PTPN18

Summary

PTPN18 (protein tyrosine phosphatase non-receptor type 18, HGNC:9649) is a protein-coding gene on chromosome 2q21.1, encoding Tyrosine-protein phosphatase non-receptor type 18 (Q99952). Differentially dephosphorylate autophosphorylated tyrosine kinases which are known to be overexpressed in tumor tissues.

The protein encoded by this gene is a member of the protein tyrosine phosphatase (PTP) family. PTPs are known to be signaling molecules that regulate a variety of cellular processes including cell growth, differentiation, the mitotic cycle, and oncogenic transformation. This PTP contains a PEST motif, which often serves as a protein-protein interaction domain, and may be related to protein intracellular half-live. This protein can differentially dephosphorylate autophosphorylated tyrosine kinases that are overexpressed in tumor tissues, and it appears to regulate HER2, a member of the epidermal growth factor receptor family of receptor tyrosine kinases. Two transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 26469 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 119 total
• Druggable target: yes
• MANE Select transcript: NM_014369

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9649
Approved symbol	PTPN18
Name	protein tyrosine phosphatase non-receptor type 18
Location	2q21.1
Locus type	gene with protein product
Status	Approved
Aliases	BDP1
Ensembl gene	ENSG00000072135
Ensembl biotype	protein_coding
OMIM	606587
Entrez	26469

Gene structure

Transcript identifiers

Ensembl transcripts: 23 — 11 retained_intron, 10 protein_coding, 1 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000175756, ENST00000347849, ENST00000409022, ENST00000420717, ENST00000428843, ENST00000460992, ENST00000462321, ENST00000462996, ENST00000464576, ENST00000479295, ENST00000481492, ENST00000483617, ENST00000489215, ENST00000490137, ENST00000490812, ENST00000495400, ENST00000879455, ENST00000879456, ENST00000879457, ENST00000879458, ENST00000937302, ENST00000937303, ENST00000954348

RefSeq mRNA: 2 — MANE Select: NM_014369 NM_001142370, NM_014369

CCDS: CCDS2161, CCDS46410

Canonical transcript exons

ENST00000175756 — 15 exons

Exon	Start	End
ENSE00000776193	130370557	130370623
ENSE00000776197	130372257	130372483
ENSE00001159610	130373157	130375405
ENSE00001776329	130356056	130356200
ENSE00003478958	130359608	130359646
ENSE00003485487	130370705	130370782
ENSE00003521817	130369765	130369827
ENSE00003531583	130369133	130369201
ENSE00003542175	130371199	130371287
ENSE00003580559	130370048	130370190
ENSE00003581606	130358867	130358975
ENSE00003615992	130370875	130370964
ENSE00003642233	130359233	130359309
ENSE00003687302	130359397	130359492
ENSE00003693583	130372873	130372947

Expression profiles

Bgee: expression breadth ubiquitous, 281 present calls, max score 98.44.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 40.3742 / max 1383.3573, expressed in 1817 samples.

FANTOM5 promoters (9 alternative TSS)

Promoter ID	TPM avg	Samples expressed
22508	19.5405	1764
22504	10.9777	1722
22511	4.2895	1553
22505	1.7515	770
22507	0.9695	698
22509	0.8869	395
22503	0.8422	468
22510	0.7272	409
202387	0.3892	216

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
granulocyte	CL:0000094	98.44	gold quality
monocyte	CL:0000576	98.43	gold quality
mononuclear cell	CL:0000842	98.27	gold quality
leukocyte	CL:0000738	98.25	gold quality
right uterine tube	UBERON:0001302	97.21	gold quality
mucosa of transverse colon	UBERON:0004991	97.19	gold quality
rectum	UBERON:0001052	97.13	gold quality
cerebellar hemisphere	UBERON:0002245	96.97	gold quality
right hemisphere of cerebellum	UBERON:0014890	96.95	gold quality
cerebellar cortex	UBERON:0002129	96.83	gold quality
spleen	UBERON:0002106	96.72	gold quality
tendon of biceps brachii	UBERON:0008188	96.50	gold quality
transverse colon	UBERON:0001157	96.43	gold quality
small intestine Peyer’s patch	UBERON:0003454	96.42	gold quality
body of pancreas	UBERON:0001150	96.26	gold quality
vermiform appendix	UBERON:0001154	96.05	gold quality
minor salivary gland	UBERON:0001830	95.81	gold quality
lymph node	UBERON:0000029	95.75	gold quality
caecum	UBERON:0001153	95.60	gold quality
blood	UBERON:0000178	95.47	gold quality
cerebellum	UBERON:0002037	95.47	gold quality
small intestine	UBERON:0002108	95.21	gold quality
body of stomach	UBERON:0001161	95.15	gold quality
right lobe of thyroid gland	UBERON:0001119	95.09	gold quality
endocervix	UBERON:0000458	95.04	gold quality
gall bladder	UBERON:0002110	94.82	gold quality
saliva-secreting gland	UBERON:0001044	94.69	gold quality
metanephros cortex	UBERON:0010533	94.53	gold quality
pancreas	UBERON:0001264	94.43	gold quality
right lobe of liver	UBERON:0001114	94.30	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-MTAB-8410	yes	4.57
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

78 targeting PTPN18, 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-3120-5P	100.00	65.56	965
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-4481	100.00	66.42	1669
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-6888-3P	99.97	65.95	1170
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-6780A-5P	99.88	66.69	2776
HSA-MIR-3919	99.87	69.45	2489
HSA-MIR-383-3P	99.85	65.84	1359
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-6817-3P	99.79	68.35	2126
HSA-MIR-1273H-5P	99.77	66.32	2471
HSA-MIR-4319	99.76	69.83	2586
HSA-MIR-92A-2-5P	99.75	67.01	2164
HSA-MIR-6752-3P	99.72	66.71	1587
HSA-MIR-30B-3P	99.70	65.76	2325
HSA-MIR-3689A-3P	99.70	65.73	2306
HSA-MIR-3689B-3P	99.70	65.71	2311
HSA-MIR-3689C	99.70	65.71	2311
HSA-MIR-6779-5P	99.70	65.76	2363
HSA-MIR-6766-5P	99.68	67.70	2325
HSA-MIR-1827	99.63	68.57	3265
HSA-MIR-6126	99.62	68.09	996
HSA-MIR-1207-5P	99.49	69.11	2983
HSA-MIR-1275	99.47	67.90	2749
HSA-MIR-6722-3P	99.45	67.62	1919
HSA-MIR-125A-5P	99.36	70.59	1640

Literature-anchored findings (GeneRIF, showing 8)

• BDP1 has a role in negative regulation of HER2 signaling (PMID:14660651)
• novel isoform of PTPN18 based on analysis of expressed sequence tags was discovered; deletion of 4 exons in the catalytic domain of the isoform may alter enzymatic activity; 2 of the novel isoform predictions were experimentally validated through RT-PCR (PMID:16303740)
• PTPN18 regulates HER2-mediated cellular functions through defining both its phosphorylation and ubiquitination barcodes. (PMID:25081058)
• PTPN12, PTPRN and PTPN18 were independent prognostic factors in Hepatocellular Carcinoma. (PMID:29742497)
• Downregulation of PTPN18 can inhibit proliferation and metastasis and promote apoptosis of endometrial cancer (PMID:31034093)
• Phospho-PTM proteomic discovery of novel EPO- modulated kinases and phosphatases, including PTPN18 as a positive regulator of EPOR/JAK2 Signaling. (PMID:32027948)
• PTPN18 Serves as a Potential Oncogene for Glioblastoma by Enhancing Immune Suppression. (PMID:36846716)
• Hepatitis B Virus X Protein Represses Expression of Tumor Suppressor PTPN18 in Hepatocellular Carcinoma. (PMID:38787319)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Ptpn18	ENSMUSG00000026126
rattus_norvegicus	Ptpn18	ENSRNOG00000013415

Paralogs (35): PTPRN (ENSG00000054356), PTPRU (ENSG00000060656), PTPN3 (ENSG00000070159), PTPN21 (ENSG00000070778), PTPN23 (ENSG00000076201), PTPRH (ENSG00000080031), PTPRC (ENSG00000081237), PTPN4 (ENSG00000088179), PTPRS (ENSG00000105426), PTPRZ1 (ENSG00000106278), PTPN5 (ENSG00000110786), PTPN6 (ENSG00000111679), PTPRB (ENSG00000127329), PTPN12 (ENSG00000127947), PTPRE (ENSG00000132334), PTPRA (ENSG00000132670), PTPN22 (ENSG00000134242), PTPRF (ENSG00000142949), PTPN7 (ENSG00000143851), PTPRG (ENSG00000144724), PTPRJ (ENSG00000149177), PTPRO (ENSG00000151490), PTPN14 (ENSG00000152104), PTPRK (ENSG00000152894), PTPRR (ENSG00000153233), PTPRD (ENSG00000153707), PTPRN2 (ENSG00000155093), PTPN13 (ENSG00000163629), PTPN9 (ENSG00000169410), PTPRM (ENSG00000173482), PTPN2 (ENSG00000175354), PTPN11 (ENSG00000179295), PTPRT (ENSG00000196090), PTPN1 (ENSG00000196396), PTPN20 (ENSG00000204179)

Protein

Protein identifiers

Tyrosine-protein phosphatase non-receptor type 18 — Q99952 (reviewed: Q99952)

Alternative names: Brain-derived phosphatase

All UniProt accessions (3): Q99952, E7EMB8, F8WBM9

UniProt curated annotations — full annotation on UniProt →

Function. Differentially dephosphorylate autophosphorylated tyrosine kinases which are known to be overexpressed in tumor tissues.

Subunit / interactions. Interacts with PSTPIP1.

Subcellular location. Nucleus. Cytoplasm.

Tissue specificity. Expressed in brain, colon and several tumor-derived cell lines.

Similarity. Belongs to the protein-tyrosine phosphatase family. Non-receptor class 4 subfamily.

Isoforms (2)

UniProt ID	Names	Canonical?
Q99952-1	1	yes
Q99952-2	2

RefSeq proteins (2): NP_001135842, NP_055184* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000242	PTP_cat	Domain
IPR000387	Tyr_Pase_dom	Domain
IPR003595	Tyr_Pase_cat	Domain
IPR016130	Tyr_Pase_AS	Active_site
IPR029021	Prot-tyrosine_phosphatase-like	Homologous_superfamily
IPR047170	PTN12/18/22	Family
IPR047254	PTN18_cat	Domain

Pfam: PF00102

Enzyme classification (BRENDA):

• EC 3.1.3.48 — protein-tyrosine-phosphatase (BRENDA: 59 organisms, 501 substrates, 1326 inhibitors, 270 Km, 165 kcat entries)

Substrate kinetics (BRENDA)

70 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
4-NITROPHENYL PHOSPHATE	0.0008–148	84
6,8-DIFLUORO-4-METHYLUMBELLIFERYL PHOSPHATE	0.0039–0.862	27
P-NITROPHENYL PHOSPHATE	0.0024–10	20
DADEPYLIPQQG	0.0003–0.1	12
PHOSPHOTYROSINE	0.012–30	11
LYSOZYME	0.0003–0.012	5
MYELIN BASIC PROTEIN	0.0001–0.022	5
ACETYL-DADEPY-NH2	0.0228–0.219	4
ACETYL-DADEPYL-NH2	1.1–97.5	4
4,6,8-TRIMETHYL-2-OXO-2H-CHROMEN-7-YL DIHYDROGEN	0.02–0.156	3
SASASPYSASA	0.53–2.3	3
1-NAPHTHYL PHOSPHATE	1.19–1.88	2
3,6-FLUORESCEIN DIPHOSPHATE	15–19	2
4-METHYLUMBELLIFERYL PHOSPHATE	0.953–2.41	2
BOVINE SERUM ALBUMIN	0.0001–0.0003	2

Catalyzed reactions (Rhea), 1 shown:

• O-phospho-L-tyrosyl-[protein] + H2O = L-tyrosyl-[protein] + phosphate (RHEA:10684)

UniProt features (43 total): helix 13, strand 13, modified residue 3, binding site 3, sequence conflict 2, compositionally biased region 2, chain 1, domain 1, splice variant 1, sequence variant 1, region of interest 1, turn 1, active site 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
2OC3	X-RAY DIFFRACTION	1.5
4GFU	X-RAY DIFFRACTION	2
4GFV	X-RAY DIFFRACTION	2.1
4NND	X-RAY DIFFRACTION	2.5

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q99952-F1	78.06	0.63

Functional residue map

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

Catalytic / active sites (1): 229 (phosphocysteine intermediate)

Ligand- & substrate-binding residues (3): 197; 229–235; 276

Post-translational modifications (3): 393, 426, 389

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-8863795	Downregulation of ERBB2 signaling
R-HSA-9008059	Interleukin-37 signaling

MSigDB gene sets: 344 (showing top): GSE45365_NK_CELL_VS_BCELL_UP, GSE18804_SPLEEN_MACROPHAGE_VS_COLON_TUMORAL_MACROPHAGE_UP, REACTOME_RNA_POLYMERASE_III_TRANSCRIPTION_INITIATION_FROM_TYPE_3_PROMOTER, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, GOBP_REGULATION_OF_ERBB_SIGNALING_PATHWAY, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, GOBP_NEGATIVE_REGULATION_OF_ERBB_SIGNALING_PATHWAY, GOBP_TRANSCRIPTION_BY_RNA_POLYMERASE_III, KYNG_DNA_DAMAGE_DN, GOBP_BLASTOCYST_FORMATION, GOBP_IN_UTERO_EMBRYONIC_DEVELOPMENT, GOBP_ERBB_SIGNALING_PATHWAY, GOBP_BLASTOCYST_DEVELOPMENT, GOBP_DNA_TEMPLATED_TRANSCRIPTION_INITIATION

GO Biological Process (4): blastocyst formation (GO:0001825), protein dephosphorylation (GO:0006470), negative regulation of ERBB signaling pathway (GO:1901185), dephosphorylation (GO:0016311)

GO Molecular Function (5): protein tyrosine phosphatase activity (GO:0004725), non-membrane spanning protein tyrosine phosphatase activity (GO:0004726), phosphoprotein phosphatase activity (GO:0004721), protein binding (GO:0005515), hydrolase activity (GO:0016787)

GO Cellular Component (4): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), cytosol (GO:0005829)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Signaling by ERBB2	1
Interleukin-1 family signaling	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
blastocyst development	1
anatomical structure formation involved in morphogenesis	1
dephosphorylation	1
protein modification process	1
negative regulation of signal transduction	1
ERBB signaling pathway	1
regulation of ERBB signaling pathway	1
phosphate-containing compound metabolic process	1
phosphoprotein phosphatase activity	1
protein tyrosine phosphatase activity	1
phosphatase activity	1
catalytic activity, acting on a protein	1
binding	1
catalytic activity	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
intracellular anatomical structure	1
cytoplasm	1

Protein interactions and networks

STRING

974 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PTPN18	PSTPIP1	O43586	682
PTPN18	PTS	Q03393	609
PTPN18	CIMIP5	Q96LR7	507
PTPN18	PSTPIP2	Q9H939	417
PTPN18	ARHGEF4	Q9NR80	416
PTPN18	AMER3	Q8N944	364
PTPN18	MPP1	Q00013	345
PTPN18	TMEM158	Q8WZ71	325
PTPN18	HERC2	O95714	322
PTPN18	CSK	P41240	313
PTPN18	DAPP1	Q9UN19	295
PTPN18	NFE2L2	Q16236	294
PTPN18	RRP7A	Q9Y3A4	292
PTPN18	EIF2B3	Q9NR50	278
PTPN18	CYB5D2	Q8WUJ1	274

IntAct

140 interactions, top by confidence:

A	B	Type	Score
PSTPIP1	PTPN18	psi-mi:“MI:0915”(physical association)	0.700
PSTPIP1	PTPN18	psi-mi:“MI:0407”(direct interaction)	0.700
PTPN18	PSTPIP1	psi-mi:“MI:0915”(physical association)	0.700
PTPN18	ERBB2	psi-mi:“MI:0407”(direct interaction)	0.560
EGFR	PTPN18	psi-mi:“MI:0915”(physical association)	0.550
PTPN18	EGFR	psi-mi:“MI:0915”(physical association)	0.550
GRB2	SH3PXD2B	psi-mi:“MI:0914”(association)	0.530
	PTPN18	psi-mi:“MI:0407”(direct interaction)	0.440
PTPN18	MAST2	psi-mi:“MI:0407”(direct interaction)	0.440
PTPN18	LNX2	psi-mi:“MI:0407”(direct interaction)	0.440
SHANK1	PTPN18	psi-mi:“MI:0407”(direct interaction)	0.440
PTPN18	MAST1	psi-mi:“MI:0407”(direct interaction)	0.440
PTPN18	PDZD7	psi-mi:“MI:0407”(direct interaction)	0.440
MAGI2	PTPN18	psi-mi:“MI:0407”(direct interaction)	0.440
PTPN18	TAMALIN	psi-mi:“MI:0407”(direct interaction)	0.440
PTPN18	GRID2IP	psi-mi:“MI:0407”(direct interaction)	0.440
PTPN18	SNX27	psi-mi:“MI:0407”(direct interaction)	0.440
PTPN18	DLG1	psi-mi:“MI:0407”(direct interaction)	0.440
PTPN18	MAGI2	psi-mi:“MI:0407”(direct interaction)	0.440
PTPN18	NHERF2	psi-mi:“MI:0407”(direct interaction)	0.440
HTRA1	PTPN18	psi-mi:“MI:0407”(direct interaction)	0.440
SNTA1	PTPN18	psi-mi:“MI:0407”(direct interaction)	0.440
PTPN18	ARHGEF11	psi-mi:“MI:0407”(direct interaction)	0.440

BioGRID (65): PTPN18 (Affinity Capture-RNA), PTPN18 (Affinity Capture-RNA), PTPN18 (Two-hybrid), PTPN18 (PCA), AIFM1 (Affinity Capture-MS), AIP (Affinity Capture-MS), ATP5A1 (Affinity Capture-MS), ATXN2 (Affinity Capture-MS), BAG2 (Affinity Capture-MS), BAG5 (Affinity Capture-MS), DNAJA2 (Affinity Capture-MS), DNAJB1 (Affinity Capture-MS), DNAJC7 (Affinity Capture-MS), IRS4 (Affinity Capture-MS), MLLT11 (Affinity Capture-MS)

ESM2 similar proteins: A0A8I3NFE2, A2AP18, A6QP29, A6QPL4, A8WFU8, B1AVH7, B5DFA1, D2H0G5, D7PF45, O15357, O43304, O75038, O75808, Q0GNC1, Q0QWG9, Q14807, Q27J81, Q3V300, Q4R918, Q5I0E8, Q5REP4, Q5VV41, Q5XI63, Q60443, Q60806, Q61152, Q61846, Q69ZT1, Q6DT37, Q6L512, Q6P3R1, Q6P549, Q6ZMV9, Q7ZYL5, Q80UW5, Q8BL80, Q8C7W7, Q99952, Q9BVG8, Q9BW19

Diamond homologs: A0A6I8TCE0, A1L1L3, A2ALK8, A4IFW2, B0V2N1, B0X4T2, B1AUH1, B2GV87, B2RU80, B3DK56, B9EKR1, E9Q0N2, E9Q612, F1NWE3, G5EC24, G5EGJ9, H2KZM6, O02695, O08617, O13016, O35239, O55082, P06800, P16620, P17706, P18031, P18052, P18433, P20417, P23467, P23468, P23469, P23470, P23471, P26045, P28191, P29074, P29350, P29351, P29352

SIGNOR signaling

5 interactions.

A	Effect	B	Mechanism
PTPN18	“down-regulates quantity by destabilization”	ERBB2	dephosphorylation
PSTPIP1	“up-regulates activity”	PTPN18	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 93 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Ras activation upon Ca2+ influx through NMDA receptor	5	48.4×	4e-06
Unblocking of NMDA receptors, glutamate binding and activation	5	46.1×	4e-06
Negative regulation of NMDA receptor-mediated neuronal transmission	5	46.1×	4e-06
Long-term potentiation	5	40.3×	6e-06
Assembly and cell surface presentation of NMDA receptors	9	38.7×	2e-10
Neurexins and neuroligins	10	33.4×	9e-11
Protein-protein interactions at synapses	6	27.0×	5e-06
RAF/MAP kinase cascade	8	8.3×	2e-04

GO biological processes:

GO term	Partners	Fold	FDR
establishment or maintenance of epithelial cell apical/basal polarity	10	64.6×	1e-13
protein localization to synapse	6	51.1×	2e-07
receptor clustering	7	48.5×	3e-08
regulation of postsynaptic membrane neurotransmitter receptor levels	7	38.5×	1e-07
epidermal growth factor receptor signaling pathway	5	13.8×	2e-03
cell-cell adhesion	10	11.3×	2e-06
protein-containing complex assembly	7	8.9×	8e-04
chemical synaptic transmission	7	6.0×	6e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	87
Likely benign	1
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

2884 predictions. Top by Δscore:

Variant	Effect	Δscore
2:130356153:G:GT	donor_gain	1.0000
2:130356199:GC:G	donor_gain	1.0000
2:130356201:G:GG	donor_gain	1.0000
2:130358842:T:TA	acceptor_gain	1.0000
2:130358852:A:AG	acceptor_gain	1.0000
2:130358852:ATAAT:A	acceptor_gain	1.0000
2:130358853:T:G	acceptor_gain	1.0000
2:130358854:A:AG	acceptor_gain	1.0000
2:130358854:AAT:A	acceptor_gain	1.0000
2:130358855:A:G	acceptor_gain	1.0000
2:130358856:T:A	acceptor_gain	1.0000
2:130358856:T:G	acceptor_gain	1.0000
2:130358864:CA:C	acceptor_loss	1.0000
2:130358865:A:AG	acceptor_gain	1.0000
2:130358865:AG:A	acceptor_gain	1.0000
2:130358866:G:GA	acceptor_gain	1.0000
2:130358866:GG:G	acceptor_gain	1.0000
2:130358866:GGA:G	acceptor_gain	1.0000
2:130358866:GGAC:G	acceptor_gain	1.0000
2:130358947:G:GT	donor_gain	1.0000
2:130358971:GCCTT:G	donor_gain	1.0000
2:130358972:CCTT:C	donor_gain	1.0000
2:130358973:CTT:C	donor_gain	1.0000
2:130358974:TT:T	donor_gain	1.0000
2:130358975:TGT:T	donor_loss	1.0000
2:130358976:G:C	donor_loss	1.0000
2:130358976:G:GG	donor_gain	1.0000
2:130358977:T:G	donor_loss	1.0000
2:130359222:T:G	acceptor_gain	1.0000
2:130359224:T:TA	acceptor_gain	1.0000

AlphaMissense

2978 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:130359463:T:A	W116R	0.975
2:130359463:T:C	W116R	0.975
2:130359300:C:A	N90K	0.967
2:130359300:C:G	N90K	0.967
2:130356195:T:C	F30L	0.966
2:130356197:C:A	F30L	0.966
2:130356197:C:G	F30L	0.966
2:130370084:T:A	W195R	0.961
2:130370084:T:C	W195R	0.961
2:130358953:C:A	N60K	0.959
2:130358953:C:G	N60K	0.959
2:130373159:T:C	F440L	0.951
2:130373161:C:A	F440L	0.951
2:130373161:C:G	F440L	0.951
2:130370070:T:C	L190P	0.948
2:130359432:A:C	Q105H	0.943
2:130359432:A:T	Q105H	0.943
2:130370585:T:C	C240R	0.939
2:130359460:T:C	F115L	0.938
2:130359462:C:A	F115L	0.938
2:130359462:C:G	F115L	0.938
2:130359294:T:A	N88K	0.935
2:130359294:T:G	N88K	0.935
2:130359296:G:A	G89D	0.935
2:130370177:T:C	C226R	0.934
2:130369808:T:C	L176P	0.931
2:130369151:T:A	W145R	0.930
2:130369151:T:C	W145R	0.930
2:130370181:T:A	V227D	0.930
2:130359425:C:A	A103D	0.929

dbSNP variants (sampled 300 via entrez): RS1000130156 (2:130360114 G>A,T), RS1000251010 (2:130362851 G>A,C), RS1000403384 (2:130356848 T>C), RS1000407346 (2:130357146 C>G), RS1000500798 (2:130360568 GT>G), RS1000648558 (2:130374792 G>C), RS1000703842 (2:130375036 C>G,T), RS1000811239 (2:130368513 C>G), RS1001079961 (2:130368167 G>T), RS1001332761 (2:130372010 A>C,G), RS1001342885 (2:130365491 T>C), RS1001346690 (2:130355819 ACCCCC>A,ACCCC,ACCCCCC), RS1001398827 (2:130355609 C>T), RS1001415607 (2:130373478 C>T), RS1001479840 (2:130365823 C>T)

Disease associations

OMIM: gene MIM:606587 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3351197 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases expression	2
Benzo(a)pyrene	decreases expression, increases methylation	2
Tobacco Smoke Pollution	decreases expression	2
bisphenol F	affects cotreatment, increases expression	1
dicrotophos	increases expression	1
triphenyl phosphate	affects expression	1
terbufos	decreases methylation	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
cobaltous chloride	decreases expression	1
nickel sulfate	increases expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
abrine	decreases expression	1
jinfukang	increases expression	1
(+)-JQ1 compound	decreases expression	1
Sunitinib	decreases expression	1
Leflunomide	decreases expression	1
Caffeine	increases phosphorylation	1
Dexamethasone	affects cotreatment, increases expression	1
Doxorubicin	decreases expression	1
Fonofos	decreases methylation	1
Estradiol	decreases expression	1
Indomethacin	affects cotreatment, increases expression	1
Methotrexate	decreases expression	1
Parathion	decreases methylation	1
Selenium	increases expression	1
Silicon Dioxide	decreases expression	1
Smoke	decreases expression	1
Tretinoin	increases expression	1
Valproic Acid	increases methylation	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
CHEMBL3384865	Binding	Inhibition of PTPN18 (unknown origin) assessed as reduction in pNPP hydrolysis	Fast identification of novel lymphoid tyrosine phosphatase inhibitors using target-ligand interaction-based virtual screening. — J Med Chem

Cellosaurus cell lines

1 cell lines: 1 telomerase immortalized cell line

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

Cellosaurus	Name	Category	Sex
CVCL_C3KE	N/Tert-1 PTPN18	Telomerase immortalized cell line	Male

Clinical trials (associated diseases)

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