ABCG5

Chr 2AR

ATP binding cassette subfamily G member 5

Also known as: STSL, STSL2

NCBI Gene: 64240ENSG00000138075UniProt: Q9H222OMIM: 605459

The 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 White subfamily. The protein encoded by this gene functions as a half-transporter to limit intestinal absorption and promote biliary excretion of sterols. It is expressed in a tissue-specific manner in the liver, colon, and intestine. This gene is tandemly arrayed on chromosome 2, in a head-to-head orientation with family member ABCG8. Mutations in this gene may contribute to sterol accumulation and atheroschlerosis, and have been observed in patients with sitosterolemia. [provided by RefSeq, Jul 2008]

GeneReviewsOMIMResearchGenerating clinical summary…
LOFmechanismARLOEUF 1.391 OMIM phenotype
Clinical Summary— ABCG5
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Gene-Disease Validity (ClinGen)
sitosterolemia · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
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ClinVar Variants
78 unique Pathogenic / Likely Pathogenic· 472 VUS of 971 total submissions
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Clinical Trials
2 active or recruiting trials — potential therapeutic options may be available
Explore recent and relevant literature in Research Assistant →
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GeneReview available — ABCG5
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?
1.39LOEUF
pLI 0.000
Z-score -0.13
OE 1.03 (0.77–1.39)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?
-0.74Z-score
OE missense 1.11 (1.02–1.20)
410 obs / 369.8 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios?
LoF OE?1.03 (0.77–1.39)
0≤0.351.4
Missense OE?1.11 (1.02–1.20)
0≤0.61.4
Synonymous OE?1.15
0≤1.21.6
LoF obs/exp: 31 / 30.2Missense obs/exp: 410 / 369.8Syn Z: -1.48
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveABCG5-related sitosterolemiaLOFAR

This gene — mechanism propensity

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.7034th %ile
GOF
0.79top 25%
LOF
0.2581th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

971 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic42
Likely Pathogenic36
VUS472
Likely Benign303
Benign43
Conflicting70
42
Pathogenic
36
Likely Pathogenic
472
VUS
303
Likely Benign
43
Benign
70
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
36
3
3
0
42
Likely Pathogenic
32
2
2
0
36
VUS
4
423
36
9
472
Likely Benign
0
19
112
172
303
Benign
0
3
40
0
43
Conflicting
—70
Total72450193181966

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

14 pathogenic / likely-pathogenic (of 26) ClinVar copy-number / structural variants overlap ABCG5 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →

Protein Context — Lollipop Plot

ABCG5 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients