PTPRH

protein-coding

protein tyrosine phosphatase receptor type H, the group of Fibronectin type III 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 possesses an extracellular region, a single transmembrane region, and a single intracytoplasmic catalytic domain, and thus represents a receptor-type PTP. The extracellular region contains eight fibronectin type III-like repeats and multiple N-glycosylation sites. The gene was shown to be expressed primarily in brain and liver, and at a lower level in heart and stomach. It was also found to be expressed in several cancer cell lines, but not in the corresponding normal tissues. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jun 2009]

MANE transcript

NM_002842.5

Inheritance

—

ClinVar variants

U:216B:29

Top phenotype

PTPRH-related disorder

gnomAD constraint

pLI —, LoF o/e 0.95

Max pathogenic AF

—

Genomic locus

chr19:55,181,247-55,209,506

External References & Databases

Ensembl (ENSG00000080031)

Transcript & Mutation Effects

hg38 • Region Span ~28.3 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 PTPRH variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 228

not providedTotal: 2

PTPRH-related disorderTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_002842.5. 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			2 clinvar	2 clinvar		4
missense			211 clinvar	27 clinvar		238
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	216	29	0	245

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 51 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_002842.5	RefSeq	NP_002833.4	20	MANE Select
ENST00000376350.8	Ensembl	ENSP00000365528.2	20	MANE Select
NM_001161440.3	RefSeq	NP_001154912.2	18	Standard
ENST00000263434.5	Ensembl	ENSP00000263434.4	18	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Biological Process

protein dephosphorylation
apoptotic process
peptidyl-tyrosine dephosphorylation

Molecular Function

transmembrane receptor protein tyrosine phosphatase activity
protein binding

Cellular Component

cytoplasm
integral component of plasma membrane
apical plasma membrane
microvillus membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000376350
Coding exons: 20
Length: 28259
Individuals with no LoFs: 124373
Homozygous LoFs: 9
Heterozygous LoFs: 1366
Defined: 125748
p: 0.00548

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.793	711	654	1.09	0.0000378	7192
Missense (PolyPhen)		198	203.36	0.97365		2328
Synonymous	-0.502	294	283	1.04	0.0000192	2279
Loss of Function	0.375	57	60.1	0.948	0.00000319	594

Population LoF Frequency

Population	CAF	p-value	Status
African	0.0013	0.0013	notable
Latino/Admixed American	0.0059	0.0058	notable
Ashkenazi Jewish	0.025	0.024	notable
East Asian	0.0013	0.0013	notable
Finnish	0.00097	0.00097	rare
European (Non-Finnish)	0.0061	0.0060	notable
South Asian	0.0044	0.0044	notable
Other	0.0082	0.0082	notable

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Protein phosphatase that may contribute to contact inhibition of cell growth and motility by mediating the dephosphorylation of focal adhesion-associated substrates and thus negatively regulating integrin-promoted signaling processes. Induces apoptotic cell death by at least two distinct mechanisms: inhibition of cell survival signaling mediated by PI 3-kinase, Akt, and ILK and activation of a caspase-dependent proapoptotic pathway. Inhibits the basal activity of LCK and its activation in response to TCR stimulation and TCR-induced activation of MAP kinase and surface expression of CD69. Inhibits TCR-induced tyrosine phosphorylation of LAT and ZAP70. Inhibits both basal activity of DOK1 and its CD2-induced tyrosine phosphorylation. Induces dephosphorylation of BCAR1, focal adhesion kinase and SRC. Reduces migratory activity of activity of Jurkat cells. Reduces tyrosine phosphorylation of CEACAM20 and thereby contributes to suppress the intestinal immune response CEACAM20 (By similarity). {ECO:0000250|UniProtKB:E9Q0N2, ECO:0000269|PubMed:11278335, ECO:0000269|PubMed:12101188, ECO:0000269|PubMed:12837766, ECO:0000269|PubMed:15850787}.;

Intolerance Scores

LoFtool: 0.573
RVIS EVS: 1.11
RVIS percentile EVS: 92.07

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.581

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	High	High	High
Primary Immunodeficiency	High	High	High
Cancer	High	High	High