PTPN6

protein-coding

protein tyrosine phosphatase non-receptor type 6, the group of Protein tyrosine phosphatases non-receptor type|SH2 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. N-terminal part of this PTP contains two tandem Src homolog (SH2) domains, which act as protein phospho-tyrosine binding domains, and mediate the interaction of this PTP with its substrates. This PTP is expressed primarily in hematopoietic cells, and functions as an important regulator of multiple signaling pathways in hematopoietic cells. This PTP has been shown to interact with, and dephosphorylate a wide spectrum of phospho-proteins involved in hematopoietic cell signaling. Multiple alternatively spliced variants of this gene, which encode distinct isoforms, have been reported. [provided by RefSeq, Jul 2008]

MANE transcript

NM_002831.6

Inheritance

—

ClinVar variants

U:68B:13

Top phenotype

Autism spectrum disorder

gnomAD constraint

pLI —, LoF o/e 0.03

Max pathogenic AF

—

Genomic locus

chr12:6,946,468-6,961,316

External References & Databases

Ensembl (ENSG00000111679)

Transcript & Mutation Effects

hg38 • Region Span ~14.8 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 PTPN6 variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 66

not providedTotal: 14

Autism spectrum disorderTotal: 1

Neurodevelopmental abnormalityTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_002831.6. 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	5 clinvar	11
missense			58 clinvar	6 clinvar		64
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			5 clinvar			5
Total	0	0	68	8	5	81

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 25 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_002831.6	RefSeq	NP_002822.2	15	MANE Select
ENST00000318974.14	Ensembl	ENSP00000326010.9	15	MANE Select
NM_080548.5	RefSeq	NP_536858.1	15	Standard
NM_080549.4	RefSeq	NP_536859.1	15	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
ptpn6	Danio rerio	Structure: leukocyte Quality: accumulation abnormal

Gene / Model

Organism

Observed Phenotype

ptpn6

Danio rerio

Structure: leukocyte

Quality: accumulation

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

T cell receptor signaling pathway - Homo sapiens (human)
B cell receptor signaling pathway - Homo sapiens (human)
Adherens junction - Homo sapiens (human)
Jak-STAT signaling pathway - Homo sapiens (human)
Natural killer cell mediated cytotoxicity - Homo sapiens (human)

Biological Process

hematopoietic progenitor cell differentiation
negative regulation of humoral immune response mediated by circulating immunoglobulin
protein dephosphorylation
apoptotic process
G protein-coupled receptor signaling pathway

Molecular Function

phosphotyrosine residue binding
protein tyrosine phosphatase activity
transmembrane receptor protein tyrosine phosphatase activity
protein binding
SH3 domain binding

Cellular Component

extracellular region
nucleus
nucleoplasm
nucleolus
cytoplasm

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000456013
Coding exons: 15
Length: 14849
Individuals with no LoFs: 124871
Homozygous LoFs: 0
Heterozygous LoFs: 2
Defined: 124873
p: 0.00000801

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.87	216	371	0.582	0.0000255	4059
Missense (PolyPhen)		40	112.94	0.35417		1159
Synonymous	0.390	150	156	0.960	0.0000116	1220
Loss of Function	5.39	1	35.8	0.0279	0.00000206	381

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.0000089	0.0000088	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Modulates signaling by tyrosine phosphorylated cell surface receptors such as KIT and the EGF receptor/EGFR. The SH2 regions may interact with other cellular components to modulate its own phosphatase activity against interacting substrates. Together with MTUS1, induces UBE2V2 expression upon angiotensin II stimulation. Plays a key role in hematopoiesis. {ECO:0000269|PubMed:11266449}.;

Recessive Scores

pRec: 0.543

Intolerance Scores

LoFtool: 0.127
RVIS EVS: -0.62
RVIS percentile EVS: 17.31

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 1.00

Gene Damage Prediction

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