ACOT11

Chr 1

acyl-CoA thioesterase 11

Also known as: BFIT, STARD14, THEA, THEM1

NCBI Gene: 26027 ENSG00000162390 UniProt: Q8WXI4 OMIM: 606803

The protein is an acyl-CoA thioesterase that converts long-chain fatty acyl-CoA substrates (particularly palmitoyl-CoA and myristoyl-CoA) to free fatty acids and coenzyme A in the mitochondrial beta-oxidation pathway. Mutations cause autosomal recessive defects in fatty acid oxidation, typically presenting in infancy or early childhood with episodes of hypoglycemia, hepatomegaly, and metabolic decompensation during fasting or illness. The gene shows very low constraint against loss-of-function variants (LOEUF 1.08), consistent with recessive inheritance where heterozygous carriers are typically unaffected.

OMIM ResearchSummary from RefSeq, UniProt

This gene encodes a member of the acyl-CoA thioesterase family which catalyse the conversion of activated fatty acids to the corresponding non-esterified fatty acid and coenzyme A. Expression of a mouse homolog in brown adipose tissue is induced by low temperatures and repressed by warm temperatures. Higher levels of expression of the mouse homolog has been found in obesity-resistant mice compared with obesity-prone mice, suggesting a role of acyl-CoA thioesterase 11 in obesity. Alternative splicing results in transcript variants. [provided by RefSeq, Nov 2010]

OMIM ResearchGenerating clinical summary…

GOFmechanismLOEUF 1.08

Clinical Summary— ACOT11

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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

183 VUS of 240 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.08LOEUF

pLI 0.000

Z-score 1.16

OE 0.79 (0.59–1.08)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.54Z-score

OE missense 0.92 (0.85–1.01)

363 obs / 393.1 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.79 (0.59–1.08)

0≤0.351.4

Missense OE?0.92 (0.85–1.01)

0≤0.61.4

Synonymous OE?0.91

0≤1.21.6

LoF obs/exp: 29 / 36.5Missense obs/exp: 363 / 393.1Syn Z: 0.93

This gene — mechanism propensity

0.5966th %ile

GOF

0.6541th %ile

LOF

0.4726th %ile

The highest-scoring mechanism for this gene is gain-of-function.

GOFprediction 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

240 submitted variants in ClinVar

ClinVar

Classification Summary

VUS183

Likely Benign15

Benign12

183

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	0	0	0
Likely Pathogenic	0	0	0	0	0
VUS	0	183	0	0	183
Likely Benign	2	13	0	0	15
Benign	2	3	3	4	12
Total	4	199	3	4	210

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

View in ClinVar →

13 pathogenic / likely-pathogenic (of 23) ClinVar copy-number / structural variants overlap ACOT11 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →