PTPN4

protein-coding

protein tyrosine phosphatase non-receptor type 4, the group of FERM domain containing|Protein tyrosine phosphatases non-receptor type|PDZ 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 protein contains a C-terminal PTP domain and an N-terminal domain homologous to the band 4.1 superfamily of cytoskeletal-associated proteins. This PTP has been shown to interact with glutamate receptor delta 2 and epsilon subunits, and is thought to play a role in signalling downstream of the glutamate receptors through tyrosine dephosphorylation. [provided by RefSeq, Jul 2008]

MANE transcript

NM_002830.4

Inheritance

ClinVar variants

P:14U:129B:18

Top phenotype

neurodevelopmental disorder

gnomAD constraint

pLI —, LoF o/e 0.16

Max pathogenic AF

—

Genomic locus

chr2:119,759,922-119,984,899

External References & Databases

Ensembl (ENSG00000088179)

Transcript & Mutation Effects

hg38 • Region Span ~225.0 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

neurodevelopmental disorderSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0700092

Submitter: PanelApp Australia

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to PTPN4 variants in ClinVar

10 Conditions Cataloged

Inborn genetic diseasesTotal: 109

not providedTotal: 22

PTPN4-related disorderTotal: 11

Neurodevelopmental disorderTotal: 5

not specifiedTotal: 3

PTPN4-related Neurodevelopmental DisorderTotal: 2

PTPN4-associated disorderTotal: 1

PTPN4-related aberrant neurodevelopment and growthTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_002830.4. 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			3 clinvar	2 clinvar		5
missense		1 clinvar	111 clinvar	15 clinvar	1 clinvar	128
nonsense	3 clinvar	4 clinvar	3 clinvar			10
start loss						0
frameshift		3 clinvar	4 clinvar			7
splice donor/acceptor (+/-2bp)		3 clinvar	8 clinvar			11
Total	3	11	129	17	1	161

Highest pathogenic variant AF is 0.0000068683635

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 46 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_002830.4	RefSeq	NP_002821.1	26	MANE Select
ENST00000263708.7	Ensembl	ENSP00000263708.2	26	MANE Select
ENST00000420482.5	Ensembl	ENSP00000405763.1	2	Standard
ENST00000430976.5	Ensembl	ENSP00000395603.1	4	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Toll-Like Receptors Cascades
Innate Immune System
Immune System
Toll Like Receptor 4 (TLR4) Cascade

Biological Process

protein dephosphorylation
peptidyl-tyrosine dephosphorylation
cellular response to cytokine stimulus

Molecular Function

non-membrane spanning protein tyrosine phosphatase activity
protein binding
cytoskeletal protein binding

Cellular Component

nucleoplasm
cytoplasm
cytosol
cytoskeleton
cytoplasmic side of plasma membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000263708
Coding exons: 26
Length: 224188
Individuals with no LoFs: 125724
Homozygous LoFs: 0
Heterozygous LoFs: 20
Defined: 125744
p: 0.0000795

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.65	314	477	0.659	0.0000242	6058
Missense (PolyPhen)		95	204.25	0.46512		2531
Synonymous	2.55	122	164	0.746	0.00000798	1697
Loss of Function	6.04	10	60.9	0.164	0.00000362	705

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00013	0.00012	rare
Latino/Admixed American	0.00015	0.00014	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0.000092	0.000092	rare
European (Non-Finnish)	0.000098	0.000097	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: May act at junctions between the membrane and the cytoskeleton.;

Recessive Scores

pRec: 0.124

Intolerance Scores

LoFtool: 0.343
RVIS EVS: -0.02
RVIS percentile EVS: 52.15

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.957

Gene Damage Prediction

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