CLDN25

Summary

CLDN25 (claudin 25, HGNC:37218) is a protein-coding gene on chromosome 11q23.2, encoding Claudin-25 (C9JDP6). Plays a major role in tight junction-specific obliteration of the intercellular space, through calcium-independent cell-adhesion activity.

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.

Source: NCBI Gene 644672 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 45 total
• MANE Select transcript: NM_001101389

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:37218
Approved symbol	CLDN25
Name	claudin 25
Location	11q23.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000228607
Ensembl biotype	protein_coding
OMIM	620812
Entrez	644672

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000453129

RefSeq mRNA: 1 — MANE Select: NM_001101389 NM_001101389

CCDS: CCDS44736

Canonical transcript exons

ENST00000453129 — 1 exons

Exon	Start	End
ENSE00001702676	113779796	113780485

Expression profiles

Bgee: expression breadth tissue_specific, 8 present calls, max score 52.00.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
olfactory segment of nasal mucosa	UBERON:0005386	52.00	gold quality
adenohypophysis	UBERON:0002196	39.60	gold quality
granulocyte	CL:0000094	38.95	gold quality
pituitary gland	UBERON:0000007	37.46	gold quality
skeletal muscle tissue	UBERON:0001134	37.40	silver 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
ganglionic eminence	UBERON:0004023	35.49	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
stromal cell of endometrium	CL:0002255	29.87	gold quality
muscle of leg	UBERON:0001383	28.65	gold quality
duodenum	UBERON:0002114	28.14	gold quality
gastrocnemius	UBERON:0001388	28.00	gold quality
leukocyte	CL:0000738	27.86	silver quality
lymph node	UBERON:0000029	27.57	gold quality
monocyte	CL:0000576	27.18	silver quality
tonsil	UBERON:0002372	27.05	gold quality
vermiform appendix	UBERON:0001154	26.42	gold quality
blood	UBERON:0000178	26.15	gold quality
gall bladder	UBERON:0002110	25.98	gold quality
placenta	UBERON:0001987	25.81	gold quality
urinary bladder	UBERON:0001255	25.72	gold quality
uterine cervix	UBERON:0000002	25.56	gold quality
primary visual cortex	UBERON:0002436	24.61	gold quality
superior frontal gyrus	UBERON:0002661	24.08	gold quality
cortex of kidney	UBERON:0001225	23.94	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.98

Regulation

Is transcription factor: no

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Cldn25	ENSMUSG00000105298
rattus_norvegicus	Cldn25	ENSRNOG00000057454

Paralogs (22): CLDN11 (ENSG00000013297), CLDN18 (ENSG00000066405), CLDN15 (ENSG00000106404), 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), CLDN34 (ENSG00000234469), CLDN23 (ENSG00000253958)

Protein

Protein identifiers

Claudin-25 — C9JDP6 (reviewed: C9JDP6)

All UniProt accessions (1): C9JDP6

UniProt curated annotations — full annotation on UniProt →

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

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

Similarity. Belongs to the claudin family.

RefSeq proteins (1): NP_001094859* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004031	PMP22/EMP/MP20/Claudin	Family
IPR006187	Claudin	Family

Pfam: PF00822

UniProt features (11 total): topological domain 5, transmembrane region 4, chain 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-C9JDP6-F1	82.88	0.58

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 11 (showing top): GOCC_CELL_CELL_JUNCTION, GOCC_ANCHORING_JUNCTION, GOMF_STRUCTURAL_MOLECULE_ACTIVITY, GOCC_TIGHT_JUNCTION, GOCC_APICAL_JUNCTION_COMPLEX, KEGG_MEDICUS_REFERENCE_TIGHT_JUNCTION_ACTIN_SIGNALING_PATHWAY, GSE3720_UNSTIM_VS_PMA_STIM_VD1_GAMMADELTA_TCELL_DN, GSE6259_FLT3L_INDUCED_VS_WT_SPLENIC_DC_33D1_POS_DN, chr11q23, GSE37605_C57BL6_VS_NOD_FOXP3_IRES_GFP_TREG_UP, GSE37605_C57BL6_VS_NOD_FOXP3_FUSION_GFP_TCONV_UP

GO Biological Process (2): cell adhesion (GO:0007155), bicellular tight junction assembly (GO:0070830)

GO Molecular Function (1): structural molecule activity (GO:0005198)

GO Cellular Component (5): plasma membrane (GO:0005886), bicellular tight junction (GO:0005923), tight junction (GO:0070160), membrane (GO:0016020), anchoring junction (GO:0070161)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular process	1
apical junction assembly	1
tight junction assembly	1
molecular_function	1
membrane	1
cell periphery	1
apical junction complex	1
tight junction	1
cell-cell junction	1
cellular anatomical structure	1
cell junction	1

Protein interactions and networks

STRING

1615 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CLDN25	CLDN34	H7C241	582
CLDN25	CLDN17	P56750	500
CLDN25	CLDN16	Q9Y5I7	484
CLDN25	CLDN12	P56749	480
CLDN25	CLDN8	P56748	440
CLDN25	CLDN11	O75508	412
CLDN25	TJP3	O95049	345
CLDN25	CLDND1	Q9NY35	342
CLDN25	MARVELD2	Q8N4S9	322
CLDN25	MRM2	Q9UI43	316
CLDN25	J3KSM2	J3KSM2	308
CLDN25	CLDN23	Q96B33	286
CLDN25	F11R	Q9Y624	270
CLDN25	TJP2	Q9UDY2	266
CLDN25	MARVELD1	Q9BSK0	262

IntAct

0 interactions, top by confidence:

ESM2 similar proteins: A6NDP7, A6NFC5, A8MUP6, B1AQL3, B2RZ87, C9JDP6, E9Q9H8, O75204, P0C5X8, Q02644, Q08DL4, Q0IIL2, Q16617, Q1HG44, Q2KIG8, Q2KJ11, Q2KJ98, Q3SZ72, Q3SZT1, Q3UUA0, Q3YBM2, Q497B3, Q53RY4, Q5R8D6, Q6AYL2, Q6ICI0, Q7YQI4, Q7Z7M1, Q7Z7N9, Q80WE5, Q8BGP5, Q8CIP5, Q8K177, Q8R1W2, Q8WXS4, Q95KI5, Q96B33, Q96DZ7, Q96HP8, Q96JT2

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

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	43
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

187 predictions. Top by Δscore:

Variant	Effect	Δscore
11:113779970:G:GT	donor_gain	0.9100
11:113779970:G:T	donor_gain	0.9100
11:113779991:GCC:G	donor_gain	0.8900
11:113780049:T:TA	donor_gain	0.8700
11:113780050:A:AA	donor_gain	0.8700
11:113779983:TGTGC:T	donor_gain	0.8400
11:113779985:TGC:T	donor_gain	0.8300
11:113780027:CAG:C	donor_loss	0.8000
11:113780028:AGG:A	donor_loss	0.8000
11:113780029:GG:G	donor_loss	0.8000
11:113780030:GTA:G	donor_loss	0.8000
11:113780031:T:C	donor_loss	0.8000
11:113779987:C:T	donor_gain	0.7900
11:113780112:A:AG	acceptor_gain	0.7200
11:113780113:G:GG	acceptor_gain	0.7200
11:113779894:G:GT	donor_gain	0.7100
11:113779949:G:T	donor_gain	0.6900
11:113779813:TGCAA:T	donor_gain	0.6800
11:113780113:GT:G	acceptor_gain	0.6700
11:113779954:C:A	donor_gain	0.6600
11:113780110:CCA:C	acceptor_loss	0.6500
11:113780113:G:A	acceptor_loss	0.6500
11:113780395:T:A	acceptor_gain	0.6500
11:113779949:G:GT	donor_gain	0.6400
11:113779910:G:GT	donor_gain	0.6200
11:113780021:G:GT	donor_gain	0.6100
11:113780391:T:TA	acceptor_gain	0.5900
11:113779952:GTC:G	donor_gain	0.5800
11:113779953:TCT:T	donor_gain	0.5800
11:113780211:G:A	acceptor_gain	0.5700

AlphaMissense

1476 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:113780237:T:C	F148L	0.912
11:113780239:C:A	F148L	0.912
11:113780239:C:G	F148L	0.912
11:113779994:T:C	F67L	0.882
11:113779996:T:A	F67L	0.882
11:113779996:T:G	F67L	0.882
11:113779894:G:C	W33C	0.877
11:113779894:G:T	W33C	0.877
11:113779892:T:A	W33R	0.833
11:113779892:T:C	W33R	0.833
11:113780275:G:C	W160C	0.828
11:113780275:G:T	W160C	0.828
11:113779948:G:C	W51C	0.811
11:113779948:G:T	W51C	0.811
11:113779897:G:C	K34N	0.808
11:113779897:G:T	K34N	0.808
11:113780303:T:A	W170R	0.781
11:113780303:T:C	W170R	0.781
11:113779856:T:A	W21R	0.751
11:113779856:T:C	W21R	0.751
11:113780279:T:C	F162L	0.751
11:113780281:T:A	F162L	0.751
11:113780281:T:G	F162L	0.751
11:113779933:G:C	W46C	0.740
11:113779933:G:T	W46C	0.740
11:113779893:G:T	W33L	0.711
11:113780003:T:C	F70L	0.710
11:113780005:C:A	F70L	0.710
11:113780005:C:G	F70L	0.710
11:113779893:G:C	W33S	0.707

dbSNP variants (sampled 300 via entrez): RS1000552043 (11:113778279 G>A), RS1000587808 (11:113778052 C>G,T), RS1002060944 (11:113778716 C>T), RS1002495449 (11:113778419 C>T), RS1003089659 (11:113779707 C>A,T), RS1004728169 (11:113778726 A>C,G,T), RS1005508833 (11:113778770 C>T), RS1007283022 (11:113780407 C>A,T), RS1007355320 (11:113780719 C>A), RS1009352484 (11:113778640 G>A,C), RS1009384960 (11:113778343 C>T), RS1010388994 (11:113779650 C>G), RS1010662364 (11:113778090 A>G), RS1011446276 (11:113780796 C>A), RS1011636984 (11:113779177 T>G)

Disease associations

OMIM: gene MIM:620812 | 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

5 total (human), top 5 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
maleic acid	increases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Copper	affects cotreatment, decreases expression	1
Testosterone	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1

Clinical trials (associated diseases)

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