Features include always present findings: Mild intellectual disability, Seizure, Hyperhomocystinemia, and Megaloblastic anemia and others; and rarely findings: Autoimmunity. 23 total HPO annotations.

MTHFD1 encodes methylenetetrahydrofolate dehydrogenase, cyclohydrolase and formyltetrahydrofolate synthetase 1 (935 aa). Trifunctional enzyme that catalyzes the interconversion of three forms of one-carbon-substituted tetrahydrofolate: (6R)-5,10-methylene-5,6,7,8-tetrahydrofolate, 5,10-methenyltetrahydrofolate and (6S)-10-formyltetrahydrofolate. Highest expression in Cells EBV-transformed lymphocytes (65.3 TPM) and Liver (36.3 TPM).

Combined immunodeficiency and megaloblastic anemia with or without hyperhomocysteinemia is associated with mutations in the MTHFD1 gene on chromosome 14.

The MTHFD1 protein participates in MTHFD1L transforms 10-formyl-THF to HCOOH and THF, 5,10-methyleneTHF polyglutamate + NADP+ 5,10-methenylTHF polyglutamate + NADPH + H+, and 5,10-methenylTHF polyglutamate + H2O 10-formylTHF polyglutamate pathways.

MTHFD1 is classified as a druggable target (Enzyme category) with score 1.0.

Genetic testing for MTHFD1 is available. Testing is considered confirmatory for diagnosis.

Biomarker and diagnostic research for combined immunodeficiency and megaloblastic anemia with or without hyperhomocysteinemia has been reported in the published literature.

Phenotype severity distribution: 11 always present features.

Estimated prevalence: <1 in 1,000,000 (VERY_RARE).

No clinical trials have been registered for combined immunodeficiency and megaloblastic anemia with or without hyperhomocysteinemia.

205 publications have been identified in PubMed for combined immunodeficiency and megaloblastic anemia with or without hyperhomocysteinemia. Kisho has analyzed 84 by research type. Research spans Review / Meta-Analysis (48%), Basic Science / Preclinical (27%), and Epidemiology / Natural History (15%).