PANX3

Summary

PANX3 (pannexin 3, HGNC:20573) is a protein-coding gene on chromosome 11q24.2, encoding Pannexin-3 (Q96QZ0). Regulator of osteoblast differentiation by functioning as a Ca(2+) channel in the endoplasmic reticulum which regulates calmodulin (CaM) pathways.

The protein encoded by this gene belongs to the innexin family. Innexin family members are known to be the structural components of gap junctions.

Source: NCBI Gene 116337 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 49 total
• MANE Select transcript: NM_052959

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:20573
Approved symbol	PANX3
Name	pannexin 3
Location	11q24.2
Locus type	gene with protein product
Status	Approved
Aliases	Px3
Ensembl gene	ENSG00000154143
Ensembl biotype	protein_coding
OMIM	608422
Entrez	116337

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000284288

RefSeq mRNA: 1 — MANE Select: NM_052959 NM_052959

CCDS: CCDS8447

Canonical transcript exons

ENST00000284288 — 4 exons

Exon	Start	End
ENSE00001014266	124619296	124620356
ENSE00001014267	124612980	124613122
ENSE00001014268	124617274	124617488
ENSE00001014269	124611428	124611737

Expression profiles

Bgee: expression breadth broad, 31 present calls, max score 91.90.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 8.9080 / max 771.5001, expressed in 62 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
117363	6.1170	60
117364	0.9989	61
117362	0.9506	59
117365	0.8416	58

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
tibia	UBERON:0000979	91.90	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	75.13	silver quality
buccal mucosa cell	CL:0002336	65.80	silver quality
tibialis anterior	UBERON:0001385	59.44	silver quality
cardiac muscle of right atrium	UBERON:0003379	54.94	gold quality
left ventricle myocardium	UBERON:0006566	54.23	gold quality
kidney epithelium	UBERON:0004819	53.93	gold quality
epithelial cell of pancreas	CL:0000083	53.55	gold quality
upper arm skin	UBERON:0004263	53.52	gold quality
ileal mucosa	UBERON:0000331	52.67	silver quality
mucosa of paranasal sinus	UBERON:0005030	51.38	gold quality
pancreatic ductal cell	CL:0002079	50.96	silver quality
deltoid	UBERON:0001476	50.96	gold quality
myocardium	UBERON:0002349	50.50	gold quality
nasal cavity epithelium	UBERON:0005384	47.03	gold quality
quadriceps femoris	UBERON:0001377	47.01	gold quality
cartilage tissue	UBERON:0002418	46.63	silver quality
vastus lateralis	UBERON:0001379	45.40	gold quality
putamen	UBERON:0001874	44.53	gold quality
layer of synovial tissue	UBERON:0007616	43.55	gold quality
upper leg skin	UBERON:0004262	43.50	silver quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	43.37	gold quality
minor salivary gland	UBERON:0001830	42.89	gold quality
secondary oocyte	CL:0000655	42.57	gold quality
mouth mucosa	UBERON:0003729	42.50	gold quality
muscle tissue	UBERON:0002385	41.87	gold quality
skeletal muscle tissue	UBERON:0001134	41.84	gold quality
saliva-secreting gland	UBERON:0001044	41.71	gold quality
placenta	UBERON:0001987	41.61	silver quality
superficial temporal artery	UBERON:0001614	41.33	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.13

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

20 targeting PANX3, 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-511-3P	99.99	68.85	1467
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163
HSA-MIR-23C	99.95	73.92	3192
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-129-5P	99.88	70.26	3273
HSA-MIR-651-5P	99.64	68.49	1104
HSA-MIR-4328	99.57	71.06	4094
HSA-MIR-6740-3P	99.48	68.49	1392
HSA-MIR-223-5P	99.24	68.82	1206
HSA-MIR-330-5P	98.73	67.63	1788
HSA-MIR-7155-5P	98.65	66.14	1290
HSA-MIR-648	98.64	66.13	553
HSA-MIR-9903	98.47	66.70	748
HSA-MIR-326	98.25	66.44	1565
HSA-MIR-6881-5P	98.16	67.38	665
HSA-MIR-3650	97.88	64.89	693
HSA-MIR-6836-3P	97.08	64.99	712
HSA-MIR-210-3P	92.54	65.16	165

Literature-anchored findings (GeneRIF, showing 15)

• These studies show that Panx1 and Panx3 have many characteristics that are distinct from Cx43 and that these proteins probably play an important biological role as single membrane channels. (PMID:17925379)
• although Panx1 and Panx3 share a common endoplasmic reticulum to Golgi secretory pathway to Cx43, their ultimate cell surface residency appears to be independent of cell contacts and the need for intact microtubules (PMID:20086016)
• Panx3 functions to switch the chondrocyte cell fate from proliferation to differentiation by regulating the intracellular ATP/cAMP levels (PMID:20404334)
• The 70 kDa immunoreactive species of Panx3 highly regulated during keratinocyte differentiation was shown to most likely correspond to another Panx3 isoform. (PMID:22947051)
• 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)
• Panx1 and Panx3 are co-expressed in human skeletal muscle myoblasts and play a pivotal role in dictating the proliferation and differentiation. (PMID:25239622)
• 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)
• Panx3 hemichannel is expressed in human odontoblast-like cells and mediates ATP release into the extracellular space. (PMID:26263540)
• Case Report: osteosarcomatous transformation of axillary sweat gland neoplasm with high PANX3 expression. (PMID:27391460)
• Panx3 channels regulate the proliferation, differentiation, and fusion of skeletal muscle myoblasts. (Review) (PMID:27518505)
• Panx3 has a defensive role in dental pulp inflammation. (PMID:27679980)
• Influence of the three-dimensional culture of human bone marrow mesenchymal stromal cells within a macroporous polysaccharides scaffold on Pannexin 1 and Pannexin 3. (PMID:29222846)
• Panx3 was upregulated during osteogenic differentiation in a time-dependent manner. Panx3 overexpression promoted osteogenic differentiation of human dental pulp-derived mesenchymal stromal cells, whereas depletion of Panx3 resulted in a decline of differentiation. (PMID:29241211)
• All three pannexins Panx1, Panx2, and Panx3 mRNAs were expressed in all of the analyzed undifferentiated stem cell lines. (PMID:29357945)
• Noncoding rare variants in PANX3 are associated with chronic back pain. (PMID:36448979)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	panx3	ENSDARG00000004627
mus_musculus	Panx3	ENSMUSG00000011118
rattus_norvegicus	Panx3	ENSRNOG00000031675

Paralogs (2): PANX2 (ENSG00000073150), PANX1 (ENSG00000110218)

Protein

Protein identifiers

Pannexin-3 — Q96QZ0 (reviewed: Q96QZ0)

All UniProt accessions (1): Q96QZ0

UniProt curated annotations — full annotation on UniProt →

Function. Regulator of osteoblast differentiation by functioning as a Ca(2+) channel in the endoplasmic reticulum which regulates calmodulin (CaM) pathways. Allows ATP release into the extracellular space and activation or purinergic receptors.

Subunit / interactions. Homoheptameric.

Subcellular location. Cell membrane. Cell junction. Gap junction. Endoplasmic reticulum membrane.

Similarity. Belongs to the pannexin family.

RefSeq proteins (1): NP_443191* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000990	Innexin	Family
IPR039099	Pannexin	Family

Pfam: PF00876

Catalyzed reactions (Rhea), 2 shown:

• Ca(2+)(in) = Ca(2+)(out) (RHEA:29671)
• ATP(in) = ATP(out) (RHEA:75687)

UniProt features (47 total): helix 18, strand 10, turn 6, topological domain 5, transmembrane region 4, sequence variant 2, chain 1, glycosylation site 1

Structure

Experimental structures (PDB)

15 structures.

PDB	Method	Resolution (Å)
8WZA	ELECTRON MICROSCOPY	2.77
9KRG	ELECTRON MICROSCOPY	2.9
9JCD	ELECTRON MICROSCOPY	3.2
9KOM	ELECTRON MICROSCOPY	3.2
7XL6	ELECTRON MICROSCOPY	3.25
9JCC	ELECTRON MICROSCOPY	3.4
8GYP	ELECTRON MICROSCOPY	3.5
8HWQ	ELECTRON MICROSCOPY	3.58
8GYT	ELECTRON MICROSCOPY	3.68
9JCJ	ELECTRON MICROSCOPY	3.7
8GTR	ELECTRON MICROSCOPY	3.91
9JCF	ELECTRON MICROSCOPY	4
9JCG	ELECTRON MICROSCOPY	4.2
9JCT	ELECTRON MICROSCOPY	4.5
9JCH	ELECTRON MICROSCOPY	4.6

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96QZ0-F1	81.64	0.29

Functional residue map

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

Glycosylation sites (1): 71

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 57 (showing top): GOBP_OSTEOBLAST_DIFFERENTIATION, GOBP_POSITIVE_REGULATION_OF_CYTOKINE_PRODUCTION, GOBP_INTERLEUKIN_1_PRODUCTION, GOBP_MONOATOMIC_CATION_TRANSPORT, GOBP_CELL_CELL_SIGNALING, CATRRAGC_UNKNOWN, GOBP_CYTOKINE_PRODUCTION, GOBP_POSITIVE_REGULATION_OF_INTERLEUKIN_1_PRODUCTION, GOBP_OSSIFICATION, GOCC_CELL_CELL_JUNCTION, GOBP_CALCIUM_ION_TRANSMEMBRANE_TRANSPORT, GOBP_TRANSMEMBRANE_TRANSPORT, GOBP_POSITIVE_REGULATION_OF_MULTICELLULAR_ORGANISMAL_PROCESS, GOCC_NUCLEAR_OUTER_MEMBRANE_ENDOPLASMIC_RETICULUM_MEMBRANE_NETWORK, GOCC_ANCHORING_JUNCTION

GO Biological Process (7): osteoblast differentiation (GO:0001649), monoatomic cation transport (GO:0006812), cell-cell signaling (GO:0007267), positive regulation of interleukin-1 production (GO:0032732), monoatomic ion transport (GO:0006811), monoatomic ion transmembrane transport (GO:0034220), calcium ion transmembrane transport (GO:0070588)

GO Molecular Function (5): structural molecule activity (GO:0005198), calcium channel activity (GO:0005262), wide pore channel activity (GO:0022829), gap junction hemi-channel activity (GO:0055077), channel activity (GO:0015267)

GO Cellular Component (6): endoplasmic reticulum membrane (GO:0005789), plasma membrane (GO:0005886), gap junction (GO:0005921), endoplasmic reticulum (GO:0005783), membrane (GO:0016020), anchoring junction (GO:0070161)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
monoatomic ion transport	2
ossification	1
cell differentiation	1
cell communication	1
signaling	1
positive regulation of cytokine production	1
interleukin-1 production	1
regulation of interleukin-1 production	1
transport	1
transmembrane transport	1
calcium ion transport	1
monoatomic cation transmembrane transport	1
molecular_function	1
monoatomic cation channel activity	1
calcium ion transmembrane transporter activity	1
channel activity	1
gap junction channel activity	1
wide pore channel activity	1
passive transmembrane transporter activity	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
membrane	1
cell periphery	1
cell-cell junction	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1
cellular anatomical structure	1
cell junction	1

Protein interactions and networks

STRING

340 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PANX3	GJA1	P17302	512
PANX3	GJB1	P08034	492
PANX3	GJA4	P35212	470
PANX3	GJB2	P29033	452
PANX3	GJC1	P36383	451
PANX3	P2RX2	Q9UBL9	435
PANX3	ENTPD8	Q5MY95	414
PANX3	GJB6	O95452	400
PANX3	C1QTNF3	Q9BXJ4	382
PANX3	GJA3	Q9Y6H8	377
PANX3	GJA5	P36382	376
PANX3	ENTPD3	O75355	375
PANX3	GJD2	Q9UKL4	372
PANX3	GJC3	Q8NFK1	370
PANX3	P2RY2	P41231	366

IntAct

2 interactions, top by confidence:

A	B	Type	Score
BCL6	CACNA1A	psi-mi:“MI:0914”(association)	0.350

BioGRID (2): PANX3 (Affinity Capture-MS), PANX3 (Affinity Capture-MS)

ESM2 similar proteins: A0PJX8, A1L1L2, A4FUN9, A4FV45, H2MCM1, J3QMI4, O70491, P08033, P28230, P60572, Q0V8E7, Q2HJ63, Q4QR83, Q561R8, Q5FWS4, Q5JW98, Q5R3K3, Q5R7B4, Q5RJQ8, Q5T197, Q5T1A1, Q5U1Y0, Q5ZJY9, Q640M6, Q66H44, Q6DF19, Q6NRI4, Q6NUQ4, Q7L4E1, Q86XJ0, Q8BM55, Q8BSD4, Q8C9E8, Q8CE93, Q8CEG0, Q8N5C1, Q8NFK1, Q8R100, Q8VEC4, Q8WTR4

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

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	44
Likely benign	2
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

579 predictions. Top by Δscore:

Variant	Effect	Δscore
11:124611736:TGG:T	donor_loss	1.0000
11:124611737:GGTAA:G	donor_loss	1.0000
11:124611738:G:GG	donor_gain	1.0000
11:124617484:GAGAA:G	donor_gain	1.0000
11:124617485:AGAAG:A	donor_loss	1.0000
11:124617486:G:GT	donor_gain	1.0000
11:124617486:GAA:G	donor_gain	1.0000
11:124617488:AGT:A	donor_loss	1.0000
11:124617489:G:GG	donor_gain	1.0000
11:124617489:GTG:G	donor_loss	1.0000
11:124611733:CTCTG:C	donor_gain	0.9900
11:124611734:TCTG:T	donor_gain	0.9900
11:124611735:CTG:C	donor_gain	0.9900
11:124611736:TG:T	donor_gain	0.9900
11:124611737:GG:G	donor_gain	0.9900
11:124617019:T:TA	acceptor_gain	0.9900
11:124617020:G:A	acceptor_gain	0.9900
11:124617474:GAA:G	donor_gain	0.9900
11:124617485:AGAA:A	donor_gain	0.9900
11:124617487:AA:A	donor_gain	0.9900
11:124617490:T:A	donor_loss	0.9900
11:124613078:G:GT	donor_gain	0.9800
11:124617491:GAGTT:G	donor_loss	0.9800
11:124619287:A:AG	acceptor_gain	0.9800
11:124619288:C:G	acceptor_gain	0.9800
11:124619289:T:A	acceptor_gain	0.9800
11:124613118:ACAAG:A	donor_loss	0.9700
11:124613119:CAAGG:C	donor_loss	0.9700
11:124613120:AAG:A	donor_loss	0.9700
11:124613121:AGGTA:A	donor_loss	0.9700

AlphaMissense

2537 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:124619353:G:C	K199N	0.996
11:124619353:G:T	K199N	0.996
11:124617407:G:C	R153P	0.995
11:124619321:T:C	F189L	0.995
11:124619323:C:A	F189L	0.995
11:124619323:C:G	F189L	0.995
11:124617400:T:G	Y151D	0.993
11:124619781:C:T	S342F	0.993
11:124617368:T:C	L140P	0.992
11:124619679:T:A	L308H	0.991
11:124619730:A:T	D325V	0.991
11:124619343:T:C	L196P	0.990
11:124619682:C:A	P309Q	0.990
11:124619730:A:C	D325A	0.989
11:124619781:C:A	S342Y	0.989
11:124617392:A:T	D148V	0.988
11:124619679:T:C	L308P	0.988
11:124617389:T:C	L147P	0.987
11:124617410:C:T	S154F	0.986
11:124619474:T:C	F240L	0.986
11:124619476:C:A	F240L	0.986
11:124619476:C:G	F240L	0.986
11:124619729:G:C	D325H	0.986
11:124619763:A:T	N336I	0.986
11:124619764:C:A	N336K	0.986
11:124619764:C:G	N336K	0.986
11:124617409:T:C	S154P	0.985
11:124617419:T:C	L157P	0.985
11:124619679:T:G	L308R	0.985
11:124619682:C:G	P309R	0.985

dbSNP variants (sampled 300 via entrez): RS1000456121 (11:124611733 C>T), RS1001038679 (11:124618224 G>A,C,T), RS1001098424 (11:124619182 T>C), RS1001425122 (11:124609703 A>G), RS1001462648 (11:124617632 T>A), RS1001544772 (11:124611458 A>C,G), RS1002006960 (11:124611388 G>A,T), RS1002100883 (11:124617948 C>T), RS1002468874 (11:124616330 G>A), RS1002976010 (11:124609906 T>A,C), RS1003037528 (11:124615306 C>G,T), RS1003107069 (11:124616675 T>G), RS1003208082 (11:124620282 C>T), RS1003372126 (11:124615006 T>G), RS1003416265 (11:124609584 C>T)

Disease associations

OMIM: gene MIM:608422 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

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

6 total (human), top 6 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
pirinixic acid	affects binding, decreases expression, increases activity	1
S-(1,2-dichlorovinyl)cysteine	affects cotreatment, increases expression	1
tebuconazole	decreases expression	1
Benzo(a)pyrene	affects methylation	1
Lipopolysaccharides	affects cotreatment, increases expression	1
Aflatoxin B1	decreases methylation	1

Clinical trials (associated diseases)

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