NANS

Chr 9

N-acetylneuraminate synthase

Also known as: HEL-S-100, SAS, SEMDCG, SEMDG

NCBI Gene: 54187 ENSG00000095380 UniProt: Q9NR45

The NANS protein is a sialic acid synthase that catalyzes the synthesis of phosphorylated forms of sialic acids, including N-acetylneuraminic acid and deaminoneuraminic acid, which are required for brain and skeletal development. Mutations cause spondyloepimetaphyseal dysplasia, Genevieve type, a skeletal dysplasia with autosomal recessive inheritance. This condition affects both the skeletal system and brain development.

ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes an enzyme that functions in the biosynthetic pathways of sialic acids. In vitro, the encoded protein uses N-acetylmannosamine 6-phosphate and mannose 6-phosphate as substrates to generate phosphorylated forms of N-acetylneuraminic acid (Neu5Ac) and 2-keto-3-deoxy-D-glycero-D-galacto-nononic acid (KDN), respectively; however, it exhibits much higher activity toward the Neu5Ac phosphate product. In insect cells, expression of this gene results in Neu5Ac and KDN production. This gene is related to the E. coli sialic acid synthase gene neuB, and it can partially restore sialic acid synthase activity in an E. coli neuB-negative mutant. [provided by RefSeq, Jul 2008]

ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtSpondyloepimetaphyseal dysplasia, Genevieve type

Clinical highlights

Gene-disease validity (ClinGen)

spondyloepimetaphyseal dysplasia, Genevieve type · ARDefinitivesufficient evidence for diagnostic panels

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

—

LOEUF

LOF

Mechanism· G2P

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429