NANS

Summary

NANS (N-acetylneuraminate synthase, HGNC:19237) is a protein-coding gene on chromosome 9q22.33, encoding N-acetylneuraminate-9-phosphate synthase (Q9NR45). Catalyzes the condensation of phosphoenolpyruvate (PEP) and N-acetylmannosamine 6-phosphate (ManNAc-6-P) to synthesize N-acetylneuraminate-9-phosphate (Neu5Ac-9-P).

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.

Source: NCBI Gene 54187 — RefSeq curated summary.

At a glance

• Gene–disease (curated): spondyloepimetaphyseal dysplasia, Genevieve type (Definitive, ClinGen)
• GWAS associations: 3
• Clinical variants (ClinVar): 186 total — 7 pathogenic, 8 likely-pathogenic
• Phenotypes (HPO): 49
• Druggable target: yes
• MANE Select transcript: NM_018946

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:19237
Approved symbol	NANS
Name	N-acetylneuraminate synthase
Location	9q22.33
Locus type	gene with protein product
Status	Approved
Aliases	SAS
Ensembl gene	ENSG00000095380
Ensembl biotype	protein_coding
OMIM	605202
Entrez	54187

Gene structure

Transcript identifiers

Ensembl transcripts: 16 — 13 protein_coding, 3 protein_coding_CDS_not_defined

ENST00000210444, ENST00000415280, ENST00000427646, ENST00000461452, ENST00000480925, ENST00000495319, ENST00000869789, ENST00000869790, ENST00000869791, ENST00000924303, ENST00000924304, ENST00000924305, ENST00000924306, ENST00000924307, ENST00000956796, ENST00000956797

RefSeq mRNA: 1 — MANE Select: NM_018946 NM_018946

CCDS: CCDS6733

Canonical transcript exons

ENST00000210444 — 6 exons

Exon	Start	End
ENSE00002208054	98056732	98056940
ENSE00003458926	98080816	98081082
ENSE00003460525	98082846	98083077
ENSE00003475117	98060782	98060997
ENSE00003510064	98078193	98078347
ENSE00003644698	98076918	98077017

Expression profiles

Bgee: expression breadth ubiquitous, 285 present calls, max score 98.55.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 49.9566 / max 308.3490, expressed in 1823 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
97599	48.6578	1823
97600	1.2988	870

Top tissues by expression

289 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
mucosa of sigmoid colon	UBERON:0004993	98.55	gold quality
mucosa of transverse colon	UBERON:0004991	98.54	gold quality
rectum	UBERON:0001052	98.16	gold quality
colonic mucosa	UBERON:0000317	98.12	gold quality
epithelium of nasopharynx	UBERON:0001951	98.06	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	98.04	gold quality
palpebral conjunctiva	UBERON:0001812	97.80	gold quality
parotid gland	UBERON:0001831	97.60	gold quality
transverse colon	UBERON:0001157	96.85	gold quality
prostate gland	UBERON:0002367	96.72	gold quality
nasal cavity mucosa	UBERON:0001826	96.53	gold quality
trachea	UBERON:0003126	96.43	gold quality
saliva-secreting gland	UBERON:0001044	96.37	gold quality
bronchial epithelial cell	CL:0002328	96.31	gold quality
minor salivary gland	UBERON:0001830	95.97	gold quality
epithelium of bronchus	UBERON:0002031	95.85	gold quality
bronchus	UBERON:0002185	95.85	gold quality
pylorus	UBERON:0001166	95.66	gold quality
body of stomach	UBERON:0001161	95.24	gold quality
tonsil	UBERON:0002372	95.21	gold quality
mouth mucosa	UBERON:0003729	95.14	gold quality
body of pancreas	UBERON:0001150	95.02	gold quality
vermiform appendix	UBERON:0001154	94.90	gold quality
monocyte	CL:0000576	94.84	gold quality
large intestine	UBERON:0000059	94.80	gold quality
colon	UBERON:0001155	94.72	gold quality
caecum	UBERON:0001153	94.56	gold quality
amniotic fluid	UBERON:0000173	94.55	gold quality
cervix squamous epithelium	UBERON:0006922	94.40	silver quality
mononuclear cell	CL:0000842	94.39	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-GEOD-125970	yes	43.37
E-MTAB-8410	yes	11.41
E-HCAD-1	yes	7.99
E-MTAB-7606	no	419.67
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 4)

• sialic acid synthases kinetics and preliminary mutagenesis experiments reveal the importance of C-terminal antifreeze protein domain (PMID:16274664)
• The structure of the C-terminal antifreeze-like domain of human sialic acid synthase was determined. The structure comprises one alpha- and two single-turn 3(10)-helices and two beta-strands, and is similar to those of the type III antifreeze proteins. (PMID:16597820)
• NANS deficiency is associated with defect in brain and skeletal development. (PMID:27213289)
• Neurodevelopmental defects in human cortical organoids with N-acetylneuraminic acid synthase mutation. (PMID:38000033)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	nansa	ENSDARG00000045620
danio_rerio	nansb	ENSDARG00000101164
mus_musculus	Nans	ENSMUSG00000028334
rattus_norvegicus	Nans	ENSRNOG00000008945
drosophila_melanogaster	NANS	FBGN0038045

Protein

Protein identifiers

N-acetylneuraminate-9-phosphate synthase — Q9NR45 (reviewed: Q9NR45)

Alternative names: 3-deoxy-D-glycero-D-galacto-nononate 9-phosphate synthase, N-acetylneuraminic acid phosphate synthase, Sialic acid phosphate synthase, Sialic acid synthase

All UniProt accessions (3): Q9NR45, Q5TBR0, Q5TBR1

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes the condensation of phosphoenolpyruvate (PEP) and N-acetylmannosamine 6-phosphate (ManNAc-6-P) to synthesize N-acetylneuraminate-9-phosphate (Neu5Ac-9-P). Also catalyzes the condensation of PEP and D-mannose 6-phosphate (Man-6-P) to produce 3-deoxy-D-glycero-beta-D-galacto-non-2-ulopyranosonate 9-phosphate (KDN-9-P). Neu5Ac-9-P and KDN-9-P are the phosphorylated forms of sialic acids N-acetylneuraminic acid (Neu5Ac) and deaminoneuraminic acid (KDN), respectively. Required for brain and skeletal development.

Tissue specificity. Ubiquitous.

Disease relevance. Spondyloepimetaphyseal dysplasia, Genevieve type (SEMDG) [MIM:610442] An autosomal recessive disorder characterized by global developmental delay with infantile onset, intellectual disability, skeletal dysplasia, and short stature. Skeletal findings include flat vertebral bodies with irregular vertebral plates, irregular and flared metaphyses with vertical striations, small and irregular epiphyses, premature carpal ossification and small carpal bones. The disease is caused by variants affecting the gene represented in this entry.

RefSeq proteins (1): NP_061819* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR006013	Antifreeze_III	Family
IPR006190	SAF_AFP_Neu5Ac	Domain
IPR013132	PseI/NeuA/B-like_N	Domain
IPR013785	Aldolase_TIM	Homologous_superfamily
IPR013974	SAF	Domain
IPR036732	AFP_Neu5c_C_sf	Homologous_superfamily
IPR051690	PseI-like	Family
IPR057736	SAF_PseI/NeuA/NeuB	Domain

Pfam: PF03102, PF08666

Enzyme classification (BRENDA):

• EC 2.5.1.132 — 3-deoxy-D-glycero-D-galacto-nonulopyranosonate 9-phosphate synthase (BRENDA: 5 organisms, 13 substrates, 2 inhibitors, 5 Km, 4 kcat entries)
• EC 2.5.1.56 — N-acetylneuraminate synthase (BRENDA: 10 organisms, 21 substrates, 26 inhibitors, 18 Km, 8 kcat entries)
• EC 2.5.1.57 — N-acylneuraminate-9-phosphate synthase (BRENDA: 7 organisms, 13 substrates, 13 inhibitors, 13 Km, 7 kcat entries)

Substrate kinetics (BRENDA)

11 substrates with measured Km, best-characterized 11. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
N-ACETYL-D-MANNOSAMINE 6-PHOSPHATE	0.035–1.72	8
N-ACETYL-D-MANNOSAMINE	5.6–18	6
PHOSPHOENOLPYRUVATE	0.04–7.3	6
D-MANNOSE 6-PHOSPHATE	1.4–3.66	3
D-MANNOSE 6-PHOSPHATE	2.62	2
PHOSPHOENOLPYRUVATE	0.11	1
N-BUTANOYL-D-MANNOSAMINE	15	1
N-PENTANOYL-D-MANNOSAMINE	31.1	1
N-PROPANOYL-D-MANNOSAMINE	5.5	1
N-GLYCOLYL-D-MANNOSAMINE 6-PHOSPHATE	1.6	1
PHOSPHOENOLPYRUVATE	0.1	1

Catalyzed reactions (Rhea), 2 shown:

• aldehydo-D-mannose 6-phosphate + phosphoenolpyruvate + H2O = 3-deoxy-D-glycero-beta-D-galacto-non-2-ulopyranosonate 9-phosphate + phosphate (RHEA:49200)
• aldehydo-N-acetyl-D-mannosamine 6-phosphate + phosphoenolpyruvate + H2O = N-acetylneuraminate 9-phosphate + phosphate (RHEA:80835)

UniProt features (26 total): sequence variant 8, strand 5, modified residue 5, helix 3, sequence conflict 2, initiator methionine 1, chain 1, domain 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
1WVO	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NR45-F1	96.04	0.97

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (5): 61, 74, 79, 275, 290

Function

Pathways and Gene Ontology

Reactome pathways

6 pathways

ID	Pathway
R-HSA-4085001	Sialic acid metabolism
R-HSA-392499	Metabolism of proteins
R-HSA-446193	Biosynthesis of the N-glycan precursor (dolichol lipid-linked oligosaccharide, LLO) and transfer to a nascent protein
R-HSA-446203	Asparagine N-linked glycosylation
R-HSA-446219	Synthesis of substrates in N-glycan biosythesis
R-HSA-597592	Post-translational protein modification

MSigDB gene sets: 299 (showing top): MODULE_255, MODULE_317, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_AMINO_SUGAR_BIOSYNTHETIC_PROCESS, GOBP_NUCLEOSIDE_PHOSPHATE_BIOSYNTHETIC_PROCESS, GOBP_ORGANOPHOSPHATE_BIOSYNTHETIC_PROCESS, GOBP_ORGANIC_ACID_BIOSYNTHETIC_PROCESS, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, GOBP_NUCLEOBASE_CONTAINING_SMALL_MOLECULE_METABOLIC_PROCESS, GOBP_SMALL_MOLECULE_BIOSYNTHETIC_PROCESS, ONKEN_UVEAL_MELANOMA_UP, ATF1_Q6, GOBP_AMIDE_METABOLIC_PROCESS, GOBP_CARBOHYDRATE_DERIVATIVE_BIOSYNTHETIC_PROCESS, GOBP_AMIDE_BIOSYNTHETIC_PROCESS

GO Biological Process (5): CMP-N-acetylneuraminate biosynthetic process (GO:0006055), carbohydrate biosynthetic process (GO:0016051), N-acetylneuraminate biosynthetic process (GO:0046380), N-acetylneuraminate metabolic process (GO:0006054), obsolete glycosylation (GO:0070085)

GO Molecular Function (3): N-acylneuraminate-9-phosphate synthase activity (GO:0047444), transferase activity (GO:0016740), N-acetylneuraminate synthase activity (GO:0050462)

GO Cellular Component (3): cytoplasm (GO:0005737), cytosol (GO:0005829), extracellular exosome (GO:0070062)

Reactome top-level categories

Rollup of top-5 pathways:

Category	Pathways
Synthesis of substrates in N-glycan biosythesis	1
Asparagine N-linked glycosylation	1
Post-translational protein modification	1
Biosynthesis of the N-glycan precursor (dolichol lipid-linked oligosaccharide, LLO) and transfer to a nascent protein	1
Metabolism of proteins	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
transferase activity, transferring alkyl or aryl (other than methyl) groups	2
cellular anatomical structure	2
nucleotide-sugar biosynthetic process	1
CMP-N-acetylneuraminate metabolic process	1
carbohydrate metabolic process	1
biosynthetic process	1
N-acetylneuraminate metabolic process	1
amino sugar biosynthetic process	1
carboxylic acid biosynthetic process	1
amino sugar metabolic process	1
carboxylic acid metabolic process	1
catalytic activity	1
intracellular anatomical structure	1
cytoplasm	1
extracellular vesicle	1

Protein interactions and networks

STRING

1366 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NANS	GNE	Q9Y223	880
NANS	NANP	Q8TBE9	745
NANS	CMAS	Q8NFW8	735
NANS	SLC35A1	P78382	715
NANS	SIAE	Q9HAT2	591
NANS	SGO1	Q5FBB7	579
NANS	RNF38	Q9H0F5	575
NANS	UAP1	Q16222	546
NANS	ST8SIA4	Q92187	528
NANS	ST6GAL1	P15907	515
NANS	ST3GAL5	Q9UNP4	512
NANS	ST6GALNAC1	Q9NSC7	510
NANS	GMPPB	Q9Y5P6	479
NANS	FANCL	Q9NW38	478
NANS	ST8SIA2	Q92186	465

IntAct

57 interactions, top by confidence:

A	B	Type	Score
CD27	TCAF2	psi-mi:“MI:0914”(association)	0.640
MSRB2	BLTP3B	psi-mi:“MI:0914”(association)	0.530
DDX21	MED19	psi-mi:“MI:2364”(proximity)	0.480
	NANS	psi-mi:“MI:0915”(physical association)	0.400
APC	NANS	psi-mi:“MI:0915”(physical association)	0.370
NANS	AURKA	psi-mi:“MI:0915”(physical association)	0.370
NANS	BCL10	psi-mi:“MI:0915”(physical association)	0.370
NANS	BUB1	psi-mi:“MI:0915”(physical association)	0.370
CDH1	NANS	psi-mi:“MI:0915”(physical association)	0.370
NANS	CTNNA1	psi-mi:“MI:0915”(physical association)	0.370
NANS	EGFR	psi-mi:“MI:0915”(physical association)	0.370
FBXW7	NANS	psi-mi:“MI:0915”(physical association)	0.370
FLCN	NANS	psi-mi:“MI:0915”(physical association)	0.370
MCC	NANS	psi-mi:“MI:0915”(physical association)	0.370
NANS	MLH3	psi-mi:“MI:0915”(physical association)	0.370
MSH6	NANS	psi-mi:“MI:0915”(physical association)	0.370
ODC1	NANS	psi-mi:“MI:0915”(physical association)	0.370
PDGFRL	NANS	psi-mi:“MI:0915”(physical association)	0.370
PTPRJ	NANS	psi-mi:“MI:0915”(physical association)	0.370
SRC	NANS	psi-mi:“MI:0915”(physical association)	0.370
STK11	NANS	psi-mi:“MI:0915”(physical association)	0.370
TLR2	NANS	psi-mi:“MI:0915”(physical association)	0.370
M		psi-mi:“MI:0914”(association)	0.350
ZDHHC5	IGKV2D-24	psi-mi:“MI:0914”(association)	0.350
DDA1	PGK1	psi-mi:“MI:0914”(association)	0.350
MAPT	SHTN1	psi-mi:“MI:0914”(association)	0.350
BLVRB	NDUFA3	psi-mi:“MI:0914”(association)	0.350
NANS	NDUFA3	psi-mi:“MI:0914”(association)	0.350
PHGDH	TIMM44	psi-mi:“MI:0914”(association)	0.350
RNASEH2A	NDUFA3	psi-mi:“MI:0914”(association)	0.350

BioGRID (108): NANS (Affinity Capture-RNA), NANS (Affinity Capture-RNA), AKR1A1 (Co-fractionation), ASS1 (Co-fractionation), FAHD1 (Co-fractionation), GOT1 (Co-fractionation), MPI (Co-fractionation), NANS (Co-fractionation), NANS (Co-fractionation), NANS (Co-fractionation), NANS (Co-fractionation), NANS (Co-fractionation), NANS (Co-fractionation), NANS (Co-fractionation), PRDX1 (Co-fractionation)

ESM2 similar proteins: A1AAE2, A6V1F2, A7ZKY9, A7ZZF1, B1ITN8, B1LH85, B1XAQ6, B2TZW3, B5YXN3, B6I9T0, B7LGX6, B7LSH5, B7LXX2, B7MKB7, B7MTZ9, B7N426, B7NUY1, B7UQA3, C4ZTQ6, C5CSV4, O13831, O50044, O62619, P00548, P0A715, P0A716, P0DY06, P11974, P11979, P11980, P13228, P14618, P39625, P52480, Q02RA8, Q0T5I0, Q0TIF5, Q1RCM3, Q31ZQ8, Q32GZ2

Diamond homologs: P07457, P12100, P12101, P12102, P12416, P12417, P19604, P19605, P19606, P19607, P19608, P19609, P19611, P19612, P19613, P19614, P24028, P35751, P35753, Q99J77, Q9NR45, O24980, P39625, Q0P8T1, Q0P8U0, Q58465, Q5ZXH9, Q939J8, Q9VG74, P0DY06

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

186 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	7
Likely pathogenic	8
Uncertain significance	82
Likely benign	62
Benign	15

Top pathogenic / likely-pathogenic (15)

Variant ID	HGVS	Classification
1459209	NM_018946.4(NANS):c.92del (p.Gly31fs)	Pathogenic
1684568	NM_018946.4(NANS):c.133-12T>A	Pathogenic
235188	NM_018946.4(NANS):c.398G>T (p.Gly133Val)	Pathogenic
2507214	NM_018946.4(NANS):c.772G>T (p.Glu258Ter)	Pathogenic
3605083	NM_018946.4(NANS):c.256C>T (p.Arg86Ter)	Pathogenic
3683755	NM_018946.4(NANS):c.655dup (p.Thr219fs)	Pathogenic
872553	NM_018946.4(NANS):c.449-9_449-5del	Pathogenic
1341506	NM_018946.4(NANS):c.476T>G (p.Met159Arg)	Likely pathogenic
1684567	NM_018946.4(NANS):c.207del (p.Arg69fs)	Likely pathogenic
1686634	NM_018946.4(NANS):c.607T>C (p.Tyr203His)	Likely pathogenic
235184	NM_018946.4(NANS):c.449-10_449-5delinsATGG	Likely pathogenic
2507125	NM_018946.4(NANS):c.200T>C (p.Leu67Ser)	Likely pathogenic
2572433	NM_018946.4(NANS):c.735G>A (p.Trp245Ter)	Likely pathogenic
2823588	NM_018946.4(NANS):c.349-2A>G	Likely pathogenic
810396	NM_018946.4(NANS):c.1A>G (p.Met1Val)	Likely pathogenic

SpliceAI

1501 predictions. Top by Δscore:

Variant	Effect	Δscore
9:98056938:AAGGT:A	donor_loss	1.0000
9:98056939:AGG:A	donor_loss	1.0000
9:98056941:G:GA	donor_loss	1.0000
9:98056941:G:GG	donor_gain	1.0000
9:98060781:GGAGT:G	acceptor_gain	1.0000
9:98060998:G:C	donor_loss	1.0000
9:98060999:T:A	donor_loss	1.0000
9:98078345:TCG:T	donor_gain	1.0000
9:98078345:TCGG:T	donor_loss	1.0000
9:98078347:GGT:G	donor_loss	1.0000
9:98078348:G:C	donor_loss	1.0000
9:98078348:G:GG	donor_gain	1.0000
9:98078349:T:A	donor_loss	1.0000
9:98082844:A:AG	acceptor_gain	1.0000
9:98082844:AGCT:A	acceptor_gain	1.0000
9:98082844:AGCTG:A	acceptor_gain	1.0000
9:98082845:G:GG	acceptor_gain	1.0000
9:98082845:GCT:G	acceptor_gain	1.0000
9:98082845:GCTG:G	acceptor_gain	1.0000
9:98082845:GCTGG:G	acceptor_gain	1.0000
9:98056939:AG:A	donor_gain	0.9900
9:98056940:GG:G	donor_gain	0.9900
9:98056942:T:G	donor_loss	0.9900
9:98060778:GTAGG:G	acceptor_loss	0.9900
9:98060995:GAG:G	donor_gain	0.9900
9:98060998:G:GG	donor_gain	0.9900
9:98076915:TA:T	acceptor_loss	0.9900
9:98076916:A:AG	acceptor_gain	0.9900
9:98076917:G:GG	acceptor_gain	0.9900
9:98076917:G:GT	acceptor_loss	0.9900

AlphaMissense

2371 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:98078296:T:G	C184W	1.000
9:98056879:A:T	E24V	0.999
9:98056892:C:A	N28K	0.999
9:98056892:C:G	N28K	0.999
9:98060904:A:C	K85N	0.999
9:98060904:A:T	K85N	0.999
9:98076962:A:C	K131N	0.999
9:98076962:A:T	K131N	0.999
9:98078295:G:A	C184Y	0.999
9:98078300:A:C	S186R	0.999
9:98078302:C:A	S186R	0.999
9:98078302:C:G	S186R	0.999
9:98080850:G:A	G213E	0.999
9:98080924:C:G	H238D	0.999
9:98080926:C:A	H238Q	0.999
9:98080926:C:G	H238Q	0.999
9:98080958:A:T	D249V	0.999
9:98080959:C:A	D249E	0.999
9:98080959:C:G	D249E	0.999
9:98056885:G:A	G26D	0.998
9:98056893:C:G	H29D	0.998
9:98060805:G:C	K52N	0.998
9:98060805:G:T	K52N	0.998
9:98060811:G:C	Q54H	0.998
9:98060811:G:T	Q54H	0.998
9:98060942:T:C	L98P	0.998
9:98076960:A:G	K131E	0.998
9:98078213:A:C	S157R	0.998
9:98078215:T:A	S157R	0.998
9:98078215:T:G	S157R	0.998

dbSNP variants (sampled 300 via entrez): RS1000195538 (9:98063679 C>T), RS1000203275 (9:98056627 C>A,G,T), RS1000260111 (9:98075092 G>C), RS1000377708 (9:98055818 A>G), RS1000982954 (9:98057061 G>A,T), RS1001080004 (9:98057314 C>T), RS1001080536 (9:98069977 A>G), RS1001319260 (9:98058606 A>T), RS1001376851 (9:98054745 A>C), RS1001504712 (9:98077590 T>C), RS1001645251 (9:98071361 C>G), RS1001884522 (9:98076480 T>A), RS1001962501 (9:98073863 T>C), RS1002017832 (9:98077812 A>G), RS1002022902 (9:98070352 A>G)

Disease associations

OMIM: gene MIM:605202 | disease phenotypes: MIM:610442

GenCC curated gene-disease

Disease	Classification	Inheritance
spondyloepimetaphyseal dysplasia, Genevieve type	Strong	Autosomal recessive

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
spondyloepimetaphyseal dysplasia, Genevieve type	Definitive	AR

Mondo (1): spondyloepimetaphyseal dysplasia, Genevieve type (MONDO:0012495)

Orphanet (1): Spondyloepimetaphyseal dysplasia, Geneviève type (Orphanet:168454)

HPO phenotypes

49 total (30 of 49 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000179	Thick lower lip vermilion
HP:0000248	Brachycephaly
HP:0000252	Microcephaly
HP:0000280	Coarse facial features
HP:0000286	Epicanthus
HP:0000294	Low anterior hairline
HP:0000414	Bulbous nose
HP:0000445	Wide nose
HP:0000470	Short neck
HP:0000486	Strabismus
HP:0000639	Nystagmus
HP:0000664	Synophrys
HP:0000926	Platyspondyly
HP:0001007	Hirsutism
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001251	Ataxia
HP:0001252	Hypotonia
HP:0001270	Motor delay
HP:0001290	Generalized hypotonia
HP:0001382	Joint hypermobility
HP:0001498	Carpal bone hypoplasia
HP:0002059	Cerebral atrophy
HP:0002079	Hypoplasia of the corpus callosum
HP:0002119	Ventriculomegaly
HP:0002162	Low posterior hairline
HP:0002651	Spondyloepimetaphyseal dysplasia
HP:0002868	Narrow iliac wing
HP:0003015	Flared metaphysis

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST004866_3	Alopecia areata	9.000000e-07
GCST010241_344	Apolipoprotein A1 levels	4.000000e-08
GCST010242_274	HDL cholesterol levels	3.000000e-09

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004614	apolipoprotein A 1 measurement
EFO:0004612	high density lipoprotein cholesterol measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C535785	Spondyloepimetaphyseal dysplasia, Genevieve type (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6067105 (SINGLE PROTEIN)

PharmGKB: 1 entry (VIP=true, CPIC=false)

ChEMBL bioactivities

2 potent at pChembl≥5 of 4 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.05	Kd	89.95	nM	CHEMBL5653589
7.05	ED50	89.95	nM	CHEMBL5653589

PubChem BioAssay actives

1 with measured affinity, of 4 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148819: Binding affinity to human NANS incubated for 45 mins by Kinobead based pull down assay	kd	0.0900	uM

CTD chemical–gene interactions

56 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression	7
trichostatin A	affects cotreatment, increases expression	3
Arsenic Trioxide	affects binding, decreases reaction, decreases expression	3
Acetaminophen	increases expression, affects response to substance	3
bisphenol A	increases expression, decreases expression	2
entinostat	increases expression, affects cotreatment	2
Vorinostat	affects cotreatment, increases expression	2
Panobinostat	increases expression, affects cotreatment	2
Tretinoin	affects cotreatment, decreases expression	2
Tunicamycin	increases expression	2
Thapsigargin	increases expression	2
Okadaic Acid	decreases expression, increases expression	2
aristolochic acid I	increases expression	1
bisphenol F	increases expression	1
TL8-506	increases expression, affects cotreatment	1
methylmercuric chloride	increases expression	1
triphenyl phosphate	affects expression	1
sodium arsenate	decreases expression	1
decabromobiphenyl ether	decreases expression	1
arsenite	affects binding, increases reaction	1
sodium arsenite	decreases expression	1
tetrabromobisphenol A	decreases expression	1
perfluorooctanoic acid	decreases expression	1
4-aminophenylarsenoxide	affects binding, decreases reaction	1
CGP 52608	increases reaction, affects binding	1
tanespimycin	affects cotreatment, decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
pentabrominated diphenyl ether 100	decreases expression	1
hexabrominated diphenyl ether 153	decreases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5651861	Binding	Binding affinity to human NANS incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Cellosaurus cell lines

4 cell lines: 2 cancer cell line, 1 induced pluripotent stem cell, 1 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_A4EG	NCCSEDi001-A-1	Induced pluripotent stem cell	Male
CVCL_B3BU	Abcam HEK293T NANS KO	Transformed cell line	Female
CVCL_SZ91	HAP1 NANS (-) 1	Cancer cell line	Male
CVCL_SZ92	HAP1 NANS (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.