NAGPA

Summary

NAGPA (N-acetylglucosamine-1-phosphodiester alpha-N-acetylglucosaminidase, HGNC:17378) is a protein-coding gene on chromosome 16p13.3, encoding N-acetylglucosamine-1-phosphodiester alpha-N-acetylglucosaminidase (Q9UK23). Catalyzes the second step in the formation of the mannose 6-phosphate targeting signal on lysosomal enzyme oligosaccharides by removing GlcNAc residues from GlcNAc-alpha-P-mannose moieties, which are formed in the first step.

Hydrolases are transported to lysosomes after binding to mannose 6-phosphate receptors in the trans-Golgi network. This gene encodes the enzyme that catalyzes the second step in the formation of the mannose 6-phosphate recognition marker on lysosomal hydrolases. Commonly known as ‘uncovering enzyme’ or UCE, this enzyme removes N-acetyl-D-glucosamine (GlcNAc) residues from GlcNAc-alpha-P-mannose moieties and thereby produces the recognition marker. The encoded preproprotein is proteolytically processed by furin to generate the mature enzyme, a homotetramer of two disulfide-linked homodimers. Mutations in this gene are associated with developmental stuttering in human patients.

Source: NCBI Gene 51172 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 126 total
• Druggable target: yes
• MANE Select transcript: NM_016256

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17378
Approved symbol	NAGPA
Name	N-acetylglucosamine-1-phosphodiester alpha-N-acetylglucosaminidase
Location	16p13.3
Locus type	gene with protein product
Status	Approved
Aliases	APAA, UCE
Ensembl gene	ENSG00000103174
Ensembl biotype	protein_coding
OMIM	607985
Entrez	51172

Gene structure

Transcript identifiers

Ensembl transcripts: 29 — 15 protein_coding, 5 retained_intron, 5 nonsense_mediated_decay, 4 protein_coding_CDS_not_defined

ENST00000312251, ENST00000381955, ENST00000561580, ENST00000562037, ENST00000562346, ENST00000562746, ENST00000563578, ENST00000564397, ENST00000564922, ENST00000565876, ENST00000566137, ENST00000567739, ENST00000568202, ENST00000568528, ENST00000569296, ENST00000569793, ENST00000591478, ENST00000649828, ENST00000866188, ENST00000866189, ENST00000866190, ENST00000866191, ENST00000933627, ENST00000933628, ENST00000948537, ENST00000948538, ENST00000948539, ENST00000948540, ENST00000948541

RefSeq mRNA: 1 — MANE Select: NM_016256 NM_016256

CCDS: CCDS10527

Canonical transcript exons

ENST00000312251 — 10 exons

Exon	Start	End
ENSE00000667442	5033273	5033728
ENSE00001237108	5024844	5025685
ENSE00003464201	5027846	5027893
ENSE00003509690	5027980	5028185
ENSE00003528489	5027278	5027379
ENSE00003602439	5031745	5031884
ENSE00003615565	5028880	5029008
ENSE00003632859	5027135	5027198
ENSE00003676951	5030385	5030493
ENSE00003844023	5033829	5033935

Expression profiles

Bgee: expression breadth ubiquitous, 237 present calls, max score 92.94.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 6.0834 / max 79.4832, expressed in 1728 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
156142	3.7309	1628
156141	2.1983	1089
156140	0.1542	64

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
middle temporal gyrus	UBERON:0002771	92.94	gold quality
Brodmann (1909) area 10	UBERON:0013541	92.63	gold quality
right frontal lobe	UBERON:0002810	92.38	gold quality
oocyte	CL:0000023	92.12	gold quality
primary visual cortex	UBERON:0002436	91.88	gold quality
Brodmann (1909) area 9	UBERON:0013540	91.34	gold quality
occipital lobe	UBERON:0002021	90.84	gold quality
secondary oocyte	CL:0000655	90.62	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	90.23	gold quality
Brodmann (1909) area 23	UBERON:0013554	90.11	gold quality
prefrontal cortex	UBERON:0000451	90.03	gold quality
granulocyte	CL:0000094	89.67	gold quality
frontal cortex	UBERON:0001870	89.46	gold quality
monocyte	CL:0000576	89.38	gold quality
cingulate cortex	UBERON:0003027	89.29	gold quality
nucleus accumbens	UBERON:0001882	89.23	gold quality
anterior cingulate cortex	UBERON:0009835	89.18	gold quality
mononuclear cell	CL:0000842	89.11	gold quality
neocortex	UBERON:0001950	89.06	gold quality
leukocyte	CL:0000738	88.92	gold quality
cerebral cortex	UBERON:0000956	88.22	gold quality
superior frontal gyrus	UBERON:0002661	87.81	gold quality
telencephalon	UBERON:0001893	87.48	gold quality
type B pancreatic cell	CL:0000169	87.42	gold quality
frontal pole	UBERON:0002795	87.26	gold quality
putamen	UBERON:0001874	87.23	gold quality
parietal lobe	UBERON:0001872	86.97	gold quality
caudate nucleus	UBERON:0001873	86.82	gold quality
mucosa of transverse colon	UBERON:0004991	86.61	gold quality
postcentral gyrus	UBERON:0002581	86.46	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.99

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

43 targeting NAGPA, 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-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-34C-5P	99.97	70.45	1577
HSA-MIR-449B-5P	99.97	70.26	1580
HSA-MIR-6753-3P	99.93	66.57	637
HSA-MIR-7107-3P	99.93	66.73	627
HSA-MIR-6744-5P	99.93	66.82	748
HSA-MIR-1297	99.91	73.41	3162
HSA-MIR-3686	99.90	70.53	2432
HSA-MIR-8062	99.88	68.43	995
HSA-MIR-182-5P	99.87	74.03	2589
HSA-MIR-26A-5P	99.78	73.52	2303
HSA-MIR-26B-5P	99.78	73.51	2305
HSA-MIR-202-5P	99.78	67.65	991
HSA-MIR-4465	99.71	72.56	2096
HSA-MIR-298	99.63	67.56	1916
HSA-MIR-7150	99.62	66.80	1322
HSA-MIR-6513-3P	99.59	69.77	1102
HSA-MIR-12122	99.56	69.33	1672
HSA-MIR-12123	99.52	71.79	2990
HSA-MIR-766-3P	99.47	65.24	1811
HSA-MIR-516A-3P	99.46	67.96	1378
HSA-MIR-516B-3P	99.46	67.96	1378
HSA-MIR-7162-5P	99.46	68.08	1368
HSA-MIR-5693	99.24	66.67	1106

Literature-anchored findings (GeneRIF, showing 11)

• synthesis as a proenzyme that is activated by furin [mannose 6-phosphate-uncovering enzyme] (PMID:12058031)
• The mannose 6-phosphate uncovering enzyme participates in the uncovering of the mannose 6-phosphate recognition tag on lysosomal enzymes, a process that facilitates recognition of those enzymes by mannose 6-phosphate receptors to delivery to lysosomes. (PMID:15976452)
• identified three mutations in the NAGPA gene associated with stuttering (PMID:20147709)
• Analysis of mannose 6-phosphate uncovering enzyme mutations associated with persistent stuttering. (PMID:21956109)
• To date mutations in GNPTAB, GNPTG, and NAGPA have been associated with stuttering. These genes encode the lysosomal enzyme targeting pathway, defective in mucolipidosis. (Review) (PMID:22884963)
• Mutational analysis of several residues in a highly conserved surface cavity of hUCE revealed that they are essential for function. (PMID:23572527)
• SNPs covering GNPTAB, GNPTG and NAGPA were subjected to genotyping, association analysis was performed on all SNPs. Significant association of rs17031962 in GNPTAB and rs882294 in NAGPA with developmental dyslexia in a Chinese population was identified after false discovery rate correction for multiple comparisons. (PMID:25643770)
• 14 variations were found in GNPTAB, GNPTG and NAGPA genes. (PMID:29289611)
• We evaluated 51 stuttering individuals with a mutation in either the GNPTAB, GNPTG, NAGPA, or AP4E1 gene. Mutation carriers achieved significantly less resolution in PSI following therapy, with PSI scores showing significantly less improvement in individuals who carry a mutation (p = 0.0157, RR = 1.75, OR = 2.92) while the group difference in DWS between carriers and non-carriers was statistically not significant. (PMID:31003007)
• Crystal Structure of the Mannose-6-Phosphate Uncovering Enzyme. (PMID:32109365)
• Identification of a shared genetic risk locus for Kawasaki disease and immunoglobulin A vasculitis by a cross-phenotype meta-analysis. (PMID:33993232)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	nagpa	ENSDARG00000075149
mus_musculus	Nagpa	ENSMUSG00000023143
rattus_norvegicus	Nagpa	ENSRNOG00000002895
drosophila_melanogaster	Ten-m	FBGN0004449
drosophila_melanogaster	Ten-a	FBGN0267001
caenorhabditis_elegans		WBGENE00017892
caenorhabditis_elegans		WBGENE00018237

Paralogs (4): TENM1 (ENSG00000009694), TENM2 (ENSG00000145934), TENM4 (ENSG00000149256), TENM3 (ENSG00000218336)

Protein

Protein identifiers

N-acetylglucosamine-1-phosphodiester alpha-N-acetylglucosaminidase — Q9UK23 (reviewed: Q9UK23)

Alternative names: Mannose 6-phosphate-uncovering enzyme, Phosphodiester alpha-GlcNAcase

All UniProt accessions (6): Q9UK23, K7EJ25, K7EK96, K7EL75, K7EPH3, K7ERI4

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes the second step in the formation of the mannose 6-phosphate targeting signal on lysosomal enzyme oligosaccharides by removing GlcNAc residues from GlcNAc-alpha-P-mannose moieties, which are formed in the first step. Also hydrolyzes UDP-GlcNAc, a sugar donor for Golgi N-acetylglucosaminyltransferases.

Subunit / interactions. Homotetramer arranged as two disulfide-linked homodimers. Interacts with AP4M1.

Subcellular location. Golgi apparatus. Golgi stack membrane. trans-Golgi network.

Tissue specificity. Isoform 2 may be brain-specific.

Post-translational modifications. The precursor is cleaved and activated in the trans-Golgi network by a furin endopeptidase.

Disease relevance. Defects in NAGPA have been suggested to play a role in susceptibility to persistent stuttering. Stuttering is a common speech disorder characterized by repetitions, prolongations, and interruptions in the flow of speech.

Domain organisation. The tyrosine-based internalization signal may be essential for its retrieval from the plasma membrane to the TGN. The C-terminal NPFKD sequence is an attractive candidate for either an endocytosis signal acting at the plasma membrane or a retrieval signal acting at the TGN to return the enzyme to the cis/medial-Golgi.

Pathway. Protein modification; protein glycosylation.

Isoforms (3)

UniProt ID	Names	Canonical?
Q9UK23-1	1	yes
Q9UK23-2	2
Q9UK23-3	3

RefSeq proteins (1): NP_057340* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000742	EGF	Domain
IPR018711	NAGPA	Domain

Pfam: PF09992

Enzyme classification (BRENDA):

• EC 3.1.4.45 — N-acetylglucosamine-1-phosphodiester alpha-N-acetylglucosaminidase (BRENDA: 8 organisms, 22 substrates, 38 inhibitors, 16 Km, 2 kcat entries)

Substrate kinetics (BRENDA)

8 substrates with measured Km, best-characterized 8. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
METHYL 6-O-(N-ACETYL-ALPHA-D-GLUCOSAMINYL)PHOSPH	0.19–0.76	7
UDP-GLCNAC	0.734–0.94	3
4-NITROPHENYL ALPHA-N-ACETYL-D-GLUCOSAMINIDE	0.0011	1
DINITROPHENYL ALPHA-N-ACETYL-DGLUCOSAMINIDE	0.74	1
N-ACETYLGLUCOSAMINE 1-PHOSPHATE	1.6	1
N-ACETYLGLUCOSAMINE-PHOSPHATE	31	1
N-[6-O-(N-ACETYL-ALPHA-D-GLUCOSAMINYL)PHOSPHO-AL	0.04	1
UDP-N-ACETYLGLUCOSAMINE	1.3	1

Catalyzed reactions (Rhea), 1 shown:

• N(4)-[6-(N-acetyl-alpha-D-glucosaminyl-1-phospho)-alpha-D-mannosyl-(1->2)-alpha-D-mannosyl-(glycan)]-L-asparaginyl-[protein] + H2O = N(4)-[6-phospho-alpha-D-mannosyl-(1->2)-alpha-D-mannosyl-(glycan)]-L-asparaginyl-[protein] + N-acetyl-D-glucosamine + H(+) (RHEA:24372)

UniProt features (48 total): mutagenesis site 19, glycosylation site 6, disulfide bond 5, splice variant 3, sequence variant 3, topological domain 2, sequence conflict 2, short sequence motif 2, signal peptide 1, propeptide 1, chain 1, transmembrane region 1, domain 1, region of interest 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UK23-F1	81.97	0.59

Functional residue map

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

Disulfide bonds (5): 115–148, 132–323, 307–314, 362–373, 380–389

Glycosylation sites (6): 208, 214, 296, 366, 388, 420

Mutagenesis-validated functional residues (19):

Position	Phenotype
51	65% of wild-type of activity.
115	15% of wild-type of activity, and almost no traffic to golgi.
132	no traffic to golgi.
137	11% of wild-type of activity.
221	10% of wild-type of activity; when associated with m-51.
225	6% of wild-type of activity.
227	complete loss of activity.
247	87% of wild-type of activity.
284	22% of wild-type of activity.
286	complete loss of activity.
287	16% of wild-type of activity.
288	complete loss of activity.
289	complete loss of activity.
290	complete loss of activity.
320	43% of wild-type of activity.
322	67% of wild-type of activity.
486	interaction with ap4m1 is abolished.
488	interaction with ap4m1 is abolished.
491	interaction with ap4m1 is abolished.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 175 (showing top): GOBP_LYSOSOMAL_TRANSPORT, GOBP_VACUOLE_ORGANIZATION, GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, GOBP_PROTEIN_TARGETING, GOBP_VACUOLAR_TRANSPORT, KEGG_LYSOSOME, GOBP_ESTABLISHMENT_OF_PROTEIN_LOCALIZATION_TO_ORGANELLE, GOBP_PROTEIN_LOCALIZATION_TO_LYSOSOME, GOBP_PROTEIN_LOCALIZATION_TO_VACUOLE, GROSS_HYPOXIA_VIA_ELK3_AND_HIF1A_UP, CASORELLI_APL_SECONDARY_VS_DE_NOVO_UP, GOBP_CARBOHYDRATE_METABOLIC_PROCESS, GOBP_SECRETION, GARCIA_TARGETS_OF_FLI1_AND_DAX1_DN, SCHLOSSER_SERUM_RESPONSE_DN

GO Biological Process (6): carbohydrate metabolic process (GO:0005975), protein targeting to lysosome (GO:0006622), lysosome organization (GO:0007040), secretion of lysosomal enzymes (GO:0033299), protein modification process (GO:0036211), obsolete protein glycosylation (GO:0006486)

GO Molecular Function (3): N-acetylglucosamine-1-phosphodiester alpha-N-acetylglucosaminidase activity (GO:0003944), protein binding (GO:0005515), hydrolase activity (GO:0016787)

GO Cellular Component (3): membrane (GO:0016020), Golgi cisterna membrane (GO:0032580), Golgi apparatus (GO:0005794)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
primary metabolic process	1
protein targeting to vacuole	1
lysosomal transport	1
protein localization to lysosome	1
lytic vacuole organization	1
protein secretion	1
protein metabolic process	1
macromolecule modification	1
hexosaminidase activity	1
binding	1
catalytic activity	1
cellular anatomical structure	1
organelle membrane	1
Golgi cisterna	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

742 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NAGPA	GNPTG	Q9UJJ9	983
NAGPA	GNPTAB	Q3T906	975
NAGPA	AP4E1	Q9UPM8	688
NAGPA	WDR64	B1ANS9	574
NAGPA	ATP2C2	O75185	574
NAGPA	PPT1	P50897	574
NAGPA	FURIN	P09958	539
NAGPA	CMIP	Q8IY22	521
NAGPA	M6PR	P20645	506
NAGPA	RERE	Q9P2R6	474
NAGPA	PIGT	Q969N2	442
NAGPA	GOLPH3L	Q9H4A5	441
NAGPA	FOXP2	O15409	441
NAGPA	SPPL3	Q8TCT6	432
NAGPA	DCDC2C	A8MYV0	424

IntAct

25 interactions, top by confidence:

A	B	Type	Score
LRRC32	SMPD2	psi-mi:“MI:0914”(association)	0.640
FSHR	UPK3BL1	psi-mi:“MI:0914”(association)	0.530
LGALS1	PODXL	psi-mi:“MI:0914”(association)	0.530
TMX1	NRP1	psi-mi:“MI:0914”(association)	0.530
LGALS1	LAMA5	psi-mi:“MI:0914”(association)	0.530
FBXO2	TMEM131L	psi-mi:“MI:0914”(association)	0.530
NAGPA	BDKRB1	psi-mi:“MI:0915”(physical association)	0.370
NAGPA	CCR8	psi-mi:“MI:0915”(physical association)	0.370
NAGPA	DEGS1	psi-mi:“MI:0915”(physical association)	0.370
NAGPA	ZHX2	psi-mi:“MI:0915”(physical association)	0.370
PCDHGA9	TMEM223	psi-mi:“MI:0914”(association)	0.350
CHRNA4	TMEM223	psi-mi:“MI:0914”(association)	0.350
ADGRE5	TMEM223	psi-mi:“MI:0914”(association)	0.350
AP2M1	C1orf226	psi-mi:“MI:0914”(association)	0.350
FADS3	PEX7	psi-mi:“MI:0914”(association)	0.350
SLAMF7	HUS1	psi-mi:“MI:0914”(association)	0.350
NAGPA	CALR	psi-mi:“MI:0914”(association)	0.350
RTN3	ESYT2	psi-mi:“MI:0914”(association)	0.350
ADGRE5	SCAMP3	psi-mi:“MI:0914”(association)	0.350
AP2M1	PER1	psi-mi:“MI:0914”(association)	0.350
CLGN	TMEM131L	psi-mi:“MI:0914”(association)	0.350
DUOXA2	CHRNB1	psi-mi:“MI:0914”(association)	0.350
SPACA1	PLPP3	psi-mi:“MI:0914”(association)	0.350

BioGRID (41): NAGPA (Affinity Capture-MS), NAGPA (Affinity Capture-MS), NGLY1 (Affinity Capture-MS), TYW3 (Affinity Capture-MS), NAGPA (Affinity Capture-MS), NAGPA (Affinity Capture-MS), UBR3 (Affinity Capture-MS), NAGPA (Affinity Capture-MS), NAGPA (Affinity Capture-MS), NAGPA (Affinity Capture-MS), WDR54 (Affinity Capture-MS), NAGPA (Synthetic Lethality), EPS15 (Reconstituted Complex), AP2A1 (Reconstituted Complex), NAGPA (Two-hybrid)

ESM2 similar proteins: A8T644, A8T650, A8T655, A8T658, A8T662, A8T666, A8T672, A8T677, A8T682, A8T688, A8T695, A8T6A1, A8T6A6, D3Z7H8, O75173, O95450, O95479, P09958, P21709, P23188, P23377, P29121, P29122, P34821, P56201, P59996, P68827, P79331, Q13219, Q16549, Q5RFQ8, Q60750, Q61139, Q62849, Q6UW60, Q78EH2, Q80W65, Q8BJ48, Q8BNJ2, Q8C9W3

Diamond homologs: P68827, Q8BJ48, Q9UK23

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	79
Likely benign	13
Benign	6

Top pathogenic / likely-pathogenic (0)

SpliceAI

1738 predictions. Top by Δscore:

Variant	Effect	Δscore
16:5025681:CGGTC:C	acceptor_gain	1.0000
16:5025686:C:CC	acceptor_gain	1.0000
16:5027194:CTTTA:C	acceptor_gain	1.0000
16:5027199:C:CC	acceptor_gain	1.0000
16:5027376:CACT:C	acceptor_gain	1.0000
16:5027378:CT:C	acceptor_gain	1.0000
16:5027382:A:C	acceptor_gain	1.0000
16:5027840:TCCTA:T	donor_loss	1.0000
16:5027841:CCTA:C	donor_loss	1.0000
16:5027842:CTACC:C	donor_loss	1.0000
16:5027843:TACCT:T	donor_loss	1.0000
16:5027844:A:T	donor_loss	1.0000
16:5027845:C:A	donor_loss	1.0000
16:5027890:CCGG:C	acceptor_gain	1.0000
16:5027891:CGG:C	acceptor_gain	1.0000
16:5027891:CGGC:C	acceptor_gain	1.0000
16:5027978:A:AC	donor_gain	1.0000
16:5027978:ACTCT:A	donor_gain	1.0000
16:5027979:C:CC	donor_gain	1.0000
16:5027979:CT:C	donor_gain	1.0000
16:5027979:CTCT:C	donor_gain	1.0000
16:5027979:CTCTC:C	donor_gain	1.0000
16:5027982:T:A	donor_gain	1.0000
16:5028875:CTTA:C	donor_loss	1.0000
16:5028877:TACCA:T	donor_loss	1.0000
16:5028878:A:AC	donor_gain	1.0000
16:5028879:C:CG	donor_loss	1.0000
16:5028879:C:CT	donor_gain	1.0000
16:5028879:CCA:C	donor_gain	1.0000
16:5029004:TGATG:T	acceptor_gain	1.0000

AlphaMissense

3344 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:5030478:A:C	F233C	0.998
16:5030477:A:C	F233L	0.997
16:5030477:A:T	F233L	0.997
16:5030479:A:G	F233L	0.997
16:5028170:C:A	W312C	0.996
16:5028170:C:G	W312C	0.996
16:5028948:G:C	N284K	0.996
16:5028948:G:T	N284K	0.996
16:5031817:A:G	W204R	0.996
16:5031817:A:T	W204R	0.996
16:5031779:G:C	S216R	0.995
16:5031779:G:T	S216R	0.995
16:5031781:T:G	S216R	0.995
16:5031815:C:A	W204C	0.995
16:5031815:C:G	W204C	0.995
16:5028165:C:G	C314S	0.994
16:5028166:A:T	C314S	0.994
16:5028880:C:G	C307S	0.994
16:5028881:A:T	C307S	0.994
16:5028897:A:C	S301R	0.994
16:5028897:A:T	S301R	0.994
16:5028899:T:G	S301R	0.994
16:5028943:T:A	D286V	0.994
16:5031843:A:C	F195C	0.994
16:5028956:C:G	A282P	0.993
16:5030456:C:A	R240S	0.993
16:5030456:C:G	R240S	0.993
16:5028880:C:T	C307Y	0.992
16:5030457:C:G	R240T	0.991
16:5033372:C:G	C148S	0.991

dbSNP variants (sampled 300 via entrez): RS1000030761 (16:5027510 C>A,T), RS1000252431 (16:5029039 A>T), RS1000964933 (16:5025985 G>C), RS1001085883 (16:5029357 G>A), RS1001138392 (16:5029472 G>A,C), RS1001170 (16:5032230 T>A,C,G), RS1001171 (16:5032288 A>G,T), RS1001218915 (16:5025170 G>A,C,T), RS1001353693 (16:5025780 G>A,C), RS1001633389 (16:5033765 C>A,T), RS1001784679 (16:5033977 C>T), RS1001804023 (16:5029317 A>C), RS1002308321 (16:5029321 G>C), RS1003050143 (16:5028500 A>C), RS1003325113 (16:5026286 C>G)

Disease associations

OMIM: gene MIM:607985 | disease phenotypes: MIM:609261

GenCC curated gene-disease

Mondo (1): stuttering, familial persistent, 2 (MONDO:0012232)

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST006585_1313	Blood protein levels	2.000000e-18

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C563756	Stuttering, Familial Persistent 2 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5920 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

22 total (human), top 22 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Cisplatin	affects expression, affects cotreatment, increases expression	2
Valproic Acid	decreases methylation, increases expression	2
beta-lapachone	decreases expression, increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
cobaltous chloride	increases expression	1
propionic acid	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	increases expression	1
CGP 52608	affects binding, increases reaction	1
abrine	decreases expression	1
jinfukang	affects cotreatment, increases expression	1
Decitabine	affects expression	1
Atrazine	decreases expression	1
Benzo(a)pyrene	increases methylation	1
Diazinon	increases methylation	1
Doxorubicin	decreases expression	1
Estradiol	decreases expression	1
Rotenone	decreases expression	1
Smoke	decreases expression	1
Tobacco Smoke Pollution	affects expression	1
Cyclosporine	decreases expression	1
Antirheumatic Agents	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
CHEMBL929314	Binding	Inhibition of human family 84 O-GLcNAcase	Small molecule inhibitors of a glycoside hydrolase attenuate inducible AmpC-mediated beta-lactam resistance. — J Biol Chem

Clinical trials (associated diseases)

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