PTPRD

protein-coding

protein tyrosine phosphatase receptor type D, the group of Fibronectin type III domain containing|I-set domain containing|Protein tyrosine phosphatases receptor type

Gene summary

The protein encoded by this gene is a member of the protein tyrosine phosphatase (PTP) family. PTPs are known to be signaling molecules that regulate a variety of cellular processes including cell growth, differentiation, mitotic cycle, and oncogenic transformation. This PTP contains an extracellular region, a single transmembrane segment and two tandem intracytoplasmic catalytic domains, and thus represents a receptor-type PTP. The extracellular region of this protein is composed of three Ig-like and eight fibronectin type III-like domains. Studies of the similar genes in chicken and fly suggest the role of this PTP is in promoting neurite growth, and regulating neurons axon guidance. Multiple alternatively spliced transcript variants of this gene have been reported. A related pseudogene has been identified on chromosome 5. [provided by RefSeq, Jan 2010]

MANE transcript

NM_002839.4

Inheritance

—

ClinVar variants

U:244B:54

Top phenotype

PTPRD-related disorder

gnomAD constraint

pLI —, LoF o/e 0.05

Max pathogenic AF

—

Genomic locus

chr9:8,314,246-10,613,002

External References & Databases

Ensembl (ENSG00000153707)

Transcript & Mutation Effects

hg38 • Region Span ~2,298.8 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to PTPRD variants in ClinVar

6 Conditions Cataloged

not specifiedTotal: 222

PTPRD-related disorderTotal: 51

not providedTotal: 40

EBV-positive nodal T- and NK-cell lymphomaTotal: 1

Neurodevelopmental disorderTotal: 1

Prostate cancerTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_002839.4. 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.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			1 clinvar	33 clinvar	10 clinvar	44
missense			235 clinvar	8 clinvar	3 clinvar	246
nonsense			3 clinvar			3
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			5 clinvar			5
Total	0	0	244	41	13	298

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 82 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_002839.4	RefSeq	NP_002830.1	35	MANE Select
ENST00000381196.9	Ensembl	ENSP00000370593.3	35	MANE Select
NM_001040712.2	RefSeq	NP_001035802.1	30	Standard
NM_001171025.2	RefSeq	NP_001164496.1	29	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Neuronal System
Synaptic adhesion-like molecules
Receptor-type tyrosine-protein phosphatases
Protein-protein interactions at synapses

Biological Process

protein dephosphorylation
phosphate-containing compound metabolic process
heterophilic cell-cell adhesion via plasma membrane cell adhesion molecules
transmembrane receptor protein tyrosine phosphatase signaling pathway
neuron differentiation

Molecular Function

transmembrane receptor protein tyrosine phosphatase activity
signaling receptor binding
protein binding
cell adhesion molecule binding

Cellular Component

plasma membrane
integral component of plasma membrane
extracellular exosome
glutamatergic synapse

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000381196
Coding exons: 35
Length: 2298478
Individuals with no LoFs: 125730
Homozygous LoFs: 0
Heterozygous LoFs: 17
Defined: 125747
p: 0.0000676

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.273	1058	1.08e+3	0.977	0.0000604	12469
Missense (PolyPhen)		605	718.29	0.84228		8268
Synonymous	-5.58	536	395	1.36	0.0000229	3744
Loss of Function	8.52	5	94.2	0.0531	0.00000483	1139

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00027	0.00025	rare
Latino/Admixed American	0.000058	0.000058	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.000054	0.000054	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000062	0.000062	rare
South Asian	0.000073	0.000065	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Can bidirectionally induce pre- and post-synaptic differentiation of neurons by mediating interaction with IL1RAP and IL1RAPL1 trans-synaptically. Involved in pre-synaptic differentiation through interaction with SLITRK2. {ECO:0000250|UniProtKB:Q64487}.;

Recessive Scores

pRec: 0.174

Intolerance Scores

LoFtool: 0.0868
RVIS EVS: -3.08
RVIS percentile EVS: 0.48

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Indispensability pred.: E
Indispensability score: 0.773

Gene Damage Prediction

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