Cells with Downregulated ZEB2 Become Resistant to Resveratrol by Concomitant Induction of ABCG2 Expression
Title: [Hepatocellular Carcinoma Cells with Downregulated ZEB2 Become Resistant to Resveratrol by Concomitant Induction of ABCG2 Expression].
Results suggest that genetic factors affecting ATP binding cassette subfamily G member 2 (ABCG2) function should be routinely considered in a hyperuricemia/gout diagnosis, especially in pediatric-onset patients.
Title: The impact of dysfunctional variants of ABCG2 on hyperuricemia and gout in pediatric-onset patients.
Over expression of ABCG2 transporter gene is one of the factors responsible for drug resistance in Cancer stem cells (CSCs), which causes efflux of therapeutic drugs from these cells. Curcumin and quinacrine synergistically promote CSCs death by increasing the concentration of quinacrine in the cells and thus causing the DNA damage and inhibiting the DNA repair pathways through modulating the ABCG2 activity.
Title: Quinacrine and curcumin synergistically increased the breast cancer stem cells death by inhibiting ABCG2 and modulating DNA damage repair pathway.
No significant differences of afatinib exposure were found between the ABCG2 wild-type and heterozygous groups
Title: Effects of the <i>ABCB1</i> and <i>ABCG2</i> polymorphisms on the pharmacokinetics of afatinib in healthy Chinese volunteers.
Enhanced drug retention was achieved by downregulation of SOX2 and ABCG2, both of which contribute to drug resistance of the cancer stem cells (CSC). In addition, nWdl prevented epithelial-to-mesenchymal transition, suppressed cell migration and invasion, and reduced the percentage of breast cancer stem cells (BCSC) in MDA-MB-231 cells.
Title: Enhancing Chemosensitivity of Breast Cancer Stem Cells by Downregulating SOX2 and ABCG2 Using Wedelolactone-encapsulated Nanoparticles.
The di-leucine motif acts as a valve that controls drug extrusion. Moreover, the extracellular structure engages the re-entry helix and all extracellular loops to form a roof architecture on top of the upper cavity. Disulfide bridges and a salt bridge limit roof flexibility, but provide a lid-like function to control drug release.
Title: The ABCG2 multidrug transporter is a pump gated by a valve and an extracellular lid.
we aimed to summarize and highlight the current knowledge of the metabolism and transport of silymarin. It was concluded that the major efflux transporters of silybin are multidrug resistance-associated protein (MRP2) and breast cancer resistance protein (BCRP) based on results from the transporter-overexpressing cell lines and MRP2-deficient (TR(-)) rats.
Title: Metabolism, Transport and Drug-Drug Interactions of Silymarin.

Submit: New GeneRIF Correction See all GeneRIFs (716)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Blood group, Junior system MedGen: C3280986 OMIM: 614490 GeneReviews: Not available	not available
Uric acid concentration, serum, quantitative trait locus 1 MedGen: C1841837 OMIM: 138900 GeneReviews: Not available	Compare labs

NHGRI GWAS Catalog

Description
A genome-wide association study identifies common variants influencing serum uric acid concentrations in a Chinese population. NHGRI GWA Catalog NHGRI GWA CatalogPubMed
Association of three genetic loci with uric acid concentration and risk of gout: a genome-wide association study. NHGRI GWA Catalog NHGRI GWA CatalogPubMed
Genetic determinants of statin-induced low-density lipoprotein cholesterol reduction: the Justification for the Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin (JUPITER) trial. NHGRI GWA Catalog NHGRI GWA CatalogPubMed
Genetic variants in LPL, OASL and TOMM40/APOE-C1-C2-C4 genes are associated with multiple cardiovascular-related traits. NHGRI GWA Catalog NHGRI GWA CatalogPubMed
Genome-wide association analyses identify 18 new loci associated with serum urate concentrations. NHGRI GWA Catalog NHGRI GWA CatalogPubMed
Genome-wide association of serum uric acid concentration: replication of sequence variants in an island population of the Adriatic coast of Croatia. NHGRI GWA Catalog NHGRI GWA CatalogPubMed
Genome-wide association study evaluating lipoprotein-associated phospholipase A2 mass and activity at baseline and after rosuvastatin therapy. NHGRI GWA Catalog NHGRI GWA CatalogPubMed
Genome-wide association study of hematological and biochemical traits in a Japanese population. NHGRI GWA Catalog NHGRI GWA CatalogPubMed
Genome-wide meta-analysis identifies six novel loci associated with habitual coffee consumption. NHGRI GWA Catalog NHGRI GWA CatalogPubMed
GWAS of dental caries patterns in the permanent dentition. NHGRI GWA Catalog NHGRI GWA CatalogPubMed
Identification of low-frequency variants associated with gout and serum uric acid levels. NHGRI GWA Catalog NHGRI GWA CatalogPubMed
Meta-analysis identifies multiple loci associated with kidney function-related traits in east Asian populations. NHGRI GWA Catalog NHGRI GWA CatalogPubMed
Meta-analysis of 28,141 individuals identifies common variants within five new loci that influence uric acid concentrations. NHGRI GWA Catalog NHGRI GWA CatalogPubMed
Multiple genetic loci influence serum urate levels and their relationship with gout and cardiovascular disease risk factors. NHGRI GWA Catalog NHGRI GWA CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Protein interactions

Protein	Gene	Interaction	Pubs
Tat	tat	HIV-1 Tat protein upregulates ABCG2 (BRCP) expression and enhances efflux mediated by this host protein significantly	PubMed

Go to the HIV-1, Human Interaction Database

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

SHGC-24753 (e-PCR)
- UniSTS:64270

RH18379 (e-PCR)
- UniSTS:62742

STS-AA001604 (e-PCR)
- UniSTS:47154

SHGC-59795 (e-PCR)
- UniSTS:64580

SHGC-67418 (e-PCR)
- UniSTS:66120

ABCG2_1993 (e-PCR)
- UniSTS:280425

ABCG2 (e-PCR)
- UniSTS:503454

D4S2623 (e-PCR), detects polymorphism
- UniSTS:3249

ABCG2 (e-PCR)
- UniSTS:519123

Homology

Homologs of the ABCG2 gene: The ABCG2 gene is conserved in chimpanzee, Rhesus monkey, dog, cow, mouse, rat, chicken, zebrafish, fruit fly, mosquito, C.elegans, S.cerevisiae, K.lactis, E.gossypii, M.oryzae, N.crassa, A.thaliana, rice, and frog.
Orthologs from Annotation Pipeline: 199 organisms have orthologs with human gene ABCG2
Orthologs

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
ATP binding	IEA Inferred from Electronic Annotation more info
ATPase activity	IEA Inferred from Electronic Annotation more info
ATPase activity, coupled to transmembrane movement of substances	IBA Inferred from Biological aspect of Ancestor more info	PubMed
ATPase activity, coupled to transmembrane movement of substances	IMP Inferred from Mutant Phenotype more info	PubMed
biotin transmembrane transporter activity	ISS Inferred from Sequence or Structural Similarity more info
efflux transmembrane transporter activity	IMP Inferred from Mutant Phenotype more info	PubMed
efflux transmembrane transporter activity	ISS Inferred from Sequence or Structural Similarity more info
identical protein binding	IPI Inferred from Physical Interaction more info	PubMed
protein binding	IPI Inferred from Physical Interaction more info	PubMed
protein homodimerization activity	IDA Inferred from Direct Assay more info	PubMed
riboflavin transmembrane transporter activity	IDA Inferred from Direct Assay more info	PubMed
urate transmembrane transporter activity	IMP Inferred from Mutant Phenotype more info	PubMed
xenobiotic transmembrane transporter activity	ISS Inferred from Sequence or Structural Similarity more info
xenobiotic transmembrane transporting ATPase activity	IDA Inferred from Direct Assay more info	PubMed

Process	Evidence Code	Pubs
biotin transport	ISS Inferred from Sequence or Structural Similarity more info
cellular detoxification	IDA Inferred from Direct Assay more info	PubMed
cellular iron ion homeostasis	TAS Traceable Author Statement more info
drug transport across blood-brain barrier	IC Inferred by Curator more info
drug transport across blood-brain barrier	IDA Inferred from Direct Assay more info	PubMed
export across plasma membrane	ISS Inferred from Sequence or Structural Similarity more info
riboflavin transport	IDA Inferred from Direct Assay more info	PubMed
transepithelial transport	IDA Inferred from Direct Assay more info	PubMed
transmembrane transport	IBA Inferred from Biological aspect of Ancestor more info	PubMed
transmembrane transport	IMP Inferred from Mutant Phenotype more info	PubMed
urate metabolic process	IMP Inferred from Mutant Phenotype more info	PubMed
urate salt excretion	IMP Inferred from Mutant Phenotype more info	PubMed
urate transport	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
apical plasma membrane	ISS Inferred from Sequence or Structural Similarity more info
brush border membrane	IDA Inferred from Direct Assay more info	PubMed
cell	IEA Inferred from Electronic Annotation more info
external side of apical plasma membrane	ISS Inferred from Sequence or Structural Similarity more info	PubMed
integral component of membrane	IEA Inferred from Electronic Annotation more info
membrane raft	IDA Inferred from Direct Assay more info	PubMed
mitochondrial membrane	IEA Inferred from Electronic Annotation more info
nucleoplasm	IDA Inferred from Direct Assay more info
plasma membrane	IBA Inferred from Biological aspect of Ancestor more info	PubMed
plasma membrane	IDA Inferred from Direct Assay more info	PubMed
plasma membrane	TAS Traceable Author Statement more info

General protein information

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Preferred Names: broad substrate specificity ATP-binding cassette transporter ABCG2

Names: ABC transporter; ATP-binding cassette transporter G2; ATP-binding cassette, sub-family G (WHITE), member 2 (Junior blood group); breast cancer resistance protein; mitoxantrone resistance-associated protein; multi drug resistance efflux transport ATP-binding cassette sub-family G (WHITE) member 2; placenta specific MDR protein; placenta-specific ATP-binding cassette transporter; urate exporter

NP_001244315.1

EC 7.6.2.2

NP_001335914.1

EC 7.6.2.2

NP_001335915.1

EC 7.6.2.2

NP_001335916.1

EC 7.6.2.2

NP_001335917.1

EC 7.6.2.2

NP_001335918.1

EC 7.6.2.2

NP_004818.2

EC 7.6.2.2

XP_005263412.1

EC 7.6.2.2

XP_011530722.1

EC 7.6.2.2

XP_016864341.1

EC 7.6.2.2

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_032067.2 RefSeqGene

Range

77684..146054

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001257386.2 → NP_001244315.1 broad substrate specificity ATP-binding cassette transporter ABCG2 isoform 2

Status: REVIEWED

Description

Transcript Variant: This variant (2) differs in the 5' UTR and uses an alternate splice site in the 3' coding region which results in a frameshift. The resulting protein (isoform 2) is shorter and has a distinct and shorter C-terminus compared to isoform 1.

Source sequence(s)

AC084732, AC097484

Consensus CDS

CCDS58910.1

UniProtKB/Swiss-Prot

Q9UNQ0

Related

ENSP00000426917.1, ENST00000515655.5

Conserved Domains (3) summary

cd03213
Location:34 → 268

ABCG_EPDR; Eye pigment and drug resistance transporter subfamily G of the ATP-binding cassette superfamily

COG1131
Location:60 → 338

CcmA; ABC-type multidrug transport system, ATPase component [Defense mechanisms]

pfam01061
Location:380 → 549

ABC2_membrane; ABC-2 type transporter
NM_001348985.1 → NP_001335914.1 broad substrate specificity ATP-binding cassette transporter ABCG2 isoform 1

