PTPN23 (protein tyrosine phosphatase non-receptor type 23)

Gene

• Entrez ID: 25930
• Gene name: Protein tyrosine phosphatase non-receptor type 23
• Gene symbol: PTPN23
• Synonyms (NCBI Gene): HD-PTP, HDPTP, NEDBASS, PTP-TD14
• Chromosome: 3
• Chromosome location: 3p21.31
• 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)

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs138076291	C>G,T	Likely-pathogenic	Missense variant, coding sequence variant
rs147293860	A>C,G	Likely-pathogenic	Coding sequence variant, missense variant
rs148689441	G>A	Likely-pathogenic	Coding sequence variant, missense variant
rs150712932	C>T	Likely-pathogenic	Coding sequence variant, missense variant
rs577689618	G>A,T	Likely-pathogenic	Missense variant, coding sequence variant
rs730882229	G>A,T	Likely-pathogenic	Missense variant, coding sequence variant
rs751809435	AAG>-	Likely-pathogenic	Coding sequence variant, inframe deletion
rs760022693	CAGCCCCATCCT>-,CAGCCCCATCCTCAGCCCCATCCT	Likely-pathogenic	Inframe deletion, inframe insertion, coding sequence variant
rs770692989	A>G	Likely-pathogenic	Coding sequence variant, missense variant
rs779096974	AGTTGCAGGTCTCCCCTCGGCCCCACC>-,AGTTGCAGGTCTCCCCTCGGCCCCACCAGTTGCAGGTCTCCCCTCGGCCCCACC	Likely-pathogenic	Inframe insertion, inframe deletion, coding sequence variant
rs967738491	C>T	Likely-pathogenic	Missense variant, coding sequence variant
rs1576235873	->CC	Likely-pathogenic	Frameshift variant, coding sequence variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT051946	hsa-let-7b-5p	CLASH	23622248
MIRT050524	hsa-miR-20a-5p	CLASH	23622248
MIRT048027	hsa-miR-148a-3p	CLASH	23622248
MIRT053242	hsa-miR-142-3p	Luciferase reporter assay, qRT-PCR, Western blot	23843459
MIRT2081113	hsa-miR-1912	CLIP-seq
MIRT2081113	hsa-miR-1912	CLIP-seq
MIRT2457454	hsa-miR-596	CLIP-seq

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0004721	Function	Phosphoprotein phosphatase activity	IEA
GO:0004725	Function	Protein tyrosine phosphatase activity	IEA
GO:0004725	Function	Protein tyrosine phosphatase activity	IMP	21724833
GO:0005515	Function	Protein binding	IPI	17174262, 18434552, 18835089, 19523899, 20936779, 21179510, 21724833, 25416956, 28514442, 31515488, 32079660, 32296183, 33961781
GO:0005634	Component	Nucleus	IDA	21179510
GO:0005634	Component	Nucleus	IEA
GO:0005654	Component	Nucleoplasm	IDA
GO:0005654	Component	Nucleoplasm	TAS
GO:0005737	Component	Cytoplasm	IDA	21179510
GO:0005737	Component	Cytoplasm	IEA
GO:0005768	Component	Endosome	IBA
GO:0005768	Component	Endosome	IDA	21179510
GO:0005768	Component	Endosome	IEA
GO:0005769	Component	Early endosome	IDA	21757351
GO:0005769	Component	Early endosome	IEA
GO:0005829	Component	Cytosol	IDA
GO:0005856	Component	Cytoskeleton	IEA
GO:0005929	Component	Cilium	IEA
GO:0010633	Process	Negative regulation of epithelial cell migration	IMP	21724833
GO:0015031	Process	Protein transport	IEA
GO:0016604	Component	Nuclear body	IDA
GO:0016787	Function	Hydrolase activity	IEA
GO:0019901	Function	Protein kinase binding	IPI	21724833
GO:0030030	Process	Cell projection organization	IEA
GO:0031410	Component	Cytoplasmic vesicle	IEA
GO:0032456	Process	Endocytic recycling	IBA
GO:0032456	Process	Endocytic recycling	IMP	24821423
GO:0034451	Component	Centriolar satellite	IDA
GO:0036064	Component	Ciliary basal body	IDA	20393563
GO:0042995	Component	Cell projection	IEA
GO:0043162	Process	Ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway	IMP	21757351
GO:0043328	Process	Protein transport to vacuole involved in ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway	IBA
GO:0045022	Process	Early endosome to late endosome transport	IBA
GO:0045022	Process	Early endosome to late endosome transport	IMP	24821423
GO:0060271	Process	Cilium assembly	IMP	20393563
GO:0061357	Process	Positive regulation of Wnt protein secretion	IMP	24821423
GO:0070062	Component	Extracellular exosome	HDA	19056867
GO:1903387	Process	Positive regulation of homophilic cell adhesion	IMP	21724833
GO:1903393	Process	Positive regulation of adherens junction organization	IMP	21724833
GO:2000643	Process	Positive regulation of early endosome to late endosome transport	IMP	21724833

Other IDs

• MIM: 606584
• HGNC: 14406
• e!Ensembl: ENSG00000076201

Protein

• UniProt ID: Q9H3S7
• Protein name: Tyrosine-protein phosphatase non-receptor type 23 (EC 3.1.3.48) (His domain-containing protein tyrosine phosphatase) (HD-PTP) (Protein tyrosine phosphatase TD14) (PTP-TD14)
• Protein 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 (PubMed:184345
• PDB: 3RAU, 5CRU, 5CRV, 5LM1, 5LM2, 5MJY, 5MJZ, 5MK0, 5MK1, 5MK2, 5MK3
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF03097	BRO1	9 → 380	BRO1-like domain	Domain
  PF13949	ALIX_LYPXL_bnd	416 → 702	ALIX V-shaped domain binding to HIV	Domain
  PF00102	Y_phosphatase	1217 → 1451	Protein-tyrosine phosphatase	Domain

• Sequence:

  MEAVPRMPMIWLDLKEAGDFHFQPAVKKFVLKNYGENPEAYNEELKKLELLRQNAVRVPR
  DFEGCSVLRKYLGQLHYLQSRVPMGSGQEAAVPVTWTEIFSGKSVAHEDIKYEQACILYN
  LGALHSMLGAMDKRVSEEGMKVSCTHFQCAAGAFAYLREHFPQAYSVDMSRQILTLNVNL
  MLGQAQECLLEKSMLDNRKSFLVARISAQVVDYYKEACRALENPDTASLLGRIQKDWKKL
  VQMKIYYFAAVAHLHMGKQAEEQQKFGERVAYFQSALDKLNEAIKLAKGQPDTVQDALRF
  TMDVIGGKYNSAKKDNDFIYHEAVPALDTLQPVKGAPLVKPLPVNPTDPAVTGPDIFAKL
  VPMAAHEASSLYSEEKAKLLREMMAKIEDKNEVLDQFMDSMQLDPETVDNLDAYSHIPPQ
  LMEKCAALSVRPDTVRNLVQSMQVLSGVFTDVEASLKDIRDLLEEDELLEQKFQEAVGQA
  GAISITSKAELAEVRREWAKYMEVHEKASFTNSELHRAMNLHVGNLRLLSGPLDQVRAAL
  PTPALSPEDKAVLQNLKRILAKVQEMRDQRVSLEQQLRELIQKDDITASLVTTDHSEMKK
  LFEEQLKKYDQLKVYLEQNLAAQDRVLCALTEANVQYAAVRRVLSDLDQKWNSTLQTLVA
  SYEAYEDLMKKSQEGRDFYADLESKVAALLERTQSTCQAREAARQQLLDRELKKKPPPRP
  TAPKPLLPRREESEAVEAGDPPEELRSLPPDMVAGPRLPDTFLGSATPLHFPPSPFPSST
  GPGPHYLSGPLPPGTYSGPTQLIQPRAPGPHAMPVAPGPALYPAPAYTPELGLVPRSSPQ
  HGVVSSPYVGVGPAPPVAGLPSAPPPQFSGPELAMAVRPATTTVDSIQAPIPSHTAPRPN
  PTPAPPPPCFPVPPPQPLPTPYTYPAGAKQPIPAQHHFSSGIPAGFPAPRIGPQPQPHPQ
  PHPSQAFGPQPPQQPLPLQHPHLFPPQAPGLLPPQSPYPYAPQPGVLGQPPPPLHTQLYP
  GPAQDPLPAHSGALPFPSPGPPQPPHPPLAYGPAPSTRPMGPQAAPLTIRGPSSAGQSTP
  SPHLVPSPAPSPGPGPVPPRPPAAEPPPCLRRGAAAADLLSSSPESQHGGTQSPGGGQPL
  LQPTKVDAAEGRRPQALRLIERDPYEHPERLRQLQQELEAFRGQLGDVGALDTVWRELQD
  AQEHDARGRSIAIARCYSLKNRHQDVMPYDSNRVVLRSGKDDYINASCVEGLSPYCPPLV
  ATQAPLPGTAADFWLMVHEQKVSVIVMLVSEAEMEKQKVARYFPTERGQPMVHGALSLAL
  SSVRSTETHVERVLSLQFRDQSLKRSLVHLHFPTWPELGLPDSPSNLLRFIQEVHAHYLH
  QRPLHTPIIVHCSSGVGRTGAFALLYAAVQEVEAGNGIPELPQLVRRMRQQRKHMLQEKL
  HLRFCYEAVVRHVEQVLQRHGVPPPCKPLASASISQKNHLPQDSQDLVLGGDVPISSIQA
  TIAKLSIRPPGGLESPVASLPGPAEPPGLPPASLPESTPIPSSSPPPLSSPLPEAPQPKE
  EPPVPEAPSSGPPSSSLELLASLTPEAFSLDSSLRGKQRMSKHNFLQAHNGQGLRATRPS
  DDPLSLLDPLWTLNKT

• Sequence length: 1636

Pathways

Reactome:

Interleukin-37 signaling

Associated diseases

Evidence Score:

• ★☆☆☆☆  Gene-disease association found in Text Mining only
• ★★☆☆☆  Found in Text Mining and Unknown/Other Associations
• ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources
• ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants)
• ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Causal
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession	Evidence Score
Brain atrophy	Likely pathogenic; Pathogenic	rs730882229, rs779096974	RCV000162148 RCV000853206	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Global developmental delay	Likely pathogenic; Pathogenic	rs730882229, rs779096974	RCV000162148 RCV000853206	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Hereditary spastic paraplegia	Likely pathogenic	rs2107730191	RCV001729907	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Neurodevelopmental disorder and structural brain anomalies with or without seizures and spasticity	Likely pathogenic; Pathogenic	rs2107713521, rs758419807, rs760750644, rs730882229, rs2546247192, rs2546247318, rs779096974, rs151119137, rs1401681748, rs1705261594, rs748130198	RCV001775221 RCV001808181 RCV002221912 RCV001171375 RCV003223536 RCV003226810 RCV001171372 RCV001171368 RCV001171369 RCV001171370 RCV001171371	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
PTPN23-related disorder	Likely pathogenic	rs2546247318	RCV003954072	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Seizure	Likely pathogenic; Pathogenic	rs730882229	RCV000162148	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
Clear cell carcinoma of kidney	Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Colon adenocarcinoma	Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Gastric cancer	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
GOUT	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Hepatocellular carcinoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Malignant tumor of urinary bladder	Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Neurodevelopmental disorder	Conflicting classifications of pathogenicity; Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
NEURODEVELOPMENTAL DISORDERS	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
NON-SPECIFIC SYNDROMIC INTELLECTUAL DISABILITY	—	Disgenet, Orphanet Disgenet, Orphanet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
PTPN23-related neurodevelopmental disorder	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SPASTIC PARAPLEGIA, HEREDITARY	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Thyroid cancer, nonmedullary, 1	Uncertain significance; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
TYPE 2 DIABETES MELLITUS	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Brain atrophy	Brain atrophy	BEFREE	29899372		★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Brain atrophy	Brain atrophy	CLINVAR_DG			★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Brain Diseases	Brain disease	Pubtator	31395947	Associate	★☆☆☆☆ Found in Text Mining only
Breast Carcinoma	Breast Carcinoma	BEFREE	21724833, 29066500		★☆☆☆☆ Found in Text Mining only
Breast Neoplasms	Breast neoplasm	Pubtator	21724833	Associate	★☆☆☆☆ Found in Text Mining only
Cerebral atrophy	Cerebral Atrophy	BEFREE	29899372		★☆☆☆☆ Found in Text Mining only
Demyelinating Diseases	Demyelinating diseases	Pubtator	29899372	Associate	★☆☆☆☆ Found in Text Mining only
Developmental Disabilities	Developmental disability	Pubtator	29899372, 31395947	Associate	★☆☆☆☆ Found in Text Mining only
Diabetes Mellitus, Non-Insulin-Dependent	Diabetes Mellitus	GWASCAT_DG	29632382		★☆☆☆☆ Found in Text Mining only
Epilepsy	Epilepsy	Pubtator	29899372	Associate	★☆☆☆☆ Found in Text Mining only
Epilepsy	Epilepsy	CLINVAR_DG			★☆☆☆☆ Found in Text Mining only
Epileptic encephalopathy	Epileptic encephalopathy	BEFREE	29090338, 29899372		★☆☆☆☆ Found in Text Mining only
Epileptic Encephalopathy Early Infantile 3	Developmental and epileptic encephalopathy	Pubtator	29899372, 31957018	Associate	★☆☆☆☆ Found in Text Mining only
Germ cell tumor	Tumor	BEFREE	23843459		★☆☆☆☆ Found in Text Mining only
Global developmental delay	Developmental Delay	CLINVAR_DG			★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Hydrocephalus	Hydrocephalus	Pubtator	31395947	Associate	★☆☆☆☆ Found in Text Mining only
Hypersensitivity Delayed	Hypersensitivity	Pubtator	31395947	Associate	★☆☆☆☆ Found in Text Mining only
Intellectual Disability	Mental retardation	GENOMICS_ENGLAND_DG	25558065		★☆☆☆☆ Found in Text Mining only
Intellectual Disability	Intellectual developmental disorder	Pubtator	31395947	Associate	★☆☆☆☆ Found in Text Mining only
Language Disorders	Language development disorders	Pubtator	31395947	Associate	★☆☆☆☆ Found in Text Mining only
Lung Neoplasms	Lung neoplasms	Pubtator	37821451	Inhibit	★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of breast	Breast Cancer	BEFREE	21724833, 29066500		★☆☆☆☆ Found in Text Mining only
Malignant Neoplasms	Malignant Neoplasm	BEFREE	27210750, 28620046		★☆☆☆☆ Found in Text Mining only
Mammary Neoplasms	Mammary Neoplasms	BEFREE	29066500		★☆☆☆☆ Found in Text Mining only
Microcephaly	Microcephaly	Pubtator	31395947	Associate	★☆☆☆☆ Found in Text Mining only
Myopia	Myopia	BEFREE	29378961		★☆☆☆☆ Found in Text Mining only
Neoplasms	Neoplasms	BEFREE	21724833, 23843459, 27210750, 28620046, 29066500		★☆☆☆☆ Found in Text Mining only
Optic Atrophy	Optic atrophy	Pubtator	31395947	Associate	★☆☆☆☆ Found in Text Mining only
Sarcoidosis	Sarcoidosis	BEFREE	19946248		★☆☆☆☆ Found in Text Mining only
Seizures	Seizures	Pubtator	31395947	Associate	★☆☆☆☆ Found in Text Mining only