NANP

Summary

NANP (N-acetylneuraminic acid phosphatase, HGNC:16140) is a protein-coding gene on chromosome 20p11.21, encoding N-acylneuraminate-9-phosphatase (Q8TBE9). Catalyzes the dephosphorylation of N-acylneuraminate 9-phosphate (Neu5Ac-9-P) to N-acetylneuraminic acid (Neu5Ac or sialic acid).

Enables N-acylneuraminate-9-phosphatase activity. Involved in CMP-N-acetylneuraminate biosynthetic process; N-acetylneuraminate biosynthetic process; and glycosylation. Predicted to be active in cytosol.

Source: NCBI Gene 140838 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 40 total — 1 likely-pathogenic
• Druggable target: yes
• MANE Select transcript: NM_152667

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16140
Approved symbol	NANP
Name	N-acetylneuraminic acid phosphatase
Location	20p11.21
Locus type	gene with protein product
Status	Approved
Aliases	dJ694B14.3, MGC26833
Ensembl gene	ENSG00000170191
Ensembl biotype	protein_coding
OMIM	610763
Entrez	140838

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000304788

RefSeq mRNA: 1 — MANE Select: NM_152667 NM_152667

CCDS: CCDS13173

Canonical transcript exons

ENST00000304788 — 2 exons

Exon	Start	End
ENSE00001160069	25612935	25616581
ENSE00001282249	25623859	25624014

Expression profiles

Bgee: expression breadth ubiquitous, 219 present calls, max score 86.47.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 9.3833 / max 71.0773, expressed in 1774 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
186808	9.3833	1774

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
kidney epithelium	UBERON:0004819	86.47	silver quality
tibialis anterior	UBERON:0001385	83.61	silver quality
secondary oocyte	CL:0000655	83.50	gold quality
parietal pleura	UBERON:0002400	82.79	gold quality
tibia	UBERON:0000979	82.74	gold quality
palpebral conjunctiva	UBERON:0001812	82.12	gold quality
esophagus squamous epithelium	UBERON:0006920	81.80	gold quality
cartilage tissue	UBERON:0002418	80.94	gold quality
visceral pleura	UBERON:0002401	80.43	gold quality
epithelial cell of pancreas	CL:0000083	80.20	silver quality
islet of Langerhans	UBERON:0000006	79.73	gold quality
cardiac muscle of right atrium	UBERON:0003379	79.42	gold quality
left ventricle myocardium	UBERON:0006566	79.33	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	78.99	gold quality
deltoid	UBERON:0001476	78.94	silver quality
ileal mucosa	UBERON:0000331	78.55	gold quality
epithelium of nasopharynx	UBERON:0001951	78.39	silver quality
adrenal tissue	UBERON:0018303	77.89	gold quality
pancreatic ductal cell	CL:0002079	77.82	silver quality
thymus	UBERON:0002370	77.46	gold quality
upper arm skin	UBERON:0004263	76.32	gold quality
right adrenal gland cortex	UBERON:0035827	75.58	gold quality
epithelium of mammary gland	UBERON:0003244	75.50	gold quality
mammary duct	UBERON:0001765	75.44	gold quality
germinal epithelium of ovary	UBERON:0001304	75.43	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	75.36	gold quality
stromal cell of endometrium	CL:0002255	75.10	gold quality
right adrenal gland	UBERON:0001233	74.87	gold quality
thoracic mammary gland	UBERON:0005200	74.79	gold quality
mammary gland	UBERON:0001911	74.72	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	3.01

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

116 targeting NANP, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-4487	99.96	64.58	1252
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-1-3P	99.93	72.35	1914
HSA-MIR-206	99.93	72.50	1893
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-10523-5P	99.91	69.22	2038

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	nanp	ENSDARG00000075143
mus_musculus	Nanp	ENSMUSG00000053916
rattus_norvegicus	Nanp	ENSRNOG00000074422
drosophila_melanogaster	CG15771	FBGN0029801

Paralogs (1): HDHD3 (ENSG00000119431)

Protein

Protein identifiers

N-acylneuraminate-9-phosphatase — Q8TBE9 (reviewed: Q8TBE9)

Alternative names: Haloacid dehalogenase-like hydrolase domain-containing protein 4, N-acetylneuraminate-9-phosphate phosphatase, Neu5Ac-9-Pase

All UniProt accessions (1): Q8TBE9

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes the dephosphorylation of N-acylneuraminate 9-phosphate (Neu5Ac-9-P) to N-acetylneuraminic acid (Neu5Ac or sialic acid). Can also use N-glycoloylneuraminate 9-phosphate as substrate.

Activity regulation. Inhibited by calcium. Inhibited by vanadate, sodium orthovanadate and phosphonate.

Pathway. Amino-sugar metabolism; N-acetylneuraminate biosynthesis.

Similarity. Belongs to the HAD-like hydrolase superfamily. NANP family.

RefSeq proteins (1): NP_689880* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR006439	HAD-SF_hydro_IA	Family
IPR011950	HAD-SF_hydro_IA_CTE7	Family
IPR023214	HAD_sf	Homologous_superfamily
IPR036412	HAD-like_sf	Homologous_superfamily
IPR051400	HAD-like_hydrolase	Family

Pfam: PF00702

Catalyzed reactions (Rhea), 2 shown:

• N-acetylneuraminate 9-phosphate + H2O = N-acetylneuraminate + phosphate (RHEA:80839)
• N-glycoloylneuraminate 9-phosphate + H2O = N-glycoloylneuraminate + phosphate (RHEA:83303)

UniProt features (34 total): helix 13, binding site 8, strand 7, turn 4, chain 1, sequence conflict 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
4KNV	X-RAY DIFFRACTION	1.99
2W4M	X-RAY DIFFRACTION	2.6
4KNW	X-RAY DIFFRACTION	2.7

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8TBE9-F1	94.92	0.89

Functional residue map

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

Ligand- & substrate-binding residues (8): 12; 13; 14; 14; 131; 132; 164; 189

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: 123 (showing top): TGGTGCT_MIR29A_MIR29B_MIR29C, 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, GOBP_AMIDE_METABOLIC_PROCESS, GOBP_CARBOHYDRATE_DERIVATIVE_BIOSYNTHETIC_PROCESS, GOBP_AMIDE_BIOSYNTHETIC_PROCESS, GOBP_AMINO_SUGAR_METABOLIC_PROCESS, GOBP_ORGANIC_ACID_METABOLIC_PROCESS, ZHANG_BREAST_CANCER_PROGENITORS_UP

GO Biological Process (6): N-acetylglucosamine biosynthetic process (GO:0006045), CMP-N-acetylneuraminate biosynthetic process (GO:0006055), N-acetylneuraminate biosynthetic process (GO:0046380), N-acetylneuraminate metabolic process (GO:0006054), obsolete glycosylation (GO:0070085), carbohydrate derivative biosynthetic process (GO:1901137)

GO Molecular Function (2): N-acylneuraminate-9-phosphatase activity (GO:0050124), hydrolase activity (GO:0016787)

GO Cellular Component (1): cytosol (GO:0005829)

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
N-acetylglucosamine metabolic process	1
glucosamine-containing compound biosynthetic process	1
nucleotide-sugar biosynthetic process	1
CMP-N-acetylneuraminate metabolic 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
biosynthetic process	1
carbohydrate derivative metabolic process	1
phosphatase activity	1
catalytic activity	1
cytoplasm	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1231 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NANP	NEU1	Q99519	769
NANP	NANS	Q9NR45	745
NANP	TBC1D24	Q9ULP9	691
NANP	CMAS	Q8NFW8	652
NANP	NPPA	P01160	603
NANP	GNE	Q9Y223	564
NANP	ST8SIA5	O15466	529
NANP	NPPB	P16860	506
NANP	KLHL30	Q0D2K2	505
NANP	SLC35A1	P78382	479
NANP	NPL	Q9BXD5	456
NANP	SERPINH1	P29043	428
NANP	PMM1	Q92871	393
NANP	UAP1	Q16222	393
NANP	NPPC	P23582	392

IntAct

7 interactions, top by confidence:

A	B	Type	Score
MLH1	CAPZA2	psi-mi:“MI:0914”(association)	0.350
VAPA		psi-mi:“MI:0914”(association)	0.350
PCDHB15	HLA-A	psi-mi:“MI:0914”(association)	0.350
Cdkn2aip	SF1	psi-mi:“MI:0914”(association)	0.350
PML	ATP5MF-PTCD1	psi-mi:“MI:0914”(association)	0.350
NANP		psi-mi:“MI:0915”(physical association)	0.000

BioGRID (26): ESD (Co-fractionation), LDHB (Co-fractionation), MIF (Co-fractionation), NANP (Co-fractionation), NANP (Affinity Capture-MS), NANP (Affinity Capture-MS), NANP (Affinity Capture-MS), NANP (Affinity Capture-MS), NANP (Affinity Capture-MS), NANP (Affinity Capture-MS), NANP (Affinity Capture-MS), NANP (Proximity Label-MS), NANP (Proximity Label-MS), NANP (Co-fractionation), C12orf5 (Co-fractionation)

ESM2 similar proteins: A4FV42, A4IG53, A4IGU3, A4QP75, A6QP81, A6QQV6, A8E7D2, B3DLB3, D9IVE5, F1QCV2, F4ZGF2, P0C5J1, P83006, Q13057, Q28CZ7, Q28IN4, Q3T0H0, Q3U3W5, Q3UZW7, Q4V9P6, Q501S4, Q502I6, Q5BLD8, Q5F389, Q5M969, Q5RE14, Q5RFM7, Q5U4E8, Q5ZIB9, Q6NTR1, Q6P4Z6, Q6PCI6, Q6QHF9, Q803A8, Q865R1, Q8BLU2, Q8C0L6, Q8MIR4, Q8N7N1, Q8R123

Diamond homologs: A0ALG5, A0RKU8, A7Z971, A8FHS1, A9VQ75, B7GL49, B7HEG2, B7HWY7, B7IPS5, B7JFI8, B8DBN0, B9J4R5, C1EZE2, C1KYP8, C3LED0, C3P0C8, O26311, O59346, O67359, P28624, P54607, Q183T0, Q2RPW9, Q3J8A0, Q51645, Q60099, Q631J2, Q6HBC8, Q6HQY9, Q71WU6, Q72XV8, Q815I8, Q88M11, Q8ENK3, Q8R821, Q8TBE9, Q8TWR2, Q8U040, Q8XIY6, Q8Y4G3

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	33
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
979562	GRCh37/hg19 20p11.23-q11.21(chr20:19750804-30479077)x3	Likely pathogenic

SpliceAI

318 predictions. Top by Δscore:

Variant	Effect	Δscore
20:25623853:CGTTA:C	donor_loss	0.9900
20:25623856:TACCT:T	donor_loss	0.9900
20:25623858:C:CG	donor_loss	0.9900
20:25623860:T:TA	donor_gain	0.9900
20:25623873:T:A	donor_gain	0.9900
20:25621301:TGCCA:T	donor_gain	0.9700
20:25623860:TCCA:T	donor_gain	0.9600
20:25623868:G:A	donor_gain	0.9600
20:25623857:A:AC	donor_gain	0.9500
20:25623858:C:CC	donor_gain	0.9500
20:25623468:G:GT	donor_gain	0.9400
20:25623858:CCT:C	donor_gain	0.9400
20:25621311:A:AC	donor_gain	0.9300
20:25621312:C:CC	donor_gain	0.9300
20:25623499:G:T	donor_gain	0.9100
20:25623470:C:A	donor_gain	0.8800
20:25623821:G:T	donor_gain	0.8800
20:25616301:T:TA	donor_gain	0.8700
20:25616923:ATG:A	donor_gain	0.8300
20:25623857:ACCT:A	donor_gain	0.8300
20:25623858:CCTC:C	donor_gain	0.8300
20:25623881:G:A	donor_gain	0.8300
20:25623467:C:CT	donor_gain	0.8200
20:25623034:A:AC	donor_gain	0.8000
20:25623035:C:CC	donor_gain	0.8000
20:25623483:TCCA:T	donor_gain	0.8000
20:25623484:CCAC:C	donor_gain	0.8000
20:25621324:T:C	donor_gain	0.7800
20:25613503:ACTTT:A	acceptor_gain	0.7700
20:25613506:T:C	acceptor_gain	0.7700

AlphaMissense

1623 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
20:25623908:T:A	D14V	0.998
20:25616052:A:T	V207D	0.996
20:25616091:T:G	D194A	0.996
20:25616109:C:A	G188V	0.996
20:25623907:G:C	D14E	0.996
20:25623907:G:T	D14E	0.996
20:25616091:T:A	D194V	0.995
20:25616092:C:G	D194H	0.995
20:25616182:T:G	K164Q	0.995
20:25623908:T:G	D14A	0.995
20:25623913:G:C	D12E	0.995
20:25623913:G:T	D12E	0.995
20:25616090:G:C	D194E	0.994
20:25616090:G:T	D194E	0.994
20:25616091:T:C	D194G	0.994
20:25616162:A:C	F170L	0.994
20:25616162:A:T	F170L	0.994
20:25616164:A:G	F170L	0.994
20:25616258:C:A	Q138H	0.994
20:25616258:C:G	Q138H	0.994
20:25616446:A:G	W76R	0.994
20:25616446:A:T	W76R	0.994
20:25623899:A:T	L17H	0.994
20:25623909:C:G	D14H	0.994
20:25623914:T:A	D12V	0.994
20:25616106:T:G	D189A	0.993
20:25616109:C:T	G188D	0.993
20:25616181:T:A	K164I	0.993
20:25616182:T:C	K164E	0.993
20:25616276:A:C	N132K	0.993

dbSNP variants (sampled 300 via entrez): RS1000069696 (20:25620724 T>A,G), RS1000190628 (20:25625351 C>G), RS1000228916 (20:25612497 A>G), RS1000281565 (20:25619167 C>A), RS1000834130 (20:25614325 A>G), RS1000896778 (20:25625046 C>T), RS1001287440 (20:25620707 G>C), RS1001736806 (20:25622332 T>C), RS1001766540 (20:25614360 C>T), RS1001945661 (20:25614574 G>T), RS1002133247 (20:25615412 A>G,T), RS1002294494 (20:25622593 C>T), RS1002872802 (20:25617363 C>G,T), RS1002918185 (20:25623707 G>A,T), RS1003024769 (20:25623884 C>G,T)

Disease associations

OMIM: gene MIM:610763 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST003209_1	Colorectal or endometrial cancer	1.000000e-07
GCST009391_245	Metabolite levels	9.000000e-06
GCST010703_48	Brain morphology (MOSTest)	1.000000e-08

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004230	endometrial neoplasm
EFO:0010494	guanosine diphosphate measurement
EFO:0004346	neuroimaging measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2401602 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases expression, affects expression, increases methylation, affects cotreatment	6
sodium arsenite	decreases expression	2
Benzo(a)pyrene	affects methylation, increases expression	2
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
triphenyl phosphate	affects expression	1
hydroxyhydroquinone	decreases expression, decreases reaction	1
benzo(e)pyrene	increases methylation	1
nickel sulfate	decreases expression	1
4-aminophenylarsenoxide	affects binding, decreases reaction	1
4-aminobenzhydrazide	decreases expression, decreases reaction	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	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
jinfukang	affects cotreatment, increases expression	1
Sunitinib	increases expression	1
Arsenic Trioxide	affects binding, decreases reaction	1
Air Pollutants	decreases expression, increases abundance	1
Cisplatin	affects cotreatment, increases expression	1
Coumestrol	increases expression	1
Estradiol	increases expression	1
Formaldehyde	decreases expression	1
Hydrogen Peroxide	affects expression	1
Methapyrilene	increases methylation	1
Silver	decreases expression	1
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	1
Aflatoxin B1	increases methylation	1
Cadmium Chloride	decreases expression	1
Copper Sulfate	decreases expression	1
Particulate Matter	increases abundance, decreases expression	1

ChEMBL screening assays

2 unique, capped per target: 2 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL2404639	Binding	Reversible inhibition of recombinant HDHD4 (unknown origin) using Neu5Ac-9-P as substrate assessed as release of phosphate after 30 mins by maiachite green assay	Design, synthesis, functional and structural characterization of an inhibitor of N-acetylneuraminate-9-phosphate phosphatase: observation of extensive dynamics in an enzyme/inhibitor complex. — Bioorg Med Chem Lett

Cellosaurus cell lines

3 cell lines: 3 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_SZ88	HAP1 NANP (-) 1	Cancer cell line	Male
CVCL_SZ89	HAP1 NANP (-) 2	Cancer cell line	Male
CVCL_SZ90	HAP1 NANP (-) 3	Cancer cell line	Male

Clinical trials (associated diseases)

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