PTPRQ

protein-coding

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

Gene summary

This locus encodes a member of the type III receptor-like protein-tyrosine phosphatase family. The encoded protein catalyzes the dephosphorylation of phosphotyrosine and phosphatidylinositol and plays roles in cellular proliferation and differentiation. Mutations at this locus have been linked to autosomal recessive deafness. [provided by RefSeq, Mar 2014]

Previous symbols:

DFNB84

MANE transcript

NM_001145026.2

Inheritance

AR, SD, AD

ClinVar variants

P:85U:301B:102

Top phenotype

Deafness, autosomal recessive 84

gnomAD constraint

pLI —, LoF o/e 0.55

Max pathogenic AF

—

Genomic locus

chr12:80,402,178-80,680,273

External References & Databases

Ensembl (ENSG00000139304)

Transcript & Mutation Effects

hg38 • Region Span ~278.1 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

autosomal recessive nonsyndromic hearing loss 84ASTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0013249

Submitter: PanelApp Australia

autosomal recessive nonsyndromic hearing loss 84AMODERATE

Inheritance Pattern: SD

Disease ID:MONDO:0013249

Submitter: Ambry Genetics

autosomal recessive nonsyndromic hearing loss 84ASTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0013249

Submitter: G2P

hearing loss, autosomal recessiveSUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0019588

Submitter: Orphanet

hearing loss, autosomal dominant 73LIMITED

Inheritance Pattern: Unknown

Disease ID:MONDO:0033260

Submitter: Labcorp Genetics (formerly Invitae)

autosomal recessive nonsyndromic hearing loss 84ASTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0013249

Submitter: Labcorp Genetics (formerly Invitae)

hearing loss, autosomal dominant 73LIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0033260

Submitter: Ambry Genetics

autosomal recessive nonsyndromic hearing loss 84ADEFINITIVE

Inheritance Pattern: AR

Disease ID:MONDO:0013249

Submitter: Ambry Genetics

autosomal dominant nonsyndromic hearing lossSUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0019587

Submitter: Orphanet

hearing loss, autosomal recessiveDEFINITIVE

Inheritance Pattern: Unknown

Disease ID:MONDO:0019588

Submitter: ClinGen

hearing loss, autosomal dominant 73STRONG

Inheritance Pattern: AD

Disease ID:MONDO:0033260

Submitter: PanelApp Australia

Clinical Genomic Database (CGD)

Deafness, autosomal recessive 84AR

Manifestation: Audiologic/Otolaryngologic

Intervention: Audiologic/Otolaryngologic

Rationale: Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development

Comments: In Deafness, autosomal dominant 73, the onset of hearing loss has been described as variable but typically postlingual

Refs: 19888295; 20346435

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to PTPRQ variants in ClinVar

20 Conditions Cataloged

not providedTotal: 425

PTPRQ-related disorderTotal: 126

Autosomal recessive nonsyndromic hearing loss 84ATotal: 71

not specifiedTotal: 56

Hearing loss, autosomal dominant 73Total: 24

Inborn genetic diseasesTotal: 9

Hearing loss, autosomal recessiveTotal: 8

Hearing impairmentTotal: 7

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001145026.2. 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		16 clinvar	47 clinvar	4 clinvar	68
missense	1 clinvar	1 clinvar	279 clinvar	37 clinvar	13 clinvar	331
nonsense	9 clinvar	21 clinvar			1 clinvar	31
start loss		2 clinvar				2
frameshift	10 clinvar	23 clinvar	1 clinvar			34
splice donor/acceptor (+/-2bp)	5 clinvar	12 clinvar	5 clinvar			22
Total	26	59	301	84	18	488

Highest pathogenic variant AF is 0.00008587116

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 7 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001145026.2	RefSeq	NP_001138498.1	45	MANE Select
ENST00000644991.3	Ensembl	ENSP00000495607.1	45	MANE Select
ENST00000547376.5	Ensembl	ENSP00000448844.1	8	Standard
ENST00000547881.1	Ensembl	ENSP00000449526.1	5	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

peptidyl-tyrosine dephosphorylation
regulation of fat cell differentiation

Molecular Function

protein tyrosine phosphatase activity

Cellular Component

integral component of membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000266688
Coding exons: 50
Length: 273029
Individuals with no LoFs: 0
Homozygous LoFs: 0
Heterozygous LoFs: 0
Defined: 0
p: 0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.999	838	923	0.908	0.0000450	14874
Missense (PolyPhen)		285	337.62	0.84414		5371
Synonymous	0.177	324	328	0.988	0.0000174	4365
Loss of Function	3.93	48	87.8	0.547	0.00000440	1494

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0	0.0	absent
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Phosphatidylinositol phosphatase required for auditory function. May act by regulating the level of phosphatidylinositol 4,5-bisphosphate (PIP2) level in the basal region of hair bundles. Can dephosphorylate a broad range of phosphatidylinositol phosphates, including phosphatidylinositol 3,4,5-trisphosphate and most phosphatidylinositol monophosphates and diphosphates. Phosphate can be hydrolyzed from the D3 and D5 positions in the inositol ring. Has low tyrosine-protein phosphatase activity; however, the relevance of such activity in vivo is unclear. Plays an important role in adipogenesis of mesenchymal stem cells (MSCs). Regulates the phosphorylation state of AKT1 by suppressing the phosphatidylinositol 3,4,5-trisphosphate (PIP3) level in MSCs and preadipocyte cells. {ECO:0000269|PubMed:19351528}.;
Disease: DISEASE: Deafness, autosomal recessive, 84A (DFNB84A) [MIM:613391]: A form of non-syndromic deafness characterized by progressive, sensorineural hearing loss and vestibular dysfunction. {ECO:0000269|PubMed:20346435, ECO:0000269|PubMed:20472657}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Deafness, autosomal dominant, 73 (DFNA73) [MIM:617663]: A form of non-syndromic hearing loss characterized by mild to severe bilateral symptoms with variable age of onset from early childhood to the third decade. {ECO:0000269|PubMed:29309402}. Note=The disease may be caused by mutations affecting the gene represented in this entry.;

Recessive Scores

pRec: 0.105

Essentials

Essential (CRISPR2): N
Indispensability pred.: N
Indispensability score: 0.135

Gene Damage Prediction

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