GeneBe

PTPRO

protein-coding

protein tyrosine phosphatase receptor type O, the group of Fibronectin type III domain containing|Protein tyrosine phosphatases receptor type

Gene summary

This gene encodes a member of the R3 subtype family of receptor-type protein tyrosine phosphatases. These proteins are localized to the apical surface of polarized cells and may have tissue-specific functions through activation of Src family kinases. This gene contains two distinct promoters, and alternatively spliced transcript variants encoding multiple isoforms have been observed. The encoded proteins may have multiple isoform-specific and tissue-specific functions, including the regulation of osteoclast production and activity, inhibition of cell proliferation and facilitation of apoptosis. This gene is a candidate tumor suppressor, and decreased expression of this gene has been observed in several types of cancer. [provided by RefSeq, May 2011]

MANE transcript

NM_030667.3

Inheritance

AD, AR

ClinVar variants

P:10U:271B:99

Top phenotype

Nephrotic syndrome, type 6

gnomAD constraint

pLI —, LoF o/e 0.33

Max pathogenic AF

—

Genomic locus

chr12:15,322,257-15,602,175

External References & Databases

Ensembl (ENSG00000151490)NCBI Gene (5800)OMIM (600579)HGNC:9678GenCCUniProt (Q16827)AlphaFoldClinVar (PTPRO)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~279.9 kb
Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

familial idiopathic steroid-resistant nephrotic syndromeSUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0019006

Submitter: Orphanet

nephrotic syndrome, type 6LIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0013619

Submitter: Ambry Genetics

nephrotic syndrome, type 6STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0013619

Submitter: PanelApp Australia

nephrotic syndrome, type 6STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0013619

Submitter: Labcorp Genetics (formerly Invitae)

Clinical Genomic Database (CGD)

Nephrotic syndrome, type 6AR

Manifestation: Renal

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

Comments: Renal transplant has been described

Refs: 21722858Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to PTPRO variants in ClinVar

6 Conditions Cataloged
not providedTotal: 224
Nephrotic syndrome, type 6Total: 156
not specifiedTotal: 153
PTPRO-related disorderTotal: 42
Corticosteroids responseTotal: 2
Focal segmental glomerulosclerosisTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_030667.3. 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
19
clinvar
83
clinvar
1
clinvar
 103
missense
245
clinvar
15
clinvar
 260
nonsense
1
clinvar
1
clinvar
 2
start loss
0
frameshift
2
clinvar
2
clinvar
2
clinvar
 6
splice donor/acceptor (+/-2bp)
2
clinvar
3
clinvar
4
clinvar
 9
Total55271981380

Highest pathogenic variant AF is 0.000006569094

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 37 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_030667.3RefSeqNP_109592.126MANE Select
ENST00000281171.9EnsemblENSP00000281171.426MANE Select
NM_002848.4RefSeqNP_002839.125Standard
NM_030668.3RefSeqNP_109593.112Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / ModelOrganismObserved Phenotype
ptproDanio rerio

Structure: post-vent region

Quality: curved

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

  • Primary Focal Segmental Glomerulosclerosis FSGS
  • Signaling events mediated by Stem cell factor receptor (c-Kit)

Biological Process

  • cell morphogenesis
  • monocyte chemotaxis
  • regulation of glomerular filtration
  • negative regulation of glomerular filtration
  • protein dephosphorylation

Molecular Function

  • protein tyrosine phosphatase activity
  • transmembrane receptor protein tyrosine phosphatase activity
  • protein binding
  • phosphatase activity
  • Wnt-protein binding

Cellular Component

  • plasma membrane
  • integral component of plasma membrane
  • integral component of membrane
  • apical plasma membrane
  • lateral plasma membrane

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000281171
Coding exons
26
Length
275003
Individuals with no LoFs
125705
Homozygous LoFs
0
Heterozygous LoFs
43
Defined
125748
p
0.000171
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense1.305616550.8570.00003408037
Missense (PolyPhen)151233.970.645392816
Synonymous-1.692732401.140.00001372272
Loss of Function4.972163.80.3290.00000306784

Population LoF Frequency

PopulationCAFp-valueStatus
African0.000120.00012rare
Latino/Admixed American0.000690.00038rare
Ashkenazi Jewish0.000400.00040rare
East Asian0.000110.00011rare
Finnish0.0000930.000092rare
European (Non-Finnish)0.000160.00016rare
South Asian00.0absent
Other0.000330.00033rare

dbNSFP Gene Annotations

Source: dbNSFP

Function
FUNCTION: Possesses tyrosine phosphatase activity. Plays a role in regulating the glomerular pressure/filtration rate relationship through an effect on podocyte structure and function (By similarity). {ECO:0000250, ECO:0000269|PubMed:19167335}.;
Disease
DISEASE: Nephrotic syndrome 6 (NPHS6) [MIM:614196]: A form of nephrotic syndrome, a renal disease clinically characterized by severe proteinuria, resulting in complications such as hypoalbuminemia, hyperlipidemia and edema. Kidney biopsies show non-specific histologic changes such as focal segmental glomerulosclerosis and diffuse mesangial proliferation. Some affected individuals have an inherited steroid-resistant form and progress to end-stage renal failure. {ECO:0000269|PubMed:21722858}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Intolerance Scores

LoFtool
0.150
RVIS EVS
-1.97
RVIS percentile EVS
1.83

Essentials

Essential (CRISPR)
N
Essential (CRISPR2)
N
Essential (gene trap)
N
Indispensability pred.
E
Indispensability score
0.657

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium
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