PTPRN

Summary

PTPRN (protein tyrosine phosphatase receptor type N, HGNC:9676) is a protein-coding gene on chromosome 2q35, encoding Receptor-type tyrosine-protein phosphatase-like N (Q16849). Plays a role in vesicle-mediated secretory processes.

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 possesses an extracellular region, a single transmembrane region, and a single catalytic domain, and thus represents a receptor-type PTP. This PTP was found to be an autoantigen that is reactive with insulin-dependent diabetes mellitus (IDDM) patient sera, and thus may be a potential target of autoimmunity in diabetes mellitus. Alternate splicing results in multiple transcript variants.

Source: NCBI Gene 5798 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 166 total
• MANE Select transcript: NM_002846

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9676
Approved symbol	PTPRN
Name	protein tyrosine phosphatase receptor type N
Location	2q35
Locus type	gene with protein product
Status	Approved
Aliases	IA-2, ICA512
Ensembl gene	ENSG00000054356
Ensembl biotype	protein_coding
OMIM	601773
Entrez	5798

Gene structure

Transcript identifiers

Ensembl transcripts: 32 — 22 protein_coding, 7 retained_intron, 2 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000295718, ENST00000409251, ENST00000412847, ENST00000423636, ENST00000440552, ENST00000442029, ENST00000443981, ENST00000446182, ENST00000451506, ENST00000460801, ENST00000462351, ENST00000468454, ENST00000476930, ENST00000477819, ENST00000484986, ENST00000486480, ENST00000489650, ENST00000497977, ENST00000606213, ENST00000903934, ENST00000903935, ENST00000903936, ENST00000903937, ENST00000903938, ENST00000929320, ENST00000929321, ENST00000958095, ENST00000958096, ENST00000958097, ENST00000958098, ENST00000958099, ENST00000958100

RefSeq mRNA: 3 — MANE Select: NM_002846 NM_001199763, NM_001199764, NM_002846

CCDS: CCDS2440, CCDS56167, CCDS56168

Canonical transcript exons

ENST00000295718 — 23 exons

Exon	Start	End
ENSE00001775602	219289623	219290297
ENSE00001843122	219309218	219309401
ENSE00003486679	219307792	219307842
ENSE00003498717	219307444	219307557
ENSE00003694852	219302576	219302837
ENSE00003694933	219296985	219297132
ENSE00003694968	219291470	219291523
ENSE00003695527	219299700	219299786
ENSE00003696162	219290538	219290611
ENSE00003696330	219302137	219302491
ENSE00003697361	219301588	219301719
ENSE00003698169	219303735	219303831
ENSE00003698372	219290826	219290890
ENSE00003698702	219296749	219296822
ENSE00003698730	219296226	219296345
ENSE00003698939	219299985	219300259
ENSE00003699301	219297885	219298103
ENSE00003699504	219296439	219296516
ENSE00003699657	219297233	219297433
ENSE00003699834	219300943	219300977
ENSE00003699955	219299305	219299384
ENSE00003702035	219294975	219295141
ENSE00003702406	219299047	219299111

Expression profiles

Bgee: expression breadth ubiquitous, 197 present calls, max score 98.66.

FANTOM5 (CAGE): breadth broad, TPM avg 13.5315 / max 1068.1655, expressed in 703 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
34069	13.0270	702
34071	0.2263	80
34070	0.2232	75
34068	0.0550	32

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
islet of Langerhans	UBERON:0000006	98.66	gold quality
Brodmann (1909) area 10	UBERON:0013541	97.97	gold quality
right frontal lobe	UBERON:0002810	97.96	gold quality
right hemisphere of cerebellum	UBERON:0014890	97.43	gold quality
pituitary gland	UBERON:0000007	96.88	gold quality
cerebellar hemisphere	UBERON:0002245	96.83	gold quality
cerebellar cortex	UBERON:0002129	96.76	gold quality
anterior cingulate cortex	UBERON:0009835	96.51	gold quality
cingulate cortex	UBERON:0003027	96.47	gold quality
adenohypophysis	UBERON:0002196	96.16	gold quality
frontal pole	UBERON:0002795	96.16	gold quality
nucleus accumbens	UBERON:0001882	96.11	gold quality
prefrontal cortex	UBERON:0000451	95.71	gold quality
Brodmann (1909) area 9	UBERON:0013540	95.67	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	95.61	gold quality
cerebellum	UBERON:0002037	94.94	gold quality
frontal cortex	UBERON:0001870	94.80	gold quality
type B pancreatic cell	CL:0000169	94.52	gold quality
middle frontal gyrus	UBERON:0002702	94.40	gold quality
caudate nucleus	UBERON:0001873	94.35	gold quality
neocortex	UBERON:0001950	94.14	gold quality
amygdala	UBERON:0001876	93.95	gold quality
hypothalamus	UBERON:0001898	93.92	gold quality
paraflocculus	UBERON:0005351	93.42	gold quality
cerebral cortex	UBERON:0000956	92.86	gold quality
putamen	UBERON:0001874	92.85	gold quality
forebrain	UBERON:0001890	92.67	gold quality
telencephalon	UBERON:0001893	92.46	gold quality
brain	UBERON:0000955	92.06	gold quality
central nervous system	UBERON:0001017	91.59	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-GEOD-81547	yes	1811.43
E-GEOD-83139	yes	9.13
E-ANND-3	yes	8.55
E-GEOD-84465	yes	6.49

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

39 targeting PTPRN, 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-4481	100.00	66.42	1669
HSA-MIR-4745-5P	99.98	65.95	1028
HSA-MIR-6508-5P	99.92	70.67	2465
HSA-MIR-6768-5P	99.92	67.36	1942
HSA-MIR-5680	99.91	69.83	3421
HSA-MIR-8067	99.86	69.59	2260
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-92A-2-5P	99.75	67.01	2164
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-6779-5P	99.70	65.76	2363
HSA-MIR-6883-5P	99.69	68.05	3785
HSA-MIR-12123	99.52	71.79	2990
HSA-MIR-486-3P	99.51	66.82	1901
HSA-MIR-940	99.37	66.14	2064
HSA-MIR-6808-5P	99.31	66.23	2150
HSA-MIR-6893-5P	99.31	66.25	2119
HSA-MIR-4505	99.27	67.81	2678
HSA-MIR-5787	99.22	67.86	2628
HSA-MIR-485-5P	99.10	64.78	1889
HSA-MIR-6770-5P	98.97	66.76	1853
HSA-MIR-4656	98.79	66.22	1306
HSA-MIR-6769B-5P	98.73	64.91	1092
HSA-MIR-603	98.58	68.28	1603
HSA-MIR-1178-3P	98.57	67.09	890
HSA-MIR-2117	98.48	67.97	1307
HSA-MIR-6873-5P	98.45	66.14	1417
HSA-MIR-1233-5P	98.19	66.71	1201
HSA-MIR-6778-5P	98.19	66.59	1239
HSA-MIR-6769A-5P	97.99	64.16	851

Literature-anchored findings (GeneRIF, showing 34)

• ICA512(IA-2) epitope specific assays distinguish transient from diabetes associated autoantibodies. (PMID:11908951)
• Autoantibodies to IA-2 in type 1 diabetes: measurements with a new enzyme-linked immunosorbent assay. (PMID:12021115)
• BCG vaccination and GAD65 and IA-2 autoantibodies in autoimmune diabetes in southern India. (PMID:12021127)
• findings indicate that glutamine at position 862, and residues 876-880 of the WPD loop of IA-2 are important for several of the IA-2 specific PTP domain epitopes (PMID:14624760)
• The islet cell autoantigen 512 (ICA512)/IA-2 is a receptor tyrosine phosphatase-like protein associated with the insulin secretory granules (SGs) of pancreatic beta-cells. (PMID:15596545)
• Measuring IA-2A is useful for the diagnosis and prognosis of type 1 diabetes in Japanese. (PMID:15620435)
• IA-2 is an important regulator of dense core vesicle number and glucose-induced and basal insulin secretion in beta cells. (PMID:15939893)
• identification of proteins that interact with IA-2, the IA-2 interactome; the IA-2 interactome based on pull-down experiments, currently consists of 12 proteins; identification of these interacting proteins provides clues as to how IA-2 functions (PMID:16273344)
• Autoantibodies in type 1 diabetes for this protein provide a model for other autoimmune diseases. (PMID:18373080)
• HLA class II alleles strongly influence the prevalence of IA-2A in type 1 diabetes. (PMID:18504544)
• Inexpensive, nonradioactive method for the detection of autoantibodies cell-prepared PTPRN (also known as IA-2) in diabetics. (PMID:18535195)
• The study identifies a region of IA-2 frequently recognised by antibodies in Type 1 diabetes and demonstrates that these responses are associated with T-cells secreting IL-10 in response to a neighbouring determinant. (PMID:19447008)
• Report a chimeric assay providing an efficient and economical technique to screen for islet autoantibodies reacting with IA-2 and ZnT8 in type 1 diabetes mellitus. (PMID:20035758)
• T cells stimulated in vitro by the IA-2 epitope express IFN-gamma when restimulated by the similar rotavirus VP7 peptide. (PMID:20083660)
• Data show that significantly increased expression of MCP-1, IL-2 and PTPR-N was observed in Tourette’s syndrome cases. (PMID:20193755)
• Studies indicate that T1DM can be detected by determining four autoantibodies, namely those antibodies against insulin, glutamic acid decarboxylase 65, insulinoma antigen (IA)-2 (ICA512) and the zinc transporter ZnT8. (PMID:21073664)
• Risk of autoantibody seroconversion among children followed in DPT-1 is age dependent (PMID:21270193)
• Letter: report lack of anti-IA2 autoantibodies in primary antiphospholipid syndrome. (PMID:21442164)
• Longer survival was associated with hypomethylation at specific CpG sites (e.g. GREB1, TGIF and TOB1) and hypermethylation in other genes (e.g. TMCO5, PTPRN and GUCY2C). (PMID:21577013)
• In families with type 1 diabetes, there was a female predominance and more family history of associated autoimmune diseases (AAIDs) in the group with AAIDs, and less frequent anti-IA-2 antibodies (PMID:21744463)
• ZnT8A, GADA and IA-2A are autoantibodies that may have a role in successful pancreas graft survival (PMID:21792090)
• analysis of protein-protein interactions in crystals of the human receptor-type protein tyrosine phosphatase ICA512 ectodomain (PMID:21935384)
• identification of cysteines that are critical for IA-2A binding of autoantibodies in patients with newly diagnosed type 1 diabetes (PMID:22966073)
• the IA-2A autoantibody response in children is intense with rapid maturation against immunogenic epitopes and a strong association with diabetes development (PMID:23110943)
• Humoral responses to islet antigen-2 and zinc transporter 8 are attenuated in patients carrying HLA-A*24 alleles at the onset of type 1 diabetes. (PMID:23396399)
• The binding of CREB to the promoter region, -216 to +115, enhanced IA-2 transcription by more than fivefold. (PMID:25528004)
• Kaplan-Meier survival curves estimated a worst pancreas graft survival for patients with positive IA-2 antibodies versus those patients with negative auto-antibodies and GAD65+ auto-antibodies after simultaneous pancreas kidney transplantation. (PMID:25645784)
• Identification of amino acids contributing to distinct epitopes on IA-2, with both HLA-DR and HLA-DQ alleles influencing epitope specificity. (PMID:26564179)
• RESP18HD is required for efficient sorting of ICA512 to secretory granules: RESP18HD is a key determinant for ICA512 granule targeting. (PMID:26836020)
• E. coli GI724 strain emerged as a handy source of recombinant IA-2ic, achieving high levels of expression as a thioredoxin fusion protein, adequately validated and applicable to the development of innovative and cost-effective immunoassays for IA-2A detection in most laboratories. (PMID:27881117)
• PTPN12, PTPRN and PTPN18 were independent prognostic factors in Hepatocellular Carcinoma. (PMID:29742497)
• Different interaction of onset age and duration of type 1 diabetes on the dynamics of autoantibodies to insulinoma-associated antigen-2 and zinc transporter 8. (PMID:32696593)
• Seroreactivity Against Tyrosine Phosphatase PTPRN Links Type 2 Diabetes and Colorectal Cancer and Identifies a Potential Diagnostic and Therapeutic Target. (PMID:35040477)
• Glutamic Acid Decarboxylase and Tyrosine Phosphatase-Related Islet Antigen-2 Positivity among Children and Adolescents with Diabetes in Korea. (PMID:35263538)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	ptprna	ENSDARG00000058646
danio_rerio	ptprnb	ENSDARG00000077047
mus_musculus	Ptprn	ENSMUSG00000026204
rattus_norvegicus	Ptprn	ENSRNOG00000019587

Paralogs (35): 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), PTPRN2 (ENSG00000155093), PTPN13 (ENSG00000163629), PTPN9 (ENSG00000169410), PTPRM (ENSG00000173482), PTPN2 (ENSG00000175354), PTPN11 (ENSG00000179295), PTPRT (ENSG00000196090), PTPN1 (ENSG00000196396), PTPN20 (ENSG00000204179)

Protein

Protein identifiers

Receptor-type tyrosine-protein phosphatase-like N — Q16849 (reviewed: Q16849)

Alternative names: Islet cell antigen 512, Islet cell autoantigen 3, PTP IA-2

All UniProt accessions (8): A0A1B0GX26, C9J392, C9JCQ0, C9JJL7, C9JR27, Q16849, H7C0U9, U3KQ66

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. Seems to lack intrinsic enzyme activity. May regulate catalytic active protein-tyrosine phosphatases such as PTPRA through dimerization. ICA512-TMF regulates dynamics and exocytosis of insulin secretory granules (SGs); binding of ICA512-TMF to SNTB2/beta-2-syntrophin is proposed to restrain SGs mobility and exocytosis by tethering them to the actin cytoskeleton depending on UTRN; the function is inhibited by cytoplasmic ICA512-CFF dimerizing with ICA512-TMF and displacing SNTB2. ICA512-CCF translocated to the nucleus promotes expression of insulin and other granule-related genes; the function implicates binding to and regulating activity of STAT5B probably by preventing its dephosphorylation and potentially by inducing its sumoylation by recruiting PIAS4. Enhances pancreatic beta-cell proliferation by converging with signaling by STAT5B and STAT3. ICA512-CCF located in the cytoplasm regulates dynamics and exocytosis of insulin secretory granules (SGs) by dimerizing with ICA512-TMF and displacing SNTB2 thus enhancing SGs mobility and exocytosis.

Subunit / interactions. Homodimer; shown for the unprocessed protein (proICA512) in the endoplasmic reticulum and resolved during protein maturation as ICA512-TMF seems to be predominantly monomeric in secretory granules; however, ICA512-CCF interacts with ICA512-TMF disrupting the ICA512-TMF:SNTB2 complex. The isolated lumenal RESP18 homology domain has been shown to form disulfide-linked homooligomers. Interacts (via cytoplasmic domain) with phosphorylated SNTB2; this protects PTPRN against cleavage by CAPN1 to produce ICA512-CCF. Dephosphorylation of SNTB2 upon insulin stimulation disrupts the interaction and results in PTPRN cleavage. Interacts with SNX19. ICA512-CCF interacts with PIAS4; in the nucleus. Interacts with STAT5B (phosphorylated); down-regulated by ICA512-CCF sumoylation; ICA512-CCF prevents STAT5B dephosphorylation; ICA512-CCF mediates interaction of STAT5B with PIAS4. Interacts (via RESP18 homology domain) with insulin and proinsulin. Interacts with PTPRN2, PTPRA and PTPRE.

Subcellular location. Membrane. Cytoplasmic vesicle. Secretory vesicle membrane. Perikaryon. Cell projection. Axon. Synapse. Cell membrane. Endosome Cytoplasmic vesicle. Secretory vesicle membrane Nucleus.

Tissue specificity. Expression is restricted to neuroendocrine cells. Found in pancreas, brain and pituitary.

Post-translational modifications. N-glycosylated. O-glycosylated with core 1 or possibly core 8 glycans. Subject to proteolytic cleavage at multiple sites. Subject to cleavage on a pair of basic residues. On exocytosis of secretory granules in pancreatic beta-cells ICA512-TMF is transiently inserted in the plasma-membrane and cleaved by mu-type calpain CPN1 to yield ICA512-CCF. Sumoylated at two sites including Lys-754. Sumoylation decreases interaction with STAT5.

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

Domain organisation. The RESP18 homology domain is sufficient for targeting proICA512 to secretory granules.

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

Isoforms (3)

UniProt ID	Names	Canonical?
Q16849-1	1	yes
Q16849-2	2
Q16849-3	3

RefSeq proteins (3): NP_001186692, NP_001186693, NP_002837* (*=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

UniProt features (68 total): strand 15, helix 15, region of interest 7, chain 4, compositionally biased region 4, glycosylation site 3, disulfide bond 3, mutagenesis site 3, splice variant 2, turn 2, topological domain 2, signal peptide 1, site 1, modified residue 1, cross-link 1, sequence variant 1, sequence conflict 1, transmembrane region 1, domain 1

Structure

Experimental structures (PDB)

6 structures.

PDB	Method	Resolution (Å)
2QT7	X-RAY DIFFRACTION	1.3
3N01	X-RAY DIFFRACTION	1.3
3NG8	X-RAY DIFFRACTION	1.35
3N4W	X-RAY DIFFRACTION	1.45
3NP5	X-RAY DIFFRACTION	1.8
2I1Y	X-RAY DIFFRACTION	2.23

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q16849-F1	66.66	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 (1): 448–449 (cleavage)

Post-translational modifications (2): 308, 754

Disulfide bonds (3): 40, 47, 53–62

Glycosylation sites (3): 441, 506, 524

Mutagenesis-validated functional residues (3):

Position	Phenotype
506	reduces n-glycosylation.
524	reduces n-glycosylation.
553	impairs normal processing and leads to retention in the endoplasmic reticulum and degradation.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 208 (showing top): SHEPARD_BMYB_MORPHOLINO_UP, AP1_01, GRUETZMANN_PANCREATIC_CANCER_DN, GOCC_SECRETORY_GRANULE, GOBP_VESICLE_ORGANIZATION, MODULE_64, GOBP_INSULIN_SECRETION, GOBP_CELLULAR_RESPONSE_TO_CARBOHYDRATE_STIMULUS, GOBP_REGULATION_OF_HORMONE_LEVELS, GOBP_HORMONE_TRANSPORT, GGGTGGRR_PAX4_03, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, SHEPARD_BMYB_MORPHOLINO_DN, GOBP_CELL_CELL_SIGNALING, MODULE_66

GO Biological Process (10): response to reactive oxygen species (GO:0000302), luteinization (GO:0001553), insulin secretion (GO:0030073), insulin secretion involved in cellular response to glucose stimulus (GO:0035773), positive regulation of transcription by RNA polymerase II (GO:0045944), regulation of secretion (GO:0051046), positive regulation of type B pancreatic cell proliferation (GO:1904692), dense core granule maturation (GO:1990502), protein dephosphorylation (GO:0006470), dephosphorylation (GO:0016311)

GO Molecular Function (5): transcription factor binding (GO:0008134), spectrin binding (GO:0030507), ubiquitin-like protein ligase binding (GO:0044389), protein tyrosine phosphatase activity (GO:0004725), protein binding (GO:0005515)

GO Cellular Component (16): nucleus (GO:0005634), endosome (GO:0005768), Golgi apparatus (GO:0005794), plasma membrane (GO:0005886), secretory granule (GO:0030141), transport vesicle membrane (GO:0030658), neuronal cell body (GO:0043025), perikaryon (GO:0043204), axon terminus (GO:0043679), synapse (GO:0045202), membrane (GO:0016020), transport vesicle (GO:0030133), axon (GO:0030424), cytoplasmic vesicle membrane (GO:0030659), cytoplasmic vesicle (GO:0031410), cell projection (GO:0042995)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
endomembrane system	4
cytoplasmic vesicle	3
cellular anatomical structure	3
intracellular membrane-bounded organelle	2
cytoplasm	2
response to oxidative stress	1
response to oxygen-containing compound	1
female gonad development	1
ovulation cycle process	1
protein secretion	1
peptide hormone secretion	1
insulin secretion	1
establishment of localization in cell	1
cellular response to glucose stimulus	1
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
positive regulation of DNA-templated transcription	1
secretion	1
regulation of transport	1
type B pancreatic cell proliferation	1
positive regulation of epithelial cell proliferation	1
regulation of type B pancreatic cell proliferation	1
secretory granule maturation	1
dephosphorylation	1
protein modification process	1
phosphate-containing compound metabolic process	1
protein binding	1
cytoskeletal protein binding	1
protein-containing complex binding	1
enzyme binding	1
phosphoprotein phosphatase activity	1
binding	1
membrane	1
cell periphery	1
secretory vesicle	1
transport vesicle	1
cytoplasmic vesicle membrane	1
bounding membrane of organelle	1
somatodendritic compartment	1
cell body	1

Protein interactions and networks

STRING

1540 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PTPRN	SLC30A8	Q8IWU4	965
PTPRN	GAD2	Q05329	962
PTPRN	SLC30A10	Q6XR72	932
PTPRN	INS	P01308	925
PTPRN	INSM1	Q01101	910
PTPRN	MAPK8IP1	Q9UQF2	901
PTPRN	INSM2	Q96T92	775
PTPRN	UTRN	P46939	668
PTPRN	TNFRSF25	P78507	660
PTPRN	TOR1A	O14656	641
PTPRN	CD4	P01730	636
PTPRN	TNFRSF10A	O00220	621
PTPRN	CD8A	P01732	620
PTPRN	ICA1	P78506	620
PTPRN	PTS	Q03393	604

IntAct

44 interactions, top by confidence:

A	B	Type	Score
SCGB1D1	MANBA	psi-mi:“MI:0914”(association)	0.640
PLA2G7	PTPRN	psi-mi:“MI:0915”(physical association)	0.560
FBXO2	TMEM131L	psi-mi:“MI:0914”(association)	0.530
GPIHBP1	ADAM10	psi-mi:“MI:0914”(association)	0.530
PSCA	ITGA6	psi-mi:“MI:0914”(association)	0.530
PTPRN	MADD	psi-mi:“MI:0915”(physical association)	0.510
PTPRN	PTPRT	psi-mi:“MI:0915”(physical association)	0.510
PTPRN	PTPRS	psi-mi:“MI:0915”(physical association)	0.510
SNX19	PTPRN	psi-mi:“MI:0915”(physical association)	0.510
PPIA	PTPRN	psi-mi:“MI:0915”(physical association)	0.510
MADD	PTPRN	psi-mi:“MI:0915”(physical association)	0.510
PTPRN	SNX19	psi-mi:“MI:0915”(physical association)	0.510
PTPRS	PTPRN	psi-mi:“MI:0915”(physical association)	0.510
PTPRT	PTPRN	psi-mi:“MI:0915”(physical association)	0.510
PTPRN	PPIA	psi-mi:“MI:0915”(physical association)	0.510
PTPRN	SPTBN4	psi-mi:“MI:0915”(physical association)	0.510
PTPRN	SNTB2	psi-mi:“MI:0407”(direct interaction)	0.440
PTPRN	NOS1AP	psi-mi:“MI:0407”(direct interaction)	0.440
Snta1	PTPRN	psi-mi:“MI:0915”(physical association)	0.400
SNTB2	PTPRN	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (148): PTPRN (Two-hybrid), PTPRN (Two-hybrid), PTPRN (Affinity Capture-MS), PTPRN (Two-hybrid), PTPRN (Two-hybrid), COLGALT1 (Proximity Label-MS), PLOD3 (Proximity Label-MS), CALR (Proximity Label-MS), PPIB (Proximity Label-MS), GANAB (Proximity Label-MS), UGGT1 (Proximity Label-MS), PRKCSH (Proximity Label-MS), PDIA4 (Proximity Label-MS), PLOD1 (Proximity Label-MS), TXNDC5 (Proximity Label-MS)

ESM2 similar proteins: A6NFA1, B1ATG9, D4A1F2, E7F4V6, E7F6V0, F1N4M2, F1RA39, F6PTN1, H2N4I1, O00391, O08841, O94851, P0DJQ9, P56722, P80560, Q148L1, Q14C87, Q14DG7, Q16849, Q3UN70, Q60673, Q62865, Q62888, Q62889, Q63259, Q63475, Q69ZK9, Q6DNG6, Q6IUU3, Q6P6V6, Q6S5C2, Q6ZXA0, Q76HP2, Q76HP3, Q7T2X7, Q800H9, Q8BML1, Q8BND5, Q8BYM5, Q8CEF9

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

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	135
Likely benign	13
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

3304 predictions. Top by Δscore:

Variant	Effect	Δscore
2:219290820:CCCTA:C	donor_loss	1.0000
2:219290821:CCTA:C	donor_loss	1.0000
2:219290822:CTA:C	donor_loss	1.0000
2:219290823:TACC:T	donor_loss	1.0000
2:219290824:A:T	donor_loss	1.0000
2:219290888:TCA:T	acceptor_gain	1.0000
2:219290889:CA:C	acceptor_gain	1.0000
2:219290889:CAC:C	acceptor_gain	1.0000
2:219290891:C:CC	acceptor_gain	1.0000
2:219296222:TGACC:T	donor_loss	1.0000
2:219296224:ACCTC:A	donor_loss	1.0000
2:219296225:C:G	donor_loss	1.0000
2:219296257:T:C	donor_gain	1.0000
2:219296342:CCAT:C	acceptor_gain	1.0000
2:219296343:CAT:C	acceptor_gain	1.0000
2:219296343:CATC:C	acceptor_gain	1.0000
2:219296344:ATCTA:A	acceptor_loss	1.0000
2:219296345:TCTAG:T	acceptor_loss	1.0000
2:219296346:C:CC	acceptor_gain	1.0000
2:219296347:T:C	acceptor_loss	1.0000
2:219296434:CCCA:C	donor_loss	1.0000
2:219296435:CCA:C	donor_loss	1.0000
2:219296436:CAC:C	donor_loss	1.0000
2:219296437:A:T	donor_loss	1.0000
2:219296438:C:T	donor_loss	1.0000
2:219296517:C:CC	acceptor_gain	1.0000
2:219296983:A:AC	donor_gain	1.0000
2:219296984:C:CC	donor_gain	1.0000
2:219296984:CA:C	donor_gain	1.0000
2:219296984:CAGGG:C	donor_gain	1.0000

AlphaMissense

6290 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:219290245:A:G	L974P	1.000
2:219290273:C:G	A965P	1.000
2:219290278:A:G	L963P	1.000
2:219290581:A:G	L942P	1.000
2:219290590:G:T	A939D	1.000
2:219294975:C:A	R892M	1.000
2:219295027:A:G	W875R	1.000
2:219295027:A:T	W875R	1.000
2:219295083:A:G	L856P	1.000
2:219295095:C:G	R852P	1.000
2:219295129:A:G	S841P	1.000
2:219296264:A:G	W824R	1.000
2:219296264:A:T	W824R	1.000
2:219296444:A:G	W795R	1.000
2:219296444:A:T	W795R	1.000
2:219297082:C:A	W713C	1.000
2:219297082:C:G	W713C	1.000
2:219297084:A:G	W713R	1.000
2:219297084:A:T	W713R	1.000
2:219297234:A:G	L696P	1.000
2:219297246:C:T	G692E	1.000
2:219297247:C:G	G692R	1.000
2:219297247:C:T	G692R	1.000
2:219290245:A:T	L974H	0.999
2:219290252:C:G	A972P	0.999
2:219290267:C:G	A967P	0.999
2:219290272:G:T	A965D	0.999
2:219290278:A:T	L963Q	0.999
2:219290281:G:T	A962D	0.999
2:219290289:A:C	F959L	0.999

dbSNP variants (sampled 300 via entrez): RS1000103794 (2:219300516 A>G), RS1000136165 (2:219300911 G>C), RS1000366108 (2:219307991 C>T), RS1000377845 (2:219292118 G>T), RS1000498813 (2:219289768 G>A,T), RS1000971605 (2:219309560 C>CG), RS1001000865 (2:219304884 C>G), RS1001043528 (2:219295620 C>T), RS1001098966 (2:219297737 C>T), RS1001110762 (2:219302365 G>A), RS1001150004 (2:219298171 C>A,G,T), RS1001405158 (2:219298004 G>A,C), RS1001484754 (2:219299529 T>C), RS1001510275 (2:219290989 C>T), RS1001647382 (2:219293432 G>A)

Disease associations

OMIM: gene MIM:601773 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST004611_22	High light scatter reticulocyte count	4.000000e-19
GCST004612_56	High light scatter reticulocyte percentage of red cells	4.000000e-18
GCST90002396_181	Mean reticulocyte volume	1.000000e-17

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0007986	reticulocyte count
EFO:0010701	mean reticulocyte volume

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

GtoPdb / IUPHAR curated pharmacology

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

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects cotreatment, increases abundance, increases expression	3
N,N,N’,N’-tetrakis(2-pyridylmethyl)ethylenediamine	increases expression	2
Valproic Acid	decreases methylation, increases expression	2
propionaldehyde	decreases expression	1
manganese chloride	affects cotreatment, increases abundance, increases expression	1
tamibarotene	affects expression	1
perfluorooctane sulfonic acid	increases expression	1
2-palmitoylglycerol	increases expression	1
abrine	increases expression	1
bis-N,N-dimethylamino-2-(N-methylpyrrolyl)methyl cyclopentadienyl titanium (IV)	decreases expression	1
Irinotecan	increases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Sunitinib	decreases expression	1
Amiodarone	increases expression	1
Arsenic	increases expression, affects cotreatment, increases abundance	1
Atrazine	increases expression	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Calcitriol	decreases expression	1
Doxorubicin	decreases expression	1
Estradiol	affects cotreatment, increases expression	1
Lead	affects expression	1
Manganese	increases expression, affects cotreatment, increases abundance	1
Phthalic Acids	increases methylation	1
Plant Extracts	decreases expression, affects cotreatment	1
Quercetin	decreases expression	1
Smoke	decreases expression	1
Thiram	increases expression	1
Tretinoin	affects expression	1
Zinc	increases expression	1
1-Methyl-4-phenylpyridinium	increases expression	1

Clinical trials (associated diseases)

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