NANS

N-acetylneuraminate synthase

Basic information

Region (hg38): 9:98056732-98083077

Links

ENSG00000095380 ∙ NCBI:54187 ∙ OMIM:605202 ∙ HGNC:19237 ∙ Uniprot:Q9NR45 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• spondyloepimetaphyseal dysplasia, Genevieve type (Moderate), mode of inheritance: AR
• spondyloepimetaphyseal dysplasia, Genevieve type (Strong), mode of inheritance: AR
• spondyloepimetaphyseal dysplasia, Genevieve type (Supportive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Spondyloepimetaphyseal dysplasiam Genevieve type	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Musculoskeletal; Neurologic	27213289

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the NANS gene.

• not provided (2 variants)
• Spondyloepimetaphyseal dysplasia, Genevieve type (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the NANS gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				32	5	37
missense			67	3	2	72
nonsense		1				1
start loss		1				1
frameshift	1					1
inframe indel			2			2
splice donor/acceptor (+/-2bp)	1	1				2
splice region	1	1	2	5	2	11
non coding				12	8	20
Total	2	3	69	47	15

Highest pathogenic variant AF is 0.0000131

Variants in NANS

This is a list of pathogenic ClinVar variants found in the NANS region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
9-98056788-T-G			Benign (Nov 12, 2018)
9-98056809-A-G		Spondyloepimetaphyseal dysplasia, Genevieve type	Likely pathogenic (May 01, 2019)
9-98056813-CGCTGGA-C		Inborn genetic diseases • Spondyloepimetaphyseal dysplasia, Genevieve type	Uncertain significance (Mar 29, 2024)
9-98056840-G-T			Uncertain significance (May 19, 2022)
9-98056860-C-G			Uncertain significance (Sep 01, 2022)
9-98056861-C-T		NANS-related disorder	Likely benign (Jan 07, 2024)
9-98056897-AG-A			Pathogenic (Jun 15, 2023)
9-98056903-A-C		Inborn genetic diseases	Uncertain significance (Dec 27, 2023)
9-98056906-T-G		Inborn genetic diseases	Uncertain significance (Nov 08, 2021)
9-98056910-C-T		Spondyloepimetaphyseal dysplasia, Genevieve type	Benign (Jan 31, 2024)
9-98056912-T-C			Uncertain significance (May 25, 2022)
9-98056921-G-A		Inborn genetic diseases	Uncertain significance (Jun 04, 2024)
9-98056930-G-T			Uncertain significance (Mar 07, 2022)
9-98056937-C-T			Benign (Nov 14, 2022)
9-98056939-A-C			Uncertain significance (Jan 06, 2024)
9-98056950-C-A			Likely benign (Jan 25, 2024)
9-98056954-T-TC			Likely benign (Dec 13, 2023)
9-98056960-G-A			Likely benign (Apr 30, 2022)
9-98060558-T-A			Benign (Nov 12, 2018)
9-98060658-G-A			Benign (Nov 12, 2018)
9-98060765-C-T			Likely benign (Aug 30, 2023)
9-98060770-T-A		Spondyloepimetaphyseal dysplasia, Genevieve type	Pathogenic (May 10, 2022)
9-98060775-GT-G			Likely benign (Mar 30, 2023)
9-98060777-T-G			Uncertain significance (Feb 11, 2022)
9-98060786-G-A			Uncertain significance (Feb 15, 2022)

GnomAD

Source: gnomAD

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Produces N-acetylneuraminic acid (Neu5Ac) and 2-keto-3- deoxy-D-glycero-D-galacto-nononic acid (KDN). Can also use N- acetylmannosamine 6-phosphate and mannose 6-phosphate as substrates to generate phosphorylated forms of Neu5Ac and KDN, respectively.
• Pathway: Amino sugar and nucleotide sugar metabolism - Homo sapiens (human);Sialuria or French Type Sialuria;Sialuria or French Type Sialuria;Amino Sugar Metabolism;G(M2)-Gangliosidosis: Variant B, Tay-sachs disease;Tay-Sachs Disease;Salla Disease/Infantile Sialic Acid Storage Disease;Aminosugars metabolism;Post-translational protein modification;Metabolism of proteins;CMP-<i>N</i>-acetylneuraminate biosynthesis I (eukaryotes);Sialic acid metabolism;Synthesis of substrates in N-glycan biosythesis;Biosynthesis of the N-glycan precursor (dolichol lipid-linked oligosaccharide, LLO) and transfer to a nascent protein;Asparagine N-linked glycosylation (Consensus)

Intolerance Scores

• loftool: 0.718
• rvis_EVS: 0.42
• rvis_percentile_EVS: 77.06

Haploinsufficiency Scores

• pHI: 0.189
• hipred: N
• hipred_score: 0.251

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.970

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Nans

Zebrafish Information Network

• Gene name: nansa
• Affected structure: ceratobranchial cartilage
• Phenotype tag: abnormal
• Phenotype quality: absent

Gene ontology

• Biological process: CMP-N-acetylneuraminate biosynthetic process;carbohydrate biosynthetic process
• Cellular component: cytoplasm;cytosol;extracellular exosome
• Molecular function: N-acylneuraminate cytidylyltransferase activity;N-acylneuraminate-9-phosphate synthase activity;N-acetylneuraminate synthase activity