PTPA

protein phosphatase 2 phosphatase activator, the group of Cyclophilin peptidylprolyl isomerases|Protein phosphatase 2 modulatory subunits

Basic information

Region (hg38): 9:129110949-129148946

Previous symbols: [ "PPP2R4" ]

Links

ENSG00000119383 ∙ NCBI:5524 ∙ OMIM:600756 ∙ HGNC:9308 ∙ Uniprot:Q15257 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Parkinson disease 25, autosomal recessive early-onset, with impaired intellectual development	AR	Neurologic	Levodopa has been described as beneficial in individuals with Parkinson disease	Neurologic	36073231

ClinVar

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

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PTPA 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				1	3	4
missense			1		3	4
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region				1		1
non coding			1	1		2
Total	0	0	2	2	6

Variants in PTPA

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

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

Position	Type	Phenotype	Significance	ClinVar
9-129120506-T-G			Likely benign (Apr 07, 2018)
9-129123135-C-T			Benign (Jun 01, 2018)
9-129123136-G-C		not specified	Uncertain significance (Jul 09, 2021)
9-129128034-C-T		not specified	Uncertain significance (Sep 17, 2021)
9-129129094-A-G			Benign (Jul 20, 2018)
9-129131586-C-A		Parkinson disease 25, autosomal recessive early-onset, with impaired intellectual development	Pathogenic (Aug 22, 2023)
9-129134852-G-A			Benign (Jul 15, 2018)
9-129134882-A-C			Benign (Jul 20, 2018)
9-129136522-C-T			Benign (Aug 24, 2018)
9-129142436-C-G			Likely benign (Jun 16, 2018)
9-129142446-T-G		Parkinson disease 25, autosomal recessive early-onset, with impaired intellectual development	Pathogenic (Aug 22, 2023)
9-129142498-C-T			Benign (Jul 20, 2018)
9-129147458-G-C			Likely benign (Jul 12, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PTPA	protein_coding	protein_coding	ENST00000393370	10	37997

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.991	0.00943	125742	0	5	125747	0.0000199

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.69	124	190	0.654	0.0000107	2127
Missense in Polyphen		22	68.001	0.32352		752
Synonymous	-0.322	79	75.4	1.05	0.00000477	611
Loss of Function	3.76	1	18.4	0.0543	7.84e-7	219

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000119	0.000119
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.00000882	0.00000879
Middle Eastern	0.00	0.00
South Asian	0.0000327	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: PPIases accelerate the folding of proteins. It catalyzes the cis-trans isomerization of proline imidic peptide bonds in oligopeptides. Acts as a regulatory subunit for serine/threonine- protein phosphatase 2A (PP2A) modulating its activity or substrate specificity, probably by inducing a conformational change in the catalytic subunit, a proposed direct target of the PPIase. Can reactivate inactive phosphatase PP2A-phosphatase methylesterase complexes (PP2A(i)) in presence of ATP and Mg(2+) (By similarity). Reversibly stimulates the variable phosphotyrosyl phosphatase activity of PP2A core heterodimer PP2A(D) in presence of ATP and Mg(2+) (in vitro). The phosphotyrosyl phosphatase activity is dependent of an ATPase activity of the PP2A(D):PPP2R4 complex. Is involved in apoptosis; the function appears to be independent from PP2A. {ECO:0000250, ECO:0000269|PubMed:16916641, ECO:0000269|PubMed:17333320}.
• Pathway: Insulin resistance - Homo sapiens (human);miR-targeted genes in epithelium - TarBase;miR-targeted genes in leukocytes - TarBase;miR-targeted genes in lymphocytes - TarBase;miR-targeted genes in muscle cell - TarBase;Interleukin-11 Signaling Pathway;Constitutive Androstane Receptor Pathway;Nuclear Receptors Meta-Pathway;ATM Signaling Network in Development and Disease;Wnt Signaling Pathway and Pluripotency;Glycogen Metabolism;GPCR Dopamine D1like receptor;insulin Mam;Validated targets of C-MYC transcriptional repression;p53 pathway;insulin (Consensus)

Recessive Scores

• pRec: 0.353

Intolerance Scores

• rvis_EVS: -0.01
• rvis_percentile_EVS: 53.51

Haploinsufficiency Scores

• pHI: 0.0941
• hipred: Y
• hipred_score: 0.794
• ghis: 0.491

Essentials

• essential_gene_gene_trap: E

Mouse Genome Informatics

• Gene name: Ptpa
• 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)

Gene ontology

• Biological process: protein peptidyl-prolyl isomerization;mitotic spindle organization;negative regulation of phosphoprotein phosphatase activity;positive regulation of phosphoprotein phosphatase activity;positive regulation of protein dephosphorylation;negative regulation of protein dephosphorylation;positive regulation of apoptotic process;regulation of phosphoprotein phosphatase activity
• Cellular component: protein phosphatase type 2A complex;nucleus;nucleoplasm;cytoplasm;calcium channel complex;extracellular exosome
• Molecular function: peptidyl-prolyl cis-trans isomerase activity;signaling receptor binding;protein binding;ATP binding;protein tyrosine phosphatase activator activity;ATPase activity;protein phosphatase regulator activity;protein homodimerization activity;protein heterodimerization activity;protein phosphatase 2A binding