PTPN23

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

Basic information

Region (hg38): 3:47381011-47413435

Links

ENSG00000076201

∙ NCBI:25930 ∙ OMIM:606584 ∙ HGNC:14406 ∙ Uniprot:Q9H3S7 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

neurodevelopmental disorder and structural brain anomalies with or without seizures and spasticity (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Neurodevelopmental disorder and structural brain anomalies with or without seizures and spasticity	AR	General	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	Craniofacial; Neurologic; Ophthalmologic	25558065; 27848944; 29090338; 29899372; 31395947

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PTPN23 gene.

not_provided (1353 variants)
Inborn_genetic_diseases (249 variants)
Neurodevelopmental_disorder_and_structural_brain_anomalies_with_or_without_seizures_and_spasticity (70 variants)
PTPN23-related_disorder (39 variants)
Global_developmental_delay (14 variants)
Brain_atrophy (13 variants)
not_specified (12 variants)
Neurodevelopmental_disorder (2 variants)
PTPN23-related_neurodevelopmental_disorder (1 variants)
Hereditary_spastic_paraplegia (1 variants)
Seizure (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PTPN23 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000015466.4. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous		1 clinvar	3 clinvar	446 clinvar	10 clinvar	460
missense	2 clinvar	1 clinvar	642 clinvar	32 clinvar	10 clinvar	687
nonsense	8 clinvar	3 clinvar	3 clinvar			14
start loss			1			1
frameshift	20 clinvar	9 clinvar	15 clinvar			44
splice donor/acceptor (+/-2bp)		5 clinvar	2 clinvar	2 clinvar	1 clinvar	10
Total	30	19	666	480	21

Highest pathogenic variant AF is 0.000020018817

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PTPN23	protein_coding	protein_coding	ENST00000265562	25	32431

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0313	0.969	125663	0	85	125748	0.000338

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.33	872	990	0.881	0.0000619	10480
Missense in Polyphen		115	150.34	0.76491		1565
Synonymous	-1.75	472	426	1.11	0.0000273	3513
Loss of Function	5.88	18	71.7	0.251	0.00000382	773

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000669	0.000640
Ashkenazi Jewish	0.00	0.00
East Asian	0.000327	0.000326
Finnish	0.000996	0.000971
European (Non-Finnish)	0.000266	0.000246
Middle Eastern	0.000327	0.000326
South Asian	0.000401	0.000392
Other	0.000692	0.000652

dbNSFP

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}.;
Pathway: EGFR1 (Consensus)

Recessive Scores

pRec: 0.121

Intolerance Scores

loftool: 0.516
rvis_EVS: -1.33
rvis_percentile_EVS: 4.68

Haploinsufficiency Scores

pHI: 0.0975
hipred: Y
hipred_score: 0.637
ghis: 0.593

Essentials

essential_gene_CRISPR: E
essential_gene_CRISPR2: E
essential_gene_gene_trap: K
gene_indispensability_pred: E
gene_indispensability_score: 0.745

Gene Damage Prediction

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

Mouse Genome Informatics

Gene name: Ptpn23
Phenotype: vision/eye phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); embryo phenotype; homeostasis/metabolism phenotype; growth/size/body region phenotype;

Gene ontology

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;early endosome to late endosome transport;cilium assembly;positive regulation of Wnt protein secretion;cellular response to cytokine stimulus;positive regulation of homophilic cell adhesion;positive regulation of adherens junction organization;positive regulation of early endosome to late endosome transport
Cellular component: nucleus;nucleoplasm;cytoplasm;endosome;early endosome;cytosol;nuclear body;ciliary basal body;extracellular exosome
Molecular function: protein tyrosine phosphatase activity;protein binding;protein kinase binding