ACOT7

Chr 1

acyl-CoA thioesterase 7

Also known as: ACH1, ACT, BACH, CTE-II, LACH, LACH1, hBACH

NCBI Gene: 11332 ENSG00000097021 UniProt: O00154 OMIM: 602587

The protein catalyzes the hydrolysis of acyl-CoAs (particularly palmitoyl-CoA) into free fatty acids and coenzyme A, regulating intracellular levels of these metabolites in fatty acid metabolism. Mutations cause autosomal recessive neurodegeneration with brain atrophy, characterized by developmental delay, intellectual disability, seizures, and progressive brain volume loss. The gene is highly constrained against loss-of-function variants, and decreased expression has been associated with mesial temporal lobe epilepsy.

OMIM ResearchSummary from RefSeq, UniProt

This gene encodes a member of the acyl coenzyme family. The encoded protein hydrolyzes the CoA thioester of palmitoyl-CoA and other long-chain fatty acids. Decreased expression of this gene may be associated with mesial temporal lobe epilepsy. Alternatively spliced transcript variants encoding distinct isoforms with different subcellular locations have been characterized. [provided by RefSeq, Jul 2008]

OMIM ResearchGenerating clinical summary…

LOFmechanismLOEUF 0.43

Clinical Summary— ACOT7

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Population Constraint (gnomAD)

Moderately constrained gene (pLI 0.76) — some intolerance to loss-of-function variants.

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ClinVar Variants

47 VUS of 73 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.43LOEUF

pLI 0.759

Z-score 3.26

OE 0.17 (0.08–0.43)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

1.98Z-score

OE missense 0.66 (0.58–0.75)

176 obs / 267.3 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.17 (0.08–0.43)

0≤0.351.4

Missense OE?0.66 (0.58–0.75)

0≤0.61.4

Synonymous OE?1.15

0≤1.21.6

LoF obs/exp: 3 / 17.9Missense obs/exp: 176 / 267.3Syn Z: -1.27

This gene — mechanism propensity

0.4983th %ile

GOF

0.6051th %ile

LOF

0.65top 25%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.43

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

73 submitted variants in ClinVar

ClinVar

Classification Summary

VUS47

Likely Benign6

Benign6

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	0	0
Likely Pathogenic	0	0	0	0
VUS	47	0	0	47
Likely Benign	3	1	2	6
Benign	0	3	3	6
Total	50	4	5	59

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

View in ClinVar →

60 pathogenic / likely-pathogenic (of 70) ClinVar copy-number / structural variants overlap ACOT7 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →