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Red cell disorders v1.36 NMNAT3 Chirag Patel Marked gene: NMNAT3 as ready
Red cell disorders v1.36 NMNAT3 Chirag Patel Gene: nmnat3 has been classified as Red List (Low Evidence).
Red cell disorders v1.36 NMNAT3 Chirag Patel gene: NMNAT3 was added
gene: NMNAT3 was added to Red cell disorders. Sources: Literature
Mode of inheritance for gene: NMNAT3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NMNAT3 were set to 41100733, 24739386
Phenotypes for gene: NMNAT3 were set to Familial hemolytic anemia, MONDO:0003689
Review for gene: NMNAT3 was set to RED
Added comment: NMNAT is an enzyme that plays a key role in the de novo biosynthesis and salvage of NAD+. Three isoforms of NMNAT exist in mammals (NMNAT1-3), and NMNAT3 is the predominant isoform in RBCs.

PMID:41100733
2 siblings from 1 consanguineous Turkish family with adolescent‑onset hereditary haemolytic anemia, splenomegaly and mild compensated haemolysis. Research based gene panel identified a homozygous variant in NMNAT3 gene (c.64C>T, (p.His22Tyr)) which is absent in gnomAD and located in the adenosine triphosphate (ATP) binding domain. Segregation showed mother was heterozygous and an unaffected sibling was wild-type.

Functional assays demonstrated absent NMNAT activity; decreased levels of NAD+, NADH, NAM, and NMN; and disturbed glycolysis. They noted partial hematologic improvement after NAD precursor supplementation. No contradictory evidence is reported.

PMID: 24739386
They showed that complete knockout of NMNAT3 in mice caused depletion of NAD+ and disturbed glycolytic flow in mature RBCs, resulting in haemolytic anemia and splenomegaly.
Sources: Literature