PTPN12

protein-coding

protein tyrosine phosphatase non-receptor type 12, the group of Protein tyrosine phosphatases non-receptor type

Gene summary

The protein encoded by this gene is a member of the protein tyrosine phosphatase (PTP) family. PTPs are signaling molecules that regulate a variety of cellular processes including cell growth, differentiation, mitotic cycle, and oncogenic transformation. This PTP contains a C-terminal PEST motif, which serves as a protein-protein interaction domain, and may regulate protein intracellular half-life. This PTP was found to bind and dephosphorylate the product of the oncogene c-ABL and thus may play a role in oncogenesis. This PTP was also shown to interact with, and dephosphorylate, various products related to cytoskeletal structure and cell adhesion, such as p130 (Cas), CAKbeta/PTK2B, PSTPIP1, and paxillin. This suggests it has a regulatory role in controlling cell shape and mobility. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Oct 2008]

MANE transcript

NM_002835.4

Inheritance

—

ClinVar variants

P:1U:94B:10

Top phenotype

PTPN12-related disorder

gnomAD constraint

pLI —, LoF o/e 0.07

Max pathogenic AF

—

Genomic locus

chr7:77,537,295-77,640,069

External References & Databases

Ensembl (ENSG00000127947)

Transcript & Mutation Effects

hg38 • Region Span ~102.8 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 PTPN12 variants in ClinVar

5 Conditions Cataloged

not specifiedTotal: 80

PTPN12-related disorderTotal: 8

not providedTotal: 6

Colorectal cancerTotal: 2

Carcinoma of colonTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_002835.4. 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				7 clinvar	1 clinvar	8
missense	1 clinvar		82 clinvar	2 clinvar		85
nonsense			1 clinvar			1
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)			10 clinvar			10
Total	1	0	94	9	1	105

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 35 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_002835.4	RefSeq	NP_002826.3	18	MANE Select
ENST00000248594.11	Ensembl	ENSP00000248594.6	18	MANE Select
NM_001131008.2	RefSeq	NP_001124480.1	15	Standard
NM_001131009.2	RefSeq	NP_001124481.1	14	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
ptpn12	Danio rerio	Structure: pharyngeal arch 3-7 Quality: hypoplastic abnormal

Gene / Model

Organism

Observed Phenotype

ptpn12

Danio rerio

Structure: pharyngeal arch 3-7

Quality: hypoplastic

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

EGF-EGFR Signaling Pathway
SHC1 events in ERBB2 signaling
Signal Transduction
Signaling by PDGF
TCR

Biological Process

protein dephosphorylation
peptidyl-tyrosine dephosphorylation
ERBB2 signaling pathway
regulation of epidermal growth factor receptor signaling pathway
tissue regeneration

Molecular Function

phosphoprotein phosphatase activity
protein tyrosine phosphatase activity
non-membrane spanning protein tyrosine phosphatase activity
protein binding
SH3 domain binding

Cellular Component

podosome
nucleoplasm
cytoplasm
cytosol
focal adhesion

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000248594
Coding exons: 18
Length: 102797
Individuals with no LoFs: 125715
Homozygous LoFs: 0
Heterozygous LoFs: 33
Defined: 125748
p: 0.000131

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.16	330	395	0.836	0.0000184	5123
Missense (PolyPhen)		60	93.927	0.6388		1229
Synonymous	-0.927	146	132	1.10	0.00000643	1438
Loss of Function	5.56	3	41.7	0.0719	0.00000210	537

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0.000058	0.000029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00070	0.00054	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00014	0.00014	rare
South Asian	0.00016	0.00016	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Dephosphorylates a range of proteins, and thereby regulates cellular signaling cascades (PubMed:18559503). Dephosphorylates cellular tyrosine kinases, such as ERBB2 and PTK2B/PYK2, and thereby regulates signaling via ERBB2 and PTK2B/PYK2 (PubMed:17329398, PubMed:27134172). Selectively dephosphorylates ERBB2 phosphorylated at 'Tyr-1112', 'Tyr-1196', and/or 'Tyr-1248' (PubMed:27134172). {ECO:0000269|PubMed:17329398, ECO:0000269|PubMed:18559503, ECO:0000269|PubMed:27134172}.;

Recessive Scores

pRec: 0.168

Intolerance Scores

LoFtool: 0.350
RVIS EVS: -0.49
RVIS percentile EVS: 22.65

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.234

Gene Damage Prediction

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