ABCG2

protein-coding

ATP binding cassette subfamily G member 2 (Junior blood group), the group of ATP binding cassette subfamily G|CD molecules|Blood group antigens

Gene 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]

MANE transcript

NM_004827.3

Inheritance

ClinVar variants

P:1U:57B:5

Top phenotype

Blood group, junior system

gnomAD constraint

pLI —, LoF o/e 1.21

Max pathogenic AF

—

Genomic locus

chr4:88,090,150-88,231,628

External References & Databases

Ensembl (ENSG00000118777)

Transcript & Mutation Effects

hg38 • Region Span ~141.5 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

Clinical Genomic Database (CGD)

Blood group, junior systemBG

Manifestation: Hematologic

Intervention: Hematologic

Rationale: Variants associated with a blood group may be important in specific situations (eg, related to transfusion)

Refs: 567888; 18522708; 20890084; 22246505; 22246507

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to ABCG2 variants in ClinVar

6 Conditions Cataloged

not specifiedTotal: 44

not providedTotal: 5

BLOOD GROUP, JUNIOR SYSTEMTotal: 5

ABCG2-related disorderTotal: 3

URIC ACID CONCENTRATION, SERUM, QUANTITATIVE TRAIT LOCUS 1Total: 2

Hereditary breast ovarian cancer syndromeTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_004827.3. 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				1 clinvar	1 clinvar	2
missense			47 clinvar	3 clinvar		50
nonsense			4 clinvar			4
start loss						0
frameshift		1 clinvar	2 clinvar			3
splice donor/acceptor (+/-2bp)			4 clinvar			4
Total	0	1	57	4	1	63

Highest pathogenic variant AF is 0.00004337056

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 69 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_004827.3	RefSeq	NP_004818.2	15	MANE Select
ENST00000237612.8	Ensembl	ENSP00000237612.3	15	MANE Select
NM_001257386.2	RefSeq	NP_001244315.1	15	Standard
NM_001348985.1	RefSeq	NP_001335914.1	15	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Methotrexate Pathway (Brain Cell), Pharmacokinetics
Methotrexate Pathway, Pharmacokinetics
Doxorubicin Pathway (Cancer Cell), Pharmacodynamics
Bile secretion - Homo sapiens (human)
ABC transporters - Homo sapiens (human)

Biological Process

drug transmembrane transport
cellular iron ion homeostasis
heme transport
response to drug
xenobiotic transport

Molecular Function

transporter activity
protein binding
ATP binding
xenobiotic transmembrane transporting ATPase activity
heme transporter activity

Cellular Component

nucleus
plasma membrane
integral component of membrane
mitochondrial membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000237612
Coding exons: 15
Length: 141059
Individuals with no LoFs: 125263
Homozygous LoFs: 4
Heterozygous LoFs: 481
Defined: 125748
p: 0.00193

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.881	400	353	1.13	0.0000181	4266
Missense (PolyPhen)		89	74.344	1.1971		903
Synonymous	0.690	123	133	0.924	0.00000735	1274
Loss of Function	-1.15	44	36.5	1.21	0.00000222	430

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00086	0.00086	rare
Latino/Admixed American	0.0017	0.0017	notable
Ashkenazi Jewish	0.0014	0.0014	notable
East Asian	0.0075	0.0075	notable
Finnish	0.000092	0.000092	rare
European (Non-Finnish)	0.0012	0.0012	notable
South Asian	0.0037	0.0035	notable
Other	0.0018	0.0018	notable

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: High-capacity urate exporter functioning in both renal and extrarenal urate excretion. Plays a role in porphyrin homeostasis as it is able to mediates the export of protoporhyrin IX (PPIX) both from mitochondria to cytosol and from cytosol to extracellular space, and cellular export of hemin, and heme. Xenobiotic transporter that may play an important role in the exclusion of xenobiotics from the brain. Appears to play a major role in the multidrug resistance phenotype of several cancer cell lines. Implicated in the efflux of numerous drugs and xenobiotics: mitoxantrone, the photosensitizer pheophorbide, camptothecin, methotrexate, azidothymidine (AZT), and the anthracyclines daunorubicin and doxorubicin. {ECO:0000269|PubMed:12958161, ECO:0000269|PubMed:20705604, ECO:0000269|PubMed:22132962, ECO:0000269|PubMed:23189181}.;

Recessive Scores

pRec: 0.552

Intolerance Scores

LoFtool: 0.454
RVIS EVS: -0.2
RVIS percentile EVS: 39.17

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.166

Gene Damage Prediction

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