CLDN15

Summary

CLDN15 (claudin 15, HGNC:2036) is a protein-coding gene on chromosome 7q22.1, encoding Claudin-15 (P56746). Forms paracellular channels: polymerizes in tight junction strands with cation- and water-selective channels through the strands, conveying epithelial permeability in a process known as paracellular tight junction permeability.

This gene encodes a member of the claudin family. Claudins are integral membrane proteins and components of tight junction strands. Tight junction strands serve as a physical barrier to prevent solutes and water from passing freely through the paracellular space between epithelial or endothelial cell sheets, and also play critical roles in maintaining cell polarity and signal transductions. Alternatively spliced transcript variants encoding the same protein have been found for this gene.

Source: NCBI Gene 24146 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 39 total
• MANE Select transcript: NM_014343

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2036
Approved symbol	CLDN15
Name	claudin 15
Location	7q22.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000106404
Ensembl biotype	protein_coding
OMIM	615778
Entrez	24146

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 5 protein_coding, 1 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay, 1 retained_intron

ENST00000308344, ENST00000401528, ENST00000412417, ENST00000414035, ENST00000433422, ENST00000433833, ENST00000463331, ENST00000611078

RefSeq mRNA: 2 — MANE Select: NM_014343 NM_001185080, NM_014343

CCDS: CCDS5717

Canonical transcript exons

ENST00000308344 — 5 exons

Exon	Start	End
ENSE00001682600	101234278	101234442
ENSE00003492834	101232833	101232914
ENSE00003787492	101232604	101232720
ENSE00003901976	101237365	101237802
ENSE00003903856	101232094	101232515

Expression profiles

Bgee: expression breadth ubiquitous, 212 present calls, max score 97.51.

FANTOM5 (CAGE): breadth broad, TPM avg 2.0966 / max 810.5398, expressed in 271 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
85322	1.5314	206
85323	0.4752	103
85321	0.0747	24
85320	0.0153	2

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
jejunal mucosa	UBERON:0000399	97.51	gold quality
duodenum	UBERON:0002114	97.39	gold quality
ileal mucosa	UBERON:0000331	97.05	gold quality
germinal epithelium of ovary	UBERON:0001304	96.61	gold quality
small intestine Peyer’s patch	UBERON:0003454	95.83	gold quality
small intestine	UBERON:0002108	95.17	gold quality
mucosa of transverse colon	UBERON:0004991	94.03	gold quality
omental fat pad	UBERON:0010414	93.85	gold quality
peritoneum	UBERON:0002358	93.79	gold quality
adipose tissue of abdominal region	UBERON:0007808	92.84	gold quality
jejunum	UBERON:0002115	92.08	gold quality
granulocyte	CL:0000094	91.18	gold quality
parietal pleura	UBERON:0002400	90.51	gold quality
transverse colon	UBERON:0001157	88.85	gold quality
right lobe of liver	UBERON:0001114	88.68	gold quality
metanephros cortex	UBERON:0010533	88.44	gold quality
left uterine tube	UBERON:0001303	87.99	gold quality
spleen	UBERON:0002106	87.96	gold quality
right ovary	UBERON:0002118	87.19	gold quality
subcutaneous adipose tissue	UBERON:0002190	87.00	gold quality
adipose tissue	UBERON:0001013	86.95	gold quality
left ovary	UBERON:0002119	86.39	gold quality
connective tissue	UBERON:0002384	85.93	gold quality
intestine	UBERON:0000160	85.92	gold quality
nerve	UBERON:0001021	85.80	gold quality
tibial nerve	UBERON:0001323	85.80	gold quality
body of uterus	UBERON:0009853	85.51	gold quality
endocervix	UBERON:0000458	85.13	gold quality
lower esophagus mucosa	UBERON:0035834	84.40	gold quality
ectocervix	UBERON:0012249	84.03	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-GEOD-125970	yes	63.07
E-ANND-3	yes	19.15

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CLDN5

miRNA regulators (miRDB)

13 targeting CLDN15, 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-4789-5P	99.98	70.76	2721
HSA-MIR-6764-5P	99.75	67.89	2304
HSA-MIR-10393-3P	99.72	66.56	961
HSA-MIR-6801-5P	99.72	66.50	981
HSA-MIR-586	99.65	70.40	2051
HSA-MIR-1915-3P	99.58	66.79	1988
HSA-MIR-4696	99.48	67.48	1040
HSA-MIR-3127-3P	98.94	67.34	1055
HSA-MIR-6756-3P	98.94	66.79	1104
HSA-MIR-423-5P	98.69	67.48	1522
HSA-MIR-4693-3P	95.23	65.92	735
HSA-MIR-744-5P	93.78	65.29	230
HSA-MIR-10396A-5P	93.49	65.54	172

Literature-anchored findings (GeneRIF, showing 6)

• Data show that alterations in myosin light chain kinase activity, claudin-15 and claudin-2 expression are associated with gluten-induced symptomatology and intestinal permeability changes in diarrhea-predominant irritable bowel syndrome (IBS-D). (PMID:27869798)
• analysis of claudin-15 tight junction paracellular architecture by molecular dynamics simulations (PMID:28863193)
• Differential regulation of claudin-2 and claudin-15 expression in children and adults with malabsorptive disease. (PMID:31605016)
• CLDN15 is a novel diagnostic marker for malignant pleural mesothelioma. (PMID:34131154)
• Tight junction channels claudin-10b and claudin-15: Functional mapping of pore-lining residues. (PMID:35650657)
• Unique structural features of claudin-5 and claudin-15 lead to functionally distinct tight junction strand architecture. (PMID:36114674)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	cldn15lb	ENSDARG00000100844
mus_musculus	Cldn15	ENSMUSG00000001739
rattus_norvegicus	Cldn15	ENSRNOG00000001419

Paralogs (22): CLDN11 (ENSG00000013297), CLDN18 (ENSG00000066405), CLDN16 (ENSG00000113946), CLDN10 (ENSG00000134873), CLDN17 (ENSG00000156282), CLDN8 (ENSG00000156284), CLDN14 (ENSG00000159261), CLDN1 (ENSG00000163347), CLDN19 (ENSG00000164007), CLDN3 (ENSG00000165215), 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-15 — P56746 (reviewed: P56746)

All UniProt accessions (5): P56746, C9J3Z2, C9JHQ4, H7C2D7, Q96FX9

UniProt curated annotations — full annotation on UniProt →

Function. Forms paracellular channels: polymerizes in tight junction strands with cation- and water-selective channels through the strands, conveying epithelial permeability in a process known as paracellular tight junction permeability. In intestinal epithelium, allows for sodium and water fluxes from the peritoneal side to the lumen of the intestine to regulate nutrient absorption and intestinal morphogenesis.

Subunit / interactions. Can form homo- and heteropolymeric tight junction strands.

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

Tissue specificity. Detected in colon (at protein level).

Post-translational modifications. Palmitoylated.

Similarity. Belongs to the claudin family.

RefSeq proteins (2): NP_001172009, NP_055158* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004031	PMP22/EMP/MP20/Claudin	Family
IPR006187	Claudin	Family
IPR008094	Claudin15	Family
IPR017974	Claudin_CS	Conserved_site

Pfam: PF00822

Catalyzed reactions (Rhea), 8 shown:

• NH4(+)(in) = NH4(+)(out) (RHEA:28747)
• K(+)(in) = K(+)(out) (RHEA:29463)
• H2O(in) = H2O(out) (RHEA:29667)
• Na(+)(in) = Na(+)(out) (RHEA:34963)
• methylamine(out) = methylamine(in) (RHEA:74391)
• Rb(+)(in) = Rb(+)(out) (RHEA:78547)
• Li(+)(in) = Li(+)(out) (RHEA:78551)
• Cs(+)(in) = Cs(+)(out) (RHEA:78555)

UniProt features (25 total): mutagenesis site 6, topological domain 5, transmembrane region 4, site 3, modified residue 3, region of interest 2, chain 1, disulfide bond 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P56746-F1	82.18	0.57

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 (3): 55 (important for na(+)-selective paracellular ion transport); 64 (important for na(+)-selective paracellular ion transport); 68 (important for the formation of tight-junction strand-like structures)

Post-translational modifications (3): 111, 211, 218

Disulfide bonds (1): 52–62

Mutagenesis-validated functional residues (6):

Position	Phenotype
46	no effect on charge selectivity for paracellular ion transport.
55	decreases ion conductance and cation selectivity. strongly reduces na(+)-selective paracellular transport; when associat
55	reverses the charge selectivity for paracellular ion transport, favoring cl(-) transport.
63	does not affect assembly into homopolymeric strands, ion conductance, charge selectivity or pore size.
64	impairs the charge selectivity for paracellular ion transport, favoring cl(-) transport.
64	decreases ion conductance and cation selectivity. strongly reduces na(+)-selective paracellular transport; when associat

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-420029	Tight junction interactions

MSigDB gene sets: 131 (showing top): VERHAAK_AML_WITH_NPM1_MUTATED_DN, GOBP_DIGESTION, GCANCTGNY_MYOD_Q6, IVANOVA_HEMATOPOIESIS_LATE_PROGENITOR, SATO_SILENCED_BY_DEACETYLATION_IN_PANCREATIC_CANCER, KEGG_TIGHT_JUNCTION, CAGCTG_AP4_Q5, GOBP_CELL_CELL_ADHESION, MARTINEZ_RB1_TARGETS_UP, GROSS_HYPOXIA_VIA_ELK3_ONLY_DN, MODULE_206, HESS_TARGETS_OF_HOXA9_AND_MEIS1_UP, TGANTCA_AP1_C, PPAR_DR1_Q2, GOBP_DIGESTIVE_SYSTEM_PROCESS

GO Biological Process (7): monoatomic ion transport (GO:0006811), cell adhesion (GO:0007155), calcium-independent cell-cell adhesion (GO:0016338), bicellular tight junction assembly (GO:0070830), paracellular transport (GO:0160184), regulation of intestinal D-glucose absorption (GO:1903985), regulation of intestinal lipid absorption (GO:1904729)

GO Molecular Function (4): structural molecule activity (GO:0005198), identical protein binding (GO:0042802), paracellular tight junction channel activity (GO:0160187), protein binding (GO:0005515)

GO Cellular Component (6): plasma membrane (GO:0005886), bicellular tight junction (GO:0005923), lateral plasma membrane (GO:0016328), tight junction (GO:0070160), membrane (GO:0016020), 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
transport	2
regulation of intestinal absorption	2
cellular anatomical structure	2
cellular process	1
cell-cell adhesion	1
apical junction assembly	1
tight junction assembly	1
intestinal D-glucose absorption	1
intestinal lipid absorption	1
molecular_function	1
protein binding	1
transporter activity	1
binding	1
membrane	1
cell periphery	1
apical junction complex	1
tight junction	1
plasma membrane	1
cell-cell junction	1
cell junction	1

Protein interactions and networks

STRING

960 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CLDN15	OCLN	Q16625	790
CLDN15	CLDN12	P56749	781
CLDN15	TJP1	Q07157	595
CLDN15	MARVELD2	Q8N4S9	583
CLDN15	CLDN34	H7C241	520
CLDN15	F11R	Q9Y624	512
CLDN15	TJP2	Q9UDY2	511
CLDN15	CLDN18	P56856	497
CLDN15	WDFY2	Q96P53	485
CLDN15	SOX18	P35713	449
CLDN15	TJP3	O95049	445
CLDN15	J3KSM2	J3KSM2	429
CLDN15	CDC123	O75794	428
CLDN15	CARNS1	A5YM72	423
CLDN15	CENPN	Q96H22	409

IntAct

2 interactions, top by confidence:

A	B	Type	Score
GEM	CLDN15	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (5): SLC35B2 (Two-hybrid), PPAPDC2 (Two-hybrid), CLDN15 (Affinity Capture-RNA), CLDN15 (Affinity Capture-RNA), GEM (Two-hybrid)

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

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	32
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

806 predictions. Top by Δscore:

Variant	Effect	Δscore
7:101232513:GCG:G	acceptor_gain	1.0000
7:101232514:CG:C	acceptor_gain	1.0000
7:101232514:CGC:C	acceptor_gain	1.0000
7:101232516:C:CC	acceptor_gain	1.0000
7:101232599:CTCA:C	donor_loss	1.0000
7:101232601:CAC:C	donor_loss	1.0000
7:101232717:GTACC:G	acceptor_loss	1.0000
7:101232720:CCT:C	acceptor_loss	1.0000
7:101232721:CTGC:C	acceptor_loss	1.0000
7:101232722:T:A	acceptor_loss	1.0000
7:101232724:C:CT	acceptor_gain	1.0000
7:101232728:C:CT	acceptor_gain	1.0000
7:101232822:T:TA	donor_gain	1.0000
7:101232827:A:AC	donor_gain	1.0000
7:101232828:C:CC	donor_gain	1.0000
7:101232828:CT:C	donor_gain	1.0000
7:101232828:CTCA:C	donor_gain	1.0000
7:101232830:CACT:C	donor_loss	1.0000
7:101232831:A:AC	donor_gain	1.0000
7:101232832:C:CT	donor_gain	1.0000
7:101232832:CT:C	donor_gain	1.0000
7:101232832:CTTG:C	donor_gain	1.0000
7:101232832:CTTGG:C	donor_gain	1.0000
7:101232912:TACC:T	acceptor_loss	1.0000
7:101232913:ACCT:A	acceptor_loss	1.0000
7:101232914:CCT:C	acceptor_loss	1.0000
7:101232915:C:CA	acceptor_loss	1.0000
7:101232916:T:A	acceptor_loss	1.0000
7:101234323:T:A	donor_gain	1.0000
7:101234441:CC:C	acceptor_gain	1.0000

AlphaMissense

1467 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:101237495:C:A	W29C	0.996
7:101237495:C:G	W29C	0.996
7:101237493:C:G	R30P	0.995
7:101232859:G:C	F146L	0.994
7:101232859:G:T	F146L	0.994
7:101232861:A:G	F146L	0.994
7:101232689:A:G	W166R	0.993
7:101232689:A:T	W166R	0.993
7:101234424:C:G	R79P	0.993
7:101232710:C:G	G159R	0.992
7:101237427:C:G	C52S	0.992
7:101237428:A:T	C52S	0.992
7:101237442:T:A	N47I	0.992
7:101237388:A:C	F65C	0.991
7:101232692:C:A	G165W	0.990
7:101232692:C:G	G165R	0.990
7:101232692:C:T	G165R	0.990
7:101232710:C:A	G159C	0.990
7:101237387:G:C	F65L	0.990
7:101237387:G:T	F65L	0.990
7:101237389:A:G	F65L	0.990
7:101232684:G:C	S167R	0.989
7:101232684:G:T	S167R	0.989
7:101232686:T:G	S167R	0.989
7:101232691:C:T	G165E	0.989
7:101237397:C:G	C62S	0.989
7:101237398:A:T	C62S	0.989
7:101237441:G:C	N47K	0.989
7:101237441:G:T	N47K	0.989
7:101237497:A:G	W29R	0.989

dbSNP variants (sampled 300 via entrez): RS1000534152 (7:101236598 C>A,G,T), RS1001533008 (7:101235347 T>C), RS1001625482 (7:101233326 T>C), RS1001890828 (7:101239546 G>A), RS1001968570 (7:101238571 C>T), RS1002323532 (7:101239755 G>A,C,T), RS1002399284 (7:101234891 C>T), RS1002703847 (7:101235976 T>C), RS1002777923 (7:101234600 T>C), RS1003479289 (7:101237801 A>G), RS1004424558 (7:101234217 C>A,G,T), RS1004544836 (7:101233218 G>A), RS1004717334 (7:101238096 A>G), RS1004765707 (7:101232971 G>A,T), RS1005246295 (7:101237923 G>GA,GT)

Disease associations

OMIM: gene MIM:615778 | 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)

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Tobacco Smoke Pollution	increases expression	3
Air Pollutants	increases abundance, increases expression	2
Particulate Matter	increases abundance, increases expression	2
aristolochic acid I	increases expression	1
GSK-J4	increases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	affects cotreatment, decreases methylation	1
sodium arsenite	increases expression	1
zinc chromate	increases abundance, increases expression	1
ferrous chloride	decreases expression	1
1-hydroxypyrene	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
chromium hexavalent ion	increases abundance, increases expression	1
perfluorooctane sulfonic acid	increases expression	1
abrine	increases expression	1
ON 01910	affects expression	1
NSC 689534	affects binding, increases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Fulvestrant	affects cotreatment, decreases methylation	1
Air Pollutants, Occupational	decreases expression	1
Atrazine	decreases expression	1
Benzo(a)pyrene	affects methylation	1
Copper	affects binding, increases expression	1
Cytarabine	decreases expression	1
Dichlorodiphenyl Dichloroethylene	decreases expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Smoke	decreases expression	1
Tetracycline	decreases expression	1
Thiram	increases expression	1
Triclosan	increases expression	1

Clinical trials (associated diseases)

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