PANX2

Summary

PANX2 (pannexin 2, HGNC:8600) is a protein-coding gene on chromosome 22q13.33, encoding Pannexin-2 (Q96RD6). Ion channel with a slight anion preference.

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.

Source: NCBI Gene 56666 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 105 total
• MANE Select transcript: NM_052839

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:8600
Approved symbol	PANX2
Name	pannexin 2
Location	22q13.33
Locus type	gene with protein product
Status	Approved
Aliases	hPANX2, PX2
Ensembl gene	ENSG00000073150
Ensembl biotype	protein_coding
OMIM	608421
Entrez	56666

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 2 protein_coding, 1 nonsense_mediated_decay

ENST00000159647, ENST00000395842, ENST00000402472

RefSeq mRNA: 2 — MANE Select: NM_052839 NM_001160300, NM_052839

CCDS: CCDS14085, CCDS54544

Canonical transcript exons

ENST00000395842 — 3 exons

Exon	Start	End
ENSE00001523039	50178934	50180295
ENSE00002266289	50170731	50170956
ENSE00003607237	50176939	50178402

Expression profiles

Bgee: expression breadth ubiquitous, 174 present calls, max score 92.00.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 5.2205 / max 389.4621, expressed in 1155 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
192964	3.0853	864
192967	1.0811	383
192963	1.0037	463
192966	0.0276	7
192965	0.0228	9

Top tissues by expression

245 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
right hemisphere of cerebellum	UBERON:0014890	92.00	gold quality
right frontal lobe	UBERON:0002810	91.17	gold quality
cerebellar hemisphere	UBERON:0002245	90.96	gold quality
cerebellar cortex	UBERON:0002129	90.90	gold quality
anterior cingulate cortex	UBERON:0009835	89.84	gold quality
cerebellum	UBERON:0002037	89.69	gold quality
Brodmann (1909) area 9	UBERON:0013540	88.11	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	87.51	gold quality
prefrontal cortex	UBERON:0000451	87.08	gold quality
neocortex	UBERON:0001950	86.30	gold quality
frontal cortex	UBERON:0001870	86.20	gold quality
cerebral cortex	UBERON:0000956	84.28	gold quality
amygdala	UBERON:0001876	84.18	gold quality
hypothalamus	UBERON:0001898	83.23	gold quality
brain	UBERON:0000955	82.48	gold quality
putamen	UBERON:0001874	82.40	gold quality
forebrain	UBERON:0001890	81.93	gold quality
blood	UBERON:0000178	81.66	gold quality
Ammon’s horn	UBERON:0001954	81.57	gold quality
caudate nucleus	UBERON:0001873	81.39	gold quality
postcentral gyrus	UBERON:0002581	81.38	gold quality
substantia nigra	UBERON:0002038	81.10	gold quality
primary visual cortex	UBERON:0002436	81.01	gold quality
nucleus accumbens	UBERON:0001882	80.95	gold quality
lower esophagus mucosa	UBERON:0035834	80.87	gold quality
superior frontal gyrus	UBERON:0002661	79.33	gold quality
midbrain	UBERON:0001891	79.19	gold quality
parietal lobe	UBERON:0001872	79.16	gold quality
temporal lobe	UBERON:0001871	78.83	gold quality
oviduct epithelium	UBERON:0004804	77.84	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.05

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

58 targeting PANX2, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-4500	99.99	72.72	2367
HSA-LET-7A-5P	99.98	72.29	1790
HSA-LET-7B-5P	99.98	72.31	1790
HSA-LET-7C-5P	99.98	72.29	1790
HSA-LET-7E-5P	99.98	72.29	1790
HSA-LET-7F-5P	99.98	72.56	1784
HSA-LET-7G-5P	99.98	72.37	1784
HSA-LET-7I-5P	99.98	72.37	1788
HSA-MIR-98-5P	99.98	72.33	1787
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-LET-7D-5P	99.96	71.76	1632
HSA-MIR-4458	99.96	71.64	1650
HSA-MIR-106A-5P	99.90	73.94	2683
HSA-MIR-7162-3P	99.89	68.16	1682
HSA-MIR-17-5P	99.89	73.83	2665
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-106B-5P	99.88	74.72	2795
HSA-MIR-20A-5P	99.88	74.76	2769
HSA-MIR-20B-5P	99.88	74.01	2621
HSA-MIR-519D-3P	99.88	73.97	2607
HSA-MIR-93-5P	99.88	73.98	2606
HSA-MIR-526B-3P	99.88	74.06	2587
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-202-3P	99.84	71.41	1290
HSA-MIR-3682-3P	99.58	67.63	865
HSA-MIR-762	99.58	66.61	1994

Literature-anchored findings (GeneRIF, showing 18)

• According to brain cancer gene expression database REMBRANDT, PANX2 expression levels can predict post diagnosis survival for patients with glial tumors. (PMID:16989724)
• These data do not suggest that Panx2 or Cx36 could increase the risk of schizophrenia in the Japanese population. (PMID:17427027)
• Pannexin2 is a tumor suppressor gene in C6 glioma cells. (PMID:19749789)
• Pannexin1 and Pannexin2 channels show quaternary similarities to connexons and different oligomerization numbers from each other (PMID:20516070)
• Panx1 and Panx2 expression was detected in the temporal lobe cortex of patients with temporal lobe epilepsy and in the control tissues. (PMID:24146091)
• Data suggest that both up-regulation and down-regulation of expression of pannexins (PANX1, PANX2, PANX3) are associated with disease onset and/or progression; examples include neoplasms, multiple sclerosis, migraine, and hypertension. [REVIEW] (PMID:25008946)
• There is dense expression of Panx2 in the enteric nervous system. The substantial increase in Panx2 mRNA in ulcerative colitis (UC) muscle but not protein suggests that the Panx2 translation process may be disrupted in UC. (PMID:25773474)
• The results of this study do not support a major contribution of PANX1-3 to disease risk of schizophrenia according to DSM-5. (PMID:26223428)
• Panx2 mRNA and protein levels were only upregulated in focal cortical dysplasia type IIb lesions of intractable epilepsy patients and characteristically expressed on SOX2-positive multipotential balloon cells. (PMID:28036289)
• Panx2 is an important regulator of the insulin secretory capacity and apoptosis in pancreatic beta-cells. (PMID:28390953)
• All three pannexins Panx1, Panx2, and Panx3 mRNAs were expressed in all of the analyzed undifferentiated stem cell lines. (PMID:29357945)
• The pannexin 2 (Panx2) N86Q mutant is glycosylation-deficient and tends to aggregate in the endoplasmic reticulum (ER)reducing its cell surface trafficking but it can still interact with pannexin 1 (Panx1). (PMID:29932112)
• Pannexin-2, a novel mitochondrial-associated membrane protein, may become the new strategy to treat and prevent neurological disorders. (PMID:32770209)
• The Role of miR-342 in Vascular Health. Study in Subclinical Cardiovascular Disease in Mononuclear Cells, Plasma, Inflammatory Cytokines and PANX2. (PMID:33003647)
• PANX2 and brain lower grade glioma genesis: A bioinformatic analysis. (PMID:33913372)
• Cryo-EM structure of human heptameric pannexin 2 channel. (PMID:36869038)
• Structural and functional analysis of human pannexin 2 channel. (PMID:36973289)
• PANX2 promotes malignant transformation of colorectal cancer and 5-Fu resistance through PI3K-AKT signaling pathway. (PMID:39389335)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	panx2	ENSDARG00000063019
mus_musculus	Panx2	ENSMUSG00000058441
rattus_norvegicus	Panx2	ENSRNOG00000055530

Paralogs (2): PANX1 (ENSG00000110218), PANX3 (ENSG00000154143)

Protein

Protein identifiers

Pannexin-2 — Q96RD6 (reviewed: Q96RD6)

All UniProt accessions (2): Q96RD6, F8W8Y4

UniProt curated annotations — full annotation on UniProt →

Function. Ion channel with a slight anion preference. Also able to release ATP. Plays a role in regulating neurogenesis and apoptosis in keratinocytes.

Subunit / interactions. Homoheptameric.

Subcellular location. Cell membrane. Golgi apparatus membrane. Endoplasmic reticulum membrane.

Post-translational modifications. S-palmitoylated in neural stem and progenitor cells. Cleaved by CASP3 and CASP7 during apoptosis. Cleavage has no effect on it function.

Similarity. Belongs to the pannexin family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q96RD6-3	3	yes
Q96RD6-1	1
Q96RD6-2	2

RefSeq proteins (2): NP_001153772, NP_443071* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000990	Innexin	Family
IPR039099	Pannexin	Family

Pfam: PF00876

Catalyzed reactions (Rhea), 5 shown:

• chloride(in) = chloride(out) (RHEA:29823)
• Na(+)(in) = Na(+)(out) (RHEA:34963)
• iodide(out) = iodide(in) (RHEA:66324)
• ATP(in) = ATP(out) (RHEA:75687)
• D-gluconate(in) = D-gluconate(out) (RHEA:76139)

UniProt features (42 total): helix 15, topological domain 5, strand 5, transmembrane region 4, region of interest 2, splice variant 2, mutagenesis site 2, chain 1, compositionally biased region 1, site 1, modified residue 1, glycosylation site 1, sequence variant 1, turn 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
8GYQ	ELECTRON MICROSCOPY	3.4
7XLB	ELECTRON MICROSCOPY	3.44
8F7C	ELECTRON MICROSCOPY	3.92

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96RD6-F1	57.97	0.09

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (1): 415 (cleavage; by casp3 or casp7)

Post-translational modifications (1): 593

Glycosylation sites (1): 86

Mutagenesis-validated functional residues (2):

Position	Phenotype
89	increases atp permeation. reduced currents. no effect on membrane location. no effect on ion selectivity.
89	reduced currents. no effect on membrane location. loss of ion selectivity.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-112303	Electric Transmission Across Gap Junctions

MSigDB gene sets: 87 (showing top): TGCACTT_MIR519C_MIR519B_MIR519A, GOBP_POSITIVE_REGULATION_OF_CYTOKINE_PRODUCTION, GOBP_INTERLEUKIN_1_PRODUCTION, GOBP_MONOATOMIC_CATION_TRANSPORT, GOBP_CELL_CELL_SIGNALING, NIKOLSKY_BREAST_CANCER_22Q13_AMPLICON, GOBP_RESPONSE_TO_ISCHEMIA, GOBP_CYTOKINE_PRODUCTION, MARTIN_VIRAL_GPCR_SIGNALING_DN, GOBP_POSITIVE_REGULATION_OF_INTERLEUKIN_1_PRODUCTION, GOBP_TRANSMEMBRANE_TRANSPORT, GOBP_POSITIVE_REGULATION_OF_MULTICELLULAR_ORGANISMAL_PROCESS, LEIN_MIDBRAIN_MARKERS, LEIN_PONS_MARKERS, LEIN_MEDULLA_MARKERS

GO Biological Process (7): response to ischemia (GO:0002931), monoatomic cation transport (GO:0006812), cell-cell signaling (GO:0007267), positive regulation of interleukin-1 production (GO:0032732), monoatomic ion transmembrane transport (GO:0034220), monoatomic ion transport (GO:0006811), transmembrane transport (GO:0055085)

GO Molecular Function (5): structural molecule activity (GO:0005198), gap junction channel activity (GO:0005243), wide pore channel activity (GO:0022829), protein-containing complex binding (GO:0044877), channel activity (GO:0015267)

GO Cellular Component (7): Golgi membrane (GO:0000139), endoplasmic reticulum membrane (GO:0005789), plasma membrane (GO:0005886), cytoplasm (GO:0005737), endoplasmic reticulum (GO:0005783), Golgi apparatus (GO:0005794), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Transmission across Electrical Synapses	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
monoatomic ion transport	2
transport	2
cellular anatomical structure	2
cytoplasm	2
endomembrane system	2
intracellular membrane-bounded organelle	2
response to stress	1
cell communication	1
signaling	1
positive regulation of cytokine production	1
interleukin-1 production	1
regulation of interleukin-1 production	1
transmembrane transport	1
cellular process	1
molecular_function	1
wide pore channel activity	1
channel activity	1
binding	1
passive transmembrane transporter activity	1
Golgi apparatus	1
bounding membrane of organelle	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
membrane	1
cell periphery	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

484 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PANX2	CASP7	P55210	583
PANX2	PANX1	Q96RD7	581
PANX2	GJB1	P08034	507
PANX2	GJD2	Q9UKL4	493
PANX2	GJC1	P36383	491
PANX2	GJB2	P29033	486
PANX2	GJA1	P17302	482
PANX2	GJA4	P35212	478
PANX2	CALHM1	Q8IU99	469
PANX2	CASP3	P42574	468
PANX2	GJB6	O95452	461
PANX2	SLC18B1	Q6NT16	443
PANX2	GJA5	P36382	430
PANX2	ADRA1D	P25100	427
PANX2	B3GALNT1	O75752	419

IntAct

4 interactions, top by confidence:

A	B	Type	Score
PANX2	GRB2	psi-mi:“MI:0915”(physical association)	0.400
PANX2	HMGA1	psi-mi:“MI:0915”(physical association)	0.400
PANX2	RPN1	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (8): NRF1 (Two-hybrid), ATXN1 (Two-hybrid), BANP (Two-hybrid), PANX2 (Proximity Label-MS), PANX2 (Proximity Label-MS), PANX2 (Affinity Capture-RNA), PANX2 (Affinity Capture-MS), PANX2 (Affinity Capture-MS)

ESM2 similar proteins: A0A0S2T050, B9G4M9, G5EBL2, O10282, O10309, O10336, O10358, O93058, P03172, P03315, P03316, P03318, P03586, P03587, P06487, P13897, P17471, P24380, P24653, P24872, P27285, P27407, P27408, P27409, P30325, P30738, P36342, P41428, P68329, P89676, Q01206, Q04574, Q306W7, Q53AM4, Q65361, Q66914, Q6UDF4, Q6UDK4, Q80S27, Q8JJX0

Diamond homologs: P60571, P60572, Q6IMP4, Q8CEG0, Q96QZ0, Q96RD6, P60570, Q5REE3, Q96RD7, Q9JIP4

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
STK38	“up-regulates activity”	PANX2	phosphorylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

105 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	92
Likely benign	9
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

534 predictions. Top by Δscore:

Variant	Effect	Δscore
22:50170953:GCAG:G	donor_gain	1.0000
22:50170957:G:GG	donor_gain	1.0000
22:50170958:T:A	donor_loss	1.0000
22:50175479:A:G	donor_gain	1.0000
22:50175483:G:GG	donor_gain	0.9900
22:50178933:GAT:G	acceptor_gain	0.9900
22:50178398:CAAAG:C	donor_loss	0.9800
22:50178399:AAAGG:A	donor_loss	0.9800
22:50178401:AGGTA:A	donor_loss	0.9800
22:50178403:GTAG:G	donor_loss	0.9800
22:50178404:T:G	donor_loss	0.9800
22:50178932:A:AG	acceptor_gain	0.9800
22:50178933:G:GG	acceptor_gain	0.9800
22:50178928:TTGCA:T	acceptor_loss	0.9700
22:50178929:TGCAG:T	acceptor_loss	0.9700
22:50178930:GCAG:G	acceptor_loss	0.9700
22:50178931:CAGAT:C	acceptor_loss	0.9700
22:50170889:G:GA	donor_gain	0.9500
22:50178932:AGAT:A	acceptor_gain	0.9500
22:50178933:GATG:G	acceptor_gain	0.9500
22:50170954:CAG:C	donor_gain	0.9300
22:50176937:A:AG	acceptor_gain	0.9300
22:50176938:G:GG	acceptor_gain	0.9300
22:50170888:T:TA	donor_gain	0.9100
22:50178925:T:TA	acceptor_gain	0.9100
22:50170955:AG:A	donor_gain	0.9000
22:50170956:GG:G	donor_gain	0.9000
22:50176938:GA:G	acceptor_gain	0.8900
22:50178933:GA:G	acceptor_gain	0.8900
22:50170959:G:GT	donor_gain	0.8800

AlphaMissense

4369 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
22:50170915:C:G	P62R	1.000
22:50176953:T:C	C81R	1.000
22:50176954:G:A	C81Y	1.000
22:50176955:T:G	C81W	1.000
22:50176972:T:G	F87C	1.000
22:50177008:G:A	C99Y	1.000
22:50177009:C:G	C99W	1.000
22:50177012:G:C	W100C	1.000
22:50177012:G:T	W100C	1.000
22:50177173:T:C	L154P	1.000
22:50177178:T:C	F156L	1.000
22:50177180:C:A	F156L	1.000
22:50177180:C:G	F156L	1.000
22:50177218:C:A	A169D	1.000
22:50177353:T:C	L214P	1.000
22:50177481:T:C	F257L	1.000
22:50177482:T:C	F257S	1.000
22:50177482:T:G	F257C	1.000
22:50177483:C:A	F257L	1.000
22:50177483:C:G	F257L	1.000
22:50177548:G:A	C279Y	1.000
22:50177739:G:T	D343Y	1.000
22:50177740:A:C	D343A	1.000
22:50177740:A:T	D343V	1.000
22:50177857:T:C	L382P	1.000
22:50170899:G:C	G57R	0.999
22:50170900:G:A	G57D	0.999
22:50170915:C:A	P62H	0.999
22:50170938:T:C	F70L	0.999
22:50170940:C:A	F70L	0.999

dbSNP variants (sampled 300 via entrez): RS1000053836 (22:50179725 G>A,C), RS1000217676 (22:50169406 G>A,T), RS1000244948 (22:50178688 C>T), RS1000310777 (22:50169656 G>A), RS1000597812 (22:50171675 T>C), RS1000649887 (22:50171863 C>A,G), RS1000912592 (22:50168926 G>A), RS1001191188 (22:50176603 C>T), RS1002437060 (22:50178177 G>A), RS1002499430 (22:50178430 G>A,C,T), RS1002528891 (22:50179636 C>T), RS1002607141 (22:50173824 G>A), RS1002660988 (22:50174017 T>G), RS1002675982 (22:50176845 G>T), RS1002758106 (22:50179362 T>C)

Disease associations

OMIM: gene MIM:608421 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST002481_12	Acne (severe)	4.000000e-06

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: other ic — Connexins and Pannexins

CTD chemical–gene interactions

59 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases reaction, decreases expression, affects cotreatment, increases abundance, increases expression	6
lead acetate	increases reaction, increases expression, decreases reaction	2
(+)-JQ1 compound	decreases expression	2
Arsenic	increases abundance, increases expression, affects cotreatment	2
Benzo(a)pyrene	increases methylation, increases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Tobacco Smoke Pollution	increases expression	2
Cadmium Chloride	increases expression	2
p-Chloromercuribenzoic Acid	affects cotreatment, increases expression	2
Particulate Matter	decreases reaction, increases expression, decreases expression	2
aristolochic acid I	increases expression	1
dicrotophos	increases expression	1
methyleugenol	increases expression	1
triphenyl phosphate	affects expression	1
sodium arsenate	increases abundance, increases expression	1
cinnamaldehyde	increases expression	1
beta-lapachone	increases expression	1
sulforaphane	increases expression	1
butyraldehyde	decreases expression	1
zinc chromate	increases abundance, increases expression	1
manganese chloride	affects cotreatment, increases abundance, increases expression	1
aflatoxin B2	decreases methylation	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression, affects cotreatment	1
diallyl trisulfide	increases expression	1
di-n-butylphosphoric acid	affects expression	1
chromium hexavalent ion	increases abundance, increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	increases expression, affects cotreatment	1
erucylphospho-N,N,N-trimethylpropylammonium	increases expression	1
abrine	decreases expression	1
2-methyl-2H-pyrazole-3-carboxylic acid (2-methyl-4-o-tolylazophenyl)amide	decreases reaction, increases expression	1

Cellosaurus cell lines

2 cell lines: 1 cancer cell line, 1 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_XR33	HAP1 PANX2 (-)	Cancer cell line	Male
CVCL_YA74	IDG-HEK293T-PANX2-V5-OE	Transformed cell line	Female

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.