NANS

Chr 9AR

N-acetylneuraminate synthase

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

NCBI Gene: 54187ENSG00000095380UniProt: Q9NR45

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]

Primary Disease Associations & Inheritance

Spondyloepimetaphyseal dysplasia, Genevieve typeMIM #610442
AR
239
ClinVar variants
51
Pathogenic / LP
—
pLI score
0
Active trials
Clinical Summary— NANS
🧬
Gene-Disease Validity (ClinGen)
spondyloepimetaphyseal dysplasia, Genevieve type · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

📋
ClinVar Variants
51 Pathogenic / Likely Pathogenic· 97 VUS of 239 total submissions

Population Genetics & Constraint

gnomAD

Constraint data not available from gnomAD.

ClinVar Variant Classifications

239 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic38
Likely Pathogenic13
VUS97
Likely Benign70
Benign18
Conflicting3
38
Pathogenic
13
Likely Pathogenic
97
VUS
70
Likely Benign
18
Benign
3
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
3
2
33
0
38
Likely Pathogenic
3
4
6
0
13
VUS
1
85
11
0
97
Likely Benign
0
3
23
44
70
Benign
0
2
11
5
18
Conflicting
—3
Total7968449239

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

View in ClinVar →

Protein Context — Lollipop Plot

NANS · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

NANS-related infantile-onset severe developmental delay and skeletal dysplasia

definitive
ARLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Spondyloepimetaphyseal dysplasia, Genevieve type

MIM #610442

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Integrated proteogenomic characterization of localized prostate cancer identifies biological insights and subtype-specific therapeutic strategies.
Ou W et al.·Nat Commun
2025
NANS suppresses NF-κB signaling to promote ferroptosis by perturbing iron homeostasis.
Wang Z et al.·Cell Rep
2025
Clinical and molecular findings in three Japanese patients with N-acetylneuraminic acid synthetase-congenital disorder of glycosylation (NANS-CDG).
Masunaga Y et al.·Sci Rep
2022Cohort
Transcranial Magnetic Stimulation for Pain, Headache, and Comorbid Depression: INS-NANS Expert Consensus Panel Review and Recommendation.
Leung A et al.·Neuromodulation
2020Review
NANS-CDG: Expanding clinical insights with a novel patient with novel variants.
Yoo S et al.·Am J Med Genet A
2024Case report
NANS-mediated synthesis of sialic acid is required for brain and skeletal development.
van Karnebeek CD et al.·Nat Genet
2016
Vitamin B-6 and riboflavin, their metabolic interaction, and relationship with MTHFR genotype in adults aged 18-102 years.
Jarrett H et al.·Am J Clin Nutr
2022Clinical trial
Origin and evolution of nonulosonic acid synthases and their relationship with bacterial pathogenicity revealed by a large-scale phylogenetic analysis.
Vieira AZ et al.·Microb Genom
2021
Lateral cephalometric characteristics in individuals with Down Syndrome compared to non-syndromic controls: A meta-analysis.
Bierley K et al.·J Stomatol Oral Maxillofac Surg
2023Meta-analysis
Nucleic Acid Nanocapsules as a New Platform to Deliver Therapeutic Nucleic Acids for Gene Regulation.
Pal S et al.·Acc Chem Res
2025
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools