PTPN21

protein-coding

protein tyrosine phosphatase non-receptor type 21, the group of Protein tyrosine phosphatases non-receptor type|FERM domain containing

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 contains an N-terminal domain, similar to cytoskeletal- associated proteins including band 4.1, ezrin, merlin, and radixin. This PTP was shown to specially interact with BMX/ETK, a member of Tec tyrosine kinase family characterized by a multimodular structures including PH, SH3, and SH2 domains. The interaction of this PTP with BMX kinase was found to increase the activation of STAT3, but not STAT2 kinase. Studies of the similar gene in mice suggested the possible roles of this PTP in liver regeneration and spermatogenesis. [provided by RefSeq, Jul 2008]

MANE transcript

NM_007039.4

Inheritance

—

ClinVar variants

U:192B:13

Top phenotype

Prostate cancer

gnomAD constraint

pLI —, LoF o/e 0.48

Max pathogenic AF

—

Genomic locus

chr14:88,465,778-88,555,007

External References & Databases

Ensembl (ENSG00000070778)

Transcript & Mutation Effects

hg38 • Region Span ~89.2 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 PTPN21 variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 183

not providedTotal: 7

Prostate cancerTotal: 1

Myoepithelial tumorTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_007039.4. 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			2 clinvar	4 clinvar	1 clinvar	7
missense			182 clinvar	6 clinvar	2 clinvar	190
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			7 clinvar			7
Total	0	0	192	10	3	205

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 17 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_007039.4	RefSeq	NP_008970.2	18	MANE Select
ENST00000556564.6	Ensembl	ENSP00000452414.1	18	MANE Select
ENST00000328736.7	Ensembl	ENSP00000330276.3	18	Standard
ENST00000536337.5	Ensembl	ENSP00000443951.1	2	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
ptpn21	Danio rerio	Structure: melanocyte Quality: mislocalised abnormal

Gene / Model

Organism

Observed Phenotype

ptpn21

Danio rerio

Structure: melanocyte

Quality: mislocalised

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Signaling events mediated by focal adhesion kinase

Biological Process

protein dephosphorylation
peptidyl-tyrosine dephosphorylation

Molecular Function

protein tyrosine phosphatase activity
protein binding

Cellular Component

cytoplasm
cytoskeleton

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000556564
Coding exons: 18
Length: 88956
Individuals with no LoFs: 125655
Homozygous LoFs: 0
Heterozygous LoFs: 93
Defined: 125748
p: 0.000370

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.513	685	724	0.946	0.0000465	7602
Missense (PolyPhen)		221	284.64	0.77641		3106
Synonymous	-0.778	329	312	1.06	0.0000223	2313
Loss of Function	3.77	30	62.1	0.483	0.00000362	644

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00031	0.00031	rare
Latino/Admixed American	0.00029	0.00029	rare
Ashkenazi Jewish	0.00020	0.00020	rare
East Asian	0.00045	0.00044	rare
Finnish	0.000093	0.000046	rare
European (Non-Finnish)	0.00041	0.00038	rare
South Asian	0.00080	0.00078	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Recessive Scores

pRec: 0.146

Intolerance Scores

LoFtool: 0.438
RVIS EVS: 0.44
RVIS percentile EVS: 77.36

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Indispensability pred.: E
Indispensability score: 0.637

Gene Damage Prediction

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