GeneBe

PTPN23

protein-coding

protein tyrosine phosphatase non-receptor type 23, the group of Protein tyrosine phosphatases non-receptor type

Gene summary

This gene encodes a member of the non-receptor type protein-tyrosine phosphatase family. The encoded protein may be involved in the regulation of small nuclear ribonucleo protein assembly and pre-mRNA splicing by modifying the survival motor neuron (SMN) complex. The encoded protein additionally plays a role in ciliogenesis and is part of endosomal sorting complex required for transport (ESCRT) pathways. This gene may serve a tumor suppressor function. [provided by RefSeq, Jul 2016]

MANE transcript

NM_015466.4

Inheritance

AR

ClinVar variants

P:56U:708B:538

Top phenotype

Neurodevelopmental disorder and structural brain anomalies with or without seizures and spasticity

gnomAD constraint

pLI —, LoF o/e 0.25

Max pathogenic AF

—

Genomic locus

chr3:47,381,011-47,413,435

External References & Databases

Ensembl (ENSG00000076201)NCBI Gene (25930)OMIM (606584)HGNC:14406GenCCUniProt (Q9H3S7)AlphaFoldClinVar (PTPN23)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~32.4 kb
Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

neurodevelopmental disorder and structural brain anomalies with or without seizures and spasticitySTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0030046

Submitter: Labcorp Genetics (formerly Invitae)

neurodevelopmental disorder and structural brain anomalies with or without seizures and spasticityDEFINITIVE

Inheritance Pattern: AR

Disease ID:MONDO:0030046

Submitter: G2P

neurodevelopmental disorder and structural brain anomalies with or without seizures and spasticitySTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0030046

Submitter: PanelApp Australia

Clinical Genomic Database (CGD)

Neurodevelopmental disorder and structural brain anomalies with or without seizures and spasticityAR

Manifestation: Craniofacial; Neurologic; Ophthalmologic

Intervention: General

Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing

Refs: 25558065; 27848944; 29090338; 29899372; 31395947Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to PTPN23 variants in ClinVar

12 Conditions Cataloged
not providedTotal: 1449
Inborn genetic diseasesTotal: 277
not specifiedTotal: 115
Neurodevelopmental disorder and structural brain anomalies with or without seizures and spasticityTotal: 84
PTPN23-related disorderTotal: 43
Global developmental delayTotal: 14
Brain atrophyTotal: 13
Neurodevelopmental disorderTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_015466.4. 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.

EffectPLPVUSLBBSum
synonymous
5
clinvar
489
clinvar
3
clinvar
 497
missense
2
clinvar
2
clinvar
675
clinvar
37
clinvar
9
clinvar
 725
nonsense
9
clinvar
5
clinvar
1
clinvar
 15
start loss
1
clinvar
 1
frameshift
21
clinvar
12
clinvar
15
clinvar
 48
splice donor/acceptor (+/-2bp)
5
clinvar
11
clinvar
 16
Total3224708526121302

Highest pathogenic variant AF is 0.000020018817

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 20 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_015466.4RefSeqNP_056281.125MANE Select
ENST00000265562.5EnsemblENSP00000265562.425MANE Select
NM_001304482.2RefSeqNP_001291411.121Standard
ENST00000456221.5EnsemblENSP00000396328.16Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

  • EGFR1

Biological Process

  • negative regulation of epithelial cell migration
  • protein transport
  • endocytic recycling
  • peptidyl-tyrosine dephosphorylation
  • ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway

Molecular Function

  • protein tyrosine phosphatase activity
  • protein binding
  • protein kinase binding

Cellular Component

  • nucleus
  • nucleoplasm
  • cytoplasm
  • endosome
  • early endosome

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000265562
Coding exons
25
Length
32431
Individuals with no LoFs
125663
Homozygous LoFs
0
Heterozygous LoFs
85
Defined
125748
p
0.000338
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense1.338729900.8810.000061910480
Missense (PolyPhen)115150.340.764911565
Synonymous-1.754724261.110.00002733513
Loss of Function5.881871.70.2510.00000382773

Population LoF Frequency

PopulationCAFp-valueStatus
African0.000460.00043rare
Latino/Admixed American0.000210.00020rare
Ashkenazi Jewish00.0absent
East Asian0.000330.00033rare
Finnish0.00100.00097rare
European (Non-Finnish)0.000270.00025rare
South Asian0.000400.00039rare
Other0.000690.00065rare

dbNSFP Gene Annotations

Source: dbNSFP

Function
FUNCTION: Plays a role in sorting of endocytic ubiquitinated cargos into multivesicular bodies (MVBs) via its interaction with the ESCRT-I complex (endosomal sorting complex required for transport I), and possibly also other ESCRT complexes. May act as a negative regulator of Ras-mediated mitogenic activity. Plays a role in ciliogenesis. {ECO:0000269|PubMed:18434552, ECO:0000269|PubMed:20393563, ECO:0000269|PubMed:21757351}.;

Recessive Scores

pRec
0.121

Intolerance Scores

LoFtool
0.516
RVIS EVS
-1.33
RVIS percentile EVS
4.68

Essentials

Essential (CRISPR)
E
Essential (CRISPR2)
E
Essential (gene trap)
K
Indispensability pred.
E
Indispensability score
0.745

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium
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