ACAA2

protein-coding

acetyl-CoA acyltransferase 2

Gene summary

The encoded protein catalyzes the last step of the mitochondrial fatty acid beta-oxidation spiral. Unlike most mitochondrial matrix proteins, it contains a non-cleavable amino-terminal targeting signal. [provided by RefSeq, Jul 2008]

MANE transcript

NM_006111.3

Inheritance

—

ClinVar variants

U:67B:3

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.86

Max pathogenic AF

—

Genomic locus

chr18:49,782,164-49,813,953

External References & Databases

Ensembl (ENSG00000167315)

Transcript & Mutation Effects

hg38 • Region Span ~31.8 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to ACAA2 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 62

not providedTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_006111.3. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			1 clinvar			1
missense			64 clinvar	2 clinvar	1 clinvar	67
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	67	2	1	70

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 48 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_006111.3	RefSeq	NP_006102.2	10	MANE Select
ENST00000285093.15	Ensembl	ENSP00000285093.8	10	MANE Select
ENST00000585948.5	Ensembl	ENSP00000465095.1	3	Standard
ENST00000586100.1	Ensembl	ENSP00000468157.1	3	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Fatty acid degradation - Homo sapiens (human)
Fatty acid elongation - Homo sapiens (human)
Valine, leucine and isoleucine degradation - Homo sapiens (human)
Long chain acyl-CoA dehydrogenase deficiency (LCAD)
3-Methylglutaconic Aciduria Type I

Biological Process

fatty acid beta-oxidation
cholesterol biosynthetic process
cellular response to hypoxia
negative regulation of mitochondrial outer membrane permeabilization involved in apoptotic signaling pathway
negative regulation of mitochondrial membrane permeability involved in apoptotic process

Molecular Function

RNA binding
acetyl-CoA C-acetyltransferase activity
acetyl-CoA C-acyltransferase activity
protein binding

Cellular Component

mitochondrion
mitochondrial matrix

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000285093
Coding exons: 10
Length: 30462
Individuals with no LoFs: 125661
Homozygous LoFs: 0
Heterozygous LoFs: 87
Defined: 125748
p: 0.000346

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.271	220	209	1.05	0.0000104	2551
Missense (PolyPhen)		92	84.824	1.0846		988
Synonymous	0.897	63	72.7	0.866	0.00000375	805
Loss of Function	0.559	16	18.6	0.860	9.33e-7	248

Population LoF Frequency

Population	CAF	p-value	Status
African	0.0017	0.0017	notable
Latino/Admixed American	0.00061	0.00061	rare
Ashkenazi Jewish	0.000099	0.000099	rare
East Asian	0.00016	0.00016	rare
Finnish	0.000092	0.000092	rare
European (Non-Finnish)	0.00022	0.00022	rare
South Asian	0.00026	0.00026	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Abolishes BNIP3-mediated apoptosis and mitochondrial damage. {ECO:0000269|PubMed:18371312}.;

Recessive Scores

pRec: 0.366

Intolerance Scores

LoFtool: 0.307
RVIS EVS: -0.58
RVIS percentile EVS: 18.72

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.0135

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium