PTPRN

protein-coding

protein tyrosine phosphatase receptor type N, the group of Protein tyrosine phosphatases receptor type|MicroRNA protein coding host genes

Gene summary

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.[provided by RefSeq, Dec 2010]

MANE transcript

NM_002846.4

Inheritance

—

ClinVar variants

U:150B:15

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.4

Max pathogenic AF

—

Genomic locus

chr2:219,289,623-219,309,648

External References & Databases

Ensembl (ENSG00000054356)

Transcript & Mutation Effects

hg38 • Region Span ~20.0 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to PTPRN variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 155

not providedTotal: 5

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_002846.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous				4 clinvar	2 clinvar	6
missense			149 clinvar	9 clinvar		158
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	150	13	2	165

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 44 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_002846.4	RefSeq	NP_002837.1	23	MANE Select
ENST00000295718.7	Ensembl	ENSP00000295718.2	23	MANE Select
NM_001199763.2	RefSeq	NP_001186692.1	22	Standard
NM_001199764.2	RefSeq	NP_001186693.1	21	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Type I diabetes mellitus - Homo sapiens (human)

Biological Process

response to reactive oxygen species
luteinization
cytokine-mediated signaling pathway
insulin secretion
response to insulin

Molecular Function

protein tyrosine phosphatase activity
protein binding
transcription factor binding
spectrin binding
ubiquitin-like protein ligase binding

Cellular Component

nucleus
endosome
Golgi apparatus
plasma membrane
synaptic vesicle

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000295718
Coding exons: 23
Length: 20026
Individuals with no LoFs: 125690
Homozygous LoFs: 0
Heterozygous LoFs: 58
Defined: 125748
p: 0.000231

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.60	485	595	0.815	0.0000353	6239
Missense (PolyPhen)		182	247.18	0.73631		2622
Synonymous	0.747	228	243	0.939	0.0000138	2125
Loss of Function	3.86	19	47.8	0.398	0.00000213	538

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00037	0.00037	rare
Latino/Admixed American	0.00027	0.00026	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00022	0.00022	rare
Finnish	0.00060	0.00060	rare
European (Non-Finnish)	0.00019	0.00018	rare
South Asian	0.00013	0.00013	rare
Other	0.00017	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Plays a role in vesicle-mediated secretory processes (PubMed:24843546). Required for normal accumulation of secretory vesicles in hippocampus, pituitary and pancreatic islets (By similarity). Required for the accumulation of normal levels of insulin-containing vesicles and preventing their degradation (PubMed:24843546). Plays a role in insulin secretion in response to glucose stimuli (PubMed:24843546). Required for normal accumulation of the neurotransmitters norepinephrine, dopamine and serotonin in the brain (By similarity). 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) (By similarity). Required to maintain normal levels of renin expression and renin release (By similarity). Seems to lack intrinsic enzyme activity (By similarity). May regulate catalytic active protein-tyrosine phosphatases such as PTPRA through dimerization (By similarity). {ECO:0000250|UniProtKB:Q60673, ECO:0000269|PubMed:24843546}.; FUNCTION: ICA512-cleaved cytosolic fragment: 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 (PubMed:15596545, PubMed:16622421, PubMed:18178618). Enhances pancreatic beta-cell proliferation by converging with signaling by STAT5B and STAT3 (PubMed:15596545, PubMed:16622421, PubMed:18178618). 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 (PubMed:18824546, PubMed:20886068). {ECO:0000269|PubMed:15596545, ECO:0000269|PubMed:16622421, ECO:0000269|PubMed:18178618, ECO:0000269|PubMed:18824546, ECO:0000269|PubMed:20886068}.;
Disease: DISEASE: Note=Autoantigen in insulin-dependent diabetes mellitus (IDDM). {ECO:0000269|PubMed:8144912, ECO:0000269|PubMed:8641276}.;

Recessive Scores

pRec: 0.323

Intolerance Scores

LoFtool: 0.469
RVIS EVS: -1.39
RVIS percentile EVS: 4.27

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.855

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium