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…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.22

LOEUF

Multiple*

Mechanism· predicted

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

Background carrier burden — how many people carry a rare variant somewhere in PANX2?

gnomAD v4 · ~730k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 72

954 rare PASS variants

Rare truncating (LoF)

1 in 880

140 rare PASS variants

Rare synonymous (reference)

1 in 100

551 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for PANX2. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 89	1 in 1,200
South Asian	~43k	1 in 56	1 in 1,200
Remaining (unassigned)	~30k	1 in 63	1 in 720
European (Finnish)	~26k	1 in 220	1 in 1,300
Admixed American	~22k	1 in 100	1 in 840
African / African American	~21k	1 in 85	1 in 720
East Asian	~20k	1 in 120	1 in 560
Ashkenazi Jewish	~13k	1 in 220	1 in 500
Middle Eastern	~2,884	1 in 53	≈ 1 in 1,300

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 2 of 3 coding exons well covered in gnomAD exomes; exon 1 marginal. Genomes: all 3.? see exons ↓