P2RX5

Chr 17

purinergic receptor P2X 5

Also known as: LRH-1, P2X5, P2X5R

NCBI Gene: 5026 ENSG00000083454 UniProt: Q93086 OMIM: 602836

The P2RX5 protein functions as an ATP-gated ion channel that is permeable to potassium, sodium, calcium, and uniquely among P2X receptors, also chloride. Currently, no Mendelian diseases have been definitively associated with P2RX5 mutations in clinical databases. The gene shows low constraint against loss-of-function variants, suggesting that complete loss of P2RX5 function may be tolerated in humans.

OMIM ResearchSummary from RefSeq, UniProt

The product of this gene belongs to the family of purinoceptors for ATP. This receptor functions as a ligand-gated ion channel. Alternative splicing results in multiple transcript variants. Read-through transcription also exists between this gene and the neighboring downstream gene, TAX1BP3 (Tax1 binding protein 3). [provided by RefSeq, Mar 2011]

OMIM ResearchGenerating clinical summary…

GOFmechanismLOEUF 1.27

Clinical Summary— P2RX5

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

95 VUS of 112 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.27LOEUF

pLI 0.000

Z-score 0.55

OE 0.88 (0.62–1.27)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.74Z-score

OE missense 1.13 (1.03–1.25)

283 obs / 250.0 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.88 (0.62–1.27)

0≤0.351.4

Missense OE?1.13 (1.03–1.25)

0≤0.61.4

Synonymous OE?1.09

0≤1.21.6

LoF obs/exp: 21 / 23.9Missense obs/exp: 283 / 250.0Syn Z: -0.72

This gene — mechanism propensity

0.5870th %ile

GOF

0.6737th %ile

LOF

0.2971th %ile

The highest-scoring mechanism for this gene is gain-of-function.

GOFprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

112 submitted variants in ClinVar

ClinVar

Classification Summary

VUS95

Likely Benign6

Benign2

Conflicting1

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	0	0	0
Likely Pathogenic	0	0	0	0	0
VUS	1	94	0	0	95
Likely Benign	0	4	1	1	6
Benign	2	0	0	0	2
Conflicting	—				1
Total	3	98	1	1	104

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

33 pathogenic / likely-pathogenic (of 58) ClinVar copy-number / structural variants overlap P2RX5 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →