ACSF3

acyl-CoA synthetase family member 3, the group of Acyl-CoA synthetase family

Basic information

Region (hg38): 16:89088375-89164121

Links

ENSG00000176715

∙ NCBI:197322 ∙ OMIM:614245 ∙ HGNC:27288 ∙ Uniprot:Q4G176 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

combined malonic and methylmalonic acidemia (Strong), mode of inheritance: AR
combined malonic and methylmalonic acidemia (Supportive), mode of inheritance: AD
combined malonic and methylmalonic acidemia (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Combined malonic and methylmalonic aciduria	AR	Biochemical	Although the optimal treatment (as well as the requirement thereof) is currently unclear, additional monitoring may be warranted to determine whether medical management would be beneficial	Biochemical; Neurologic	9700595; 21785126; 21841779; 30740739

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ACSF3 gene.

Combined_malonic_and_methylmalonic_acidemia (851 variants)
Inborn_genetic_diseases (109 variants)
not_provided (87 variants)
Methylmalonic_acidemia (66 variants)
not_specified (59 variants)
ACSF3-related_disorder (31 variants)
Global_developmental_delay (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ACSF3 gene is commonly pathogenic or not. These statistics are base on transcript: NM_001243279.3. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous		2 clinvar	15 clinvar	339 clinvar	6 clinvar	362
missense	1 clinvar	18 clinvar	242 clinvar	18 clinvar		279
nonsense	16 clinvar	46 clinvar				62
start loss		1				1
frameshift	23 clinvar	55 clinvar	1 clinvar			79
splice donor/acceptor (+/-2bp)	2 clinvar	31 clinvar				33
Total	42	153	258	357	6

Highest pathogenic variant AF is 0.0045165

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ACSF3	protein_coding	protein_coding	ENST00000317447	9	67472

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
2.32e-26	0.00000743	125624	1	123	125748	0.000493

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-1.30	426	357	1.19	0.0000238	3652
Missense in Polyphen		153	128.82	1.1877		1337
Synonymous	-2.81	207	161	1.28	0.0000122	1207
Loss of Function	-1.62	34	25.2	1.35	0.00000134	264

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000844	0.000843
Ashkenazi Jewish	0.0000993	0.0000992
East Asian	0.00127	0.00125
Finnish	0.0000928	0.0000924
European (Non-Finnish)	0.000385	0.000378
Middle Eastern	0.00127	0.00125
South Asian	0.000915	0.000882
Other	0.000653	0.000652

dbNSFP

Source: dbNSFP

Function: FUNCTION: Catalyzes the initial reaction in intramitochondrial fatty acid synthesis, by activating malonate and methylmalonate, but not acetate, into their respective CoA thioester. May have some preference toward very-long-chain substrates. {ECO:0000269|PubMed:17762044, ECO:0000269|PubMed:21841779}.;
Disease: DISEASE: Combined malonic and methylmalonic aciduria (CMAMMA) [MIM:614265]: A metabolic disease characterized by malonic and methylmalonic aciduria, with urinary excretion of much larger amounts of methylmalonic acid than malonic acid, in the presence of normal malonyl-CoA decarboxylase activity. Clinical features include coma, ketoacidosis, hypoglycemia, failure to thrive, microcephaly, dystonia, axial hypotonia and/or developmental delay, and neurologic manifestations including seizures, psychiatric disease and/or cognitive decline. {ECO:0000269|PubMed:21841779}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Pathway: Valine, leucine and isoleucine degradation - Homo sapiens (human);Metabolism of lipids;Fatty acyl-CoA biosynthesis;Metabolism;Fatty acid metabolism;Synthesis of very long-chain fatty acyl-CoAs (Consensus)

Intolerance Scores

loftool: 0.925
rvis_EVS: -0.88
rvis_percentile_EVS: 10.54

Haploinsufficiency Scores

pHI: 0.105
hipred: N
hipred_score: 0.213
ghis: 0.535

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: N
essential_gene_gene_trap: N
gene_indispensability_pred: N
gene_indispensability_score: 0.300

Gene Damage Prediction

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

Mouse Genome Informatics

Gene name: Acsf3
Phenotype

Gene ontology

Biological process: fatty acid metabolic process;fatty acid biosynthetic process;long-chain fatty-acyl-CoA biosynthetic process;malonate catabolic process
Cellular component: mitochondrion;mitochondrial matrix
Molecular function: ATP binding;acid-thiol ligase activity;very long-chain fatty acid-CoA ligase activity;malonyl-CoA synthetase activity