Status: REVIEWED

Source sequence(s)

AC084732, AC097484

Consensus CDS

CCDS3628.1

Related

ENSP00000498246.1, ENST00000650821.1

Conserved Domains (1) summary

cl28180
Location:55 → 649

PRK10535; macrolide transporter ATP-binding /permease protein; Provisional
NM_001348986.1 → NP_001335915.1 broad substrate specificity ATP-binding cassette transporter ABCG2 isoform 1

Status: REVIEWED

Source sequence(s)

AC084732, AC097484

Consensus CDS

CCDS3628.1

Conserved Domains (1) summary

cl28180
Location:55 → 649

PRK10535; macrolide transporter ATP-binding /permease protein; Provisional
NM_001348987.1 → NP_001335916.1 broad substrate specificity ATP-binding cassette transporter ABCG2 isoform 3

Status: REVIEWED

Source sequence(s)

AC084732, AC097484

Conserved Domains (1) summary

cl28180
Location:55 → 647

PRK10535; macrolide transporter ATP-binding /permease protein; Provisional
NM_001348988.1 → NP_001335917.1 broad substrate specificity ATP-binding cassette transporter ABCG2 isoform 1

Status: REVIEWED

Source sequence(s)

AC084732, AC097484

Consensus CDS

CCDS3628.1

Conserved Domains (1) summary

cl28180
Location:55 → 649

PRK10535; macrolide transporter ATP-binding /permease protein; Provisional
NM_001348989.1 → NP_001335918.1 broad substrate specificity ATP-binding cassette transporter ABCG2 isoform 1

Status: REVIEWED

Source sequence(s)

AC084732, AC097484

Consensus CDS

CCDS3628.1

Conserved Domains (1) summary

cl28180
Location:55 → 649

PRK10535; macrolide transporter ATP-binding /permease protein; Provisional
NM_004827.3 → NP_004818.2 broad substrate specificity ATP-binding cassette transporter ABCG2 isoform 1

See identical proteins and their annotated locations for NP_004818.2

Status: REVIEWED

Description

Transcript Variant: This variant (1) encodes the longest isoform (1).

Source sequence(s)

BC021281, BC092408, BI598784

Consensus CDS

CCDS3628.1

UniProtKB/Swiss-Prot

Q9UNQ0

UniProtKB/TrEMBL

A0A024RDD4

Related

ENSP00000237612.3, ENST00000237612.8

Conserved Domains (1) summary

cl28180
Location:55 → 649

PRK10535; macrolide transporter ATP-binding /permease protein; Provisional

RefSeqs of Annotated Genomes: Homo sapiens Updated Annotation Release 109.

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p13 Primary Assembly

Genomic

NC_000004.12 Reference GRCh38.p13 Primary Assembly

Range

88090264..88231626 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_005263355.4 → XP_005263412.1 broad substrate specificity ATP-binding cassette transporter ABCG2 isoform X1

See identical proteins and their annotated locations for XP_005263412.1

UniProtKB/Swiss-Prot

Q9UNQ0

UniProtKB/TrEMBL

A0A024RDD4

Conserved Domains (1) summary

cl28180
Location:55 → 649

PRK10535; macrolide transporter ATP-binding /permease protein; Provisional
XM_011532420.3 → XP_011530722.1 broad substrate specificity ATP-binding cassette transporter ABCG2 isoform X1

See identical proteins and their annotated locations for XP_011530722.1

UniProtKB/Swiss-Prot

Q9UNQ0

UniProtKB/TrEMBL

A0A024RDD4

Conserved Domains (1) summary

cl28180
Location:55 → 649

PRK10535; macrolide transporter ATP-binding /permease protein; Provisional
XM_017008852.2 → XP_016864341.1 broad substrate specificity ATP-binding cassette transporter ABCG2 isoform X2

Conserved Domains (1) summary

cl28180
Location:55 → 647

PRK10535; macrolide transporter ATP-binding /permease protein; Provisional