ABCG8

ATP binding cassette subfamily G member 8, the group of ATP binding cassette subfamily G

Basic information

Region (hg38): 2:43831942-43882988

Links

ENSG00000143921 ∙ NCBI:64241 ∙ OMIM:605460 ∙ HGNC:13887 ∙ Uniprot:Q9H221 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• sitosterolemia (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 1	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; 12840092; 16029460; 15996216; 31901240

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ABCG8 gene.

• not provided (21 variants)
• Sitosterolemia 1 (8 variants)
• Cardiovascular phenotype (3 variants)
• Abnormal circulating lipid concentration (1 variants)
• Hypercholesterolemia (1 variants)
• ABCG8-related disorder (1 variants)
• Sitosterolemia (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ABCG8 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			9	123	3	135
missense		2	299	15	3	319
nonsense	11	4				15
start loss		2				2
frameshift	8	2	1			11
inframe indel		1				1
splice donor/acceptor (+/-2bp)	4	8	1		1	14
splice region			13	10	4	27
non coding	4	1	98	93	48	244
Total	27	20	408	231	55

Highest pathogenic variant AF is 0.000256

Variants in ABCG8

This is a list of pathogenic ClinVar variants found in the ABCG8 region.

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

Position	Type	Phenotype	Significance	ClinVar
2-43831944-C-A		Sitosterolemia	Uncertain significance (May 08, 2022)
2-43831951-A-C		Cardiovascular phenotype	Uncertain significance (Aug 27, 2022)
2-43831952-G-C		not specified	Uncertain significance (Aug 07, 2023)
2-43831954-A-T		Cardiovascular phenotype	Uncertain significance (Apr 05, 2023)
2-43831956-G-A		Cardiovascular phenotype	Likely benign (Oct 20, 2019)
2-43831957-T-C		Sitosterolemia • Sitosterolemia 2 • ABCG5-related disorder • not specified	Uncertain significance (Aug 07, 2024)
2-43831958-A-G		Sitosterolemia 2	Uncertain significance (Feb 24, 2023)
2-43831963-A-G		Cardiovascular phenotype	Uncertain significance (Aug 22, 2023)
2-43831965-G-A		Sitosterolemia	Likely benign (Mar 19, 2023)
2-43831966-C-A		Cardiovascular phenotype	Uncertain significance (Feb 10, 2023)
2-43831966-C-G		Cardiovascular phenotype	Uncertain significance (Mar 16, 2023)
2-43831972-T-C		Cardiovascular phenotype	Uncertain significance (May 07, 2023)
2-43831982-C-A		Sitosterolemia	Pathogenic (Jun 09, 2023)
2-43831983-C-G		Cardiovascular phenotype • Sitosterolemia • ABCG5-related disorder	Likely benign (May 19, 2022)
2-43831984-C-T		ABCG5-related disorder	Uncertain significance (Sep 26, 2016)
2-43831992-C-T		Sitosterolemia	Likely benign (Oct 26, 2022)
2-43831994-C-CCCGG		Sitosterolemia 2	Likely pathogenic (Jul 25, 2023)
2-43831996-C-G		Cardiovascular phenotype	Uncertain significance (Sep 22, 2023)
2-43832000-C-G		Cardiovascular phenotype	Uncertain significance (Apr 18, 2023)
2-43832006-C-T		Sitosterolemia • not specified	Uncertain significance (Nov 27, 2023)
2-43832007-A-G		Sitosterolemia	Likely benign (Jan 18, 2020)
2-43832013-C-T		Sitosterolemia	Likely benign (Dec 11, 2022)
2-43832013-C-CT		Cardiovascular phenotype	Pathogenic (Aug 24, 2023)
2-43832016-C-T		Cardiovascular phenotype	Likely benign (Aug 19, 2019)
2-43832018-C-A		Sitosterolemia	Uncertain significance (May 21, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ABCG8	protein_coding	protein_coding	ENST00000272286	13	39503

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
2.38e-20	0.00188	125357	0	391	125748	0.00156

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-2.49	518	381	1.36	0.0000249	4386
Missense in Polyphen		166	132.51	1.2527		1542
Synonymous	-2.20	202	166	1.22	0.0000122	1346
Loss of Function	-0.0337	30	29.8	1.01	0.00000159	338

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00320	0.00320
Ashkenazi Jewish	0.00	0.00
East Asian	0.000381	0.000381
Finnish	0.00254	0.00254
European (Non-Finnish)	0.00176	0.00176
Middle Eastern	0.000381	0.000381
South Asian	0.000719	0.000719
Other	0.00163	0.00163

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. Plays an essential role in the selective transport of the dietary cholesterol in and out of the enterocytes and in the selective sterol excretion by the liver into bile (PubMed:11099417, PubMed:11452359, PubMed:27144356, PubMed:15054092). Required for normal sterol homeostasis (PubMed:11099417, PubMed:11452359, PubMed:15054092). The heterodimer with ABCG5 has ATPase activity (PubMed:16893193, PubMed:20210363, PubMed:27144356). {ECO:0000269|PubMed:11099417, ECO:0000269|PubMed:11452359, ECO:0000269|PubMed:15054092, ECO:0000269|PubMed:16893193, ECO:0000269|PubMed:27144356}.
• Disease: DISEASE: Gallbladder disease 4 (GBD4) [MIM:611465]: One of the major digestive diseases. Gallstones composed of cholesterol (cholelithiasis) are the common manifestations in western countries. Most people with gallstones, however, remain asymptomatic through their lifetimes. {ECO:0000269|PubMed:17632509}. Note=Disease susceptibility may be associated with variations affecting the gene represented in this entry.; 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:11099417, ECO:0000269|PubMed:11452359, 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;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: 0.333

Intolerance Scores

• loftool: 0.275
• rvis_EVS: 0.74
• rvis_percentile_EVS: 86.38

Haploinsufficiency Scores

• pHI: 0.138
• hipred: N
• hipred_score: 0.251

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.676

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	High	High	High
Primary Immunodeficiency	High	High	High
Cancer	High	High	High

Mouse Genome Informatics

• Gene name: Abcg8
• Phenotype: liver/biliary system phenotype; digestive/alimentary phenotype; cellular phenotype; homeostasis/metabolism phenotype

Gene ontology

• Biological process: drug transmembrane transport;response to nutrient;excretion;negative regulation of intestinal phytosterol absorption;phospholipid transport;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