ACSF3

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

Basic information

Region (hg38): 16:89088375-89164121

Links

ENSG00000176715NCBI:197322OMIM:614245HGNC:27288Uniprot:Q4G176AlphaFoldGenCCjaxSfariGnomADPubmedClinVar

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

ConditionInheritanceIntervention CategoriesIntervention/Rationale Manifestation CategoriesReferences
Combined malonic and methylmalonic aciduriaARBiochemicalAlthough the optimal treatment (as well as the requirement thereof) is currently unclear, additional monitoring may be warranted to determine whether medical management would be beneficialBiochemical; Neurologic9700595; 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.

EffectPLPVUSLBBSum
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

GeneTypeBio TypeTranscript Coding Exons Length
ACSF3protein_codingprotein_codingENST00000317447 967472
pLI Probability
LOF Intolerant
pRec Probability
LOF Recessive
Individuals with
no LOFs
Individuals with
Homozygous LOFs
Individuals with
Heterozygous LOFs
Defined p
2.32e-260.0000074312562411231257480.000493
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense-1.304263571.190.00002383652
Missense in Polyphen153128.821.18771337
Synonymous-2.812071611.280.00001221207
Loss of Function-1.623425.21.350.00000134264

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.0008440.000843
Ashkenazi Jewish0.00009930.0000992
East Asian0.001270.00125
Finnish0.00009280.0000924
European (Non-Finnish)0.0003850.000378
Middle Eastern0.001270.00125
South Asian0.0009150.000882
Other0.0006530.000652

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

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium

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