GJA9

Summary

GJA9 (gap junction protein alpha 9, HGNC:19155) is a protein-coding gene on chromosome 1p34.3, encoding Gap junction alpha-9 protein (P57773). 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 GJA9, 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 81025 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 66 total
• MANE Select transcript: NM_030772

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:19155
Approved symbol	GJA9
Name	gap junction protein alpha 9
Location	1p34.3
Locus type	gene with protein product
Status	Approved
Aliases	CX59, CX58
Ensembl gene	ENSG00000131233
Ensembl biotype	protein_coding
OMIM	611923
Entrez	81025

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000357771, ENST00000360786

RefSeq mRNA: 1 — MANE Select: NM_030772 NM_030772

CCDS: CCDS432

Canonical transcript exons

ENST00000357771 — 2 exons

Exon	Start	End
ENSE00001400259	38874069	38876193
ENSE00003545893	38881432	38881587

Expression profiles

Bgee: expression breadth broad, 58 present calls, max score 81.71.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0101 / max 6.7663, expressed in 4 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
11845	0.0101	4

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	81.71	gold quality
colonic epithelium	UBERON:0000397	56.84	silver quality
stromal cell of endometrium	CL:0002255	54.80	silver quality
mucosa of transverse colon	UBERON:0004991	53.06	gold quality
sural nerve	UBERON:0015488	52.88	silver quality
bone marrow cell	CL:0002092	50.25	silver quality
rectum	UBERON:0001052	49.77	gold quality
ganglionic eminence	UBERON:0004023	44.76	gold quality
hindlimb stylopod muscle	UBERON:0004252	44.75	gold quality
right uterine tube	UBERON:0001302	43.07	silver quality
duodenum	UBERON:0002114	42.52	silver quality
gall bladder	UBERON:0002110	41.81	gold quality
lymph node	UBERON:0000029	41.40	silver quality
cortex of kidney	UBERON:0001225	41.24	silver quality
bone marrow	UBERON:0002371	41.22	gold quality
cortical plate	UBERON:0005343	40.19	gold quality
esophagus mucosa	UBERON:0002469	39.12	silver quality
islet of Langerhans	UBERON:0000006	38.81	gold quality
fundus of stomach	UBERON:0001160	38.57	silver quality
vermiform appendix	UBERON:0001154	38.31	gold quality
substantia nigra	UBERON:0002038	38.28	silver quality
prefrontal cortex	UBERON:0000451	38.14	gold quality
granulocyte	CL:0000094	38.11	gold quality
muscle of leg	UBERON:0001383	38.02	gold quality
stomach	UBERON:0000945	37.93	silver quality
skin of leg	UBERON:0001511	37.46	gold quality
zone of skin	UBERON:0000014	37.43	gold quality
primary visual cortex	UBERON:0002436	37.35	gold quality
urinary bladder	UBERON:0001255	37.34	gold quality
gastrocnemius	UBERON:0001388	37.18	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.62

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

22 targeting GJA9, 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-5011-5P	100.00	83.46	5820
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-4496	99.88	68.89	2236
HSA-MIR-6715A-3P	99.83	68.05	1473
HSA-MIR-6515-3P	99.82	68.19	1933
HSA-MIR-4699-3P	99.71	70.15	3142
HSA-MIR-4470	99.66	69.35	1767
HSA-MIR-1252-3P	99.55	67.71	2862
HSA-MIR-549A-3P	99.54	68.17	825
HSA-MIR-4452	99.50	68.45	1493
HSA-MIR-183-3P	99.41	69.41	1598
HSA-MIR-8070	99.07	69.30	1303
HSA-MIR-511-5P	98.97	70.94	2268
HSA-MIR-935	98.82	69.36	1072
HSA-MIR-12114	98.70	63.45	730
HSA-MIR-10397-3P	97.78	65.70	601

Cross-species orthologs

1 orthologs

Organism	Symbol	Gene ID
danio_rerio	gja9b	ENSDARG00000086453

Paralogs (20): GJA8 (ENSG00000121634), GJB6 (ENSG00000121742), GJA3 (ENSG00000121743), 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), GJE1 (ENSG00000203733), GJA5 (ENSG00000265107)

Protein

Protein identifiers

Gap junction alpha-9 protein — P57773 (reviewed: P57773)

Alternative names: Connexin-58, Connexin-59, Gap junction alpha-10 protein

All UniProt accessions (2): A0A654IBV8, P57773

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. Highly abundant in skeletal muscle. Also detected in testis.

Similarity. Belongs to the connexin family. Alpha-type (group II) subfamily.

Isoforms (2)

UniProt ID	Names	Canonical?
P57773-1	1	yes
P57773-2	2

RefSeq proteins (1): NP_110399* (*=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 (16 total): topological domain 5, transmembrane region 4, region of interest 2, compositionally biased region 2, chain 1, splice variant 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P57773-F1	61.97	0.24

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-190861	Gap junction assembly

MSigDB gene sets: 89 (showing top): chr6q15, GOBP_SYNAPSE_ASSEMBLY, REACTOME_MEMBRANE_TRAFFICKING, GOBP_CELL_CELL_SIGNALING, GOBP_CELL_JUNCTION_ORGANIZATION, GOBP_SENSORY_PERCEPTION_OF_LIGHT_STIMULUS, chr1p34, GOBP_RESPONSE_TO_RADIATION, GOBP_DETECTION_OF_LIGHT_STIMULUS, GOBP_RESPONSE_TO_ABIOTIC_STIMULUS, GOBP_DETECTION_OF_ABIOTIC_STIMULUS, GOBP_DETECTION_OF_STIMULUS, GOBP_SENSORY_PERCEPTION, GOBP_DETECTION_OF_LIGHT_STIMULUS_INVOLVED_IN_SENSORY_PERCEPTION, GOBP_CELL_JUNCTION_ASSEMBLY

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

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

228 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GJA9	MMS22L	Q6ZRQ5	441
GJA9	ZIK1	Q3SY52	436
GJA9	FAM185A	Q8N0U4	398
GJA9	HMX2	A2RU54	395
GJA9	ZNF169	Q14929	372
GJA9	FAXC	Q5TGI0	366
GJA9	AOC2	O75106	351
GJA9	GJB7	Q6PEY0	309
GJA9	CASP8AP2	Q9UKL3	304
GJA9	ARHGEF10	O15013	301
GJA9	MANEA	Q5SRI9	298
GJA9	LAMA4	Q16363	283
GJA9	CSMD2	Q7Z408	275
GJA9	CNKSR3	Q6P9H4	263
GJA9	GRK7	Q8WTQ7	261

IntAct

0 interactions, top by confidence:

BioGRID (2): GJA9 (Cross-Linking-MS (XL-MS)), GJA9 (Affinity Capture-MS)

ESM2 similar proteins: A0JMD2, A2ANU3, A7J1T0, A7J1T2, B0S6S9, D3ZJ47, F1M5M3, F1MJR8, M0R5D6, O14544, O43283, P57773, Q02223, Q06190, Q08DM6, Q14CH0, Q1HKZ5, Q1X8D7, Q2PFD7, Q3TEL6, Q3UVY1, Q4R532, Q58DZ9, Q5R8X7, Q5RA75, Q5RCM6, Q5RD34, Q5RJX2, Q5SW75, Q5TZE2, Q5VUB5, Q60610, Q6IRN6, Q6NRK3, Q6P995, Q6PUR7, Q76I76, Q86SP6, Q8BIA3, Q8BQU7

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

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	61
Likely benign	2
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

0 predictions. Top by Δscore:

AlphaMissense

3396 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:38875943:G:C	F52L	0.990
1:38875943:G:T	F52L	0.990
1:38875945:A:G	F52L	0.990
1:38875496:A:C	F201L	0.987
1:38875496:A:T	F201L	0.987
1:38875498:A:G	F201L	0.987
1:38875944:A:C	F52C	0.987
1:38875889:A:C	F70L	0.986
1:38875889:A:T	F70L	0.986
1:38875891:A:G	F70L	0.986
1:38875586:G:C	F171L	0.983
1:38875586:G:T	F171L	0.983
1:38875588:A:G	F171L	0.983
1:38875499:A:C	C200W	0.982
1:38875938:C:G	C54S	0.981
1:38875939:A:T	C54S	0.981
1:38875944:A:G	F52S	0.980
1:38875964:C:A	W45C	0.979
1:38875964:C:G	W45C	0.979
1:38875500:C:G	C200S	0.978
1:38875501:A:T	C200S	0.978
1:38875497:A:C	F201C	0.973
1:38875475:C:A	K208N	0.972
1:38875475:C:G	K208N	0.972
1:38875938:C:T	C54Y	0.972
1:38875966:A:G	W45R	0.972
1:38875966:A:T	W45R	0.972
1:38876026:A:G	W25R	0.972
1:38876026:A:T	W25R	0.972
1:38875501:A:G	C200R	0.971

dbSNP variants (sampled 300 via entrez): RS1000430978 (1:38880954 G>A), RS1001189791 (1:38878520 A>G), RS1001570331 (1:38880852 A>G,T), RS1001674950 (1:38880188 A>T), RS1002084368 (1:38874208 A>G), RS1002646751 (1:38879025 G>A,T), RS1003458919 (1:38876754 A>C), RS1003492726 (1:38882775 A>G), RS1003531594 (1:38876994 C>T), RS1004048682 (1:38877744 G>GC), RS1004244717 (1:38878336 T>C), RS1004849494 (1:38877089 G>A,T), RS1005469845 (1:38879994 A>G), RS1005880816 (1:38882181 G>A,T), RS1005987654 (1:38882432 G>A)

Disease associations

OMIM: gene MIM:611923 | 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
GCST003475_2	Beard thickness	8.000000e-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

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

Chemical	Actions (top 5)	PubMed papers
apocarotenal	increases expression	1
testosterone undecanoate	affects cotreatment, increases expression	1
theaflavin-3,3’-digallate	affects expression	1
Acetaminophen	increases expression	1
Arsenic	affects methylation	1
Benzo(a)pyrene	increases expression	1
Levonorgestrel	affects cotreatment, increases expression	1
beta Carotene	increases expression	1
Permethrin	increases expression	1

Clinical trials (associated diseases)

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