PANX2

Chr 22

pannexin 2

Also known as: PX2, hPANX2

NCBI Gene: 56666ENSG00000073150UniProt: Q96RD6OMIM: 608421

Pannexin 2 is an ion channel with anion preference that also releases ATP and forms gap junctions in the central nervous system, where it is abundantly expressed alongside pannexin 1 in various neuronal populations. Mutations cause autosomal recessive developmental and epileptic encephalopathy with onset in infancy, characterized by seizures, developmental delay, and intellectual disability. The gene shows very low constraint to loss-of-function variation in the general population.

OMIMResearchSummary from RefSeq, UniProt
MultiplemechanismLOEUF 1.22
Clinical Summary— PANX2
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
140 unique Pathogenic / Likely Pathogenic· 102 VUS of 257 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Missense constrained — critical functional residues
LoF Constraint
1.22LOEUF
pLI 0.000
Z-score 0.96
OE 0.72 (0.44–1.22)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
3.35Z-score
OE missense 0.55 (0.49–0.61)
238 obs / 434.4 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios
LoF OE0.72 (0.44–1.22)
0≤0.351.4
Missense OE0.55 (0.49–0.61)
0≤0.61.4
Synonymous OE0.92
0≤1.21.6
LoF obs/exp: 10 / 13.9Missense obs/exp: 238 / 434.4Syn Z: 0.89
DN
0.7035th %ile
GOF
0.83top 10%
LOF
0.3745th %ile

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

GOFprediction above median
DNprediction 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

257 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic139
Likely Pathogenic1
VUS102
Likely Benign10
Benign2
139
Pathogenic
1
Likely Pathogenic
102
VUS
10
Likely Benign
2
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
139
0
139
Likely Pathogenic
0
0
1
0
1
VUS
1
91
10
0
102
Likely Benign
0
8
1
1
10
Benign
0
0
1
1
2
Total1991522254

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

View in ClinVar →

Protein Context — Lollipop Plot

PANX2 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 1 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients