PANX1

Summary

PANX1 (pannexin 1, HGNC:8599) is a protein-coding gene on chromosome 11q21, encoding Pannexin-1 (Q96RD7). Ion channel involved in a variety of physiological functions such as blood pressure regulation, apoptotic cell clearance and oogenesis.

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 2 are abundantly expressed in central nerve system (CNS) and are coexpressed in various neuronal populations. Studies in Xenopus oocytes suggest that this protein alone and in combination with pannexin 2 may form cell type-specific gap junctions with distinct properties.

Source: NCBI Gene 24145 — RefSeq curated summary.

At a glance

• Gene–disease (curated): oocyte maturation defect 7 (Strong, GenCC)
• GWAS associations: 13
• Clinical variants (ClinVar): 105 total — 3 pathogenic
• Phenotypes (HPO): 8
• Druggable target: yes
• MANE Select transcript: NM_015368

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:8599
Approved symbol	PANX1
Name	pannexin 1
Location	11q21
Locus type	gene with protein product
Status	Approved
Aliases	MRS1, UNQ2529, PX1
Ensembl gene	ENSG00000110218
Ensembl biotype	protein_coding
OMIM	608420
Entrez	24145

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 3 protein_coding

ENST00000227638, ENST00000436171, ENST00000931248

RefSeq mRNA: 1 — MANE Select: NM_015368 NM_015368

CCDS: CCDS8296

Canonical transcript exons

ENST00000227638 — 5 exons

Exon	Start	End
ENSE00000744341	94179602	94180257
ENSE00000989417	94153491	94153630
ENSE00000989418	94178369	94178592
ENSE00001121938	94128841	94129493
ENSE00002233983	94180790	94181968

Expression profiles

Bgee: expression breadth ubiquitous, 222 present calls, max score 94.21.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 16.9059 / max 271.5945, expressed in 1800 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
116250	11.5342	1783
116252	3.1566	1393
116251	2.2150	1296

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cortical plate	UBERON:0005343	94.21	gold quality
ganglionic eminence	UBERON:0004023	90.17	gold quality
stromal cell of endometrium	CL:0002255	87.39	gold quality
adrenal tissue	UBERON:0018303	87.05	gold quality
secondary oocyte	CL:0000655	86.97	gold quality
islet of Langerhans	UBERON:0000006	85.85	gold quality
monocyte	CL:0000576	85.78	gold quality
ventricular zone	UBERON:0003053	85.46	gold quality
mononuclear cell	CL:0000842	85.20	gold quality
leukocyte	CL:0000738	84.92	gold quality
calcaneal tendon	UBERON:0003701	84.77	gold quality
gastrocnemius	UBERON:0001388	84.00	gold quality
muscle of leg	UBERON:0001383	83.78	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	83.02	gold quality
right coronary artery	UBERON:0001625	82.42	gold quality
descending thoracic aorta	UBERON:0002345	81.77	gold quality
oocyte	CL:0000023	81.52	gold quality
gall bladder	UBERON:0002110	81.34	gold quality
thoracic aorta	UBERON:0001515	81.29	gold quality
ascending aorta	UBERON:0001496	81.26	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	81.06	gold quality
left coronary artery	UBERON:0001626	81.03	gold quality
smooth muscle tissue	UBERON:0001135	80.93	gold quality
aorta	UBERON:0000947	80.79	gold quality
popliteal artery	UBERON:0002250	80.57	gold quality
tibial artery	UBERON:0007610	80.57	gold quality
tendon	UBERON:0000043	79.92	gold quality
hindlimb stylopod muscle	UBERON:0004252	79.85	gold quality
coronary artery	UBERON:0001621	79.40	gold quality
tibialis anterior	UBERON:0001385	79.06	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.80

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

49 targeting PANX1, 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-4668-3P	100.00	68.74	2635
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-9-3P	99.96	70.88	2068
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-579-3P	99.86	71.66	3628
HSA-MIR-664B-3P	99.84	71.65	3590
HSA-MIR-6079	99.84	68.54	1170
HSA-MIR-6875-3P	99.82	70.26	2983
HSA-MIR-636	99.80	69.58	1500
HSA-MIR-202-5P	99.78	67.65	991
HSA-MIR-148A-3P	99.74	73.77	1700
HSA-MIR-148B-3P	99.74	73.75	1700
HSA-MIR-152-3P	99.74	73.75	1703
HSA-MIR-132-3P	99.73	70.56	1424
HSA-MIR-212-3P	99.73	70.65	1424
HSA-MIR-1825	99.72	68.11	1089
HSA-MIR-4677-5P	99.70	70.09	1940
HSA-MIR-466	99.67	70.85	2863
HSA-MIR-141-5P	99.57	67.86	897
HSA-MIR-12122	99.56	69.33	1672
HSA-MIR-105-5P	99.54	69.24	2060
HSA-MIR-7853-5P	99.54	69.30	2055
HSA-MIR-549A-3P	99.54	68.17	825
HSA-MIR-6740-3P	99.48	68.49	1392
HSA-MIR-516A-3P	99.46	67.96	1378
HSA-MIR-516B-3P	99.46	67.96	1378
HSA-MIR-7162-5P	99.46	68.08	1368
HSA-MIR-578	99.46	68.36	1787
HSA-MIR-3182	99.40	68.15	2454

Literature-anchored findings (GeneRIF, showing 40)

• Data show that erythrocytes express the gap junction protein pannexin 1. (PMID:16682648)
• Pannexin-1 in pyramidal neurons is activated by ischemia and may play an important role ionic dysregulation (PMID:16690868)
• Overexpression of PanX1 results in the formation of Ca(2+)-permeable gap junction channels between adjacent cells, thus, allowing direct intercellular Ca(2+) diffusion and facilitating intercellular Ca(2+) wave propagation. (PMID:16908669)
• Panx1 in the plasma membrane of the macrophage couples to the purinergic P2X7 receptor and permeabilize the macrophage membrane, this signaling is required for the processing and release of interleukin-1beta in response to P2X7 receptor activation. (PMID:17036048)
• pannexin-1 is required for processing of caspase-1 and release of mature IL-1beta induced by P2X(7) receptor activation. (PMID:17036048)
• pannexin1 appears to be the molecular substrate for the permeabilization pore (or death receptor channel) recruited into the P2X(7)R signaling complex (PMID:17240370)
• PANX1 channels contain a glycosylation site that targets the hexamer to the cell membrane. (PMID:17715132)
• 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)
• Explored the pharmacological action of compounds known to block gap junctions on Panx1 channels activated by the P2X(7)R and the mechanisms involved in the interaction between these two proteins. (PMID:18596211)
• It is demonstrated that pannexin-1 is activated by NMDA receptor stimulation and contributes to epileptic like bursting activity in the hippocampus. (PMID:19056988)
• In this study, they investigated whether endogenous panx-1 was activated and contributed to membrane current in osmotically swollen HEK-293 cells. (PMID:19150332)
• Pannexin 1 contributes to ATP release in airway epithelia. (PMID:19213873)
• 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)
• Pannexin1 and Pannexin2 channels show quaternary similarities to connexons and different oligomerization numbers from each other (PMID:20516070)
• Pannexin 1 is the conduit for ATP release from erythrocytes in response to lowered O(2) tension. (PMID:20622111)
• T-cell receptor stimulation results in the translocation of P2X1 and P2X4 receptors and pannexin-1 hemichannels to the immune synapse. (PMID:20660288)
• immunostimulatory effects of hypertonic stress treatment are mediated by the controlled cellular release of ATP through Panx1 hemichannels . (PMID:20884646)
• data identify PANX1 as a plasma membrane channel mediating the regulated release of find-me signals and selective plasma membrane permeability during apoptosis, and a new mechanism of PANX1 activation by caspases (PMID:20944749)
• TRPV4 and Rho transduce cell membrane stretch/strain into pannexin 1-mediated ATP release in airway epithelia. (PMID:21606493)
• indicate that the oligomerization and trafficking of Panx1 are regulated by the C-terminal domain, whereas internalization of long lived Panx1 channels occurs in a manner that is distinct from classical endocytic pathways (PMID:21659516)
• MSR1 was significantly associated with the presence of Barrett esophagus/esophageal adenocarcinoma in derivation and validation samples (PMID:21791690)
• both P2X(7) and Panx-1 are required for GM-CSF promotion of multinucleated macrophages fusion (PMID:21865551)
• Panx1 assembles into a membrane anion channel with a relatively low single-channel conductance. (PMID:22311122)
• mechanism of PANX1 channel regulation (PMID:22311983)
• while Panx1 is present in skin melanocytes it is up-regulated during melanoma tumor progression, and tumorigenesis can be inhibited by the knockdown of Panx1 raising the possibility that Panx1 may be a viable target for the treatment of melanoma. (PMID:22753409)
• Panx1 level is modulated during keratinocyte differentiation and carcinogenesis and reveal distinct localization pattern for Panx1 in human adnexal structures. (PMID:22947051)
• These results suggest that panx1 contributes to pathophysiological ATP release in lipoapoptosis induced by saturated FFA; panx1 may play a role in hepatic inflammation by mediating an increase in extracellular ATP concentration in lipotoxic liver injury. (PMID:22972801)
• S-nitrosylation of Panx1 at Cys-40 and Cys-346 inhibits Panx1 channel currents and ATP release. (PMID:23033481)
• Blocking Panx1 hemichannels by reducing their opening or protein expression inhibited HIV replication in CD4(+) T lymphocytes (PMID:23456773)
• Overexpression of Panx1 in THP-1 cells also failed to increase the infl ammasome activity as revealed by similar IL-1beta and caspase-1 activity in comparison with normal THP-1 cells (PMID:23549611)
• Pannexin-1 immunoreactivity was mainly localized to enteric ganglia, blood vessel endothelium, erythrocytes, epithelial and goblet cells. In ulcerative colitis myenteric ganglia, there was a significant reduction in Panx1. (PMID:23594276)
• Panx1 localizes to chlamydial inclusions but its absence does not effect chlamydial development during infection of cells. (PMID:23700432)
• findings suggest that chemoattractant receptors require PANX1 to trigger excitatory and inhibitory signals that synergize to fine-tune chemotactic responses at the front and back of neutrophils (PMID:23798685)
• histamine induces ATP release from human subcutaneous fibroblasts, via pannexin-1 hemichannels, leading to [Ca(2+)]i mobilization and cell growth through the cooperation of H1 and P2 (probably P2Y1) receptors. (PMID:23918924)
• P2X4 assembles with P2X7 and pannexin-1 in gingival epithelial cells and modulates ATP-induced reactive oxygen species production and inflammasome activation during P. gingivalis infection. (PMID:23936165)
• Panx1 and Panx2 expression was detected in the temporal lobe cortex of patients with temporal lobe epilepsy and in the control tissues. (PMID:24146091)
• The critical involvement of Panx1 despite its absence in epiplexus cells was while it was not surprising that ATP could activate the epiplexus cells. (PMID:24418937)
• These findings suggest that nonmetal hapten reactivity to thiol residues causes membrane disruption of keratinocytes and reactive oxygen species production that leads to ATP release through opening of Panx hemichannels. (PMID:24531690)
• data identify a novel linkage between an antibiotic, pannexin channels and cellular integrity, and suggest that re-engineering certain quinolones might help develop newer antibacterials (PMID:24646995)
• Panx1 is expressed on human platelets and amplifies Ca(2+) influx, ATP release and aggregation through the secondary activation of P2X1 receptors. (PMID:24655807)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	panx1b	ENSDARG00000014910
danio_rerio	panx1a	ENSDARG00000025285
mus_musculus	Panx1	ENSMUSG00000031934
rattus_norvegicus	Panx1	ENSRNOG00000010060

Paralogs (2): PANX2 (ENSG00000073150), PANX3 (ENSG00000154143)

Protein

Protein identifiers

Pannexin-1 — Q96RD7 (reviewed: Q96RD7)

All UniProt accessions (1): Q96RD7

UniProt curated annotations — full annotation on UniProt →

Function. Ion channel involved in a variety of physiological functions such as blood pressure regulation, apoptotic cell clearance and oogenesis. Forms anion-selective channels with relatively low conductance and an order of permeabilities: nitrate>iodide>chlroride»aspartate=glutamate=gluconate. Can release ATP upon activation through phosphorylation or cleavage at C-terminus. May play a role as a Ca(2+)-leak channel to regulate ER Ca(2+) homeostasis. During apoptosis, the C terminal tail is cleaved by caspases, which opens the main pore acting as a large-pore ATP efflux channel with a broad distribution, which allows the regulated release of molecules and ions smaller than 1 kDa, such as nucleotides ATP and UTP, and selective plasma membrane permeability to attract phagocytes that engulf the dying cells.

Subunit / interactions. Homoheptameric.

Subcellular location. Cell membrane. Endoplasmic reticulum membrane.

Tissue specificity. Widely expressed. Highest expression is observed in oocytes and brain. Detected at very low levels in sperm cells.

Post-translational modifications. S-nitrosylation inhibits channel currents and ATP release. N-glycosylation plays a role in cell surface targeting. Glycosylation at its extracellular surface makes unlikely that two oligomers could dock to form an intercellular channel such as in gap junctions. Exists in three glycosylation states: non-glycosylated (GLY0), high-mannose glycosylated (GLY1), and fully mature glycosylated (GLY2). Cleaved by CASP3 and CASP7 during apoptosis. Cleavage opens the channel for the release of metabolites and induces plasma membrane permeability during apoptosis. Phosphorylated at Tyr-199 by SRC. Phosphorylation activates ATP release. Constitutively phosphorylated in vascular smooth muscle cells.

Disease relevance. Oocyte/zygote/embryo maturation arrest 7 (OZEMA7) [MIM:618550] An autosomal dominant infertility disorder due to oocyte degeneration and death, which may occur before or after fertilization. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the pannexin family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q96RD7-1	1	yes
Q96RD7-2	2

RefSeq proteins (1): NP_056183* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000990	Innexin	Family
IPR039099	Pannexin	Family

Pfam: PF00876

Catalyzed reactions (Rhea), 11 shown:

• K(+)(in) = K(+)(out) (RHEA:29463)
• Ca(2+)(in) = Ca(2+)(out) (RHEA:29671)
• chloride(in) = chloride(out) (RHEA:29823)
• nitrate(in) = nitrate(out) (RHEA:34923)
• Na(+)(in) = Na(+)(out) (RHEA:34963)
• spermidine(in) = spermidine(out) (RHEA:35039)
• iodide(out) = iodide(in) (RHEA:66324)
• L-aspartate(out) = L-aspartate(in) (RHEA:66332)
• L-glutamate(out) = L-glutamate(in) (RHEA:66336)
• ATP(in) = ATP(out) (RHEA:75687)
• D-gluconate(in) = D-gluconate(out) (RHEA:76139)

UniProt features (80 total): helix 22, strand 11, mutagenesis site 10, sequence variant 7, turn 6, topological domain 5, transmembrane region 4, modified residue 3, chain 2, compositionally biased region 2, disulfide bond 2, sequence conflict 2, region of interest 1, site 1, glycosylation site 1, splice variant 1

Structure

Experimental structures (PDB)

33 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
9OQK	ELECTRON MICROSCOPY	2.5
9OQG	ELECTRON MICROSCOPY	2.58
9OQH	ELECTRON MICROSCOPY	2.58
9OQP	ELECTRON MICROSCOPY	2.62
9OQI	ELECTRON MICROSCOPY	2.66
9OQJ	ELECTRON MICROSCOPY	2.66
9OQL	ELECTRON MICROSCOPY	2.77
9OQM	ELECTRON MICROSCOPY	2.8
6WBF	ELECTRON MICROSCOPY	2.83
6WBN	ELECTRON MICROSCOPY	2.83
6WBM	ELECTRON MICROSCOPY	2.86
6WBG	ELECTRON MICROSCOPY	2.97
6LTN	ELECTRON MICROSCOPY	3.1
6LTO	ELECTRON MICROSCOPY	3.1
7DWB	ELECTRON MICROSCOPY	3.15
9OQN	ELECTRON MICROSCOPY	3.19
6M02	ELECTRON MICROSCOPY	3.2
8GTT	ELECTRON MICROSCOPY	3.2
9OQQ	ELECTRON MICROSCOPY	3.25
7F8N	ELECTRON MICROSCOPY	3.4
9OQO	ELECTRON MICROSCOPY	3.45
6M67	ELECTRON MICROSCOPY	3.6
7F8J	ELECTRON MICROSCOPY	3.6
7F8O	ELECTRON MICROSCOPY	3.6
6V6D	ELECTRON MICROSCOPY	3.77
8GYO	ELECTRON MICROSCOPY	3.8
8GTS	ELECTRON MICROSCOPY	3.87
6M66	ELECTRON MICROSCOPY	4.1
6WBI	ELECTRON MICROSCOPY	4.39
7WSV	ELECTRON MICROSCOPY	4.5

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96RD7-F1	74.80	0.26

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): 376–379 (cleavage; by casp3 or casp7)

Post-translational modifications (3): 40, 199, 347

Disulfide bonds (2): 66–265, 84–246

Glycosylation sites (1): 255

Mutagenesis-validated functional residues (10):

Position	Phenotype
74	no effect on voltage-dependence. altered anion selectivity with equal permeability for iodide and choride.
75	loss of voltage-dependence and anion selectivity. strong increase in permeability of sodium over chloride.
164–167	not cleaved by casp3 or casp7.
255	impaired glycosylation. forms gap junctions by 2 hemichannels.
255	impaired glycosylation. loss of gly1 and gly2 forms. no effect on oocyte survival. located in the cytoplasm. decreased l
338	impaired glycosylation; loss of gly2 form; oocyte death.
376–379	not cleaved by casp3 or casp7. reduces channel activation.
379	no effect on cell membrane location. decreased levels of pro-il1b upon lps priming and atp stimulation. attenuated pyrop
394	no change in glycosylation pattern.
424	no effect on cell membrane location. promoted pyroptotic cell death induced by lps and atp.

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-112303	Electric Transmission Across Gap Junctions
R-HSA-844456	The NLRP3 inflammasome
R-HSA-9856530	High laminar flow shear stress activates signaling by PIEZO1 and PECAM1:CDH5:KDR in endothelial cells
R-HSA-9856532	Mechanical load activates signaling by PIEZO1 and integrins in osteocytes

MSigDB gene sets: 251 (showing top): GOBP_RESPONSE_TO_NITROGEN_COMPOUND, REACTOME_INNATE_IMMUNE_SYSTEM, REACTOME_THE_NLRP3_INFLAMMASOME, REACTOME_INFLAMMASOMES, REACTOME_NUCLEOTIDE_BINDING_DOMAIN_LEUCINE_RICH_REPEAT_CONTAINING_RECEPTOR_NLR_SIGNALING_PATHWAYS, GOBP_OOGENESIS, GOBP_POSITIVE_REGULATION_OF_CYTOKINE_PRODUCTION, GOBP_INTERLEUKIN_1_PRODUCTION, GOBP_NUCLEOTIDE_TRANSPORT, GOBP_MONOATOMIC_CATION_TRANSPORT, GOBP_CELL_CELL_SIGNALING, GOBP_ORGANOPHOSPHATE_ESTER_TRANSPORT, MISSIAGLIA_REGULATED_BY_METHYLATION_UP, GOBP_RESPONSE_TO_ISCHEMIA, GOBP_CYTOKINE_PRODUCTION

GO Biological Process (16): response to ischemia (GO:0002931), monoatomic cation transport (GO:0006812), calcium ion transport (GO:0006816), cell-cell signaling (GO:0007267), ATP transport (GO:0015867), positive regulation of interleukin-1 alpha production (GO:0032730), positive regulation of interleukin-1 beta production (GO:0032731), response to ATP (GO:0033198), oogenesis (GO:0048477), positive regulation of macrophage cytokine production (GO:0060907), monoatomic anion transmembrane transport (GO:0098656), monoatomic ion transport (GO:0006811), cell differentiation (GO:0030154), positive regulation of interleukin-1 production (GO:0032732), monoatomic ion transmembrane transport (GO:0034220), calcium ion transmembrane transport (GO:0070588)

GO Molecular Function (17): protease binding (GO:0002020), signaling receptor binding (GO:0005102), structural molecule activity (GO:0005198), gap junction channel activity (GO:0005243), monoatomic anion channel activity (GO:0005253), calcium channel activity (GO:0005262), ATP transmembrane transporter activity (GO:0005347), wide pore channel activity (GO:0022829), leak channel activity (GO:0022840), identical protein binding (GO:0042802), transmembrane transporter binding (GO:0044325), actin filament binding (GO:0051015), scaffold protein binding (GO:0097110), actin binding (GO:0003779), protein binding (GO:0005515), channel activity (GO:0015267), protein-containing complex binding (GO:0044877)

GO Cellular Component (7): endoplasmic reticulum (GO:0005783), endoplasmic reticulum membrane (GO:0005789), plasma membrane (GO:0005886), gap junction (GO:0005921), membrane (GO:0016020), bleb (GO:0032059), protein-containing complex (GO:0032991)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
Transmission across Electrical Synapses	1
Inflammasomes	1
Response of endothelial cells to shear stress	1
Cellular responses to mechanical stimuli	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein binding	4
monoatomic ion transport	2
positive regulation of interleukin-1 production	2
binding	2
response to stress	1
metal ion transport	1
cell communication	1
signaling	1
purine ribonucleotide transport	1
adenine nucleotide transport	1
interleukin-1 alpha production	1
regulation of interleukin-1 alpha production	1
interleukin-1 beta production	1
regulation of interleukin-1 beta production	1
response to purine-containing compound	1
response to organophosphorus	1
response to oxygen-containing compound	1
germ cell development	1
female gamete generation	1
macrophage cytokine production	1
regulation of macrophage cytokine production	1
positive regulation of myeloid leukocyte cytokine production involved in immune response	1
monoatomic anion transport	1
monoatomic ion transmembrane transport	1
transport	1
cellular developmental process	1
positive regulation of cytokine production	1
interleukin-1 production	1
regulation of interleukin-1 production	1
transmembrane transport	1
calcium ion transport	1
monoatomic cation transmembrane transport	1
enzyme binding	1
molecular_function	1
wide pore channel activity	1
monoatomic ion channel activity	1
monoatomic anion transmembrane transporter activity	1
monoatomic cation channel activity	1
calcium ion transmembrane transporter activity	1
adenine nucleotide transmembrane transporter activity	1

Protein interactions and networks

STRING

1092 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PANX1	P2RX7	Q99572	986
PANX1	P2RX4	Q99571	855
PANX1	CASP1	P29466	827
PANX1	GJA1	P17302	822
PANX1	MRS2	Q9HD23	772
PANX1	P2RX1	P51575	767
PANX1	GJB2	P29033	746
PANX1	KCNAB3	O43448	739
PANX1	CALHM1	Q8IU99	728
PANX1	P2RY2	P41231	721
PANX1	NLRP1	Q9C000	717
PANX1	P2RX2	Q9UBL9	705
PANX1	GJB1	P08034	702
PANX1	ENTPD8	Q5MY95	692
PANX1	NLRC4	Q9NPP4	689

IntAct

80 interactions, top by confidence:

A	B	Type	Score
CDC37	IKBKB	psi-mi:“MI:0914”(association)	0.850
CFHR5	PANX1	psi-mi:“MI:0915”(physical association)	0.560
TMEM229B	PANX1	psi-mi:“MI:0915”(physical association)	0.560
	PANX1	psi-mi:“MI:0915”(physical association)	0.560
TNF	PANX1	psi-mi:“MI:0915”(physical association)	0.560
PANX1	APOL2	psi-mi:“MI:0915”(physical association)	0.560
PANX1	CFHR5	psi-mi:“MI:0915”(physical association)	0.560
FDFT1	PANX1	psi-mi:“MI:0915”(physical association)	0.560
AQP2	PANX1	psi-mi:“MI:0915”(physical association)	0.560
VAMP5	PANX1	psi-mi:“MI:0915”(physical association)	0.560
PANX1	SLC38A7	psi-mi:“MI:0915”(physical association)	0.560
APOA2	PANX1	psi-mi:“MI:0915”(physical association)	0.560
FAXDC2	PANX1	psi-mi:“MI:0915”(physical association)	0.560
BCL2L2	PANX1	psi-mi:“MI:0915”(physical association)	0.560
WFDC2	PANX1	psi-mi:“MI:0915”(physical association)	0.560
ARLN	DEGS1	psi-mi:“MI:0914”(association)	0.530
PANX1	CASP3	psi-mi:“MI:0570”(protein cleavage)	0.440
PANX1	CASP7	psi-mi:“MI:0570”(protein cleavage)	0.440
PANX1	P2rx7	psi-mi:“MI:0915”(physical association)	0.400
PANX1	BUD31	psi-mi:“MI:0915”(physical association)	0.370
Kif4	UMPS	psi-mi:“MI:0914”(association)	0.350
Smo	METTL8	psi-mi:“MI:0914”(association)	0.350
BAG3	HTT	psi-mi:“MI:0914”(association)	0.350
FBXO7	ELOC	psi-mi:“MI:0914”(association)	0.350
C5AR2	ILVBL	psi-mi:“MI:0914”(association)	0.350
GRPR	GPR89A	psi-mi:“MI:0914”(association)	0.350

BioGRID (306): PANX1 (Reconstituted Complex), GNAS (Reconstituted Complex), PANX1 (Affinity Capture-MS), PANX1 (Proximity Label-MS), PANX1 (Affinity Capture-MS), PANX1 (Affinity Capture-MS), PANX1 (Affinity Capture-MS), PANX1 (Affinity Capture-MS), PANX1 (Affinity Capture-MS), PANX1 (Affinity Capture-MS), PANX1 (Affinity Capture-MS), PANX1 (Affinity Capture-MS), PANX1 (Affinity Capture-MS), PANX1 (Affinity Capture-MS), PANX1 (Proximity Label-MS)

ESM2 similar proteins: A2AF53, A4FV75, A5A6S6, A6ZIQ8, B8AT51, D3ZEH5, O60337, Q08DE2, Q0JAW2, Q0VC58, Q15005, Q28250, Q2TBU2, Q2V4F9, Q3TMP8, Q4R512, Q4R5B4, Q58DA4, Q5JZQ8, Q5M8Y1, Q5R8H8, Q5R9W1, Q5RAY6, Q5REE3, Q5RF53, Q5XIK2, Q5ZK43, Q6GLK9, Q6P2T0, Q6P8F8, Q6ZQ89, Q7SYC7, Q7ZY07, Q80YV4, Q8CIF6, Q8NBJ9, Q8NFB2, Q8R3R5, Q8TCT6, Q8VIJ8

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

SIGNOR signaling

4 interactions.

A	Effect	B	Mechanism
SRC	“up-regulates activity”	PANX1	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 72 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

GO biological processes:

GO term	Partners	Fold	FDR
response to hypoxia	7	10.5×	2e-03
positive regulation of cytosolic calcium ion concentration	5	9.1×	9e-03
G protein-coupled receptor signaling pathway	9	5.1×	8e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	3
Likely pathogenic	0
Uncertain significance	64
Likely benign	12
Benign	14

Top pathogenic / likely-pathogenic (3)

Variant ID	HGVS	Classification
689421	NM_015368.4(PANX1):c.1174C>T (p.Gln392Ter)	Pathogenic
689422	NM_015368.4(PANX1):c.1040G>C (p.Cys347Ser)	Pathogenic
689423	NM_015368.4(PANX1):c.1036A>G (p.Lys346Glu)	Pathogenic

SpliceAI

806 predictions. Top by Δscore:

Variant	Effect	Δscore
11:94129489:GATTG:G	donor_gain	1.0000
11:94129492:TGG:T	donor_loss	1.0000
11:94129494:G:GG	donor_gain	1.0000
11:94178367:A:AG	acceptor_gain	1.0000
11:94178368:G:GG	acceptor_gain	1.0000
11:94179593:A:AG	acceptor_gain	1.0000
11:94179597:TTTA:T	acceptor_loss	1.0000
11:94179600:A:AG	acceptor_gain	1.0000
11:94179600:A:AT	acceptor_loss	1.0000
11:94179600:AGTTT:A	acceptor_gain	1.0000
11:94179601:G:GT	acceptor_gain	1.0000
11:94179601:GT:G	acceptor_gain	1.0000
11:94179601:GTT:G	acceptor_gain	1.0000
11:94179601:GTTT:G	acceptor_gain	1.0000
11:94179601:GTTTG:G	acceptor_gain	1.0000
11:94177597:GC:G	donor_gain	0.9900
11:94178363:TTTCA:T	acceptor_loss	0.9900
11:94178364:TTCA:T	acceptor_loss	0.9900
11:94178365:TCAG:T	acceptor_loss	0.9900
11:94178366:CA:C	acceptor_loss	0.9900
11:94178367:A:T	acceptor_loss	0.9900
11:94178368:GT:G	acceptor_gain	0.9900
11:94178368:GTT:G	acceptor_gain	0.9900
11:94178368:GTTT:G	acceptor_gain	0.9900
11:94178368:GTTTT:G	acceptor_gain	0.9900
11:94178477:G:GT	donor_gain	0.9900
11:94178588:CAAAG:C	donor_loss	0.9900
11:94178590:AAGGT:A	donor_loss	0.9900
11:94178591:AGGTA:A	donor_loss	0.9900
11:94178592:GGTA:G	donor_loss	0.9900

AlphaMissense

2795 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:94153561:C:G	C84W	0.998
11:94153505:T:C	C66R	0.997
11:94153507:T:G	C66W	0.997
11:94153560:G:A	C84Y	0.997
11:94153564:G:C	W85C	0.997
11:94153564:G:T	W85C	0.997
11:94179849:T:A	C265S	0.997
11:94179850:G:C	C265S	0.997
11:94153506:G:A	C66Y	0.996
11:94153559:T:A	C84S	0.996
11:94153560:G:C	C84S	0.996
11:94153559:T:C	C84R	0.995
11:94178468:T:C	F141L	0.995
11:94178470:T:A	F141L	0.995
11:94178470:T:G	F141L	0.995
11:94179849:T:C	C265R	0.995
11:94179851:C:G	C265W	0.995
11:94153505:T:A	C66S	0.994
11:94153506:G:C	C66S	0.994
11:94179786:T:C	F244L	0.994
11:94179788:T:A	F244L	0.994
11:94179788:T:G	F244L	0.994
11:94153508:T:C	F67L	0.993
11:94153510:C:A	F67L	0.993
11:94153510:C:G	F67L	0.993
11:94153560:G:T	C84F	0.993
11:94178484:T:C	L146P	0.993
11:94179787:T:G	F244C	0.993
11:94179850:G:A	C265Y	0.993
11:94179885:A:C	S277R	0.993

dbSNP variants (sampled 300 via entrez): RS1000016498 (11:94167621 T>G), RS1000085824 (11:94153370 T>G), RS1000289672 (11:94165951 G>A,C), RS1000314564 (11:94162007 A>C,G), RS1000325409 (11:94132022 C>T), RS1000388477 (11:94142118 G>A), RS1000454692 (11:94153141 C>A,T), RS1000494255 (11:94167327 C>T), RS1000503174 (11:94141942 A>T), RS1000504611 (11:94161454 A>G), RS1000622795 (11:94130952 T>A), RS1000644700 (11:94157635 T>G), RS1000694006 (11:94136565 G>C), RS1000705110 (11:94178729 T>G), RS1000728214 (11:94136448 G>A,T)

Disease associations

OMIM: gene MIM:608420 | disease phenotypes: MIM:618550

GenCC curated gene-disease

Disease	Classification	Inheritance
oocyte maturation defect 7	Strong	Autosomal dominant

Mondo (1): oocyte maturation defect 7 (MONDO:0032810)

Orphanet (0):

HPO phenotypes

8 total (8 of 8 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000147	Polycystic ovaries
HP:0008222	Female infertility
HP:0008669	Abnormal spermatogenesis
HP:0020155	Abnormal oocyte morphology
HP:0031515	Abnormal meiosis
HP:0031516	Metaphase I oocyte maturation arrest
HP:0032571	Increased oocyte death

GWAS associations

13 associations (top):

Study	Trait	p-value
GCST004750_35	Squamous cell lung carcinoma	4.000000e-06
GCST005998_24	Alanine transaminase levels	6.000000e-18
GCST005999_20	Aspartate aminotransferase levels	3.000000e-11
GCST007932_18	Medication use (thyroid preparations)	5.000000e-11
GCST010571_53	Autoimmune thyroid disease	5.000000e-09
GCST011351_18	Aspartate aminotransferase levels	5.000000e-12
GCST011352_40	Alanine aminotransferase levels	1.000000e-24
GCST90002397_536	Mean spheric corpuscular volume	5.000000e-09
GCST90011898_6	Alanine aminotransferase levels	7.000000e-55
GCST90011899_179	Aspartate aminotransferase levels	9.000000e-38
GCST90013405_88	Liver enzyme levels (alanine transaminase)	2.000000e-83
GCST90013663_20	Alanine aminotransferase levels	2.000000e-86
GCST90013664_80	Aspartate aminotransferase levels	7.000000e-49

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004736	aspartate aminotransferase measurement
EFO:0009933	Thyroid preparation use measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3779756 (SINGLE PROTEIN)

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

Most potent curated ligand interactions (1 total), top 1:

Ligand	Action	Affinity	Parameter
EG-2184	Inhibitor	7.27	pIC50

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases expression, decreases expression, affects methylation, affects cotreatment, increases abundance	4
Adenosine Triphosphate	decreases activity, decreases reaction, increases export	2
Arsenic	increases abundance, increases expression, decreases expression, affects cotreatment	2
Benzo(a)pyrene	increases expression	2
Nickel	increases expression	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	2
Aflatoxin B1	increases expression, affects expression, decreases methylation	2
TAK-243	decreases sumoylation	1
triphenyl phosphate	affects expression	1
bisphenol A	decreases methylation	1
manganese chloride	increases expression, affects cotreatment, increases abundance	1
cupric chloride	increases expression	1
CGP 52608	affects binding, increases reaction	1
K 7174	increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Leflunomide	decreases expression	1
Acetaminophen	decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Cadmium	increases abundance, increases expression	1
Carbamazepine	affects expression	1
Carbenoxolone	decreases reaction, increases export	1
Cisplatin	increases expression	1
Doxorubicin	decreases expression	1
Ethyl Methanesulfonate	increases expression	1
Formaldehyde	increases expression	1
Hydrogen Peroxide	affects expression	1
Manganese	increases expression, affects cotreatment, increases abundance	1
Methyl Methanesulfonate	increases expression	1
Phenobarbital	affects expression	1
Plant Extracts	increases expression, affects cotreatment	1

ChEMBL screening assays

6 unique, capped per target: 6 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3784394	Binding	Binding affinity to pannexin 1 channel (unknown origin)	Inhibiting the Inflammasome: A Chemical Perspective. — J Med Chem

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D1Y3	Abcam A-549 PANX1 KO	Cancer cell line	Male
CVCL_D2CB	Abcam HCT 116 PANX1 KO	Cancer cell line	Male

Clinical trials (associated diseases)

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