GJB7

Summary

GJB7 (gap junction protein beta 7, HGNC:16690) is a protein-coding gene on chromosome 6q14.3-q15, encoding Gap junction beta-7 protein (Q6PEY0). One gap junction consists of a cluster of closely packed pairs of transmembrane channels, the connexons, through which materials of low MW diffuse from one cell to a neighboring cell.

Connexins, such as GJB7, are involved in the formation of gap junctions, intercellular conduits that directly connect the cytoplasms of contacting cells. Each gap junction channel is formed by docking of 2 hemichannels, each of which contains 6 connexin subunits (Sohl et al., 2003 [PubMed 12881038]).

Source: NCBI Gene 375519 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 40 total
• MANE Select transcript: NM_198568

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16690
Approved symbol	GJB7
Name	gap junction protein beta 7
Location	6q14.3-q15
Locus type	gene with protein product
Status	Approved
Aliases	CX25, bA136M9.1
Ensembl gene	ENSG00000164411
Ensembl biotype	protein_coding
OMIM	611921
Entrez	375519

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 3 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000369576, ENST00000442973, ENST00000525899, ENST00000935994

RefSeq mRNA: 1 — MANE Select: NM_198568 NM_198568

CCDS: CCDS5008

Canonical transcript exons

ENST00000525899 — 3 exons

Exon	Start	End
ENSE00001434166	87322866	87323043
ENSE00002166281	87282980	87284939
ENSE00002461990	87329138	87329278

Expression profiles

Bgee: expression breadth broad, 94 present calls, max score 89.03.

Top tissues by expression

106 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	89.03	gold quality
right uterine tube	UBERON:0001302	80.63	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	80.27	gold quality
placenta	UBERON:0001987	71.52	gold quality
pituitary gland	UBERON:0000007	70.46	gold quality
adenohypophysis	UBERON:0002196	66.58	gold quality
fallopian tube	UBERON:0003889	64.88	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	62.15	gold quality
bone marrow cell	CL:0002092	61.11	silver quality
right lung	UBERON:0002167	57.69	gold quality
bone marrow	UBERON:0002371	55.39	silver quality
mucosa of transverse colon	UBERON:0004991	53.73	gold quality
endometrium	UBERON:0001295	52.27	gold quality
right testis	UBERON:0004534	52.27	gold quality
left testis	UBERON:0004533	52.03	gold quality
testis	UBERON:0000473	51.77	gold quality
granulocyte	CL:0000094	51.16	silver quality
calcaneal tendon	UBERON:0003701	49.62	gold quality
tonsil	UBERON:0002372	49.00	gold quality
urinary bladder	UBERON:0001255	47.76	gold quality
left uterine tube	UBERON:0001303	47.10	gold quality
adrenal tissue	UBERON:0018303	44.47	silver quality
blood	UBERON:0000178	43.21	silver quality
lung	UBERON:0002048	42.83	gold quality
islet of Langerhans	UBERON:0000006	42.60	gold quality
skeletal muscle tissue	UBERON:0001134	42.01	gold quality
colonic epithelium	UBERON:0000397	41.71	gold quality
stomach	UBERON:0000945	40.55	gold quality
uterine cervix	UBERON:0000002	40.30	gold quality
body of stomach	UBERON:0001161	40.07	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.21

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

59 targeting GJB7, 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-4510	100.00	66.60	2050
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-507	99.97	70.11	1915
HSA-MIR-493-5P	99.96	72.47	2382
HSA-MIR-144-3P	99.94	73.98	2698
HSA-MIR-652-5P	99.91	67.49	505
HSA-MIR-3529-3P	99.90	73.55	3045
HSA-MIR-345-3P	99.89	70.23	1421
HSA-MIR-3121-3P	99.82	71.96	3630
HSA-MIR-6844	99.82	70.69	2423
HSA-MIR-4639-5P	99.81	67.37	1028
HSA-MIR-205-5P	99.81	70.05	1557
HSA-MIR-1299	99.77	71.24	2389
HSA-MIR-4766-5P	99.75	69.23	2662
HSA-MIR-4446-5P	99.72	69.19	2544
HSA-MIR-5580-3P	99.70	69.41	2052
HSA-MIR-4677-5P	99.70	70.09	1940
HSA-MIR-6892-3P	99.68	66.40	1178
HSA-MIR-670-5P	99.67	69.94	1565
HSA-MIR-1251-3P	99.64	67.21	1408
HSA-MIR-548AV-5P	99.60	70.84	2107
HSA-MIR-548K	99.60	70.84	2107
HSA-MIR-516B-5P	99.56	66.33	1495

Literature-anchored findings (GeneRIF, showing 1)

• High CX25 expression is associated with leukemia. (PMID:26375552)

