NANS

Chr 9AR

N-acetylneuraminate synthase

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

NCBI Gene: 54187 ENSG00000095380 UniProt: Q9NR45 OMIM: 605202

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.

OMIM 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]

OMIM ResearchGenerating clinical summary…

LOFmechanismAR1 OMIM phenotype

Clinical Summary— NANS

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Gene-Disease Validity (ClinGen)

spondyloepimetaphyseal dysplasia, Genevieve type · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

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ClinVar Variants

17 unique Pathogenic / Likely Pathogenic· 92 VUS of 208 total submissions

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Population Genetics & Constraint

gnomAD

Constraint data not available from gnomAD.

ClinVar Variant Classifications

208 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic7

Likely Pathogenic10

VUS92

Likely Benign70

Benign18

Conflicting3

Pathogenic

Likely Pathogenic

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	5	1	1	0	7
Likely Pathogenic	4	5	1	0	10
VUS	1	88	3	0	92
Likely Benign	0	3	23	44	70
Benign	0	2	11	5	18
Conflicting	—				3
Total	10	99	39	49	200

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

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34 pathogenic / likely-pathogenic (of 40) ClinVar copy-number / structural variants overlap NANS — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →