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 (21 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.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			5	405	11	421
missense			556	15	11	582
nonsense	7	1	4			12
start loss			1			1
frameshift	14	4	11			29
inframe indel			27		1	28
splice donor/acceptor (+/-2bp)		4	2	1	2	9
splice region			20	42	4	66
non coding			4	140	10	154
Total	21	9	610	561	35

Highest pathogenic variant AF is 0.0000329

Variants in PTPN23

This is a list of pathogenic ClinVar variants found in the PTPN23 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
3-47381098-T-C			Uncertain significance (Jun 14, 2022)
3-47381105-C-T			Likely benign (Jan 10, 2024)
3-47381144-G-A			Likely benign (Jun 15, 2021)
3-47381148-G-T			Uncertain significance (Jan 17, 2024)
3-47381160-T-C			Uncertain significance (Jun 13, 2022)
3-47381172-G-C			Uncertain significance (Apr 11, 2022)
3-47381173-TGAA-T			Uncertain significance (Sep 16, 2021)
3-47381182-T-A			Likely pathogenic (Jul 07, 2023)
3-47381189-G-A			Likely benign (Dec 13, 2023)
3-47381189-G-C			Likely benign (Mar 18, 2022)
3-47381190-C-G			Likely benign (Aug 10, 2023)
3-47381192-T-G			Likely benign (Jun 09, 2023)
3-47381194-C-G			Likely benign (Aug 31, 2022)
3-47381195-C-T			Likely benign (Mar 15, 2021)
3-47381196-A-G			Likely benign (Feb 10, 2023)
3-47381197-T-C			Likely benign (Apr 19, 2022)
3-47381198-C-A			Likely benign (Oct 27, 2022)
3-47381199-T-TA			Likely benign (Jan 29, 2024)
3-47381200-T-A			Likely benign (Jan 29, 2024)
3-47396129-T-C			Likely benign (Jun 27, 2022)
3-47396129-TTC-T			Likely benign (Aug 23, 2022)
3-47396139-G-C			Likely benign (Dec 19, 2023)
3-47396160-T-C			Likely benign (May 01, 2023)
3-47396167-A-G			Uncertain significance (Aug 21, 2022)
3-47396200-C-T		PTPN23-related disorder	Likely benign (Jan 14, 2024)

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