ACSM1

Chr 16

acyl-CoA synthetase medium chain family member 1

Also known as: BUCS1, MACS1

ACSM1 encodes a mitochondrial matrix enzyme that activates fatty acids by conjugating them with coenzyme A, catalyzing the first step in fatty acid metabolism and also activating medium-chain fatty acids and xenobiotics like benzoate. The gene shows extremely low constraint against loss-of-function variants (pLI near zero, LOEUF >1), and no established human disease associations have been reported to date. This gene appears to be tolerant of functional variation in the human population.

OMIMResearchSummary from RefSeq, UniProt
DNmechanismLOEUF 1.07
Clinical SummaryACSM1
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.07LOEUF
pLI 0.000
Z-score 1.21
OE 0.78 (0.571.07)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.20Z-score
OE missense 0.97 (0.881.06)
320 obs / 330.4 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.78 (0.571.07)
00.351.4
Missense OE0.97 (0.881.06)
00.61.4
Synonymous OE0.93
01.21.6
LoF obs/exp: 27 / 34.7Missense obs/exp: 320 / 330.4Syn Z: 0.64
DN
0.7130th %ile
GOF
0.5366th %ile
LOF
0.3746th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

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

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

ACSM1 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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