PTPRN2

Summary

PTPRN2 (protein tyrosine phosphatase receptor type N2, HGNC:9677) is a protein-coding gene on chromosome 7q36.3, encoding Receptor-type tyrosine-protein phosphatase N2 (Q92932). Plays a role in vesicle-mediated secretory processes.

This gene encodes a protein with sequence similarity to receptor-like protein tyrosine phosphatases. However, tyrosine phosphatase activity has not been experimentally validated for this protein. Studies of the rat ortholog suggest that the encoded protein may instead function as a phosphatidylinositol phosphatase with the ability to dephosphorylate phosphatidylinositol 3-phosphate and phosphatidylinositol 4,5-diphosphate, and this function may be involved in the regulation of insulin secretion. This protein has been identified as an autoantigen in insulin-dependent diabetes mellitus. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 5799 — RefSeq curated summary.

At a glance

• GWAS associations: 24
• Clinical variants (ClinVar): 277 total
• MANE Select transcript: NM_002847

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9677
Approved symbol	PTPRN2
Name	protein tyrosine phosphatase receptor type N2
Location	7q36.3
Locus type	gene with protein product
Status	Approved
Aliases	KIAA0387, phogrin, ICAAR, IA-2beta
Ensembl gene	ENSG00000155093
Ensembl biotype	protein_coding
OMIM	601698
Entrez	5799

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 5 protein_coding

ENST00000389413, ENST00000389416, ENST00000389418, ENST00000409483, ENST00000648371

RefSeq mRNA: 5 — MANE Select: NM_002847 NM_001308267, NM_001308268, NM_002847, NM_130842, NM_130843

CCDS: CCDS5947, CCDS5948, CCDS5949, CCDS78294

Canonical transcript exons

ENST00000389418 — 23 exons

Exon	Start	End
ENSE00001147319	158133677	158134059
ENSE00001147328	158136655	158136695
ENSE00001147335	158138294	158138515
ENSE00001289898	158489735	158489785
ENSE00001290913	157568902	157568966
ENSE00001292175	157576613	157576779
ENSE00001295610	157898673	157898737
ENSE00001301678	158192327	158192495
ENSE00001302375	157682725	157682937
ENSE00001302919	158316819	158316932
ENSE00001304923	158110829	158110915
ENSE00001315560	157621362	157621509
ENSE00001316950	157548946	157549019
ENSE00001319507	158081298	158081377
ENSE00001320738	158205171	158205273
ENSE00001322732	157604002	157604075
ENSE00001324758	157595238	157595315
ENSE00001325204	157656357	157656551
ENSE00001325921	157578021	157578140
ENSE00001330207	158166931	158167291
ENSE00001505822	157571440	157571493
ENSE00001587211	157539056	157540785
ENSE00001952569	158587558	158587823

Expression profiles

Bgee: expression breadth ubiquitous, 254 present calls, max score 97.95.

FANTOM5 (CAGE): breadth broad, TPM avg 3.7345 / max 171.8218, expressed in 280 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
87103	3.0295	237
87101	0.2338	89
87102	0.2048	90
87100	0.1286	66
87104	0.0731	43
205023	0.0514	22
87089	0.0134	4

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
lateral nuclear group of thalamus	UBERON:0002736	97.95	gold quality
middle temporal gyrus	UBERON:0002771	97.19	gold quality
lateral globus pallidus	UBERON:0002476	97.16	gold quality
Brodmann (1909) area 23	UBERON:0013554	97.14	gold quality
entorhinal cortex	UBERON:0002728	96.79	gold quality
orbitofrontal cortex	UBERON:0004167	96.75	gold quality
frontal pole	UBERON:0002795	96.68	gold quality
superior frontal gyrus	UBERON:0002661	96.40	gold quality
Brodmann (1909) area 46	UBERON:0006483	96.29	gold quality
postcentral gyrus	UBERON:0002581	96.20	gold quality
substantia nigra pars compacta	UBERON:0001965	96.19	gold quality
parietal lobe	UBERON:0001872	95.97	gold quality
bronchial epithelial cell	CL:0002328	95.43	gold quality
endothelial cell	CL:0000115	95.27	gold quality
substantia nigra pars reticulata	UBERON:0001966	95.27	gold quality
CA1 field of hippocampus	UBERON:0003881	95.26	gold quality
superior vestibular nucleus	UBERON:0007227	95.23	gold quality
primary visual cortex	UBERON:0002436	95.03	gold quality
pancreatic ductal cell	CL:0002079	95.01	gold quality
pons	UBERON:0000988	94.92	gold quality
occipital lobe	UBERON:0002021	94.85	gold quality
epithelium of bronchus	UBERON:0002031	94.81	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	94.77	gold quality
middle frontal gyrus	UBERON:0002702	94.74	gold quality
Brodmann (1909) area 10	UBERON:0013541	94.62	gold quality
temporal lobe	UBERON:0001871	94.57	gold quality
bronchus	UBERON:0002185	94.50	gold quality
nucleus accumbens	UBERON:0001882	94.47	gold quality
cingulate cortex	UBERON:0003027	94.35	gold quality
anterior cingulate cortex	UBERON:0009835	94.30	gold quality

Single-cell (SCXA)

Detected in 7 experiment(s), a significant marker in 6.

Experiment	Marker?	Max mean expression
E-HCAD-35	yes	71.11
E-MTAB-5061	yes	27.08
E-GEOD-81547	yes	25.16
E-CURD-114	yes	11.96
E-ANND-3	yes	9.13
E-GEOD-125970	yes	6.70
E-GEOD-83139	no	3.71

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): NR1I2

miRNA regulators (miRDB)

79 targeting PTPRN2, 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-7110-3P	100.00	73.18	2486
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-3689D	100.00	66.14	1181
HSA-MIR-6851-5P	100.00	65.63	1294
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-8082	99.95	67.27	1170
HSA-MIR-3143	99.93	71.96	3104
HSA-MIR-6835-3P	99.93	70.49	2904
HSA-MIR-4760-3P	99.93	70.50	2385
HSA-MIR-450B-5P	99.92	71.48	3175
HSA-MIR-5680	99.91	69.83	3421
HSA-MIR-374A-5P	99.90	71.34	2923
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-6124	99.87	69.78	3551
HSA-MIR-4503	99.85	71.45	1869
HSA-MIR-629-3P	99.85	67.99	1875
HSA-MIR-6515-3P	99.82	68.19	1933
HSA-MIR-577	99.78	69.13	2479
HSA-MIR-4713-5P	99.78	67.80	1794
HSA-MIR-4517	99.76	69.19	1867
HSA-MIR-4422	99.72	72.07	2908
HSA-MIR-518A-5P	99.70	69.01	2209

Literature-anchored findings (GeneRIF, showing 13)

• IA-2beta is involved in insulin secretion, but despite its importance as a major autoantigen in human type 1 diabetes, it is not required for the development of diabetes in NOD mice. (PMID:15220191)
• In mice IA-2beta expressed exclusively in dense core secretory vesicles (DCV) and with fractions rich in synaptic vesicles (SV) of neuroendocrine cells of brain and impairment of conditioned learning. (PMID:19361477)
• While PTPRN2 shares sequence similarity with protein tyrosine phosphatases, this study in rat suggests that this protein instead functions as a membrane bound phosphatidylinositol phosphatase. (PMID:20097759)
• The findings in this patient raise the possibility that PTPRN2 may be active during early development of the human brainstem and that its overexpression may cause bilateral Duane retraction syndrome as occurs in patients with homozygous HOXA1 mutations. (PMID:22950449)
• Data indicate the X-ray structure of the mature ectodomain of mature ectodomain of phogrin/IA-2beta (PTPRN2) (ME phogrin) at pH 7.4 and 4.6. (PMID:25421040)
• ProPTPRN2 elicited these effects through direct interaction with TRAF2. (PMID:25877877)
• Reduction in plasma membrane PI(4,5)P2 abundance by PTPRN2 and PLCbeta1 releases the PI(4,5)P2-binding protein cofilin from its inactive membrane-associated state into the cytoplasm where it mediates actin turnover dynamics. (PMID:26620550)
• Haplotype-dependent allele-specific methylation of PTPRN2 gene is associated with neurological disorders. (PMID:27153397)
• Copy-number variations are enriched for PTPRN2 and other neurodevelopmental genes in children with developmental coordination disorder. (PMID:27489308)
• The association of genetically controlled CpG methylation (cg158269415) of protein tyrosine phosphatase, receptor type N2 (PTPRN2) with childhood obesity. (PMID:30890718)
• HOXD13 promotes the malignant progression of colon cancer by upregulating PTPRN2. (PMID:34272834)
• Rab35 regulates insulin secretion via phogrin in pancreatic beta cells. (PMID:34448213)
• Interactions of genetic variations in FAS, GJB2 and PTPRN2 are associated with noise-induced hearing loss: a case-control study in China. (PMID:38212800)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	ptprn2	ENSDARG00000035970
mus_musculus	Ptprn2	ENSMUSG00000056553
rattus_norvegicus	Ptprn2	ENSRNOG00000005003

Paralogs (35): PTPRN (ENSG00000054356), PTPRU (ENSG00000060656), PTPN3 (ENSG00000070159), PTPN21 (ENSG00000070778), 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), PTPN13 (ENSG00000163629), PTPN9 (ENSG00000169410), PTPRM (ENSG00000173482), PTPN2 (ENSG00000175354), PTPN11 (ENSG00000179295), PTPRT (ENSG00000196090), PTPN1 (ENSG00000196396), PTPN20 (ENSG00000204179)

Protein

Protein identifiers

Receptor-type tyrosine-protein phosphatase N2 — Q92932 (reviewed: Q92932)

Alternative names: Islet cell autoantigen-related protein, Phogrin

All UniProt accessions (3): Q92932, A0A3B3IU41, E7EM83

UniProt curated annotations — full annotation on UniProt →

Function. Plays a role in vesicle-mediated secretory processes. Required for normal accumulation of secretory vesicles in hippocampus, pituitary and pancreatic islets. Required for the accumulation of normal levels of insulin-containing vesicles and preventing their degradation. Plays a role in insulin secretion in response to glucose stimuli. Required for normal accumulation of the neurotransmitters norepinephrine, dopamine and serotonin in the brain. In females, but not in males, required for normal accumulation and secretion of pituitary hormones, such as luteinizing hormone (LH) and follicle-stimulating hormone (FSH). Required to maintain normal levels of renin expression and renin release. May regulate catalytic active protein-tyrosine phosphatases such as PTPRA through dimerization. Has phosphatidylinositol phosphatase activity; the PIPase activity is involved in its ability to regulate insulin secretion. Can dephosphorylate phosphatidylinositol 4,5-biphosphate (PI(4,5)P2), phosphatidylinositol 5-phosphate and phosphatidylinositol 3-phosphate. Regulates PI(4,5)P2 level in the plasma membrane and localization of cofilin at the plasma membrane and thus is indirectly involved in regulation of actin dynamics related to cell migration and metastasis; upon hydrolysis of PI(4,5)P2 cofilin is released from the plasma membrane and acts in the cytoplasm in severing F-actin filaments.

Subunit / interactions. Self-associates. Interacts (via cytoplasmic domain) with PTPRN (via cytoplasmic domain). Interacts (precursor form) with CPE. Interacts with HAP1. Interacts with AP2A1 or AP2A2 and AP1G1; indicative for an association with adaptor protein complex 2 (AP-2) and adaptor protein complex 1 (AP-1). Interacts with AP2M1; indicative for an association with adaptor protein complex 2 (AP-2). Interacts with MYO5A.

Subcellular location. Cytoplasmic vesicle. Secretory vesicle membrane. Secretory vesicle. Synaptic vesicle membrane Cytoplasmic vesicle.

Tissue specificity. Highest levels in brain and pancreas. Lower levels in trachea, prostate, stomach and spinal cord.

Post-translational modifications. Subject to proteolytic cleavage at multiple sites.

Disease relevance. Autoantigen in insulin-dependent diabetes mellitus (IDDM).

Domain organisation. The cytoplasmic domain appears to contain the autoantigenic epitopes. The leucine-based sorting signal is proposed to function in trafficking at the plasma membrane. The tyrosine-based internalization signal is proposed to function at the level of clathrin-mediated endocytosis and recycling.

Similarity. Belongs to the protein-tyrosine phosphatase family. Receptor class 8 subfamily.

Isoforms (4)

UniProt ID	Names	Canonical?
Q92932-1	1	yes
Q92932-2	2
Q92932-3	3
Q92932-4	4

RefSeq proteins (5): NP_001295196, NP_001295197, NP_002838, NP_570857, NP_570858 (=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
IPR021613	Receptor_IA-2_dom	Domain
IPR029021	Prot-tyrosine_phosphatase-like	Homologous_superfamily
IPR029403	RESP18_dom	Domain
IPR033522	IA-2/IA-2_beta	Family
IPR038112	Receptor_IA-2_ectodomain_sf	Homologous_superfamily

Pfam: PF00102, PF11548, PF14948

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 (78 total): strand 16, helix 14, sequence variant 7, region of interest 6, modified residue 5, turn 4, compositionally biased region 3, binding site 3, splice variant 3, sequence conflict 3, chain 2, short sequence motif 2, topological domain 2, mutagenesis site 2, signal peptide 1, active site 1, site 1, glycosylation site 1, transmembrane region 1, domain 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
4HTI	X-RAY DIFFRACTION	1.95
4HTJ	X-RAY DIFFRACTION	2.01
2QEP	X-RAY DIFFRACTION	2.5

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q92932-F1	64.27	0.29

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 (2): 945 (phosphocysteine intermediate); 427–428 (cleavage)

Ligand- & substrate-binding residues (3): 913; 945–951; 990

Post-translational modifications (5): 436, 437, 692, 698, 970

Glycosylation sites (1): 564

Mutagenesis-validated functional residues (2):

Position	Phenotype
945	no effect to increase invasion, migration, and metastatic lung colonization in mice breast cancer model.
945	loss of activity.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-6798695	Neutrophil degranulation

MSigDB gene sets: 189 (showing top): BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, REACTOME_INNATE_IMMUNE_SYSTEM, BENPORATH_ES_WITH_H3K27ME3, GRUETZMANN_PANCREATIC_CANCER_DN, GOCC_SECRETORY_GRANULE, GOBP_INSULIN_SECRETION, ROVERSI_GLIOMA_COPY_NUMBER_UP, GOBP_CELLULAR_RESPONSE_TO_CARBOHYDRATE_STIMULUS, GOBP_REGULATION_OF_HORMONE_LEVELS, LINDGREN_BLADDER_CANCER_CLUSTER_3_DN, GOBP_NEUROTRANSMITTER_TRANSPORT, GOBP_HORMONE_TRANSPORT, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, CHANDRAN_METASTASIS_DN, VETTER_TARGETS_OF_PRKCA_AND_ETS1_DN

GO Biological Process (6): protein dephosphorylation (GO:0006470), lipid metabolic process (GO:0006629), neurotransmitter secretion (GO:0007269), insulin secretion involved in cellular response to glucose stimulus (GO:0035773), regulation of secretion (GO:0051046), dephosphorylation (GO:0016311)

GO Molecular Function (4): transmembrane receptor protein tyrosine phosphatase activity (GO:0005001), phosphoprotein phosphatase activity (GO:0004721), protein tyrosine phosphatase activity (GO:0004725), hydrolase activity (GO:0016787)

GO Cellular Component (11): plasma membrane (GO:0005886), secretory granule (GO:0030141), secretory granule membrane (GO:0030667), synaptic vesicle membrane (GO:0030672), signaling receptor complex (GO:0043235), synapse (GO:0045202), ficolin-1-rich granule membrane (GO:0101003), membrane (GO:0016020), transport vesicle membrane (GO:0030658), cytoplasmic vesicle membrane (GO:0030659), cytoplasmic vesicle (GO:0031410)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Innate Immune System	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
establishment of localization in cell	2
cytoplasmic vesicle membrane	2
bounding membrane of organelle	2
dephosphorylation	1
protein modification process	1
primary metabolic process	1
neurotransmitter transport	1
chemical synaptic transmission	1
presynapse	1
signal release from synapse	1
insulin secretion	1
cellular response to glucose stimulus	1
secretion	1
regulation of transport	1
phosphate-containing compound metabolic process	1
protein tyrosine phosphatase activity	1
transmembrane receptor protein phosphatase activity	1
phosphatase activity	1
catalytic activity, acting on a protein	1
phosphoprotein phosphatase activity	1
catalytic activity	1
membrane	1
cell periphery	1
endomembrane system	1
secretory vesicle	1
secretory granule	1
synaptic vesicle	1
exocytic vesicle membrane	1
protein-containing complex	1
cell junction	1
secretory granule membrane	1
tertiary granule	1
ficolin-1-rich granule	1
cellular anatomical structure	1
transport vesicle	1
vesicle membrane	1
cytoplasmic vesicle	1
cytoplasm	1
intracellular vesicle	1

Protein interactions and networks

STRING

1416 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PTPRN2	GHRL	Q9UBU3	691
PTPRN2	CPE	P16870	673
PTPRN2	PTS	Q03393	661
PTPRN2	PLCB1	Q9NQ66	623
PTPRN2	MBOAT4	Q96T53	619
PTPRN2	SOX4	Q06945	597
PTPRN2	GPR39	O43194	588
PTPRN2	AP5S1	Q9NUS5	586
PTPRN2	SLC30A10	Q6XR72	584
PTPRN2	SPTBN4	Q9H254	584
PTPRN2	GAD2	Q05329	580
PTPRN2	SLC30A8	Q8IWU4	580
PTPRN2	MERTK	Q12866	559
PTPRN2	CPT1A	P50416	549
PTPRN2	INS	P01308	540

IntAct

14 interactions, top by confidence:

A	B	Type	Score
PTPRN2	FAM20C	psi-mi:“MI:0217”(phosphorylation reaction)	0.440
GRB2	PTPRN2	psi-mi:“MI:0915”(physical association)	0.400
PTPRN2	CKAP5	psi-mi:“MI:0915”(physical association)	0.370
PTPRN2	SPTBN4	psi-mi:“MI:0915”(physical association)	0.370
	PTPRN2	psi-mi:“MI:0915”(physical association)	0.370
CACNA1C	DISP2	psi-mi:“MI:0914”(association)	0.350
PTPRN	SGSM2	psi-mi:“MI:0914”(association)	0.350
PTPRN2	SGSM2	psi-mi:“MI:0914”(association)	0.350
PTPRN2	TNFRSF10B	psi-mi:“MI:0914”(association)	0.350
PTPRN2	PTPRN2	psi-mi:“MI:0914”(association)	0.310
NR3C1	PTPRN2	psi-mi:“MI:0915”(physical association)	0.000
UBQLN4	PTPRN2	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (61): PTPRN2 (Synthetic Lethality), CPSF3L (Affinity Capture-MS), MON2 (Affinity Capture-MS), MOSPD2 (Affinity Capture-MS), SEC61A1 (Affinity Capture-MS), SORT1 (Affinity Capture-MS), TELO2 (Affinity Capture-MS), HID1 (Proximity Label-MS), SNX19 (Proximity Label-MS), KRT17 (Proximity Label-MS), HGS (Proximity Label-MS), KRT16 (Proximity Label-MS), STAM (Proximity Label-MS), HSPA5 (Proximity Label-MS), STIM1 (Proximity Label-MS)

ESM2 similar proteins: A2AKB4, A2RRU4, A4Q9F3, A4Q9F4, A5PJX4, A6NNM8, A8CVX7, D4A6L0, E1BBQ2, F1M5F3, O02695, O35141, P49796, P49797, P51509, P52734, P56182, P59644, P80560, P97260, P98174, Q12770, Q14679, Q15735, Q2KHI9, Q4R7H0, Q5EBH1, Q5MNU5, Q5SYB0, Q5T848, Q5XI57, Q6GQT6, Q6ZVT0, Q70EL4, Q80TE3, Q80UG8, Q8BUM9, Q8C419, Q8C4S8, Q8CDF7

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

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	189
Likely benign	39
Benign	28

Top pathogenic / likely-pathogenic (0)

SpliceAI

9738 predictions. Top by Δscore:

Variant	Effect	Δscore
7:157568896:TCTCA:T	donor_loss	1.0000
7:157568897:CTCA:C	donor_loss	1.0000
7:157568898:TCA:T	donor_loss	1.0000
7:157568899:CA:C	donor_loss	1.0000
7:157568901:C:CT	donor_loss	1.0000
7:157568962:CGTCA:C	acceptor_gain	1.0000
7:157568964:TCA:T	acceptor_gain	1.0000
7:157568965:CA:C	acceptor_gain	1.0000
7:157568965:CAC:C	acceptor_gain	1.0000
7:157568967:C:CC	acceptor_gain	1.0000
7:157576775:TTCAC:T	acceptor_gain	1.0000
7:157576776:TCAC:T	acceptor_gain	1.0000
7:157576777:CAC:C	acceptor_gain	1.0000
7:157576777:CACC:C	acceptor_gain	1.0000
7:157576777:CACCT:C	acceptor_loss	1.0000
7:157576778:AC:A	acceptor_gain	1.0000
7:157576779:CC:C	acceptor_gain	1.0000
7:157576779:CCTGG:C	acceptor_loss	1.0000
7:157576780:CT:C	acceptor_loss	1.0000
7:157576781:T:A	acceptor_loss	1.0000
7:157604000:A:AC	donor_gain	1.0000
7:157604001:C:CC	donor_gain	1.0000
7:157604072:TCAT:T	acceptor_gain	1.0000
7:157604072:TCATC:T	acceptor_loss	1.0000
7:157604073:CAT:C	acceptor_gain	1.0000
7:157604073:CATC:C	acceptor_gain	1.0000
7:157604073:CATCT:C	acceptor_loss	1.0000
7:157604074:ATC:A	acceptor_loss	1.0000
7:157604075:TCT:T	acceptor_loss	1.0000
7:157604076:C:A	acceptor_loss	1.0000

AlphaMissense

6567 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:157621459:C:A	W749C	1.000
7:157621459:C:G	W749C	1.000
7:157621461:A:G	W749R	1.000
7:157621461:A:T	W749R	1.000
7:157656370:C:T	G728D	1.000
7:157540766:A:G	L999P	0.999
7:157548989:A:G	L978P	0.999
7:157571449:A:T	V943D	0.999
7:157576679:A:G	F906S	0.999
7:157576694:C:G	R901P	0.999
7:157576721:A:G	L892P	0.999
7:157576729:G:C	S889R	0.999
7:157576729:G:T	S889R	0.999
7:157576731:T:G	S889R	0.999
7:157576733:C:A	R888M	0.999
7:157576767:A:G	S877P	0.999
7:157595243:A:G	W831R	0.999
7:157595243:A:T	W831R	0.999
7:157621494:G:C	H738D	0.999
7:157656358:A:G	L732P	0.999
7:157656371:C:G	G728R	0.999
7:157540733:A:G	L1010P	0.998
7:157540755:C:G	A1003P	0.998
7:157548956:A:T	V989D	0.998
7:157568919:A:G	L962P	0.998
7:157568928:T:A	D959V	0.998
7:157576616:C:G	R927P	0.998
7:157576619:A:G	F926S	0.998
7:157576665:A:G	W911R	0.998
7:157576665:A:T	W911R	0.998

dbSNP variants (sampled 300 via entrez): RS1000000657 (7:158215167 T>C), RS1000001895 (7:158343278 C>A,T), RS1000003871 (7:157807118 C>T), RS1000005448 (7:157752859 G>A), RS1000006562 (7:158313031 C>A), RS1000007073 (7:157566295 C>A,T), RS1000013564 (7:157703475 G>T), RS1000018376 (7:157554609 C>G), RS1000018598 (7:158490196 G>A), RS1000019191 (7:158405578 A>G), RS1000022913 (7:158421493 A>G), RS1000022936 (7:157977445 G>A), RS1000024988 (7:158014359 C>T), RS1000025211 (7:157986190 T>C), RS1000031504 (7:157843571 G>A)

Disease associations

OMIM: gene MIM:601698 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): prostate cancer (MONDO:0008315)

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

HPO phenotypes

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

GWAS associations

24 associations (top):

Study	Trait	p-value
GCST000862_6	Bipolar disorder and schizophrenia	8.000000e-06
GCST001651_45	Response to amphetamines	3.000000e-06
GCST001712_16	Myopia (pathological)	4.000000e-11
GCST001762_476	Obesity-related traits	8.000000e-06
GCST002740_18	Inflammatory skin disease	3.000000e-10
GCST002911_8	Calcium levels	6.000000e-06
GCST004162_23	Carotid plaque burden	2.000000e-06
GCST005111_2	Breast cancer in childhood cancer survivors	4.000000e-07
GCST005112_1	Breast cancer in childhood cancer survivors treated with more than 10 gray radiotherapy	2.000000e-07
GCST005173_69	Coronary artery calcified atherosclerotic plaque (130 HU threshold) in type 2 diabetes	8.000000e-07
GCST005316_77	Intelligence (MTAG)	2.000000e-08
GCST005648_4	Serum metabolite concentrations in chronic kidney disease	2.000000e-08
GCST007094_186	Diastolic blood pressure	3.000000e-08
GCST008368_19	Plasma anti-thyroid peroxidase levels	4.000000e-06
GCST008595_194	Cognitive ability, years of educational attainment or schizophrenia (pleiotropy)	2.000000e-08
GCST008876_11	Non-lobar intracerebral hemorrhage (MTAG)	8.000000e-06
GCST008922_20	Triacylglyceride levels	2.000000e-08
GCST009959_4	Retinal detachment or retinal break	3.000000e-06
GCST010002_267	Refractive error	2.000000e-37
GCST011920_2	Hearing loss in noise exposure	2.000000e-06
GCST012015_3	Chronic rhinosinusitis	2.000000e-07
GCST012490_434	Femur bone mineral density x serum urate levels interaction	2.000000e-08
GCST90000255_9	Severe COVID-19 infection with respiratory failure (analysis I)	5.000000e-06
GCST90007000_16	Gut microbiota relative abundance (unclassified genus belonging to family Ruminococcaceae)	6.000000e-06

EFO canonical traits (13, from GWAS)

EFO ID	Trait name
EFO:0004207	pathological myopia
EFO:0003939	energy intake
EFO:0004838	calcium measurement
EFO:0006501	carotid plaque build
EFO:0004723	coronary artery calcification
EFO:0004337	intelligence
EFO:0006336	diastolic blood pressure
EFO:0004784	self reported educational attainment
EFO:0010178	non-lobar intracerebral hemorrhage
EFO:0004530	triglyceride measurement
EFO:0010698	retinal break
EFO:0004531	urate measurement
EFO:0007874	gut microbiome measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
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: no

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

PharmGKB variants

2 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs221253	PTPRN2		0.00	0
rs4909237	MIR595, PTPRN2		0.00	0

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: catalytic receptor — Receptor tyrosine phosphatase (RTP) family

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases expression, decreases methylation	6
Aflatoxin B1	affects expression, decreases expression, increases methylation	5
trichostatin A	affects cotreatment, decreases expression	3
bisphenol S	decreases methylation, increases expression, affects methylation, affects cotreatment	2
Resveratrol	affects cotreatment, decreases expression, increases expression	2
Vorinostat	decreases expression, affects cotreatment	2
Panobinostat	decreases expression, affects cotreatment	2
Acetaminophen	decreases expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Tetrachlorodibenzodioxin	increases abundance, increases methylation, increases expression	2
Tobacco Smoke Pollution	decreases expression, increases methylation	2
Valproic Acid	affects cotreatment, decreases expression	2
GSK-J4	decreases expression	1
bisphenol F	increases methylation	1
triphenyl phosphate	affects expression	1
bisphenol A	affects methylation, affects cotreatment	1
ethyl-p-hydroxybenzoate	decreases expression	1
tris(2-butoxyethyl) phosphate	affects expression	1
mono-(2-ethylhexyl)phthalate	increases methylation, increases abundance	1
11-nor-delta(9)-tetrahydrocannabinol-9-carboxylic acid	decreases methylation, increases abundance	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
sodium arsenite	affects methylation	1
butyraldehyde	decreases expression	1
benzo(e)pyrene	affects methylation	1
ferrous chloride	decreases expression	1
aflatoxin B2	increases methylation	1
1-hydroxypyrene	affects cotreatment, decreases methylation	1
polyhexamethyleneguanidine	affects expression	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

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