ABCA1

Chr 9ADAR

ATP binding cassette subfamily A member 1

Also known as: ABC-1, ABC1, CERP, HDLCQTL13, HDLDT1, HPALP1, TGD

This protein catalyzes the ATP-dependent translocation of phospholipids across cell membranes and participates in cholesterol efflux to form nascent high-density lipoproteins. Mutations cause familial HDL deficiency and Tangier disease, which are inherited in autosomal recessive patterns, though some variants may act in an autosomal dominant manner. The gene is highly intolerant to loss-of-function variants, indicating that complete loss of protein function has severe consequences.

GeneReviewsOMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismAD/ARLOEUF 0.492 OMIM phenotypes
Clinical SummaryABCA1
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
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ClinVar Variants
24 unique Pathogenic / Likely Pathogenic· 217 VUS of 500 total submissions
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Clinical Trials
2 active or recruiting trials — potential therapeutic options may be available
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GeneReview available — ABCA1
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.49LOEUF
pLI 0.000
Z-score 6.23
OE 0.38 (0.300.49)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
1.75Z-score
OE missense 0.86 (0.810.90)
1029 obs / 1200.0 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.38 (0.300.49)
00.351.4
Missense OE0.86 (0.810.90)
00.61.4
Synonymous OE1.08
01.21.6
LoF obs/exp: 44 / 116.5Missense obs/exp: 1029 / 1200.0Syn Z: -1.39
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveABCA1-related Tangier diseaseLOFAR

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

DN
0.74top 25%
GOF
0.74top 25%
LOF
0.2288th %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.

Literature Evidence

DNOur results suggest that the severe reduction of HDL-C in patients with truncation mutations may be at least partly explained by dominant negative suppression of expression and activity of the remaining full-length ABCA1 allele.PMID:12401893

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

500 submitted variants in ClinVar

Classification Summary

Pathogenic15
Likely Pathogenic9
VUS217
Likely Benign197
Benign4
Conflicting1
15
Pathogenic
9
Likely Pathogenic
217
VUS
197
Likely Benign
4
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
14
0
1
0
15
Likely Pathogenic
8
1
0
0
9
VUS
0
210
6
1
217
Likely Benign
0
17
46
134
197
Benign
0
1
3
0
4
Conflicting
1
Total2222956135443

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

View in ClinVar →

Protein Context — Lollipop Plot

ABCA1 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold
Clinical Literature
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Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