ACAA1

protein-coding

acetyl-CoA acyltransferase 1

Gene summary

This gene encodes an enzyme operative in the beta-oxidation system of the peroxisomes. Deficiency of this enzyme leads to pseudo-Zellweger syndrome. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2008]

MANE transcript

NM_001607.4

Inheritance

—

ClinVar variants

U:71B:8

Top phenotype

ACAA1-related disorder

gnomAD constraint

pLI —, LoF o/e 0.74

Max pathogenic AF

—

Genomic locus

chr3:38,103,129-38,137,242

External References & Databases

Ensembl (ENSG00000060971)

Transcript & Mutation Effects

hg38 • Region Span ~34.1 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 ACAA1 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 62

ACAA1-related disorderTotal: 8

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001607.4. 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			2 clinvar	4 clinvar	1 clinvar	7
missense			63 clinvar	3 clinvar		66
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			5 clinvar			5
Total	0	0	71	7	1	79

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 78 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001607.4	RefSeq	NP_001598.1	12	MANE Select
ENST00000333167.13	Ensembl	ENSP00000333664.8	12	MANE Select
NM_001130410.2	RefSeq	NP_001123882.1	10	Standard
ENST00000301810.11	Ensembl	ENSP00000301810.7	10	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Peroxisome - Homo sapiens (human)
Biosynthesis of unsaturated fatty acids - Homo sapiens (human)
Fatty acid degradation - Homo sapiens (human)
alpha-Linolenic acid metabolism - Homo sapiens (human)
PPAR signaling pathway - Homo sapiens (human)

Biological Process

very long-chain fatty acid metabolic process
protein targeting to peroxisome
fatty acid beta-oxidation
bile acid metabolic process
phenylacetate catabolic process

Molecular Function

acetyl-CoA C-acyltransferase activity
protein binding
acetate CoA-transferase activity
palmitoyl-CoA oxidase activity

Cellular Component

extracellular region
peroxisome
peroxisomal matrix
cytosol
membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000333167
Coding exons: 12
Length: 34114
Individuals with no LoFs: 125667
Homozygous LoFs: 0
Heterozygous LoFs: 81
Defined: 125748
p: 0.000322

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.22	195	249	0.783	0.0000134	2703
Missense (PolyPhen)		73	98.717	0.73948		1025
Synonymous	-0.646	108	99.8	1.08	0.00000555	899
Loss of Function	1.14	16	21.7	0.736	0.00000121	232

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0.00018	0.00017	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00071	0.00071	rare
Finnish	0.00019	0.00018	rare
European (Non-Finnish)	0.00019	0.00018	rare
South Asian	0.0011	0.0011	notable
Other	0.00049	0.00049	rare

dbNSFP Gene Annotations

Source: dbNSFP

Recessive Scores

pRec: 0.695

Intolerance Scores

LoFtool: 0.134
RVIS EVS: 0.06
RVIS percentile EVS: 58.85

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.667

Gene Damage Prediction

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