ACSM2B

Chr 16

acyl-CoA synthetase medium chain family member 2B

Also known as: ACSM2, HXMA, HYST1046

NCBI Gene: 348158 ENSG00000066813 UniProt: Q68CK6

ACSM2B encodes a mitochondrial enzyme that activates medium-chain fatty acids (C4-C10) and certain xenobiotics like benzoate by conjugating them with CoA, representing the first step in fatty acid metabolism. This gene is not well-constrained against loss-of-function variants and no definitive disease associations have been established in the provided data. Additional clinical and genetic studies would be needed to determine if ACSM2B variants cause human disease.

ResearchSummary from RefSeq, UniProt

Enables benzoate-CoA ligase activity. Predicted to be involved in acyl-CoA metabolic process and fatty acid biosynthetic process. Located in mitochondrion. [provided by Alliance of Genome Resources, Jul 2025]

ResearchGenerating clinical summary…

DNmechanismLOEUF 1.42

Clinical Summary— ACSM2B

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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

57 VUS of 64 total submissions

Explore recent and relevant literature in Research Assistant →

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.42LOEUF

pLI 0.000

Z-score -0.43

OE 1.08 (0.83–1.42)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-1.98Z-score

OE missense 1.31 (1.21–1.42)

417 obs / 317.7 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?1.08 (0.83–1.42)

0≤0.351.4

Missense OE?1.31 (1.21–1.42)

0≤0.61.4

Synonymous OE?1.31

0≤1.21.6

LoF obs/exp: 37 / 34.3Missense obs/exp: 417 / 317.7Syn Z: -2.61

This gene — mechanism propensity

0.7035th %ile

GOF

0.6151th %ile

LOF

0.3649th %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

64 submitted variants in ClinVar

ClinVar

Classification Summary

VUS57

Likely Benign3

Benign3

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Synonymous	Total
Pathogenic	0	0	0
Likely Pathogenic	0	0	0
VUS	57	0	57
Likely Benign	3	0	3
Benign	1	2	3
Total	61	2	63

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

View in ClinVar →

14 pathogenic / likely-pathogenic (of 22) ClinVar copy-number / structural variants overlap ACSM2B — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →