PTPN21

Summary

PTPN21 (protein tyrosine phosphatase non-receptor type 21, HGNC:9651) is a protein-coding gene on chromosome 14q31.3, encoding Tyrosine-protein phosphatase non-receptor type 21 (Q16825).

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, mitotic cycle, and oncogenic transformation. This PTP contains an N-terminal domain, similar to cytoskeletal- associated proteins including band 4.1, ezrin, merlin, and radixin. This PTP was shown to specially interact with BMX/ETK, a member of Tec tyrosine kinase family characterized by a multimodular structures including PH, SH3, and SH2 domains. The interaction of this PTP with BMX kinase was found to increase the activation of STAT3, but not STAT2 kinase. Studies of the similar gene in mice suggested the possible roles of this PTP in liver regeneration and spermatogenesis.

Source: NCBI Gene 11099 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 208 total
• Druggable target: yes
• MANE Select transcript: NM_007039

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9651
Approved symbol	PTPN21
Name	protein tyrosine phosphatase non-receptor type 21
Location	14q31.3
Locus type	gene with protein product
Status	Approved
Aliases	PTPD1, PTPRL10
Ensembl gene	ENSG00000070778
Ensembl biotype	protein_coding
OMIM	603271
Entrez	11099

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 7 protein_coding, 2 protein_coding_CDS_not_defined, 2 retained_intron, 1 nonsense_mediated_decay

ENST00000328736, ENST00000536337, ENST00000553531, ENST00000554178, ENST00000554270, ENST00000554628, ENST00000555243, ENST00000556564, ENST00000557249, ENST00000872152, ENST00000940831, ENST00000940832

RefSeq mRNA: 1 — MANE Select: NM_007039 NM_007039

CCDS: CCDS9884

Canonical transcript exons

ENST00000556564 — 19 exons

Exon	Start	End
ENSE00001300493	88465778	88468265
ENSE00002438154	88554651	88555007
ENSE00003458223	88468916	88469076
ENSE00003463932	88517092	88517261
ENSE00003474320	88478920	88480352
ENSE00003474383	88505304	88505371
ENSE00003481227	88497203	88497290
ENSE00003489899	88501281	88501368
ENSE00003495925	88550238	88550619
ENSE00003498581	88507923	88508020
ENSE00003522412	88469922	88470050
ENSE00003541512	88472244	88472465
ENSE00003548735	88485076	88485160
ENSE00003552156	88473665	88473802
ENSE00003558043	88485782	88485842
ENSE00003576932	88496413	88496492
ENSE00003644943	88469499	88469733
ENSE00003669254	88500783	88500871
ENSE00003786301	88504425	88504495

Expression profiles

Bgee: expression breadth ubiquitous, 252 present calls, max score 95.23.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 3.3749 / max 37.4742, expressed in 1323 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
144415	2.1521	1177
144414	0.6838	470
144413	0.3905	209
144410	0.0649	33
144411	0.0527	35
144412	0.0308	7

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
upper leg skin	UBERON:0004262	95.23	gold quality
secondary oocyte	CL:0000655	92.93	gold quality
skin of hip	UBERON:0001554	91.86	gold quality
oocyte	CL:0000023	91.59	gold quality
lower lobe of lung	UBERON:0008949	91.49	gold quality
skin of abdomen	UBERON:0001416	90.45	gold quality
skin of leg	UBERON:0001511	90.22	gold quality
right lung	UBERON:0002167	89.56	gold quality
zone of skin	UBERON:0000014	89.50	gold quality
heart right ventricle	UBERON:0002080	89.47	gold quality
mammary duct	UBERON:0001765	89.05	gold quality
left testis	UBERON:0004533	88.50	gold quality
right testis	UBERON:0004534	88.27	gold quality
sural nerve	UBERON:0015488	88.27	gold quality
right coronary artery	UBERON:0001625	88.16	gold quality
cauda epididymis	UBERON:0004360	87.99	gold quality
testis	UBERON:0000473	87.69	gold quality
colonic epithelium	UBERON:0000397	87.50	gold quality
left lobe of thyroid gland	UBERON:0001120	87.46	gold quality
germinal epithelium of ovary	UBERON:0001304	87.40	gold quality
popliteal artery	UBERON:0002250	87.36	gold quality
aorta	UBERON:0000947	87.35	gold quality
thoracic aorta	UBERON:0001515	87.35	gold quality
tibial artery	UBERON:0007610	87.35	gold quality
ascending aorta	UBERON:0001496	87.30	gold quality
thyroid gland	UBERON:0002046	87.21	gold quality
sperm	CL:0000019	87.10	gold quality
stromal cell of endometrium	CL:0002255	87.07	gold quality
right lobe of thyroid gland	UBERON:0001119	86.73	gold quality
descending thoracic aorta	UBERON:0002345	86.66	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.42

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

174 targeting PTPN21, 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-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-518D-5P	100.00	67.51	979
HSA-MIR-518E-5P	100.00	67.66	954
HSA-MIR-518F-5P	100.00	67.51	979
HSA-MIR-519A-5P	100.00	67.66	954
HSA-MIR-519B-5P	100.00	67.66	954
HSA-MIR-519C-5P	100.00	67.66	954
HSA-MIR-520C-5P	100.00	67.51	979
HSA-MIR-522-5P	100.00	67.66	954
HSA-MIR-523-5P	100.00	67.66	954
HSA-MIR-526A-5P	100.00	67.51	979
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-3148	99.97	75.06	6478

Literature-anchored findings (GeneRIF, showing 9)

• PTPD1 is a component of a multivalent scaffold complex nucleated by FAK at specific intracellular sites (PMID:18223254)
• In colorectal tumors, microsatellite repeats mutation rates are higher than the mean mutation frequency; the highest mutation frequency among 16 PTP genes (PMID:19000305)
• PTPD1 is a novel component of the endocytic machinery that impacts on EGF receptor stability and on growth and motility of bladder cancer cells (PMID:20923765)
• The results that 2 non-synonymous markers in PTPN21 are associated with schizophrenia, further investigation of this locus is warranted. (PMID:21752600)
• Presented data suggest that the transient formation of dynamic PTPD1/EGFR signalling complexes strengthens EGF signalling by promoting the spatial propagation of EGFR phosphorylated species (PMID:25062045)
• Study demonstrates that PTPN21 activates KIF1C by binding to the stalk region. This function does not require catalytic activity of the phosphatase, and its N-terminal FERM domain alone is sufficient to stimulate the transport of KIF1C cargoes in cells as well as increasing the landing rate of KIF1C on microtubules in vitro. The cargo adapter Hook3 binds KIF1C in the same region and activates KIF1C in a similar way. (PMID:31217419)
• PTPN21-CDSlong isoform inhibits the response of acute lymphoblastic leukemia cells to NK-mediated lysis via the KIR/HLA-I axis. (PMID:31898344)
• Molecular Analysis of the Interaction between Human PTPN21 and the Oncoprotein E7 from Human Papillomavirus Genotype 18. (PMID:33431714)
• Overexpression of PTPN21 promotes proliferation of EGF-stimulated acute lymphoblastic leukemia cells via the MAPK signaling pathways. (PMID:38785187)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	ptpn21	ENSDARG00000062248
mus_musculus	Ptpn21	ENSMUSG00000021009
rattus_norvegicus	Ptpn21	ENSRNOG00000060568

Paralogs (35): PTPRN (ENSG00000054356), PTPRU (ENSG00000060656), PTPN3 (ENSG00000070159), PTPN18 (ENSG00000072135), 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 21 — Q16825 (reviewed: Q16825)

Alternative names: Protein-tyrosine phosphatase D1

All UniProt accessions (4): Q16825, G3V1Q9, G3V3S6, H0YJ59

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Cytoplasm. Cytoskeleton.

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

RefSeq proteins (1): NP_008970* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000242	PTP_cat	Domain
IPR000299	FERM_domain	Domain
IPR000387	Tyr_Pase_dom	Domain
IPR003595	Tyr_Pase_cat	Domain
IPR011993	PH-like_dom_sf	Homologous_superfamily
IPR014352	FERM/acyl-CoA-bd_prot_sf	Homologous_superfamily
IPR014392	PTP_non-rcpt_14/21	Family
IPR016130	Tyr_Pase_AS	Active_site
IPR018979	FERM_N	Domain
IPR018980	FERM_PH-like_C	Domain
IPR019747	FERM_CS	Conserved_site
IPR019748	FERM_central	Domain
IPR019749	Band_41_domain	Domain
IPR029021	Prot-tyrosine_phosphatase-like	Homologous_superfamily
IPR029071	Ubiquitin-like_domsf	Homologous_superfamily
IPR035963	FERM_2	Homologous_superfamily
IPR041782	PTPN14/21_FERM_C	Domain

Pfam: PF00102, PF00373, PF09379, PF09380

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 (81 total): strand 27, helix 20, modified residue 10, turn 6, compositionally biased region 4, region of interest 4, binding site 3, sequence variant 3, domain 2, chain 1, active site 1

Structure

Experimental structures (PDB)

5 structures.

PDB	Method	Resolution (Å)
8GVV	X-RAY DIFFRACTION	1.8
8GWH	X-RAY DIFFRACTION	2
8Y8Y	X-RAY DIFFRACTION	2.1
8GVL	X-RAY DIFFRACTION	2.1
8GXE	X-RAY DIFFRACTION	3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q16825-F1	63.73	0.36

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): 1108 (phosphocysteine intermediate)

Ligand- & substrate-binding residues (3): 1067; 1108–1114; 1152

Post-translational modifications (10): 577, 589, 590, 637, 673, 710, 711, 797, 799, 804

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 187 (showing top): BROWNE_HCMV_INFECTION_30MIN_DN, WAMUNYOKOLI_OVARIAN_CANCER_LMP_DN, MODULE_571, BERTUCCI_MEDULLARY_VS_DUCTAL_BREAST_CANCER_DN, BROWNE_HCMV_INFECTION_8HR_UP, NKX25_02, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_UP, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, BROWNE_HCMV_INFECTION_16HR_UP, GOBP_HIPPO_SIGNALING, BROWNE_HCMV_INFECTION_48HR_DN, SHETH_LIVER_CANCER_VS_TXNIP_LOSS_PAM1, SHETH_LIVER_CANCER_VS_TXNIP_LOSS_PAM6, NELSON_RESPONSE_TO_ANDROGEN_UP

GO Biological Process (2): protein dephosphorylation (GO:0006470), dephosphorylation (GO:0016311)

GO Molecular Function (4): protein tyrosine phosphatase activity (GO:0004725), phosphoprotein phosphatase activity (GO:0004721), protein binding (GO:0005515), hydrolase activity (GO:0016787)

GO Cellular Component (2): cytoplasm (GO:0005737), cytoskeleton (GO:0005856)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
dephosphorylation	1
protein modification process	1
phosphate-containing compound metabolic process	1
phosphoprotein phosphatase activity	1
phosphatase activity	1
catalytic activity, acting on a protein	1
binding	1
catalytic activity	1
intracellular anatomical structure	1
cellular anatomical structure	1
intracellular membraneless organelle	1

Protein interactions and networks

STRING

908 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PTPN21	PTS	Q03393	857
PTPN21	KIF1C	O43896	855
PTPN21	KIF1A	Q12756	707
PTPN21	DUSP4	Q13115	697
PTPN21	SRC	P12931	612
PTPN21	EML5	Q05BV3	521
PTPN21	HPGDS	O60760	514
PTPN21	PTGDS	P41222	510
PTPN21	AKAP1	Q92667	506
PTPN21	HOOK3	Q86VS8	503
PTPN21	YAP1	P46937	453
PTPN21	PTPN23	Q9H3S7	438
PTPN21	DUSP18	Q8NEJ0	432
PTPN21	PTGDR	Q13258	428
PTPN21	RPL35	P42766	418
PTPN21	SAMM50	Q9Y512	418

IntAct

99 interactions, top by confidence:

A	B	Type	Score
E7	RB1	psi-mi:“MI:0914”(association)	0.700
RHPN1	PODXL	psi-mi:“MI:0914”(association)	0.690
YWHAG	BLTP3B	psi-mi:“MI:0914”(association)	0.640
INAVA	CYTH3	psi-mi:“MI:0914”(association)	0.640
YWHAH	BLTP3B	psi-mi:“MI:0914”(association)	0.570
GOLGA2	PTPN21	psi-mi:“MI:0915”(physical association)	0.560
QARS1	PTPN21	psi-mi:“MI:0915”(physical association)	0.560
PTPN21	ZNF497	psi-mi:“MI:0915”(physical association)	0.560
VPS26C	PTPN21	psi-mi:“MI:0915”(physical association)	0.560
PTPN21	PAK5	psi-mi:“MI:0915”(physical association)	0.560
PTPN21	CATSPER1	psi-mi:“MI:0915”(physical association)	0.560
BAG3	PTPN21	psi-mi:“MI:0915”(physical association)	0.560
PTPN21	CWC22	psi-mi:“MI:0915”(physical association)	0.560
PTPN21	NSMF	psi-mi:“MI:0915”(physical association)	0.560
PTPN21	UBASH3B	psi-mi:“MI:0915”(physical association)	0.560
PTPN21	PARD6A	psi-mi:“MI:0915”(physical association)	0.560
PTPN21	SNX18	psi-mi:“MI:0915”(physical association)	0.560
PTPN21	NEK6	psi-mi:“MI:0915”(physical association)	0.560
PTPN21	MAGOHB	psi-mi:“MI:0915”(physical association)	0.560
TRIM14	PTPN21	psi-mi:“MI:0915”(physical association)	0.560
PTPN21	PIBF1	psi-mi:“MI:0915”(physical association)	0.560
PTPN21	FBXO17	psi-mi:“MI:0915”(physical association)	0.560
PTPN21	MOB3C	psi-mi:“MI:0915”(physical association)	0.560
PTPN21	ATOSB	psi-mi:“MI:0915”(physical association)	0.560
PTPN21	RASD1	psi-mi:“MI:0915”(physical association)	0.560
BMX	PTPN21	psi-mi:“MI:0915”(physical association)	0.560
PTPN21	Akap1	psi-mi:“MI:0407”(direct interaction)	0.540
PTPN21	Akap1	psi-mi:“MI:0915”(physical association)	0.540
PARD6B	ZZEF1	psi-mi:“MI:0914”(association)	0.530

BioGRID (128): PTPN21 (Affinity Capture-MS), PTPN21 (Two-hybrid), AJUBA (Affinity Capture-MS), LPP (Affinity Capture-MS), PFDN4 (Affinity Capture-MS), PFDN6 (Affinity Capture-MS), TRIP6 (Affinity Capture-MS), USP9X (Affinity Capture-MS), VBP1 (Affinity Capture-MS), WWC2 (Affinity Capture-MS), WWC1 (Affinity Capture-Western), PTPN21 (Reconstituted Complex), PTPN21 (Affinity Capture-MS), PTPN21 (Affinity Capture-MS), PTPN21 (Affinity Capture-MS)

ESM2 similar proteins: A0A0G2K2P5, A0JNJ1, B1WAP7, G9CGD6, O14640, O75122, O88382, O95049, O97758, P34908, P39447, P51141, P54792, P70175, Q05AS8, Q07157, Q16825, Q5F488, Q5IS48, Q5SGD7, Q5TCQ9, Q5XI81, Q61062, Q62136, Q62728, Q62936, Q6DKE2, Q6P9H4, Q6ZM86, Q812E4, Q86UL8, Q8BMA3, Q8IVH8, Q8JHI3, Q8TDW5, Q920B0, Q924I2, Q925T6, Q92997, Q95168

Diamond homologs: A0A6I8TCE0, A1L1L3, A2A8L5, A2ALK8, A4IFW2, A7MBJ4, B0V2N1, B0X4T2, B1AUH1, B2RU80, B3DK56, B9EKR1, E9Q0N2, E9Q612, F1NWE3, O13016, O14522, O35239, O55082, O82656, O88488, P04157, P06800, P08575, P0C5E4, P10586, P16621, P17706, P18031, P20417, P23467, P23468, P23470, P23471, P26045, P28191, P28192, P28827, P28828, P29074

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
PTPN21	up-regulates	SRC	dephosphorylation
PTPN21	“up-regulates activity”	SRC	dephosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 57 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
Activation of BAD and translocation to mitochondria	6	114.2×	1e-09
Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex	6	100.8×	1e-09
SARS-CoV-1 targets host intracellular signalling and regulatory pathways	6	100.8×	1e-09
Activation of BH3-only proteins	6	74.5×	8e-09
RHO GTPases activate PKNs	6	47.6×	1e-07
Intrinsic Pathway for Apoptosis	6	43.9×	1e-07
Apoptosis	7	29.4×	1e-07
Transcriptional and post-translational regulation of MITF-M expression and activity	6	26.8×	3e-06

GO biological processes:

GO term	Partners	Fold	FDR
protein targeting	5	36.6×	1e-04
intracellular protein localization	7	14.7×	1e-04
protein phosphorylation	6	8.2×	7e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	179
Likely benign	10
Benign	3

Top pathogenic / likely-pathogenic (0)

SpliceAI

2917 predictions. Top by Δscore:

Variant	Effect	Δscore
14:88469073:TATG:T	acceptor_gain	1.0000
14:88469075:TG:T	acceptor_gain	1.0000
14:88469088:CAA:C	acceptor_gain	1.0000
14:88469917:CCTA:C	donor_loss	1.0000
14:88469918:CTA:C	donor_loss	1.0000
14:88469919:TAC:T	donor_loss	1.0000
14:88469921:C:T	donor_loss	1.0000
14:88469921:CCT:C	donor_gain	1.0000
14:88470057:T:TC	acceptor_gain	1.0000
14:88472461:TTACA:T	acceptor_gain	1.0000
14:88472462:TACA:T	acceptor_gain	1.0000
14:88472463:ACA:A	acceptor_gain	1.0000
14:88472464:CA:C	acceptor_gain	1.0000
14:88472464:CAC:C	acceptor_gain	1.0000
14:88472465:ACTA:A	acceptor_loss	1.0000
14:88472466:C:CC	acceptor_gain	1.0000
14:88472466:CTATA:C	acceptor_loss	1.0000
14:88472467:T:C	acceptor_loss	1.0000
14:88472468:A:C	acceptor_gain	1.0000
14:88473663:AC:A	donor_gain	1.0000
14:88473664:CC:C	donor_gain	1.0000
14:88473799:TTCC:T	acceptor_gain	1.0000
14:88473800:TCCC:T	acceptor_loss	1.0000
14:88473801:CC:C	acceptor_gain	1.0000
14:88473802:CC:C	acceptor_gain	1.0000
14:88473803:C:CC	acceptor_gain	1.0000
14:88496407:A:AC	donor_gain	1.0000
14:88496407:ACTT:A	donor_loss	1.0000
14:88496408:C:CC	donor_gain	1.0000
14:88496408:CT:C	donor_loss	1.0000

AlphaMissense

7672 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
14:88469603:A:G	L1044P	1.000
14:88469978:A:G	W982R	1.000
14:88469978:A:T	W982R	1.000
14:88469052:A:T	V1087D	0.999
14:88469541:A:G	W1065R	0.999
14:88469541:A:T	W1065R	0.999
14:88469555:A:G	L1060P	0.999
14:88469562:A:G	W1058R	0.999
14:88469562:A:T	W1058R	0.999
14:88469638:G:C	F1032L	0.999
14:88469638:G:T	F1032L	0.999
14:88469640:A:G	F1032L	0.999
14:88469703:A:G	W1011R	0.999
14:88469703:A:T	W1011R	0.999
14:88472257:G:T	A953E	0.999
14:88472296:A:G	L940S	0.999
14:88497289:A:G	W256R	0.999
14:88497289:A:T	W256R	0.999
14:88517213:A:G	W77R	0.999
14:88517213:A:T	W77R	0.999
14:88550245:A:G	L58P	0.999
14:88550284:C:T	G45D	0.999
14:88469636:C:G	R1033P	0.998
14:88469639:A:G	F1032S	0.998
14:88472255:A:G	S954P	0.998
14:88472258:C:G	A953P	0.998
14:88472259:G:C	N952K	0.998
14:88472259:G:T	N952K	0.998
14:88472269:C:T	G949D	0.998
14:88472277:G:C	N946K	0.998

dbSNP variants (sampled 300 via entrez): RS1000003304 (14:88537310 G>A), RS1000009987 (14:88496856 G>T), RS1000015483 (14:88536399 G>T), RS1000061601 (14:88487986 T>A,C,G), RS1000084991 (14:88504435 G>T), RS1000111291 (14:88531787 G>A), RS1000211238 (14:88512912 C>T), RS1000233042 (14:88489964 G>A), RS1000250143 (14:88543678 GT>G), RS1000264858 (14:88543190 G>A), RS1000310673 (14:88502858 GAGA>G), RS1000334485 (14:88465954 T>C), RS1000376591 (14:88549399 G>A), RS1000432935 (14:88525256 T>A,C), RS1000513952 (14:88470404 A>C,G)

Disease associations

OMIM: gene MIM:603271 | disease phenotypes:

GenCC curated gene-disease

Mondo (2): prostate cancer (MONDO:0008315), myoepithelial tumor (MONDO:0002380)

Orphanet (1): Familial prostate cancer (Orphanet:1331)

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST004639_36	Prudent dietary pattern	7.000000e-06
GCST012279_12	Suicide attempt severity in mood disorders	6.000000e-06
GCST012280_6	Suicidality in mood disorders	6.000000e-06

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0008111	diet measurement
EFO:0006882	suicide behaviour measurement

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D009208	Myoepithelioma	C04.557.435.585
D011471	Prostatic Neoplasms	C04.588.945.440.770; C12.100.500.260.750; C12.100.500.565.625; C12.200.294.260.750; C12.200.294.565.625; C12.200.758.409.750; C12.900.619.750

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4060 (SINGLE PROTEIN)

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

Binding affinities (BindingDB)

1 measured of 1 human assays (1 total across all organisms); most potent 1 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
6-hydroxy-3-iodo-1-methyl-2-[3-[[2-oxo-2-(4-thiophen-3-ylanilino)acetyl]amino]phenyl]indole-5-carboxylic acid	IC50	2900 nM	US-9522881: Hydroxyindole carboxylic acid based inhibitors for oncogenic Src homology-2 domain containing protein tyrosine phosphatase-2 (SHP2)

ChEMBL bioactivities

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

pChembl	Type	Value	Unit	Molecule
5.07	IC50	8600	nM	CHEMBL3319356

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression, affects expression	4
sodium arsenite	decreases expression, increases expression	2
entinostat	affects cotreatment, decreases expression	2
Benzo(a)pyrene	increases expression, affects methylation	2
Estradiol	increases expression, decreases expression, affects cotreatment	2
aristolochic acid I	decreases expression	1
FR900359	increases phosphorylation	1
bisphenol A	affects cotreatment, decreases methylation	1
arsenite	affects binding, decreases reaction	1
butyraldehyde	decreases expression	1
potassium chromate(VI)	decreases expression	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, decreases expression	1
aflatoxin B2	increases methylation	1
CGP 52608	affects binding, increases reaction	1
U 0126	affects expression, affects reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	decreases expression, affects cotreatment	1
abrine	increases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
jinfukang	affects cotreatment, decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Sunitinib	decreases expression	1
Arsenic Trioxide	decreases expression	1
Fulvestrant	decreases methylation, affects cotreatment	1
Caffeine	decreases phosphorylation	1
Calcitriol	increases expression, affects cotreatment	1
Cisplatin	affects cotreatment, decreases expression	1
Coumestrol	affects cotreatment, decreases expression	1
Doxorubicin	decreases expression	1
Methotrexate	increases expression	1
Phenobarbital	affects 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
CHEMBL5730454	Binding	Inhibition Assay: For selectivity studies, the PTPs, including LYP, mPTPA, SHP1-D1C, PTP1B, LMPTP, VHR, Laforin and PTPα-D1D2 were expressed and purified from E. coli. The inhibition assay for these PTPs were performed under the same condit	Hydroxyindole carboxylic acid based inhibitors for oncogenic Src homology-2 domain containing protein tyrosine phosphatase-2 (SHP2)

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00029224	PHASE4	COMPLETED	Treatment With Zoledronic Acid in Patients With Breast Cancer, Multiple Myeloma, and Prostate Cancer With Cancer Related Bone Lesions
NCT00035997	PHASE4	COMPLETED	Open-label Trial on the Effect of I.V. Zoledronic Acid 4 mg on Bone Density in Hormone Sensitive Prostate Cancer Patients With Bone Metastasis
NCT00063609	PHASE4	COMPLETED	The Effect of Zoledronic Acid on Bone Loss in Prostate Cancer Patients Undergoing Androgen Deprivation Therapy
NCT00103623	PHASE4	SUSPENDED	The Plenaxis® Experience Study
NCT00106392	PHASE4	COMPLETED	A Safety and Efficacy Study of Prograf in the Prevention of Erectile Dysfunction After Radical Prostatectomy
NCT00185029	PHASE4	UNKNOWN	MR-Lymphography and Lymph Node Staging in Prostate Cancer
NCT00199485	PHASE4	COMPLETED	Angelica Sinensis for the Treatment of Hot Flashes in Men Undergoing LHRH Therapy for Prostate Cancer
NCT00219219	PHASE4	COMPLETED	Zoledronic Acid in the Prevention of Skeletal-related Events in Hormone Refractory and Hormone-sensitive Prostate Cancer Patients With Bone Metastases
NCT00219271	PHASE4	COMPLETED	Effect Of Zoledronic Acid On Circulating And Bone Marrow-Residing Prostate Cancer Cells In Patients With Clinically Localized Prostate Cancer
NCT00237146	PHASE4	COMPLETED	Study to Evaluate Zoledronic Acid on Quality of Life and Skeletal-related Events as Adjuvant Treatment in Patients With Hormone-naïve Prostate Cancer and Bone Metastasis Who Have Undergone Orchiectomy
NCT00242554	PHASE4	COMPLETED	Open-label Phase IV Clinical Trial to Evaluate the Safety and Tolerability of Zoledronic Acid in Patients With Prostate Cancer and Bone Metastases
NCT00280098	PHASE4	COMPLETED	Docetaxel in the Treatment of Hormone Refractory Prostate Cancer
NCT00293696	PHASE4	COMPLETED	Casodex/Zoladex Biomarkers in Localised Prostate Cancer
NCT00334139	PHASE4	COMPLETED	Effect of Zoledronic Acid on Bone Metabolism in Patients With Bone Metastasis and Prostate or Breast Cancer
NCT00375765	PHASE4	COMPLETED	Effects On Dihydrotestosterone Regulated Gene Expression In Benign Prostatic Hyperplasia Or Prostate Cancer
NCT00391690	PHASE4	COMPLETED	Evaluation of Bone Markers as Diagnostic Tools for Early Detection of Bone Metastases in Patients With High Risk Prostate Cancer
NCT00422708	PHASE4	COMPLETED	Local Anesthesia for Prostate Biopsy
NCT00526331	PHASE4	COMPLETED	Evaluation of Arterial Pressure Based Cardiac Output for Goal-Directed Perioperative Therapy
NCT00590213	PHASE4	COMPLETED	Compare the Value of Prophylactic Versus Therapeutic Breast Radiotherapy in CASODEX
NCT00629330	PHASE4	TERMINATED	Dissemination of Prostate Cancer Screening to PCP’s in African American Communities
NCT00771966	PHASE4	COMPLETED	Radical Prostatectomy and Perioperative Fluid Therapy
NCT00805701	PHASE4	COMPLETED	Study Assessing The Efficacy And Safety Of Avodart (Dutasteride) At Improving Urinary Symptoms In Men With Prostate Cancer Who Are Undergoing Seed Implantation
NCT00859027	PHASE4	COMPLETED	Effect Of Risedronate On Bone Mass In Older Men Receiving Neoadjuvant Therapy For Prostate Cancer
NCT00906269	PHASE4	UNKNOWN	Can Hyperbaric Oxygen Improve Erectile Function Following Surgery for Prostate Cancer
NCT00953277	PHASE4	COMPLETED	Study of Nerve Reconstruction Using AVANCE in Subjects Who Undergo Robotic Assisted Prostatectomy for Treatment of Prostate Cancer
NCT00982800	PHASE4	COMPLETED	Does Postoperative Gabapentin Reduce Pain, Opioid Consumption and Anxiety and Have a Positive Effect on Health Related Quality of Life After Radical Prostatectomy?
NCT01083199	PHASE4	COMPLETED	Global Performance Evaluation of the AMS CONTINUUM™ Device
NCT01136226	PHASE4	COMPLETED	Evaluate Recovery of Testosterone for Patients Using Eligard
NCT01161563	PHASE4	COMPLETED	Randomized Crossover Trial to Assess the Tolerability of Gonadotropin Releasing Hormone (GnRH) Analogue Administration
NCT01230905	PHASE4	COMPLETED	Study to Monitor the Effects of Androgen Suppression Treatment on the Heart
NCT01296672	PHASE4	COMPLETED	3 Month Finasteride Challenge Test Can Significantly Improve the Performance of Screening for Prostate Cancer
NCT01365143	PHASE4	TERMINATED	Prospective Randomized Trial Comparing Robotic Versus Open Radical Prostatectomy
NCT01379742	PHASE4	UNKNOWN	Comparison of Between ThinSeed™ and OncoSeed™ for Permanent Prostate Brachytherapy
NCT01486563	PHASE4	COMPLETED	Hydroxyethyl Starch and Renal Function After Radical Prostatectomy
NCT01511874	PHASE4	COMPLETED	Efficacy and Safety Study of ELIGARD 22.5mg With Prostate Cancer
NCT01512472	PHASE4	TERMINATED	Firmagon (Degarelix) Intermittent Therapy
NCT01547416	PHASE4	COMPLETED	The Effect of Combined General/Epidural Anesthesia Versus General Anesthesia on Diaphragmatic Function
NCT01571544	PHASE4	COMPLETED	The Use of Thermal Suits as Preventing Hypothermia During Surgery
NCT01581749	PHASE4	UNKNOWN	Evaluation of Truebeam for Low-Intermediate Risk Prostate Cancer
NCT01649635	PHASE4	COMPLETED	Study of Cabazitaxel Combined With Prednisone and Prophylaxis of Neutropenia Complications in the Treatment of Patients With Metastatic Castration-resistant Prostate Cancer