PANX2

Chr 22

pannexin 2

Also known as: PX2, hPANX2

NCBI Gene: 56666 ENSG00000073150 UniProt: Q96RD6 OMIM: 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.

OMIM ResearchSummary from RefSeq, UniProt

The protein encoded by this gene belongs to the innexin family. Innexin family members are the structural components of gap junctions. This protein and pannexin 1 are abundantly expressed in central nervous system (CNS) and are coexpressed in various neuronal populations. Studies in Xenopus oocytes suggest that this protein alone and in combination with pannexin 1 may form cell type-specific gap junctions with distinct properties. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2009]

OMIM ResearchGenerating clinical summary…

MultiplemechanismLOEUF 1.22

Clinical Summary— PANX2

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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

92 VUS of 105 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 OE?0.72 (0.44–1.22)

0≤0.351.4

Missense OE?0.55 (0.49–0.61)

0≤0.61.4

Synonymous OE?0.92

0≤1.21.6

LoF obs/exp: 10 / 13.9Missense obs/exp: 238 / 434.4Syn Z: 0.89

This gene — mechanism propensity

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

105 submitted variants in ClinVar

ClinVar

Classification Summary

VUS92

Likely Benign9

Benign1

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Synonymous	Total
Pathogenic	0	0	0	0
Likely Pathogenic	0	0	0	0
VUS	1	91	0	92
Likely Benign	0	8	1	9
Benign	0	0	1	1
Total	1	99	2	102

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

View in ClinVar →

142 pathogenic / likely-pathogenic (of 154) ClinVar copy-number / structural variants overlap PANX2 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →