PTPN22 protein tyrosine phosphatase non-receptor type 22 [Homo sapiens (human)] - Gene

Summary

Official Symbol: PTPN22provided by HGNC
Official Full Name: protein tyrosine phosphatase non-receptor type 22provided by HGNC
Primary source: HGNC:HGNC:9652
See related: Ensembl:ENSG00000134242 MIM:600716; AllianceGenome:HGNC:9652
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: LYP; PEP; LYP1; LYP2; PTPN8; PTPN22.5; PTPN22.6
Summary: This gene encodes of member of the non-receptor class 4 subfamily of the protein-tyrosine phosphatase family. The encoded protein is a lymphoid-specific intracellular phosphatase that associates with the molecular adapter protein CBL and may be involved in regulating CBL function in the T-cell receptor signaling pathway. Mutations in this gene may be associated with a range of autoimmune disorders including Type 1 Diabetes, rheumatoid arthritis, systemic lupus erythematosus and Graves' disease. Alternatively spliced transcript variants encoding distinct isoforms have been described. [provided by RefSeq, Mar 2009]
Expression: Biased expression in bone marrow (RPKM 9.6), lymph node (RPKM 7.9) and 13 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 1p13.2

Exon count:: 23

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	1	NC_000001.11 (113813811..113871759, complement)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	1	NC_060925.1 (113825481..113883420, complement)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	1	NC_000001.10 (114356433..114414334, complement)

Chromosome 1 - NC_000001.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Association of polymorphism of NLRP3, ICAM-1, PTPN22, INS genes in childhood onset type 1 diabetes in a Pakistani population.
Title: Association of polymorphism of NLRP3, ICAM-1, PTPN22, INS genes in childhood onset type 1 diabetes in a Pakistani population.
LYP regulates SLP76 and other adaptor proteins in T cells.
Title: LYP regulates SLP76 and other adaptor proteins in T cells.
A novel gain-of-function phosphorylation site modulates PTPN22 inhibition of TCR signaling.
Title: A novel gain-of-function phosphorylation site modulates PTPN22 inhibition of TCR signaling.
Increased expression of protein tyrosine phosphatase nonreceptor type 22 alters early T-cell receptor signaling and differentiation of CD4[+] T cells in chronic heart failure.
Title: Increased expression of protein tyrosine phosphatase nonreceptor type 22 alters early T-cell receptor signaling and differentiation of CD4(+) T cells in chronic heart failure.
Association between PYTPN22 rs2476601, VEGF rs833070, TNFAIP3 rs6920220 Polymorphisms and Risk for Rheumatoid Arthritis in Early Undifferentiated Arthritis Patients: A Pilot Study.
Title: Association between PYTPN22 rs2476601, VEGF rs833070, TNFAIP3 rs6920220 Polymorphisms and Risk for Rheumatoid Arthritis in Early Undifferentiated Arthritis Patients: A Pilot Study.
CircPTPN22 modulates T-cell activation by sponging miR-4689 to regulate S1PR1 expression in patients with systemic lupus erythematosus.
Title: CircPTPN22 modulates T-cell activation by sponging miR-4689 to regulate S1PR1 expression in patients with systemic lupus erythematosus.
DNA methylation differences within INS, PTPN22 and IL2RA promoters in lymphocyte subsets in children with type 1 diabetes and controls.
Title: DNA methylation differences within INS, PTPN22 and IL2RA promoters in lymphocyte subsets in children with type 1 diabetes and controls.
Targeted inhibition of PTPN22 is a novel approach to alleviate osteogenic responses in aortic valve interstitial cells and aortic valve lesions in mice.
Title: Targeted inhibition of PTPN22 is a novel approach to alleviate osteogenic responses in aortic valve interstitial cells and aortic valve lesions in mice.
Molecular Dynamic Simulations Unravel the Underlying Impact of Missense Mutation in Autoimmunity Gene PTPN22 on Predisposition to Rheumatoid Arthritis.
Title: Molecular Dynamic Simulations Unravel the Underlying Impact of Missense Mutation in Autoimmunity Gene PTPN22 on Predisposition to Rheumatoid Arthritis.
PTPN22 intron polymorphism rs1310182 (c.2054-852T>C) is associated with type 1 diabetes mellitus in patients of Armenian descent.
Title: PTPN22 intron polymorphism rs1310182 (c.2054-852T>C) is associated with type 1 diabetes mellitus in patients of Armenian descent.

Submit: New GeneRIF Correction See all GeneRIFs (452)

Phenotypes

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Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Diabetes mellitus type 1 MedGen: C0011854 OMIM: 222100 GeneReviews: Not available	Compare labs
Rheumatoid arthritis MedGen: C0003873 OMIM: 180300 GeneReviews: Not available	Compare labs
Systemic lupus erythematosus MedGen: C0024141 OMIM: 152700 GeneReviews: Not available	Compare labs

EBI GWAS Catalog

Description
A genome-wide association study identifies KIAA0350 as a type 1 diabetes gene. EBI GWAS Catalog EBI GWAS CatalogPubMed
A genome-wide association study suggests contrasting associations in ACPA-positive versus ACPA-negative rheumatoid arthritis. EBI GWAS Catalog EBI GWAS CatalogPubMed
Common variants at CD40 and other loci confer risk of rheumatoid arthritis. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genetics of rheumatoid arthritis contributes to biology and drug discovery. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association analysis of autoantibody positivity in type 1 diabetes cases. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association defines more than 30 distinct susceptibility loci for Crohn's disease. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association study and meta-analysis find that over 40 loci affect risk of type 1 diabetes. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association study meta-analysis identifies seven new rheumatoid arthritis risk loci. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide meta-analysis increases to 71 the number of confirmed Crohn's disease susceptibility loci. EBI GWAS Catalog EBI GWAS CatalogPubMed
Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease. EBI GWAS Catalog EBI GWAS CatalogPubMed
Identification of novel genetic Loci associated with thyroid peroxidase antibodies and clinical thyroid disease. EBI GWAS Catalog EBI GWAS CatalogPubMed
Large-scale genotyping identifies 41 new loci associated with breast cancer risk. EBI GWAS Catalog EBI GWAS CatalogPubMed
Meta-analysis of genome-wide association study data identifies additional type 1 diabetes risk loci. EBI GWAS Catalog EBI GWAS CatalogPubMed
Novel associations for hypothyroidism include known autoimmune risk loci. EBI GWAS Catalog EBI GWAS CatalogPubMed
Novel genetic loci identified for the pathophysiology of childhood obesity in the Hispanic population. EBI GWAS Catalog EBI GWAS CatalogPubMed
Novel rheumatoid arthritis susceptibility locus at 22q12 identified in an extended UK genome-wide association study. EBI GWAS Catalog EBI GWAS CatalogPubMed
REL, encoding a member of the NF-kappaB family of transcription factors, is a newly defined risk locus for rheumatoid arthritis. EBI GWAS Catalog EBI GWAS CatalogPubMed
Risk for myasthenia gravis maps to a (151) Pro&#x000e2;&#x00086;&#x00092;Ala change in TNIP1 and to human leukocyte antigen-B*08. EBI GWAS Catalog EBI GWAS CatalogPubMed
Robust associations of four new chromosome regions from genome-wide analyses of type 1 diabetes. EBI GWAS Catalog EBI GWAS CatalogPubMed
TRAF1-C5 as a risk locus for rheumatoid arthritis--a genomewide study. EBI GWAS Catalog EBI GWAS CatalogPubMed
Variant of TYR and autoimmunity susceptibility loci in generalized vitiligo. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

AL034193 (e-PCR)
- UniSTS:94019

SHGC-75350 (e-PCR)
- UniSTS:71520

RH117 (e-PCR)
- UniSTS:84397

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables SH3 domain binding	ISS Inferred from Sequence or Structural Similarity more info
enables histone H2AXY142 phosphatase activity	IEA Inferred from Electronic Annotation more info
enables kinase binding	ISS Inferred from Sequence or Structural Similarity more info
enables non-membrane spanning protein tyrosine phosphatase activity	IEA Inferred from Electronic Annotation more info
enables phosphatase activity	IDA Inferred from Direct Assay more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein tyrosine phosphatase activity	IBA Inferred from Biological aspect of Ancestor more info
enables protein tyrosine phosphatase activity	IDA Inferred from Direct Assay more info	PubMed
enables protein tyrosine phosphatase activity	TAS Traceable Author Statement more info
enables protein tyrosine phosphatase activity, metal-dependent	IEA Inferred from Electronic Annotation more info
enables ubiquitin protein ligase binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
involved_in T cell differentiation	ISS Inferred from Sequence or Structural Similarity more info
involved_in T cell receptor signaling pathway	IBA Inferred from Biological aspect of Ancestor more info
involved_in T cell receptor signaling pathway	TAS Traceable Author Statement more info
involved_in autophagy	IEA Inferred from Electronic Annotation more info
involved_in cellular response to muramyl dipeptide	IDA Inferred from Direct Assay more info	PubMed
involved_in chromatin remodeling	IEA Inferred from Electronic Annotation more info
involved_in lipid metabolic process	IEA Inferred from Electronic Annotation more info
involved_in lipopolysaccharide-mediated signaling pathway	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of JUN kinase activity	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of T cell activation	IBA Inferred from Biological aspect of Ancestor more info
involved_in negative regulation of T cell activation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of T cell receptor signaling pathway	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of autophagy	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of gene expression	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of interleukin-6 production	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of interleukin-8 production	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of nucleotide-binding oligomerization domain containing 2 signaling pathway	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of p38MAPK cascade	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of tumor necrosis factor production	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in phosphoanandamide dephosphorylation	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of ERK1 and ERK2 cascade	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of NLRP3 inflammasome complex assembly	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of gene expression	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of protein K63-linked ubiquitination	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of toll-like receptor 3 signaling pathway	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of toll-like receptor 4 signaling pathway	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of type I interferon production	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of type II interferon production	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in protein dephosphorylation	IDA Inferred from Direct Assay more info	PubMed
involved_in protein dephosphorylation	TAS Traceable Author Statement more info	PubMed
involved_in regulation of B cell receptor signaling pathway	NAS Non-traceable Author Statement more info	PubMed
involved_in regulation of innate immune response	IBA Inferred from Biological aspect of Ancestor more info
involved_in regulation of innate immune response	IC Inferred by Curator more info	PubMed
involved_in regulation of natural killer cell proliferation	IDA Inferred from Direct Assay more info	PubMed
involved_in regulation of non-canonical NF-kappaB signal transduction	IBA Inferred from Biological aspect of Ancestor more info
involved_in regulation of non-canonical NF-kappaB signal transduction	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in response to lipopolysaccharide	IMP Inferred from Mutant Phenotype more info	PubMed

Component	Evidence Code	Pubs
is_active_in cytoplasm	IBA Inferred from Biological aspect of Ancestor more info
located_in cytoplasm	IDA Inferred from Direct Assay more info	PubMed
located_in cytoplasm	TAS Traceable Author Statement more info	PubMed
located_in cytoplasmic side of plasma membrane	IDA Inferred from Direct Assay more info	PubMed
located_in cytosol	TAS Traceable Author Statement more info
is_active_in nucleus	IBA Inferred from Biological aspect of Ancestor more info
located_in nucleus	IDA Inferred from Direct Assay more info	PubMed
located_in perinuclear region of cytoplasm	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: tyrosine-protein phosphatase non-receptor type 22

Names: PEST-domain phosphatase; hematopoietic cell protein-tyrosine phosphatase 70Z-PEP; lymphoid-specific protein tyrosine phosphatase; protein tyrosine phosphatase, non-receptor type 22 (lymphoid); protein tyrosine phosphatase, non-receptor type 8

NP_001180360.2

EC 3.1.3.48

NP_001295226.2

EC 3.1.3.48

NP_036543.5

EC 3.1.3.48

NP_057051.4

EC 3.1.3.48

XP_011539523.1

EC 3.1.3.48

XP_011539524.1

EC 3.1.3.48

XP_011539525.1

EC 3.1.3.48

XP_011539527.1

EC 3.1.3.48

XP_016856494.1

EC 3.1.3.48

XP_016856495.1

EC 3.1.3.48

XP_047273586.1

EC 3.1.3.48

XP_047273587.1

EC 3.1.3.48

XP_047273588.1

EC 3.1.3.48

XP_054191914.1

EC 3.1.3.48

XP_054191915.1

EC 3.1.3.48

XP_054191916.1

EC 3.1.3.48

XP_054191917.1

EC 3.1.3.48

XP_054191918.1

EC 3.1.3.48

XP_054191919.1

EC 3.1.3.48

XP_054191920.1

EC 3.1.3.48

XP_054191921.1

EC 3.1.3.48

XP_054191922.1

EC 3.1.3.48

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_011432.2 RefSeqGene

Range

5047..62948

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001193431.3 → NP_001180360.2 tyrosine-protein phosphatase non-receptor type 22 isoform 3

Status: REVIEWED

Description

Transcript Variant: This variant (3) uses an alternate in-frame splice site in the central coding region, compared to variant 1, resulting in an isoform (3) that is shorter than isoform 1.

Source sequence(s)

AL137856
NM_001308297.2 → NP_001295226.2 tyrosine-protein phosphatase non-receptor type 22 isoform 4

Status: REVIEWED

Description

Transcript Variant: This variant (4) lacks an alternate in-frame exon in the 5' coding region, compared to variant 1, resulting in an isoform (4) that is shorter than isoform 1.

Source sequence(s)

AL137856

Consensus CDS

CCDS76191.1

UniProtKB/TrEMBL

F5H2S8

Related

ENSP00000439372.2, ENST00000538253.5
NM_012411.6 → NP_036543.5 tyrosine-protein phosphatase non-receptor type 22 isoform 2

Status: REVIEWED

Description

Transcript Variant: This variant (2) lacks two alternate in-frame exons in the central coding region, compared to variant 1, resulting in an isoform (2) that is shorter than isoform 1.

Source sequence(s)

AL137856

Consensus CDS

CCDS864.2

UniProtKB/TrEMBL

A0A0A0MTE6

Related

ENSP00000435176.1, ENST00000528414.5
NM_015967.8 → NP_057051.4 tyrosine-protein phosphatase non-receptor type 22 isoform 1

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (1).

Source sequence(s)

AA836401, AF001846, AF077031, AL137856, BC071670, DB145424

Consensus CDS

CCDS863.1

UniProtKB/TrEMBL

A0A0B4J1S7

Related

ENSP00000352833.5, ENST00000359785.10

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000001.11 Reference GRCh38.p14 Primary Assembly

Range

113813811..113871759 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_047417630.1 → XP_047273586.1 tyrosine-protein phosphatase non-receptor type 22 isoform X3
XM_047417631.1 → XP_047273587.1 tyrosine-protein phosphatase non-receptor type 22 isoform X4
XM_011541225.3 → XP_011539527.1 tyrosine-protein phosphatase non-receptor type 22 isoform X9

UniProtKB/TrEMBL

G3K0T4

Conserved Domains (2) summary

smart00194
Location:24 → 264

PTPc; Protein tyrosine phosphatase, catalytic domain

cd00047
Location:56 → 264

PTPc; Protein tyrosine phosphatases (PTP) catalyze the dephosphorylation of phosphotyrosine peptides; they regulate phosphotyrosine levels in signal transduction pathways. The depth of the active site cleft renders the enzyme specific for phosphorylated Tyr ...
XM_047417632.1 → XP_047273588.1 tyrosine-protein phosphatase non-receptor type 22 isoform X5
XM_011541221.2 → XP_011539523.1 tyrosine-protein phosphatase non-receptor type 22 isoform X1

UniProtKB/Swiss-Prot

A0N0K6, B1ALC8, D4NZ71, E9PLD8, E9PPI1, O95063, O95064, Q6IPX8, Q8WVM1, Q9Y2R2

Conserved Domains (2) summary

smart00194
Location:24 → 262

PTPc; Protein tyrosine phosphatase, catalytic domain

cd00047
Location:56 → 262

PTPc; Protein tyrosine phosphatases (PTP) catalyze the dephosphorylation of phosphotyrosine peptides; they regulate phosphotyrosine levels in signal transduction pathways. The depth of the active site cleft renders the enzyme specific for phosphorylated Tyr ...
XM_011541222.2 → XP_011539524.1 tyrosine-protein phosphatase non-receptor type 22 isoform X2

UniProtKB/TrEMBL

E9PMT0

Conserved Domains (2) summary

smart00194
Location:24 → 288

PTPc; Protein tyrosine phosphatase, catalytic domain

cd00047
Location:56 → 288

PTPc; Protein tyrosine phosphatases (PTP) catalyze the dephosphorylation of phosphotyrosine peptides; they regulate phosphotyrosine levels in signal transduction pathways. The depth of the active site cleft renders the enzyme specific for phosphorylated Tyr ...
XM_017001005.3 → XP_016856494.1 tyrosine-protein phosphatase non-receptor type 22 isoform X7

UniProtKB/Swiss-Prot

A0N0K6, B1ALC8, D4NZ71, E9PLD8, E9PPI1, O95063, O95064, Q6IPX8, Q8WVM1, Q9Y2R2
XM_011541223.3 → XP_011539525.1 tyrosine-protein phosphatase non-receptor type 22 isoform X6

UniProtKB/TrEMBL

E9PMT0

Conserved Domains (2) summary

smart00194
Location:24 → 288

PTPc; Protein tyrosine phosphatase, catalytic domain

cd00047
Location:56 → 288

PTPc; Protein tyrosine phosphatases (PTP) catalyze the dephosphorylation of phosphotyrosine peptides; they regulate phosphotyrosine levels in signal transduction pathways. The depth of the active site cleft renders the enzyme specific for phosphorylated Tyr ...
XM_017001006.2 → XP_016856495.1 tyrosine-protein phosphatase non-receptor type 22 isoform X8

Conserved Domains (1) summary

cd14602
Location:57 → 290

PTPc-N22; catalytic domain of tyrosine-protein phosphatase non-receptor type 22

Alternate T2T-CHM13v2.0

Genomic

NC_060925.1 Alternate T2T-CHM13v2.0

Range

113825481..113883420 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_054335941.1 → XP_054191916.1 tyrosine-protein phosphatase non-receptor type 22 isoform X3
XM_054335942.1 → XP_054191917.1 tyrosine-protein phosphatase non-receptor type 22 isoform X4
XM_054335947.1 → XP_054191922.1 tyrosine-protein phosphatase non-receptor type 22 isoform X9
XM_054335943.1 → XP_054191918.1 tyrosine-protein phosphatase non-receptor type 22 isoform X5
XM_054335939.1 → XP_054191914.1 tyrosine-protein phosphatase non-receptor type 22 isoform X1
XM_054335940.1 → XP_054191915.1 tyrosine-protein phosphatase non-receptor type 22 isoform X2
XM_054335945.1 → XP_054191920.1 tyrosine-protein phosphatase non-receptor type 22 isoform X7
XM_054335944.1 → XP_054191919.1 tyrosine-protein phosphatase non-receptor type 22 isoform X6
XM_054335946.1 → XP_054191921.1 tyrosine-protein phosphatase non-receptor type 22 isoform X8