PTPRO

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

Basic information

Region (hg38): 12:15322257-15602175

Links

ENSG00000151490 ∙ NCBI:5800 ∙ OMIM:600579 ∙ HGNC:9678 ∙ Uniprot:Q16827 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• nephrotic syndrome, type 6 (Limited), mode of inheritance: AR
• familial idiopathic steroid-resistant nephrotic syndrome (Supportive), mode of inheritance: AD
• nephrotic syndrome, type 6 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Nephrotic syndrome, type 6	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	Renal	21722858
Renal transplant has been described

ClinVar

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

• not provided (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PTPRO 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			2	42	7	51
missense			75	9	1	85
nonsense	1					1
start loss						0
frameshift	1					1
inframe indel			1			1
splice donor/acceptor (+/-2bp)		2				2
splice region				10	1	11
non coding			2	59	68	129
Total	2	2	80	110	76

Variants in PTPRO

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

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

Position	Type	Phenotype	Significance	ClinVar
12-15322293-G-A			Benign (Nov 12, 2018)
12-15322748-A-C		not specified	Uncertain significance (Aug 16, 2022)
12-15322749-T-C			Uncertain significance (Apr 20, 2022)
12-15322757-G-A		not specified	Uncertain significance (Jan 23, 2023)
12-15322757-G-T		PTPRO-related disorder	Benign (Nov 14, 2023)
12-15322773-C-G		not specified	Uncertain significance (Oct 29, 2021)
12-15322786-C-G		PTPRO-related disorder	Likely benign (Jun 27, 2022)
12-15322799-A-G			Uncertain significance (Dec 13, 2021)
12-15322810-G-C			Likely benign (Jun 01, 2022)
12-15416571-G-A		PTPRO-related disorder	Uncertain significance (Jan 19, 2023)
12-15483865-A-G			Likely benign (Apr 03, 2020)
12-15483958-C-G			Likely benign (Dec 14, 2023)
12-15483987-T-C		not specified	Uncertain significance (Aug 22, 2023)
12-15484006-T-C			Benign (Jan 25, 2024)
12-15484007-G-A		not specified	Uncertain significance (Aug 26, 2022)
12-15484007-GATA-G			Uncertain significance (Jul 05, 2022)
12-15484018-C-T			Likely benign (Aug 07, 2022)
12-15484153-G-A		PTPRO-related disorder	Likely benign (Jul 18, 2022)
12-15484234-C-T			Likely benign (Dec 21, 2023)
12-15484402-C-T			Benign (Feb 03, 2020)
12-15484458-C-A			Benign (Feb 03, 2020)
12-15484466-T-G			Benign (Nov 12, 2018)
12-15496965-T-C			Benign (Nov 12, 2018)
12-15497230-ACTTCAC-A			Likely benign (Jun 19, 2022)
12-15497392-T-C		Nephrotic syndrome, type 6 • not specified	Uncertain significance (May 04, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PTPRO	protein_coding	protein_coding	ENST00000281171	26	275003

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0000119	1.00	125705	0	43	125748	0.000171

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.30	561	655	0.857	0.0000340	8037
Missense in Polyphen		151	233.97	0.64539		2816
Synonymous	-1.69	273	240	1.14	0.0000137	2272
Loss of Function	4.97	21	63.8	0.329	0.00000306	784

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000817	0.000817
Ashkenazi Jewish	0.000399	0.000397
East Asian	0.000109	0.000109
Finnish	0.0000932	0.0000924
European (Non-Finnish)	0.000159	0.000158
Middle Eastern	0.000109	0.000109
South Asian	0.00	0.00
Other	0.000327	0.000326

dbNSFP

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.
• Pathway: Primary Focal Segmental Glomerulosclerosis FSGS;Signaling events mediated by Stem cell factor receptor (c-Kit) (Consensus)

Intolerance Scores

• loftool: 0.150
• rvis_EVS: -1.97
• rvis_percentile_EVS: 1.83

Haploinsufficiency Scores

• pHI: 0.574
• hipred: Y
• hipred_score: 0.550
• ghis: 0.566

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.657

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Ptpro
• Phenotype: normal phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); renal/urinary system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan)

Zebrafish Information Network

• Gene name: ptpro
• Affected structure: post-vent region
• Phenotype tag: abnormal
• Phenotype quality: curved

Gene ontology

• Biological process: cell morphogenesis;monocyte chemotaxis;regulation of glomerular filtration;negative regulation of glomerular filtration;protein dephosphorylation;axon guidance;negative regulation of cell-substrate adhesion;negative regulation of neuron projection development;lamellipodium assembly;glomerulus development;peptidyl-tyrosine dephosphorylation;slit diaphragm assembly;regulation of synapse organization;glomerular visceral epithelial cell differentiation;negative regulation of canonical Wnt signaling pathway;negative regulation of retinal ganglion cell axon guidance
• Cellular component: plasma membrane;integral component of plasma membrane;integral component of membrane;apical plasma membrane;lateral plasma membrane;lamellipodium;axon;growth cone;neuron projection;dendritic spine;extracellular exosome;glutamatergic synapse;GABA-ergic synapse;integral component of postsynaptic density membrane
• Molecular function: protein tyrosine phosphatase activity;transmembrane receptor protein tyrosine phosphatase activity;protein binding;phosphatase activity;Wnt-protein binding;protein homodimerization activity