ACSS1

protein-coding

acyl-CoA synthetase short chain family member 1, the group of Acyl-CoA synthetase family

Gene summary

This gene encodes a mitochondrial acetyl-CoA synthetase enzyme. A similar protein in mice plays an important role in the tricarboxylic acid cycle by catalyzing the conversion of acetate to acetyl CoA. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Nov 2011]

Previous symbols:

ACAS2L

MANE transcript

NM_032501.4

Inheritance

—

ClinVar variants

U:77B:6

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.5

Max pathogenic AF

—

Genomic locus

chr20:25,006,230-25,058,980

External References & Databases

Ensembl (ENSG00000154930)

Transcript & Mutation Effects

hg38 • Region Span ~52.8 kb

Loading mutation effect viewer...

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 ACSS1 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 72

not providedTotal: 3

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_032501.4. 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				1 clinvar	1 clinvar	2
missense			72 clinvar	3 clinvar	1 clinvar	76
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			5 clinvar			5
Total	0	0	77	4	2	83

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 58 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_032501.4	RefSeq	NP_115890.2	14	MANE Select
ENST00000323482.9	Ensembl	ENSP00000316924.4	14	MANE Select
NM_001252675.2	RefSeq	NP_001239604.1	14	Standard
NM_001252676.2	RefSeq	NP_001239605.1	13	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Pyruvate metabolism - Homo sapiens (human)
Glycolysis / Gluconeogenesis - Homo sapiens (human)
Propanoate metabolism - Homo sapiens (human)
Disulfiram Action Pathway
Malonyl-coa decarboxylase deficiency

Biological Process

ethanol oxidation
acetyl-CoA biosynthetic process
acetate biosynthetic process
acetyl-CoA biosynthetic process from acetate
propionate biosynthetic process

Molecular Function

acetate-CoA ligase activity
protein binding
ATP binding
AMP binding

Cellular Component

mitochondrial matrix

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000323482
Coding exons: 14
Length: 52749
Individuals with no LoFs: 125715
Homozygous LoFs: 0
Heterozygous LoFs: 33
Defined: 125748
p: 0.000131

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.83	313	419	0.748	0.0000248	4447
Missense (PolyPhen)		109	179.84	0.60608		1788
Synonymous	-0.624	184	174	1.06	0.0000111	1410
Loss of Function	2.62	16	32.0	0.500	0.00000163	348

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000082	0.000062	rare
Latino/Admixed American	0.000058	0.000058	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00016	0.00016	rare
Finnish	0.00014	0.00014	rare
European (Non-Finnish)	0.00019	0.00018	rare
South Asian	0.000098	0.000098	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Important for maintaining normal body temperature during fasting and for energy homeostasis. Essential for energy expenditure under ketogenic conditions (By similarity). Converts acetate to acetyl-CoA so that it can be used for oxidation through the tricarboxylic cycle to produce ATP and CO(2). {ECO:0000250, ECO:0000269|PubMed:16788062}.;

Recessive Scores

pRec: 0.195

Intolerance Scores

LoFtool: 0.669
RVIS EVS: -0.95
RVIS percentile EVS: 9.32

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.561

Gene Damage Prediction

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