Features include very common findings: Methylmalonic aciduria, Methylmalonic acidemia, Dicarboxylic aciduria, and Dicarboxylic acidemia; and common findings: Seizure. 27 total HPO annotations.

ACSF3 encodes acyl-CoA synthetase family member 3 (576 aa). Catalyzes the initial reaction in intramitochondrial fatty acid synthesis, by activating malonate and methylmalonate, but not acetate, into their respective CoA thioester. Highest expression in Cells EBV-transformed lymphocytes (15.0 TPM) and Small Intestine Terminal Ileum (12.8 TPM).

Combined malonic and methylmalonic acidemia is caused by mutations in the ACSF3 gene on chromosome 16.

The ACSF3 protein participates in ACSF3 ligates CoA-SH to VLCFA and LIPT2 transfers octanoyl group to GCSH pathways.

ACSF3 is classified as a druggable target (Enzyme category) with score 0.0.

210 pathogenic variants reported in ACSF3 in ClinVar, including hotspot variants NP_001120686.1:p.Ser527Ter (2-star review) and NP_001120686.1:p.Trp536Ter (2-star review).

Genetic testing for ACSF3 is available. Testing is considered confirmatory for diagnosis.

Biomarker and diagnostic research for combined malonic and methylmalonic acidemia has been reported in the published literature.

Phenotype severity distribution: 4 very common features, 1 common feature.

Estimated prevalence: Unknown (Unknown prevalence).

No clinical trials have been registered for combined malonic and methylmalonic acidemia.

11 publications have been identified in PubMed for combined malonic and methylmalonic acidemia. Research spans Case Report / Case Series (55%), Epidemiology / Natural History (27%), and Diagnostic / Biomarker (9%).