GJE1

Summary

GJE1 (gap junction protein epsilon 1, HGNC:33251) is a protein-coding gene on chromosome 6q24.1, encoding Gap junction epsilon-1 protein (A6NN92). Mediates calcium-independent ATP release, suggesting activity as a hemichannel.

Predicted to enable gap junction channel activity. Predicted to be involved in cell-cell signaling. Predicted to act upstream of or within cell morphogenesis; lens development in camera-type eye; and organ growth. Predicted to be located in plasma membrane. Predicted to be part of connexin complex.

Source: NCBI Gene 100126572 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 1 total
• MANE Select transcript: NM_001358410

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:33251
Approved symbol	GJE1
Name	gap junction protein epsilon 1
Location	6q24.1
Locus type	gene with protein product
Status	Approved
Aliases	CX23
Ensembl gene	ENSG00000203733
Ensembl biotype	protein_coding
Entrez	100126572

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000450456

RefSeq mRNA: 1 — MANE Select: NM_001358410 NM_001358410

CCDS: CCDS87449

Canonical transcript exons

ENST00000450456 — 3 exons

Exon	Start	End
ENSE00002202351	142133850	142134044
ENSE00003978187	142132925	142133197
ENSE00003978188	142134539	142135358

Expression profiles

Bgee: expression breadth tissue_specific, 1 present calls, max score 64.48.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	64.48	gold quality
colonic epithelium	UBERON:0000397	37.20	gold quality
ventricular zone	UBERON:0003053	36.48	gold quality
cortical plate	UBERON:0005343	36.47	gold quality
bone marrow cell	CL:0002092	36.16	gold quality
skeletal muscle tissue	UBERON:0001134	35.52	gold quality
ganglionic eminence	UBERON:0004023	35.49	gold quality
muscle tissue	UBERON:0002385	32.63	gold quality
hindlimb stylopod muscle	UBERON:0004252	32.15	gold quality
bone marrow	UBERON:0002371	31.74	gold quality
sural nerve	UBERON:0015488	30.93	gold quality
adrenal tissue	UBERON:0018303	30.66	gold quality
stromal cell of endometrium	CL:0002255	29.87	gold quality
calcaneal tendon	UBERON:0003701	29.55	gold quality
prefrontal cortex	UBERON:0000451	29.04	gold quality
duodenum	UBERON:0002114	28.14	gold quality
liver	UBERON:0002107	28.04	gold quality
lymph node	UBERON:0000029	27.57	gold quality
monocyte	CL:0000576	27.55	gold quality
leukocyte	CL:0000738	27.55	gold quality
tonsil	UBERON:0002372	27.05	gold quality
islet of Langerhans	UBERON:0000006	26.55	gold quality
vermiform appendix	UBERON:0001154	26.42	gold quality
blood	UBERON:0000178	26.19	gold quality
gall bladder	UBERON:0002110	25.98	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	25.89	gold quality
placenta	UBERON:0001987	25.81	gold quality
urinary bladder	UBERON:0001255	25.72	gold quality
muscle of leg	UBERON:0001383	25.08	gold quality
primary visual cortex	UBERON:0002436	24.61	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.47

Regulation

Is transcription factor: no

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	gje1a	ENSDARG00000054150
mus_musculus	Gje1	ENSMUSG00000019867
rattus_norvegicus	Gje1	ENSRNOG00000012092

Paralogs (20): GJA8 (ENSG00000121634), GJB6 (ENSG00000121742), GJA3 (ENSG00000121743), GJA9 (ENSG00000131233), GJA10 (ENSG00000135355), GJA1 (ENSG00000152661), GJD2 (ENSG00000159248), GJB7 (ENSG00000164411), GJB2 (ENSG00000165474), GJB1 (ENSG00000169562), GJC3 (ENSG00000176402), GJD4 (ENSG00000177291), GJC1 (ENSG00000182963), GJD3 (ENSG00000183153), GJA4 (ENSG00000187513), GJB3 (ENSG00000188910), GJB5 (ENSG00000189280), GJB4 (ENSG00000189433), GJC2 (ENSG00000198835), GJA5 (ENSG00000265107)

Protein

Protein identifiers

Gap junction epsilon-1 protein — A6NN92 (reviewed: A6NN92)

Alternative names: Connexin-23

All UniProt accessions (2): A6NN92, A0A654IE96

UniProt curated annotations — full annotation on UniProt →

Function. Mediates calcium-independent ATP release, suggesting activity as a hemichannel. Does not form functional gap junctions.

Subunit / interactions. A connexon is composed of a hexamer of connexins.

Subcellular location. Cell membrane.

Tissue specificity. Not detected in lens or retina.

Similarity. Belongs to the connexin family. Beta-type (group I) subfamily.

RefSeq proteins (1): NP_001345339* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000500	Connexin	Family
IPR013092	Connexin_N	Domain
IPR019570	Connexin_CCC	Domain
IPR038359	Connexin_N_sf	Homologous_superfamily

Pfam: PF00029

UniProt features (12 total): topological domain 5, transmembrane region 4, disulfide bond 2, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-A6NN92-F1	84.06	0.23

Functional residue map

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

Disulfide bonds (2): 53–161, 64–148

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 27 (showing top): GOBP_GROWTH, GOBP_CELL_CELL_SIGNALING, GOBP_ORGAN_GROWTH, GOBP_SENSORY_ORGAN_DEVELOPMENT, GOCC_CELL_CELL_JUNCTION, GOBP_TRANSMEMBRANE_TRANSPORT, GOBP_LENS_DEVELOPMENT_IN_CAMERA_TYPE_EYE, LEIN_OLIGODENDROCYTE_MARKERS, LEIN_MIDBRAIN_MARKERS, GOCC_MEMBRANE_PROTEIN_COMPLEX, GOCC_ANCHORING_JUNCTION, GOCC_PLASMA_MEMBRANE_PROTEIN_COMPLEX, GOCC_GAP_JUNCTION, GOMF_PASSIVE_TRANSMEMBRANE_TRANSPORTER_ACTIVITY, GOBP_DEVELOPMENTAL_GROWTH

GO Biological Process (6): cell morphogenesis (GO:0000902), lens development in camera-type eye (GO:0002088), cell-cell signaling (GO:0007267), organ growth (GO:0035265), cell communication (GO:0007154), transmembrane transport (GO:0055085)

GO Molecular Function (1): gap junction channel activity (GO:0005243)

GO Cellular Component (3): connexin complex (GO:0005922), plasma membrane (GO:0005886), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular process	2
anatomical structure morphogenesis	1
camera-type eye development	1
anatomical structure development	1
cell communication	1
signaling	1
multicellular organismal process	1
developmental growth	1
transport	1
wide pore channel activity	1
gap junction	1
plasma membrane protein complex	1
membrane	1
cell periphery	1
cellular anatomical structure	1

Protein interactions and networks

STRING

144 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GJE1	GJC1	P36383	861
GJE1	CNR2	P34972	806
GJE1	GJC2	Q5T442	661
GJE1	GJB7	Q6PEY0	629
GJE1	GJA8	P48165	609
GJE1	GJD3	Q8N144	554
GJE1	GJD2	Q9UKL4	527
GJE1	GJB6	O95452	507
GJE1	GJB4	Q9NTQ9	486
GJE1	GJB3	O75712	470
GJE1	GJB5	O95377	458
GJE1	GJA4	P35212	447
GJE1	GJA5	P36382	381
GJE1	GJD4	Q96KN9	375
GJE1	GMNN	O75496	356

IntAct

0 interactions, top by confidence:

ESM2 similar proteins: A0A1B0GTI8, A6NN92, E9Q9H8, F6RWY9, O18968, O64761, O70610, O75712, O93533, O95377, O95452, P08033, P08034, P08983, P25305, P28230, P28231, P28232, P28233, P36380, P49111, P51916, P70689, P79826, Q02738, Q02739, Q0IIL2, Q13571, Q2KJA5, Q3SZ36, Q3T110, Q3TUD9, Q49LS6, Q4VV71, Q58D78, Q5E9Z5, Q5F410, Q5JW98, Q5REZ0, Q60HF7

Diamond homologs: A6NN92, Q9CX92, U3JA75, A4GG66, A4GVD1, P18861, P28228, P28229, P28235, P36383, P57773, Q03190, Q29RK8, Q2HJ66, Q5T442, Q6NZH5, Q6PYT3, Q6R4A8, Q7ZXS7, Q80XF7, Q8BQU6, Q92052, Q969M2, Q9WUS4, O57474

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

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

Top pathogenic / likely-pathogenic (0)

SpliceAI

0 predictions. Top by Δscore:

AlphaMissense

1354 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:142133961:T:C	F51L	0.891
6:142133963:C:A	F51L	0.891
6:142133963:C:G	F51L	0.891
6:142134012:T:C	F68L	0.861
6:142134014:C:A	F68L	0.861
6:142134014:C:G	F68L	0.861
6:142134578:T:C	F92L	0.856
6:142134580:C:A	F92L	0.856
6:142134580:C:G	F92L	0.856
6:142134716:T:C	F138L	0.852
6:142134718:T:A	F138L	0.852
6:142134718:T:G	F138L	0.852
6:142133931:T:C	F41L	0.822
6:142133933:T:A	F41L	0.822
6:142133933:T:G	F41L	0.822
6:142134818:T:C	F172L	0.776
6:142134820:T:A	F172L	0.776
6:142134820:T:G	F172L	0.776
6:142134839:T:C	F179L	0.768
6:142134841:T:A	F179L	0.768
6:142134841:T:G	F179L	0.768
6:142134677:A:C	S125R	0.744
6:142134679:T:A	S125R	0.744
6:142134679:T:G	S125R	0.744
6:142134039:T:C	F77L	0.733
6:142134041:T:A	F77L	0.733
6:142134041:T:G	F77L	0.733
6:142134722:T:C	F140L	0.732
6:142134724:C:A	F140L	0.732
6:142134724:C:G	F140L	0.732

dbSNP variants (sampled 300 via entrez): RS1000306806 (6:142134610 T>A,C), RS1000467756 (6:142134132 T>G), RS1000655923 (6:142135012 A>G), RS1001398144 (6:142135578 C>G,T), RS1002415968 (6:142133560 C>A), RS1002450510 (6:142133900 G>A,T), RS1002771915 (6:142133790 T>A,C,G), RS1002806671 (6:142134157 C>T), RS1003364698 (6:142132150 C>T), RS1003823239 (6:142131804 A>G), RS1005378700 (6:142131473 G>A), RS1006519433 (6:142132346 G>C,T), RS1007926628 (6:142135641 C>A,T), RS1008877235 (6:142134571 A>G), RS1008927817 (6:142134287 C>A,T)

Disease associations

OMIM: gene `` | 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

2 total (human), top 2 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Panobinostat	affects cotreatment, affects expression	1
Cisplatin	affects cotreatment, affects expression	1

Clinical trials (associated diseases)

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