P2RX2

purinergic receptor P2X 2, the group of Purinergic receptors P2X

Basic information

Region (hg38): 12:132618775-132622388

Previous symbols: [ "DFNA41" ]

Links

ENSG00000187848 ∙ ∙ OMIM:600844 ∙ HGNC:15459 ∙ Uniprot:Q9UBL9 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• autosomal dominant nonsyndromic hearing loss 41 (Strong), mode of inheritance: AD
• autosomal dominant nonsyndromic hearing loss 41 (Limited), mode of inheritance: AD
• autosomal dominant nonsyndromic hearing loss 41 (Strong), mode of inheritance: AD
• autosomal dominant nonsyndromic hearing loss (Supportive), mode of inheritance: AD
• nonsyndromic genetic hearing loss (Moderate), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Deafness, autosomal dominant 41	AD	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	Audiologic/Otolaryngologic	12161595; 23345450; 24211385

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the P2RX2 gene.

• not provided (153 variants)
• not specified (39 variants)
• Inborn genetic diseases (26 variants)
• Autosomal dominant nonsyndromic hearing loss 41 (11 variants)
• P2RX2-related condition (2 variants)
• Bilateral sensorineural hearing impairment (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the P2RX2 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			1	18	6	25
missense	2		64	16	2	84
nonsense			4	2	1	7
start loss						0
frameshift			4	2		6
inframe indel			4			4
splice donor/acceptor (+/-2bp)			3			3
splice region			1	1	3	5
non coding			2	24	18	44
Total	2	0	82	62	27

Highest pathogenic variant AF is 0.00000657

Variants in P2RX2

This is a list of pathogenic ClinVar variants found in the P2RX2 region.

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

Position	Type	Phenotype	Significance	ClinVar
12-132618781-T-A			Likely benign (Jul 23, 2018)
12-132618781-T-C		not specified	Benign (May 09, 2017)
12-132618807-C-T		not specified	Likely benign (Dec 12, 2018)
12-132618823-G-T		not specified	Uncertain significance (Jan 29, 2024)
12-132618825-C-T		not specified	Benign (Jan 22, 2024)
12-132618851-C-T			Uncertain significance (Apr 06, 2023)
12-132618855-C-T			Uncertain significance (Apr 12, 2023)
12-132618856-G-A		not specified	Uncertain significance (Apr 06, 2022)
12-132618856-G-C			Uncertain significance (Jun 16, 2022)
12-132618858-C-T		P2RX2-related disorder	Benign/Likely benign (Jan 16, 2024)
12-132618863-G-T			Uncertain significance (Apr 08, 2022)
12-132618872-G-A		not specified	Conflicting classifications of pathogenicity (Nov 15, 2021)
12-132618874-G-A			Uncertain significance (May 06, 2022)
12-132618878-G-A		P2RX2-related disorder	Benign/Likely benign (Dec 21, 2023)
12-132618880-T-C			Uncertain significance (Mar 04, 2023)
12-132618901-G-T			Uncertain significance (Nov 22, 2022)
12-132618913-G-A			Uncertain significance (Jul 12, 2022)
12-132618934-C-A		not specified	Conflicting classifications of pathogenicity (May 24, 2023)
12-132618951-C-T			Likely benign (Jan 24, 2024)
12-132618952-C-A			Uncertain significance (Mar 14, 2022)
12-132618954-C-T			Likely benign (Dec 31, 2019)
12-132618959-T-G			Uncertain significance (Dec 30, 2021)
12-132618991-TGCGCGGGGCGCGGGGTGCGGG-T			Uncertain significance (Sep 21, 2021)
12-132618993-CGCGGGGCGCGGGGT-C		Autosomal dominant nonsyndromic hearing loss 41	Benign (Jan 31, 2024)
12-132619007-TGCGGGGC-T			Likely benign (Aug 17, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
P2RX2	protein_coding	protein_coding	ENST00000343948	10	3607

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
9.65e-13	0.0415	125452	1	292	125745	0.00117

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.232	285	296	0.962	0.0000171	3204
Missense in Polyphen		102	111.21	0.91721		1305
Synonymous	-0.610	137	128	1.07	0.00000824	1003
Loss of Function	0.180	19	19.9	0.957	8.47e-7	232

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000651	0.000632
Ashkenazi Jewish	0.0000992	0.0000992
East Asian	0.000381	0.000381
Finnish	0.00725	0.00686
European (Non-Finnish)	0.000938	0.000897
Middle Eastern	0.000381	0.000381
South Asian	0.000473	0.000457
Other	0.000500	0.000489

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Ion channel gated by extracellular ATP involved in a variety of cellular responses, such as excitatory postsynaptic responses in sensory neurons, neuromuscular junctions (NMJ) formation, hearing, perception of taste and peristalsis. In the inner ear, regulates sound transduction and auditory neurotransmission, outer hair cell electromotility, inner ear gap junctions, and K(+) recycling. Mediates synaptic transmission between neurons and from neurons to smooth muscle. {ECO:0000269|PubMed:23345450}.
• Disease: DISEASE: Deafness, autosomal dominant, 41 (DFNA41) [MIM:608224]: A form of non-syndromic deafness characterized by onset of progressive sensorineural hearing loss usually in the second decade. The hearing loss is severe and ultimately affects all frequencies. Exposure to noise exacerbates the hearing loss, particularly at high frequencies. {ECO:0000269|PubMed:23345450, ECO:0000269|PubMed:24211385}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Calcium signaling pathway - Homo sapiens (human);Neuroactive ligand-receptor interaction - Homo sapiens (human);Taste transduction - Homo sapiens (human);Hemostasis;Elevation of cytosolic Ca2+ levels;Platelet calcium homeostasis;Platelet homeostasis (Consensus)

Recessive Scores

• pRec: 0.162

Intolerance Scores

• loftool: 0.988
• rvis_EVS: -0.62
• rvis_percentile_EVS: 17.31

Haploinsufficiency Scores

• pHI: 0.464
• hipred: N
• hipred_score: 0.328
• ghis: 0.502

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.117

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: P2rx2
• Phenotype: immune system phenotype; 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); 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); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); respiratory system phenotype

Gene ontology

• Biological process: response to hypoxia;response to ischemia;detection of hypoxic conditions in blood by carotid body chemoreceptor signaling;cation transport;neuromuscular synaptic transmission;neuromuscular junction development;blood coagulation;sensory perception of sound;response to carbohydrate;positive regulation of calcium ion transport into cytosol;urinary bladder smooth muscle contraction;peristalsis;response to ATP;ion transmembrane transport;purinergic nucleotide receptor signaling pathway;behavioral response to pain;skeletal muscle fiber development;positive regulation of calcium-mediated signaling;sensory perception of taste;protein homooligomerization;excitatory postsynaptic potential;cation transmembrane transport
• Cellular component: integral component of nuclear inner membrane;plasma membrane;integral component of plasma membrane;integral component of membrane;apical plasma membrane;neuronal cell body;receptor complex;postsynapse
• Molecular function: purinergic nucleotide receptor activity;extracellularly ATP-gated cation channel activity;ATP binding;ligand-gated ion channel activity;ATP-gated ion channel activity;identical protein binding