CLDN3

Summary

CLDN3 (claudin 3, HGNC:2045) is a protein-coding gene on chromosome 7q11.23, encoding Claudin-3 (O15551). Barrier-forming claudin.

Tight junctions represent one mode of cell-to-cell adhesion in epithelial or endothelial cell sheets, forming continuous seals around cells and serving as a physical barrier to prevent solutes and water from passing freely through the paracellular space. These junctions are comprised of sets of continuous networking strands in the outwardly facing cytoplasmic leaflet, with complementary grooves in the inwardly facing extracytoplasmic leaflet. The protein encoded by this intronless gene, a member of the claudin family, is an integral membrane protein and a component of tight junction strands. It is also a low-affinity receptor for Clostridium perfringens enterotoxin, and shares aa sequence similarity with a putative apoptosis-related protein found in rat.

Source: NCBI Gene 1365 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 43 total — 7 pathogenic
• MANE Select transcript: NM_001306

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2045
Approved symbol	CLDN3
Name	claudin 3
Location	7q11.23
Locus type	gene with protein product
Status	Approved
Aliases	RVP1, CPE-R2, HRVP1
Ensembl gene	ENSG00000165215
Ensembl biotype	protein_coding
OMIM	602910
Entrez	1365

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000395145

RefSeq mRNA: 1 — MANE Select: NM_001306 NM_001306

CCDS: CCDS5559

Canonical transcript exons

ENST00000395145 — 1 exons

Exon	Start	End
ENSE00001520709	73768997	73770270

Expression profiles

Bgee: expression breadth ubiquitous, 184 present calls, max score 99.37.

FANTOM5 (CAGE): breadth broad, TPM avg 23.3567 / max 1288.5374, expressed in 530 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
84331	19.8274	501
84330	3.1935	318
84332	0.3357	222

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
mucosa of transverse colon	UBERON:0004991	99.37	gold quality
endometrium epithelium	UBERON:0004811	98.59	gold quality
colonic mucosa	UBERON:0000317	98.24	gold quality
right uterine tube	UBERON:0001302	98.20	gold quality
mucosa of sigmoid colon	UBERON:0004993	97.96	gold quality
ileal mucosa	UBERON:0000331	97.36	gold quality
left lobe of thyroid gland	UBERON:0001120	96.57	gold quality
bronchial epithelial cell	CL:0002328	96.42	gold quality
epithelium of bronchus	UBERON:0002031	96.40	gold quality
right lobe of thyroid gland	UBERON:0001119	96.17	gold quality
bronchus	UBERON:0002185	95.86	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	95.83	gold quality
thyroid gland	UBERON:0002046	95.23	gold quality
body of pancreas	UBERON:0001150	94.91	gold quality
jejunal mucosa	UBERON:0000399	93.99	gold quality
duodenum	UBERON:0002114	93.67	gold quality
metanephros cortex	UBERON:0010533	92.11	gold quality
nasal cavity epithelium	UBERON:0005384	91.96	gold quality
small intestine Peyer’s patch	UBERON:0003454	91.55	gold quality
transverse colon	UBERON:0001157	91.29	gold quality
caput epididymis	UBERON:0004358	90.19	gold quality
parotid gland	UBERON:0001831	90.09	gold quality
small intestine	UBERON:0002108	90.08	gold quality
right lobe of liver	UBERON:0001114	89.38	gold quality
saliva-secreting gland	UBERON:0001044	88.77	gold quality
minor salivary gland	UBERON:0001830	88.16	gold quality
corpus epididymis	UBERON:0004359	87.34	gold quality
nasal cavity mucosa	UBERON:0001826	87.01	gold quality
prostate gland	UBERON:0002367	86.91	gold quality
seminal vesicle	UBERON:0000998	86.67	gold quality

Single-cell (SCXA)

Detected in 21 experiment(s), a significant marker in 20.

Experiment	Marker?	Max mean expression
E-MTAB-10855	yes	2141.41
E-MTAB-9841	yes	2132.60
E-MTAB-10287	yes	1952.76
E-CURD-88	yes	1301.89
E-MTAB-10885	yes	1299.94
E-HCAD-10	yes	1049.30
E-HCAD-11	yes	1021.11
E-MTAB-9906	yes	822.37
E-MTAB-6701	yes	768.50
E-GEOD-130473	yes	531.19
E-MTAB-7381	yes	493.22
E-MTAB-10662	yes	353.19
E-MTAB-8410	yes	58.24
E-CURD-114	yes	46.22
E-MTAB-10553	yes	24.62

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

7 targets.

Target	Regulation
BEST1	Activation
EGFR	Repression
FRZB	Activation
MYC	Repression
SFRP5	Activation
SLC38A11	Activation
TTR	Activation

Upstream regulators (CollecTRI, top): EGR1, GRHL2, SMAD3, SMAD4, SNAI1, SP1

miRNA regulators (miRDB)

11 targeting CLDN3, 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-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-3119	99.92	71.34	2390
HSA-MIR-1297	99.91	73.41	3162
HSA-MIR-6762-3P	99.66	66.94	1188
HSA-MIR-6846-5P	98.81	65.86	1121
HSA-MIR-6848-5P	98.81	65.49	1126
HSA-MIR-876-3P	98.76	68.23	945
HSA-MIR-323A-5P	98.59	65.13	651

Literature-anchored findings (GeneRIF, showing 40)

• CLDN3, clustered with CLDN4 at human chromosome 7q11, is a four-transmembrane protein with WWCC motif, defined by W-X(17-22)-W-X(2)-C-X(8-10)-C. (PMID:12736707)
• Airway tight junctions are regulated by claudin interactions that confer the selectivity of the junction. (PMID:12909588)
• up-regulation of DDR1, CLDN3, and epithelial cell adhesion molecule are early events in the development of epithelial ovarian cancer (PMID:15240533)
• in breast tissue, CLDN3 expression is similar in tumours and surrounding normal tissue, as demonstrated by immunohistochemistry and real-time PCR (PMID:15743508)
• claudin-3 phosphorylation by PKA may provide a mechanism for the disruption of tight junctions in ovarian cancer (PMID:15905176)
• The expression of claudin-1, -3 and -4 was upregulated 5.7-, 1.5- and 2.4-fold, respectively, in colorectal tumor tissues in comparison to the normal ones. (PMID:16253248)
• claudin 3 and claudin 4 may play a role in transformation of ovarian surface epithelium towards the malignant phenotype (PMID:16287068)
• The gene expression profile of hepatic stem cells throughout life consists of high levels of expression of claudin-3 (CLDN-3). (PMID:16627685)
• Claudin tight junction proteins in endoscopy biopsy samples showed Barrett’s metaplasia contains more claudin-2 and claudin-3 than found in normal esophageal mucosa, but markedly lower claudins 1 and 5, indicating very different tight junction barriers. (PMID:17103306)
• Overexpression of claudin-3 is associated with uterine serous papillary carcinoma (PMID:17326053)
• When compared, small-cell-lung cancers, carcinoid tumors, and adenocarcinomas revealed significant differences re: CLDN3 expression. (PMID:17418912)
• Loss of claudin expression may enhance the grade of malignancy of gastric cancer in vivo. (PMID:17459057)
• Claudin-3 and claudin-4 receptors are highly overexpressed in carcinosarcoma (PMID:17545541)
• CLDN3 overexpression can be used as a prognostic indicator in ovarian serous carcinomas and it may be a promising target for antibody-based therapy of ovarian carcinomas. (PMID:17647191)
• siRNA-mediated knockdown of Sp1 led to a significant decrease of CLDN3 expression at both the mRNA and protein levels, demonstrating a crucial role for this transcription factor in the regulation of CLDN3. (PMID:17986852)
• Cdx2 plays an important role in the regulation of intestinal claudin expression not only in gastric mucosa with intestinal metaplasia but also gastric carcinoma. (PMID:18251778)
• Increased expression of claudin-3 and claudin-4 may contribute to aggressive phenotype of endometrial cancer of serous papillary or clear-cell histology. Possible targets for therapeutic intervention. (PMID:18313739)
• Down-regulated expression of claudin-3 and claudin-4 in ectopic endometrium suggests that claudin-3 and claudin-4 might play a pathogenic role in the formation of endometriosis. (PMID:18384777)
• Claudin-3 and claudin-7 expression in effusions independently predicts poor survival in ovarian cancer. (PMID:18439941)
• Early gastric carcinomas demonstrating I-CLDN(+) phenotype have a high risk of synchronous and metachronous secondary gastric epithelial neoplasias. (PMID:18477216)
• claudins 1 and 3 had a significant effect on overall survival in patients with urothelial carcinoma of the upper urinary tract. (PMID:18550469)
• This is the first study to demonstrate that claudin-3 is involved in the barrier function of gastric epithelial cells and that rebamipide abolishes the H2O2-induced decrease in claudin-3 protein. (PMID:18774778)
• For the first time this study proves the presence of Claudin-1, Claudin-3 and Claudin-5 in ECV304 (obtained from ECACC) cell layers and the inducibility of their expression by glioma-conditioned media. (PMID:18817843)
• The expression of claudins-2, -3 and -4 in 16 rectal well-differentiated endocrine neoplasms was studied (PMID:19082451)
• Using a panel of four genes (AHRR, p16INK4a, MT1G, and CLDN3) resulted in sensitivity and specificity of 50% and 68%, respectively and may have utility for early detection of esophageal squamous dysplasia and early ESCC. (PMID:19137073)
• Tight junction proteins claudin-1, claudin-3, claudin-4, and the adherens junction protein beta-catenin are overexpressed in colorectal carcinoma. (PMID:19184060)
• treatment of mice with nonimmunostimulatory 2’-OMe modified CLDN3 siRNA was as effective in suppressing tumor growth as unmodifed siRNA (PMID:19208807)
• claudin-3 did not serve as a prognostic marker in lung cancer (PMID:19231096)
• analysis of the interaction between Clostridium perfringens enterotoxin fragments and claudin-3 (PMID:19429681)
• Here we show for the first time in both an experimental and clinical setting a strong relation between intestinal tight junction loss and urinary claudin-3 levels (PMID:19525861)
• there was no dramatic qualititative difference in the BCC or RMS tumors associated with the mutant Blm genotype (PMID:20053926)
• Increased expressions of CLDN 2 and 3 suggest structural changes of tight junction in coeliac disease which may be, at least in part, responsible for increased permeability and proliferation observed in coeliac disease. (PMID:20143085)
• Claudin-3 expression in Epstein-Barr virus-associated nasopharyngeal carcinoma was variable (PMID:20204275)
• no mutations in CLDN3, CLDN4 and TRPV6 were found in Idiopathic infantile hypercalcaemia patients. (PMID:20466674)
• Claudin-1, -3, -4, -5, and -7 are expressed in developing human lung from week 12 to week 40 with distinct locations and in divergent quantities. (PMID:20478039)
• demonstrate that claudin-3 alters the tight junction meshwork and seals the paracellular pathway against the passage of small ions of either charge and uncharged solutes (PMID:20655293)
• Analysis of staining intensities of CLDN 1 and 3 is useful as an auxiliary diagnostic and prognostic tool in patients with salivary gland mucoepidermoid carcinoma. (PMID:21184237)
• CLDN3 may have a role in ovarian cancer, and its inhibition by short hairpin RNA could be a treatment strategy. (PMID:21519794)
• Mechanism of Clostridium perfringens enterotoxin interaction with claudin-3/-4 protein suggests structural modifications of the toxin to target specific claudins (PMID:22128179)
• Dow-regulation of Claudin-3 is associated with the progression of early gastric adenocarcinomas. (PMID:22290341)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	cldne	ENSDARG00000043128
mus_musculus	Cldn3	ENSMUSG00000070473
rattus_norvegicus	Cldn3	ENSRNOG00000046007

Paralogs (22): CLDN11 (ENSG00000013297), CLDN18 (ENSG00000066405), CLDN15 (ENSG00000106404), CLDN16 (ENSG00000113946), CLDN10 (ENSG00000134873), CLDN17 (ENSG00000156282), CLDN8 (ENSG00000156284), CLDN14 (ENSG00000159261), CLDN1 (ENSG00000163347), CLDN19 (ENSG00000164007), CLDN2 (ENSG00000165376), CLDN20 (ENSG00000171217), CLDN22 (ENSG00000177300), CLDN7 (ENSG00000181885), CLDN5 (ENSG00000184113), CLDN6 (ENSG00000184697), CLDN24 (ENSG00000185758), CLDN4 (ENSG00000189143), CLDN9 (ENSG00000213937), CLDN25 (ENSG00000228607), CLDN34 (ENSG00000234469), CLDN23 (ENSG00000253958)

Protein

Protein identifiers

Claudin-3 — O15551 (reviewed: O15551)

Alternative names: Clostridium perfringens enterotoxin receptor 2, Rat ventral prostate.1 protein homolog

All UniProt accessions (2): O15551, Q75L79

UniProt curated annotations — full annotation on UniProt →

Function. Barrier-forming claudin. Plays a major role in tight junction-specific obliteration of the intercellular space, through calcium-independent cell-adhesion activity.

Subunit / interactions. Can form homo- and heteropolymers with other CLDN. Homopolymers interact with CLDN1 and CLDN2 homopolymers. Interacts in cis (within the same plasma membrane) with CLDN19. Directly interacts with TJP1/ZO-1, TJP2/ZO-2 and TJP3/ZO-3.

Subcellular location. Cell junction. Tight junction. Cell membrane.

Disease relevance. CLDN3 is located in the Williams-Beuren syndrome (WBS) critical region. WBS results from a hemizygous deletion of several genes on chromosome 7q11.23, thought to arise as a consequence of unequal crossing over between highly homologous low-copy repeat sequences flanking the deleted region.

Similarity. Belongs to the claudin family.

RefSeq proteins (1): NP_001297* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003549	Claudin3	Family
IPR004031	PMP22/EMP/MP20/Claudin	Family
IPR006187	Claudin	Family
IPR017974	Claudin_CS	Conserved_site

Pfam: PF00822

UniProt features (14 total): topological domain 5, transmembrane region 4, modified residue 3, chain 1, region of interest 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O15551-F1	81.40	0.46

Functional residue map

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

Post-translational modifications (3): 198, 199, 209

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-420029	Tight junction interactions

MSigDB gene sets: 216 (showing top): GOBP_ENDOTHELIAL_CELL_DEVELOPMENT, GOBP_NEGATIVE_REGULATION_OF_TRANSMEMBRANE_TRANSPORT, GOBP_RESPONSE_TO_ETHANOL, GOBP_EPITHELIUM_DEVELOPMENT, KOBAYASHI_EGFR_SIGNALING_24HR_UP, GOBP_REGULATION_OF_CELL_MORPHOGENESIS, GOBP_REGULATION_OF_WOUND_HEALING, GOBP_EPITHELIAL_CELL_DEVELOPMENT, GCANCTGNY_MYOD_Q6, GOZGIT_ESR1_TARGETS_DN, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_UP, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_DN, GOBP_APICAL_JUNCTION_ASSEMBLY, GRAESSMANN_RESPONSE_TO_MC_AND_SERUM_DEPRIVATION_DN, ACEVEDO_NORMAL_TISSUE_ADJACENT_TO_LIVER_TUMOR_DN

GO Biological Process (24): response to hypoxia (GO:0001666), epithelial cell morphogenesis (GO:0003382), retinal pigment epithelium development (GO:0003406), cell adhesion (GO:0007155), negative regulation of cell population proliferation (GO:0008285), positive regulation of gene expression (GO:0010628), negative regulation of gene expression (GO:0010629), establishment of endothelial blood-brain barrier (GO:0014045), calcium-independent cell-cell adhesion (GO:0016338), regulation of cell morphogenesis (GO:0022604), actin cytoskeleton organization (GO:0030036), positive regulation of cell migration (GO:0030335), negative regulation of cell migration (GO:0030336), cell junction assembly (GO:0034329), cell junction maintenance (GO:0034331), maintenance of blood-brain barrier (GO:0035633), cell-cell junction maintenance (GO:0045217), response to ethanol (GO:0045471), bicellular tight junction assembly (GO:0070830), positive regulation of wound healing (GO:0090303), regulation of membrane permeability (GO:0090559), response to Gram-positive bacterium (GO:0140459), regulation of transepithelial transport (GO:0150111), negative regulation of phosphate transmembrane transport (GO:2000186)

GO Molecular Function (5): transmembrane signaling receptor activity (GO:0004888), structural molecule activity (GO:0005198), identical protein binding (GO:0042802), cell-cell adhesion mediator activity (GO:0098632), protein binding (GO:0005515)

GO Cellular Component (10): plasma membrane (GO:0005886), cell-cell junction (GO:0005911), bicellular tight junction (GO:0005923), membrane (GO:0016020), apicolateral plasma membrane (GO:0016327), lateral plasma membrane (GO:0016328), protein-containing complex (GO:0032991), apical junction complex (GO:0043296), tight junction (GO:0070160), anchoring junction (GO:0070161)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Cell-cell junction organization	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cell morphogenesis	2
gene expression	2
regulation of gene expression	2
cell-cell adhesion	2
cell migration	2
regulation of cell migration	2
cell junction organization	2
cellular anatomical structure	2
cell-cell junction	2
response to stress	1
response to decreased oxygen levels	1
epithelial cell development	1
retina development in camera-type eye	1
epithelium development	1
cellular process	1
cell population proliferation	1
regulation of cell population proliferation	1
negative regulation of cellular process	1
positive regulation of macromolecule biosynthetic process	1
negative regulation of macromolecule biosynthetic process	1
establishment of blood-brain barrier	1
establishment of endothelial barrier	1
regulation of anatomical structure morphogenesis	1
cytoskeleton organization	1
actin filament-based process	1
positive regulation of cell motility	1
negative regulation of cell motility	1
cellular component assembly	1
cellular component maintenance	1
tissue homeostasis	1
cell junction maintenance	1
cell-cell junction organization	1
response to alcohol	1
apical junction assembly	1
tight junction assembly	1
wound healing	1
regulation of wound healing	1
positive regulation of response to wounding	1
signaling receptor activity	1
molecular_function	1

Protein interactions and networks

STRING

1486 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CLDN3	OCLN	Q16625	997
CLDN3	CLDN12	P56749	982
CLDN3	TJP1	Q07157	976
CLDN3	TJP3	O95049	956
CLDN3	MARVELD2	Q8N4S9	904
CLDN3	CLDN5	O00501	844
CLDN3	TJP2	Q9UDY2	837
CLDN3	J3KSM2	J3KSM2	801
CLDN3	F11R	Q9Y624	693
CLDN3	CLDN16	Q9Y5I7	641
CLDN3	CDH1	P12830	630
CLDN3	EPCAM	P16422	615
CLDN3	CLDN19	Q8N6F1	610
CLDN3	CDX1	P47902	563
CLDN3	CTNNB1	P35222	543

IntAct

115 interactions, top by confidence:

A	B	Type	Score
CLDN3	GOPC	psi-mi:“MI:0407”(direct interaction)	0.590
	AP3D1	psi-mi:“MI:0914”(association)	0.460
CTSS	CLDN3	psi-mi:“MI:0570”(protein cleavage)	0.440
CLDN3	PDZD2	psi-mi:“MI:0407”(direct interaction)	0.440
CLDN3	PDZK1	psi-mi:“MI:0407”(direct interaction)	0.440
CLDN3	NOS1	psi-mi:“MI:0407”(direct interaction)	0.440
CLDN3	APBA1	psi-mi:“MI:0407”(direct interaction)	0.440
CLDN3	HTRA3	psi-mi:“MI:0407”(direct interaction)	0.440
CLDN3	HTRA1	psi-mi:“MI:0407”(direct interaction)	0.440
CLDN3	PATJ	psi-mi:“MI:0407”(direct interaction)	0.440
CLDN3	RADIL	psi-mi:“MI:0407”(direct interaction)	0.440
CLDN3	WHRN	psi-mi:“MI:0407”(direct interaction)	0.440
CLDN3	LNX2	psi-mi:“MI:0407”(direct interaction)	0.440
CLDN3	PTPN3	psi-mi:“MI:0407”(direct interaction)	0.440
CLDN3	MAST1	psi-mi:“MI:0407”(direct interaction)	0.440
CLDN3	PDZD7	psi-mi:“MI:0407”(direct interaction)	0.440
CLDN3	TJP2	psi-mi:“MI:0407”(direct interaction)	0.440
APBA3	CLDN3	psi-mi:“MI:0407”(direct interaction)	0.440
CLDN3	MAST2	psi-mi:“MI:0407”(direct interaction)	0.440
CLDN3	LIN7C	psi-mi:“MI:0407”(direct interaction)	0.440
CLDN3	MPP2	psi-mi:“MI:0407”(direct interaction)	0.440
CLDN3	PALS2	psi-mi:“MI:0407”(direct interaction)	0.440
CLDN3	SCRIB	psi-mi:“MI:0407”(direct interaction)	0.440
CLDN3	TIAM2	psi-mi:“MI:0407”(direct interaction)	0.440
CLDN3	NHERF4	psi-mi:“MI:0407”(direct interaction)	0.440
CLDN3	PICK1	psi-mi:“MI:0407”(direct interaction)	0.440
CLDN3	DLG3	psi-mi:“MI:0407”(direct interaction)	0.440
CLDN3	DLG2	psi-mi:“MI:0407”(direct interaction)	0.440
CLDN3	LIN7B	psi-mi:“MI:0407”(direct interaction)	0.440

BioGRID (22): CLDN3 (Affinity Capture-MS), CLDN3 (Proximity Label-MS), CLDN3 (Proximity Label-MS), CLDN3 (Affinity Capture-Western), CLDN1 (Affinity Capture-Western), CLDN5 (Affinity Capture-Western), CLDN3 (Affinity Capture-Western), CLDN3 (Affinity Capture-MS), TJP1 (Reconstituted Complex), DDX3Y (Affinity Capture-MS), ANKRD13D (Affinity Capture-MS), CHMP2A (Affinity Capture-MS), GOPC (Affinity Capture-MS), ISOC2 (Affinity Capture-MS), CLDN3 (Affinity Capture-MS)

ESM2 similar proteins: A0A8C0N7E5, C3VMW3, D3ZQJ0, O00501, O14493, O15551, O19005, O35054, O35912, O54942, O88551, O95471, O95484, O95832, P56745, P56746, P56747, P56748, P56750, P78369, Q2HJ22, Q2KIY2, Q3B7N4, Q5E9L0, Q5QT56, Q5R8E5, Q63400, Q6BBL6, Q6DHB5, Q6DHP1, Q6L708, Q765N9, Q8BXA6, Q8N6F1, Q95KM5, Q9D1D1, Q9ET38, Q9JKD6, Q9QYW5, Q9YH90

Diamond homologs: A0A8C0N7E5, A6NM45, C3VMW3, C9JDP6, D3ZQJ0, O00501, O14493, O15551, O19005, O35054, O54942, O75508, O88551, O88552, O95471, O95484, O95500, O95832, P56745, P56746, P56747, P56748, P56750, P56856, P56857, P56880, P57739, P78369, Q0VCN0, Q2HJ22, Q2KIY2, Q3B7N4, Q3MHK4, Q4R3L1, Q5E9L0, Q5I0E5, Q5QT56, Q5R8E5, Q60771, Q63400

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
PRKACA	unknown	CLDN3	phosphorylation
SNAI1	“down-regulates quantity by repression”	CLDN3	“transcriptional regulation”
CLDN3	down-regulates	Epithelial-mesenchymal_transition

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 80 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.

Reactome pathways:

Pathway	Partners	Fold	FDR
Ras activation upon Ca2+ influx through NMDA receptor	5	53.9×	1e-06
Unblocking of NMDA receptors, glutamate binding and activation	5	51.3×	1e-06
Negative regulation of NMDA receptor-mediated neuronal transmission	5	51.3×	1e-06
Assembly and cell surface presentation of NMDA receptors	10	47.9×	6e-13
Dopamine Neurotransmitter Release Cycle	5	46.8×	2e-06
Long-term potentiation	5	44.9×	2e-06
Neurexins and neuroligins	11	40.9×	3e-13
Protein-protein interactions at synapses	7	35.1×	7e-08

GO biological processes:

GO term	Partners	Fold	FDR
establishment or maintenance of epithelial cell apical/basal polarity	8	60.4×	3e-10
protein localization to synapse	6	59.7×	9e-08
receptor clustering	7	56.7×	7e-09
regulation of postsynaptic membrane neurotransmitter receptor levels	6	38.6×	1e-06
cell-cell adhesion	7	9.2×	7e-04
protein-containing complex assembly	6	8.9×	3e-03
chemical synaptic transmission	7	7.0×	3e-03
protein transport	8	4.6×	9e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	7
Likely pathogenic	0
Uncertain significance	36
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (7)

Variant ID	HGVS	Classification
1341969	GRCh37/hg19 7q11.23(chr7:72766313-74042787)x3	Pathogenic
154350	GRCh38/hg38 7q11.23(chr7:73755831-74131326)x1	Pathogenic
268059	GRCh37/hg19 7q11.23(chr7:72722981-74217390)x1	Pathogenic
2685248	GRCh37/hg19 7q11.23(chr7:73142034-73690195)x1	Pathogenic
443008	GRCh37/hg19 7q11.23(chr7:72677173-74143140)x3	Pathogenic
563403	GRCh37/hg19 7q11.23(chr7:72608514-74386749)x1	Pathogenic
929343	GRCh37/hg19 7q11.23(chr7:72722981-74141840)x3	Pathogenic

SpliceAI

73 predictions. Top by Δscore:

Variant	Effect	Δscore
7:73769397:T:TA	donor_gain	0.5000
7:73769599:C:CT	donor_gain	0.4600
7:73769410:AG:A	donor_gain	0.4200
7:73769560:ACAGG:A	donor_gain	0.4100
7:73769561:CAGGC:C	donor_gain	0.4100
7:73769395:AGTC:A	donor_gain	0.3900
7:73769262:T:TA	donor_gain	0.3800
7:73769462:G:GT	donor_gain	0.3800
7:73769395:AGT:A	donor_gain	0.3700
7:73769560:A:AC	donor_gain	0.3700
7:73769561:C:CC	donor_gain	0.3700
7:73769372:C:A	donor_gain	0.3600
7:73769384:C:A	donor_gain	0.3600
7:73769482:T:TA	donor_gain	0.3500
7:73769600:C:CT	acceptor_gain	0.3500
7:73769637:G:T	donor_gain	0.3500
7:73769561:CAGG:C	donor_gain	0.3300
7:73769461:C:CT	donor_gain	0.3200
7:73769691:G:A	donor_gain	0.3200
7:73769297:CG:C	donor_gain	0.3100
7:73769430:C:CA	donor_gain	0.3100
7:73769562:A:C	donor_gain	0.3100
7:73770086:CGGG:C	acceptor_gain	0.3100
7:73769383:T:TA	donor_gain	0.3000
7:73769395:A:AC	donor_gain	0.3000
7:73769724:T:TA	donor_gain	0.3000
7:73769687:G:A	donor_gain	0.2900
7:73769277:G:A	donor_gain	0.2700
7:73769964:C:CT	acceptor_gain	0.2700
7:73769490:C:CT	acceptor_gain	0.2600

AlphaMissense

1391 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:73769612:G:C	F146L	0.999
7:73769612:G:T	F146L	0.999
7:73769614:A:G	F146L	0.999
7:73769862:C:G	C63S	0.998
7:73769863:A:T	C63S	0.998
7:73769900:C:A	W50C	0.998
7:73769900:C:G	W50C	0.998
7:73769902:A:G	W50R	0.998
7:73769902:A:T	W50R	0.998
7:73769908:C:G	G48R	0.998
7:73769963:C:A	W29C	0.998
7:73769963:C:G	W29C	0.998
7:73769551:A:G	W167R	0.997
7:73769551:A:T	W167R	0.997
7:73769965:A:G	W29R	0.997
7:73769965:A:T	W29R	0.997
7:73770003:C:T	G16D	0.997
7:73770004:C:G	G16R	0.997
7:73769572:C:G	G160R	0.996
7:73769582:C:A	K156N	0.996
7:73769582:C:G	K156N	0.996
7:73769863:A:G	C63R	0.996
7:73769891:G:C	C53W	0.996
7:73769892:C:G	C53S	0.996
7:73769892:C:T	C53Y	0.996
7:73769893:A:G	C53R	0.996
7:73769893:A:T	C53S	0.996
7:73769908:C:A	G48C	0.996
7:73769948:G:C	F34L	0.996
7:73769948:G:T	F34L	0.996

dbSNP variants (sampled 300 via entrez): RS1000919133 (7:73771592 G>A), RS1001433654 (7:73771989 G>A), RS1003490578 (7:73769593 C>T), RS1003831227 (7:73770020 G>A,T), RS1005430918 (7:73769294 G>A), RS1005888366 (7:73770877 C>T), RS1007109581 (7:73770626 G>A,T), RS1007446973 (7:73772061 C>T), RS1007559819 (7:73772269 A>C), RS1009667898 (7:73772032 A>T), RS1010026704 (7:73772246 T>C,G), RS1013821609 (7:73771513 T>C), RS1015633059 (7:73769555 C>A,G,T), RS1015959449 (7:73770886 C>T), RS1017190664 (7:73770628 C>G,T)

Disease associations

OMIM: gene MIM:602910 | disease phenotypes: MIM:609757

GenCC curated gene-disease

Mondo (1): 7q11.23 microduplication syndrome (MONDO:0012342)

Orphanet (1): 7q11.23 microduplication syndrome (Orphanet:96121)

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST004599_51	Mean platelet volume	1.000000e-10
GCST004616_186	Platelet distribution width	8.000000e-19

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0007984	platelet component distribution width

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C565723	Williams-Beuren Region Duplication Syndrome (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases expression	4
Benzo(a)pyrene	decreases expression, decreases methylation, increases expression	4
Tobacco Smoke Pollution	affects expression, decreases expression, increases expression	3
trichostatin A	affects expression, increases expression, affects binding, affects cotreatment, decreases reaction (+1 more)	2
Decitabine	affects cotreatment, decreases reaction, increases reaction, increases expression, affects binding	2
Air Pollutants	increases abundance, increases expression	2
Copper	increases chemical synthesis, increases oxidation, increases reaction, increases expression, increases import (+3 more)	2
dicrotophos	decreases expression	1
propionaldehyde	increases expression	1
sanguinarine	decreases expression	1
palmidrol	affects cotreatment, decreases expression	1
pirinixic acid	increases activity, affects binding, decreases expression	1
deoxynivalenol	affects localization, decreases expression, increases expression	1
kojic acid	decreases expression	1
arsenite	affects binding, increases reaction	1
butyraldehyde	increases expression	1
doxifluridine	increases response to substance	1
ochratoxin A	affects reaction, decreases expression	1
diallyl disulfide	decreases expression	1
coumarin	decreases expression	1
1-UFT protocol	increases response to substance	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression	1
loxoprofen	increases expression	1
dibenzo(a,l)pyrene	increases expression	1
diallyl trisulfide	decreases expression	1
pentanal	increases expression	1
fumonisin B1	decreases expression, decreases reaction	1
cisplatin-DNA adduct	increases abundance	1
cordycepin	decreases expression	1
perfluorooctane sulfonic acid	increases expression	1

Cellosaurus cell lines

5 cell lines: 3 cancer cell line, 2 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_C3V9	HT-1080/hCLDN-3	Cancer cell line	Male
CVCL_D1VV	Abcam A-549 CLDN3 KO	Cancer cell line	Male
CVCL_D2AC	Abcam HCT 116 CLDN3 KO	Cancer cell line	Male
CVCL_D3PM	CHO/CLDN3	Transformed cell line	Female
CVCL_E6TP	Genomeditech HEK-293 H_CLDN3	Transformed cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT07469566	Not specified	NOT_YET_RECRUITING	Characterization of the Natural History of Microduplication Syndrome 7q11.23