Cross-species orthologs

1 orthologs

Organism	Symbol	Gene ID
danio_rerio	gjb7	ENSDARG00000071042

Paralogs (20): GJA8 (ENSG00000121634), GJB6 (ENSG00000121742), GJA3 (ENSG00000121743), GJA9 (ENSG00000131233), GJA10 (ENSG00000135355), GJA1 (ENSG00000152661), GJD2 (ENSG00000159248), GJB2 (ENSG00000165474), GJB1 (ENSG00000169562), GJC3 (ENSG00000176402), GJD4 (ENSG00000177291), GJC1 (ENSG00000182963), GJD3 (ENSG00000183153), GJA4 (ENSG00000187513), GJB3 (ENSG00000188910), GJB5 (ENSG00000189280), GJB4 (ENSG00000189433), GJC2 (ENSG00000198835), GJE1 (ENSG00000203733), GJA5 (ENSG00000265107)

Protein

Protein identifiers

Gap junction beta-7 protein — Q6PEY0 (reviewed: Q6PEY0)

Alternative names: Connexin-25

All UniProt accessions (2): A0A0A0MRM5, Q6PEY0

UniProt curated annotations — full annotation on UniProt →

Function. One gap junction consists of a cluster of closely packed pairs of transmembrane channels, the connexons, through which materials of low MW diffuse from one cell to a neighboring cell.

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

Subcellular location. Cell membrane. Cell junction. Gap junction.

Tissue specificity. Weakly expressed in placenta.

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

RefSeq proteins (1): NP_940970* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000500	Connexin	Family
IPR013092	Connexin_N	Domain
IPR017990	Connexin_CS	Conserved_site
IPR019570	Connexin_CCC	Domain
IPR038359	Connexin_N_sf	Homologous_superfamily

Pfam: PF00029

UniProt features (14 total): topological domain 5, transmembrane region 4, sequence variant 3, chain 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6PEY0-F1	83.43	0.50

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-190861	Gap junction assembly

MSigDB gene sets: 37 (showing top): chr6q15, REACTOME_MEMBRANE_TRAFFICKING, GOBP_CELL_CELL_SIGNALING, REACTOME_GAP_JUNCTION_ASSEMBLY, GOCC_CELL_CELL_JUNCTION, GOBP_TRANSMEMBRANE_TRANSPORT, GOCC_MEMBRANE_PROTEIN_COMPLEX, GOCC_ANCHORING_JUNCTION, GOCC_PLASMA_MEMBRANE_PROTEIN_COMPLEX, GOCC_GAP_JUNCTION, GOMF_PASSIVE_TRANSMEMBRANE_TRANSPORTER_ACTIVITY, GOMF_WIDE_PORE_CHANNEL_ACTIVITY, GOMF_GAP_JUNCTION_CHANNEL_ACTIVITY, GOMF_TRANSPORTER_ACTIVITY, GOCC_CONNEXIN_COMPLEX

GO Biological Process (3): cell-cell signaling (GO:0007267), transmembrane transport (GO:0055085), cell communication (GO:0007154)

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

GO Cellular Component (5): connexin complex (GO:0005922), plasma membrane (GO:0005886), gap junction (GO:0005921), membrane (GO:0016020), anchoring junction (GO:0070161)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Gap junction trafficking	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular process	2
cell communication	1
signaling	1
transport	1
wide pore channel activity	1
gap junction	1
plasma membrane protein complex	1
membrane	1
cell periphery	1
cell-cell junction	1
cellular anatomical structure	1
cell junction	1

Protein interactions and networks

STRING

330 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GJB7	GJE1	A6NN92	629
GJB7	XPR1	Q9UBH6	474
GJB7	C6orf163	Q5TEZ5	419
GJB7	LRCH1	Q9Y2L9	397
GJB7	SMIM8	Q96KF7	350
GJB7	HTR1E	P28566	348
GJB7	RWDD2A	Q9UIY3	348
GJB7	GMNN	O75496	328
GJB7	PPP1R37	O75864	324
GJB7	UBE3D	Q7Z6J8	310
GJB7	GJA9	P57773	309
GJB7	CFAP206	Q8IYR0	308
GJB7	RPS23	P39028	307
GJB7	ORC3	Q9UBD5	300
GJB7	ZNF292	O60281	288

IntAct

3 interactions, top by confidence:

A	B	Type	Score
GJB7	PALM3	psi-mi:“MI:0914”(association)	0.530

BioGRID (84): UBTD1 (Affinity Capture-MS), CCNY (Affinity Capture-MS), GRTP1 (Affinity Capture-MS), CCNYL1 (Affinity Capture-MS), NRN1 (Affinity Capture-MS), GNAZ (Affinity Capture-MS), EFR3A (Affinity Capture-MS), ERICH5 (Affinity Capture-MS), PAG1 (Affinity Capture-MS), ULBP2 (Affinity Capture-MS), PALM3 (Affinity Capture-MS), GNAQ (Affinity Capture-MS), PTPRG (Affinity Capture-MS), MICAL1 (Affinity Capture-MS), WASF2 (Affinity Capture-MS)

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: A2VE67, A4GG66, A4GVD1, A4IFL1, A6XKM2, O18968, O54851, O57474, O70610, O75712, O93533, O95377, O95452, P08033, P08034, P08050, P08983, P14154, P16863, P16864, P17302, P18246, P18860, P18861, P21994, P23242, P25305, P28228, P28229, P28230, P28231, P28232, P28233, P28234, P28235, P28236, P29033, P29414, P29415, P33725

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	36
Likely benign	0
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

477 predictions. Top by Δscore:

Variant	Effect	Δscore
6:87295428:T:TA	donor_gain	0.9800
6:87314813:A:C	donor_gain	0.9800
6:87322633:G:GG	donor_gain	0.9800
6:87322634:T:A	donor_loss	0.9800
6:87329134:TTA:T	donor_loss	0.9800
6:87329136:ACC:A	donor_loss	0.9800
6:87329137:C:CG	donor_loss	0.9800
6:87329159:C:CA	donor_gain	0.9800
6:87284938:CT:C	acceptor_gain	0.9600
6:87322628:GAAAG:G	donor_gain	0.9600
6:87284482:T:C	acceptor_gain	0.9300
6:87321831:CGTGG:C	acceptor_gain	0.9300
6:87322631:AG:A	donor_gain	0.9300
6:87322632:GG:G	donor_gain	0.9300
6:87314812:AACG:A	donor_gain	0.9200
6:87322630:AAG:A	donor_gain	0.9000
6:87314811:TA:T	donor_gain	0.8900
6:87314812:AA:A	donor_gain	0.8900
6:87284937:ACTC:A	acceptor_loss	0.8800
6:87284939:TCTG:T	acceptor_loss	0.8800
6:87284940:C:CC	acceptor_gain	0.8800
6:87284941:TG:T	acceptor_loss	0.8800
6:87284942:G:C	acceptor_loss	0.8800
6:87284943:CAAAA:C	acceptor_loss	0.8800
6:87284482:T:TC	acceptor_gain	0.8700
6:87284947:A:C	acceptor_loss	0.8700
6:87322615:G:GT	donor_gain	0.8700
6:87329175:CCGG:C	donor_gain	0.8700
6:87329201:A:AC	donor_gain	0.8700
6:87284936:GACT:G	acceptor_gain	0.8600

AlphaMissense

1475 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:87284406:G:C	F169L	0.815
6:87284406:G:T	F169L	0.815
6:87284408:A:G	F169L	0.815
6:87284499:G:C	F138L	0.798
6:87284499:G:T	F138L	0.798
6:87284501:A:G	F138L	0.798
6:87284760:A:C	F51L	0.777
6:87284760:A:T	F51L	0.777
6:87284762:A:G	F51L	0.777
6:87284466:A:C	F149L	0.774
6:87284466:A:T	F149L	0.774
6:87284468:A:G	F149L	0.774
6:87284718:A:C	F65L	0.762
6:87284718:A:T	F65L	0.762
6:87284720:A:G	F65L	0.762
6:87284376:G:C	F179L	0.718
6:87284376:G:T	F179L	0.718
6:87284378:A:G	F179L	0.718
6:87284532:G:C	S127R	0.706
6:87284532:G:T	S127R	0.706
6:87284534:T:G	S127R	0.706
6:87284820:G:C	F31L	0.664
6:87284820:G:T	F31L	0.664
6:87284822:A:G	F31L	0.664
6:87284826:A:C	F29L	0.640
6:87284826:A:T	F29L	0.640
6:87284828:A:G	F29L	0.640
6:87284487:A:C	F142L	0.638
6:87284487:A:T	F142L	0.638
6:87284489:A:G	F142L	0.638

dbSNP variants (sampled 300 via entrez): RS1000029888 (6:87290747 T>C), RS1000081899 (6:87291000 G>A), RS1000084155 (6:87301090 C>T), RS1000096296 (6:87304893 T>G), RS1000124290 (6:87318249 A>G), RS1000227413 (6:87323408 A>G), RS1000309868 (6:87286901 A>G), RS1000357826 (6:87284788 T>A,C), RS1000361570 (6:87287233 T>C), RS1000535603 (6:87302184 C>A), RS1000642369 (6:87288288 TAAAC>T), RS1000667585 (6:87311566 C>T), RS1000696691 (6:87317014 A>G), RS1000744043 (6:87329296 A>G), RS1000784501 (6:87311981 A>G)

Disease associations

OMIM: gene MIM:611921 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST004632_51	Lymphocyte percentage of white cells	6.000000e-12
GCST004633_63	Neutrophil percentage of white cells	2.000000e-18
GCST90000025_63	Appendicular lean mass	9.000000e-13

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0007993	lymphocyte percentage of leukocytes
EFO:0007990	neutrophil percentage of leukocytes
EFO:0004980	appendicular lean mass

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

9 total (human), top 9 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Aflatoxin B1	increases methylation	2
aristolochic acid I	increases expression	1
terbufos	decreases methylation	1
Arsenic Trioxide	decreases expression	1
Arsenic	affects methylation	1
Benzo(a)pyrene	increases methylation	1
Fonofos	decreases methylation	1
Parathion	decreases methylation	1
Tobacco Smoke Pollution	decreases expression	1

Clinical trials (associated diseases)

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