ABCG5

ATP binding cassette subfamily G member 5, the group of ATP binding cassette subfamily G

Basic information

Region (hg38): 2:43812471-43838865

Links

ENSG00000138075 ∙ NCBI:64240 ∙ OMIM:605459 ∙ HGNC:13886 ∙ Uniprot:Q9H222 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• sitosterolemia 1 (Definitive), mode of inheritance: AR
• sitosterolemia (Supportive), mode of inheritance: AR
• sitosterolemia 1 (Strong), mode of inheritance: AR
• sitosterolemia 1 (Definitive), mode of inheritance: AR
• sitosterolemia (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Sitosterolemia 2	AR	Biochemical; Cardiovascular	In some individuals, medical (eg, with bile acid resins/lipid-lowering agents) and dietary (eg, with cholesterol and plant fat restriction) treatment may be beneficial for some parameters, and may, along with preventive measures related to cardiovascular manifestations, reduce morbidity and mortality	Biochemical; Cardiovascular; Hematologic	11099417; 11138003; 12840092; 16029460; 16472606; 17018391; 17785700; 17976197; 19111681; 20521169; 20543520; 20719861; 21576934; 24166850; 31901240

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ABCG5 gene.

• Sitosterolemia (246 variants)
• Cardiovascular phenotype (218 variants)
• not provided (166 variants)
• Sitosterolemia 1 (80 variants)
• Sitosterolemia 2 (69 variants)
• not specified (49 variants)
• Inborn genetic diseases (31 variants)
• ABCG5-related condition (5 variants)
• Thrombocytopenia (3 variants)
• Sitosterolemia 2;Short-rib thoracic dysplasia 15 with polydactyly (2 variants)
• Hyperuricemic nephropathy, familial juvenile type 4 (1 variants)
• Abnormal bleeding;Thrombocytopenia (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ABCG5 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			12	90		102
missense		3	242	8	1	254
nonsense	9	2				11
start loss			1			1
frameshift	5	4				9
inframe indel			2			2
splice donor/acceptor (+/-2bp)	4	5	2			11
splice region			11	7		18
non coding			13	40	34	87
Total	18	14	272	138	35

Highest pathogenic variant AF is 0.000125

Variants in ABCG5

This is a list of pathogenic ClinVar variants found in the ABCG5 region.

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

Position	Type	Phenotype	Significance	ClinVar
2-43812494-G-A		Sitosterolemia 1	Benign (Jan 13, 2018)
2-43812495-G-A		Sitosterolemia 1	Uncertain significance (Jan 12, 2018)
2-43812524-C-T		Sitosterolemia 1	Uncertain significance (Jan 12, 2018)
2-43812581-G-A		Sitosterolemia 1	Benign (Apr 27, 2017)
2-43812594-C-T		Sitosterolemia 1	Benign (Jan 13, 2018)
2-43812605-G-T		Sitosterolemia 1	Uncertain significance (Jan 13, 2018)
2-43812700-C-T		Sitosterolemia 1	Benign (Jan 13, 2018)
2-43812717-G-A		Sitosterolemia 1	Benign (Jan 12, 2018)
2-43812736-A-C		Sitosterolemia 1	Benign (Apr 19, 2019)
2-43812758-T-TA		Sitosterolemia	Uncertain significance (Jun 14, 2016)
2-43812764-A-G		Sitosterolemia 1	Uncertain significance (Jan 13, 2018)
2-43812831-C-G		Sitosterolemia 1	Conflicting classifications of pathogenicity (Feb 01, 2023)
2-43812891-C-A		Sitosterolemia 1	Uncertain significance (Jan 13, 2018)
2-43812963-G-T		Sitosterolemia 1	Uncertain significance (Jan 12, 2018)
2-43813044-C-T			Likely benign (Oct 07, 2019)
2-43813120-C-T		Cardiovascular phenotype	Uncertain significance (Sep 26, 2022)
2-43813122-G-A			Uncertain significance (May 30, 2018)
2-43813127-T-G		Cardiovascular phenotype	Uncertain significance (Apr 07, 2023)
2-43813130-G-A		Cardiovascular phenotype	Uncertain significance (Jul 13, 2023)
2-43813159-C-T		Sitosterolemia	Uncertain significance (Jul 08, 2023)
2-43813162-A-G		not specified	Uncertain significance (Jul 18, 2023)
2-43813168-A-C		Cardiovascular phenotype	Uncertain significance (Jan 16, 2024)
2-43813168-A-G		Sitosterolemia 1	Uncertain significance (Jan 13, 2018)
2-43813174-G-C		Cardiovascular phenotype	Uncertain significance (Oct 19, 2021)
2-43813181-T-A		Cardiovascular phenotype	Uncertain significance (Feb 26, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ABCG5	protein_coding	protein_coding	ENST00000260645	13	26394

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
3.08e-21	0.00109	125609	0	139	125748	0.000553

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.744	410	370	1.11	0.0000223	4218
Missense in Polyphen		136	121.35	1.1207		1451
Synonymous	-1.48	179	156	1.15	0.0000102	1349
Loss of Function	-0.133	31	30.2	1.03	0.00000176	333

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000804	0.000803
Ashkenazi Jewish	0.00	0.00
East Asian	0.00223	0.00223
Finnish	0.000139	0.000139
European (Non-Finnish)	0.000371	0.000369
Middle Eastern	0.00223	0.00223
South Asian	0.000981	0.000980
Other	0.000327	0.000326

dbNSFP

Source: dbNSFP

• Function: FUNCTION: ABCG5 and ABCG8 form an obligate heterodimer that mediates Mg(2+)- and ATP-dependent sterol transport across the cell membrane (PubMed:27144356). Plays an essential role in the selective transport of dietary plant sterols and cholesterol in and out of the enterocytes and in the selective sterol excretion by the liver into bile (PubMed:11099417, PubMed:11138003, PubMed:27144356, PubMed:15054092). Required for normal sterol homeostasis (PubMed:11099417, PubMed:11138003, PubMed:15054092). The heterodimer with ABCG8 has ATPase activity (PubMed:16893193, PubMed:20210363, PubMed:27144356). {ECO:0000269|PubMed:11138003, ECO:0000269|PubMed:15054092, ECO:0000269|PubMed:16893193, ECO:0000269|PubMed:20210363, ECO:0000269|PubMed:27144356, ECO:0000303|PubMed:11590207, ECO:0000305|PubMed:11099417}.
• Disease: DISEASE: Sitosterolemia (STSL) [MIM:210250]: Rare autosomal recessive disorder characterized by increased intestinal absorption of all sterols including cholesterol, plant and shellfish sterols, and decreased biliary excretion of dietary sterols into bile. Sitosterolemia patients have hypercholesterolemia, very high levels of plant sterols in the plasma, and frequently develop tendon and tuberous xanthomas, accelerated atherosclerosis and premature coronary artery disease. {ECO:0000269|PubMed:11138003, ECO:0000269|PubMed:11452359, ECO:0000269|PubMed:11668628, ECO:0000269|PubMed:15054092}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Fat digestion and absorption - Homo sapiens (human);Bile secretion - Homo sapiens (human);ABC transporters - Homo sapiens (human);Cholesterol metabolism - Homo sapiens (human);Statin Pathway, Pharmacodynamics;Liver X Receptor Pathway;Nuclear Receptors Meta-Pathway;Nuclear Receptors in Lipid Metabolism and Toxicity;Angiopoietin Like Protein 8 Regulatory Pathway;Liver steatosis AOP;Statin Pathway;Vitamin A and Carotenoid Metabolism;ABC transporters in lipid homeostasis;Transport of small molecules;C21-steroid hormone biosynthesis and metabolism;ABC-family proteins mediated transport (Consensus)

Recessive Scores

• pRec: 0.0867

Intolerance Scores

• loftool: 0.359
• rvis_EVS: 1.16
• rvis_percentile_EVS: 92.65

Haploinsufficiency Scores

• pHI: 0.103
• hipred: N
• hipred_score: 0.261

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.664

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Abcg5
• Phenotype: muscle phenotype; cellular phenotype; homeostasis/metabolism phenotype; growth/size/body region phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); hematopoietic system phenotype; digestive/alimentary phenotype; immune system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); liver/biliary 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); reproductive system phenotype

Gene ontology

• Biological process: drug transmembrane transport;response to nutrient;excretion;response to ionizing radiation;negative regulation of intestinal phytosterol absorption;intestinal cholesterol absorption;cholesterol efflux;cholesterol homeostasis;negative regulation of intestinal cholesterol absorption;transmembrane transport
• Cellular component: plasma membrane;integral component of plasma membrane;apical plasma membrane;ATP-binding cassette (ABC) transporter complex;receptor complex
• Molecular function: protein binding;ATP binding;ATPase activity;cholesterol transporter activity;ATPase activity, coupled to transmembrane movement of substances;metal ion binding;protein heterodimerization activity