CLDN20

Summary

CLDN20 (claudin 20, HGNC:2042) is a protein-coding gene on chromosome 6q25.3, encoding Claudin-20 (P56880). 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 49861 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 34 total
• MANE Select transcript: NM_001001346

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2042
Approved symbol	CLDN20
Name	claudin 20
Location	6q25.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000171217
Ensembl biotype	protein_coding
Entrez	49861

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000367165, ENST00000909656

RefSeq mRNA: 1 — MANE Select: NM_001001346 NM_001001346

CCDS: CCDS5249

Canonical transcript exons

ENST00000367165 — 2 exons

Exon	Start	End
ENSE00001433719	155264013	155264288
ENSE00001443670	155275616	155276548

Expression profiles

Bgee: expression breadth ubiquitous, 158 present calls, max score 84.67.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
buccal mucosa cell	CL:0002336	84.67	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	76.34	gold quality
tendon of biceps brachii	UBERON:0008188	68.82	gold quality
bone marrow cell	CL:0002092	64.17	silver quality
tendon	UBERON:0000043	63.84	gold quality
adrenal tissue	UBERON:0018303	63.17	gold quality
stromal cell of endometrium	CL:0002255	62.82	gold quality
tibial nerve	UBERON:0001323	61.80	gold quality
colonic epithelium	UBERON:0000397	61.46	silver quality
calcaneal tendon	UBERON:0003701	61.04	gold quality
right adrenal gland cortex	UBERON:0035827	60.48	gold quality
right adrenal gland	UBERON:0001233	59.68	gold quality
left adrenal gland	UBERON:0001234	58.44	gold quality
smooth muscle tissue	UBERON:0001135	58.43	gold quality
left adrenal gland cortex	UBERON:0035825	58.06	gold quality
gingival epithelium	UBERON:0001949	57.77	gold quality
skin of abdomen	UBERON:0001416	57.76	gold quality
adrenal gland	UBERON:0002369	57.73	gold quality
apex of heart	UBERON:0002098	57.72	gold quality
adrenal cortex	UBERON:0001235	57.28	gold quality
medial globus pallidus	UBERON:0002477	56.81	gold quality
gingiva	UBERON:0001828	56.66	gold quality
monocyte	CL:0000576	56.61	gold quality
sural nerve	UBERON:0015488	55.69	silver quality
right lobe of thyroid gland	UBERON:0001119	55.56	gold quality
skin of leg	UBERON:0001511	55.39	gold quality
corpus callosum	UBERON:0002336	55.33	gold quality
tonsil	UBERON:0002372	55.01	gold quality
leukocyte	CL:0000738	54.84	gold quality
body of uterus	UBERON:0009853	54.84	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.95

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): TP53, TP63

miRNA regulators (miRDB)

44 targeting CLDN20, 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-559	99.95	72.28	3609
HSA-MIR-96-5P	99.95	72.80	2140
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-548A-5P	99.94	71.27	3482
HSA-MIR-548AD-5P	99.94	71.23	3502
HSA-MIR-548AE-5P	99.94	71.23	3502
HSA-MIR-548AK	99.94	71.24	3488
HSA-MIR-548AM-5P	99.94	71.24	3488
HSA-MIR-548AP-5P	99.94	71.14	3489
HSA-MIR-548AQ-5P	99.94	71.34	3426
HSA-MIR-548AR-5P	99.94	71.28	3515
HSA-MIR-548AS-5P	99.94	71.22	3482
HSA-MIR-548AU-5P	99.94	71.24	3488
HSA-MIR-548AY-5P	99.94	71.23	3502
HSA-MIR-548B-5P	99.94	71.23	3502
HSA-MIR-548BB-5P	99.94	71.27	3509
HSA-MIR-548C-5P	99.94	71.24	3488
HSA-MIR-548D-5P	99.94	71.23	3502
HSA-MIR-548H-5P	99.94	71.24	3488
HSA-MIR-548I	99.94	71.25	3481
HSA-MIR-548J-5P	99.94	71.14	3489
HSA-MIR-548O-5P	99.94	71.24	3488
HSA-MIR-548W	99.94	71.24	3488
HSA-MIR-548Y	99.94	71.28	3514
HSA-MIR-12133	99.92	71.82	2006
HSA-MIR-6844	99.82	70.69	2423
HSA-MIR-6739-5P	99.80	67.87	2806
HSA-MIR-6733-5P	99.74	67.94	2759
HSA-MIR-586	99.65	70.40	2051
HSA-MIR-9851-3P	99.63	69.68	1110

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Cldn20	ENSMUSG00000091530
rattus_norvegicus	Cldn20	ENSRNOG00000073115

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), CLDN22 (ENSG00000177300), CLDN7 (ENSG00000181885), CLDN5 (ENSG00000184113), CLDN6 (ENSG00000184697), CLDN24 (ENSG00000185758), CLDN4 (ENSG00000189143), CLDN9 (ENSG00000213937), CLDN25 (ENSG00000228607), CLDN34 (ENSG00000234469), CLDN23 (ENSG00000253958)

Protein

Protein identifiers

Claudin-20 — P56880 (reviewed: P56880)

All UniProt accessions (2): A0A140VKA2, P56880

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_001001346* (*=MANE)

Domains & families (InterPro)

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

Pfam: PF00822

UniProt features (12 total): topological domain 5, transmembrane region 4, chain 1, region of interest 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P56880-F1	81.61	0.52

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-420029	Tight junction interactions

MSigDB gene sets: 30 (showing top): GSE37336_LY6C_POS_VS_NEG_NAIVE_CD4_TCELL_DN, KEGG_TIGHT_JUNCTION, GOBP_CELL_CELL_ADHESION, chr6q25, TGACATY_UNKNOWN, GOCC_CELL_CELL_JUNCTION, KEGG_CELL_ADHESION_MOLECULES_CAMS, GOCC_ANCHORING_JUNCTION, REACTOME_TIGHT_JUNCTION_INTERACTIONS, GOMF_STRUCTURAL_MOLECULE_ACTIVITY, REACTOME_CELL_JUNCTION_ORGANIZATION, KEGG_LEUKOCYTE_TRANSENDOTHELIAL_MIGRATION, GOCC_TIGHT_JUNCTION, SOX10_TARGET_GENES, MIR6844

GO Biological Process (3): cell adhesion (GO:0007155), calcium-independent cell-cell adhesion (GO:0016338), bicellular tight junction assembly (GO:0070830)

GO Molecular Function (3): structural molecule activity (GO:0005198), identical protein binding (GO:0042802), protein binding (GO:0005515)

GO Cellular Component (7): Golgi apparatus (GO:0005794), cytosol (GO:0005829), plasma membrane (GO:0005886), bicellular tight junction (GO:0005923), 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
cytoplasm	2
cellular anatomical structure	2
cellular process	1
cell-cell adhesion	1
apical junction assembly	1
tight junction assembly	1
molecular_function	1
protein binding	1
binding	1
endomembrane system	1
intracellular membrane-bounded organelle	1
membrane	1
cell periphery	1
apical junction complex	1
tight junction	1
cell-cell junction	1
cell junction	1

Protein interactions and networks

STRING

326 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CLDN20	SCAF8	Q9UPN6	610
CLDN20	TIAM2	Q8IVF5	604
CLDN20	CNKSR3	Q6P9H4	559
CLDN20	A0A2Q2T6B6	A0A2Q2T6B6	527
CLDN20	G9CGD6	G9CGD6	527
CLDN20	CLDN12	P56749	519
CLDN20	CLDN23	Q96B33	484
CLDN20	FILIP1	Q7Z7B0	455
CLDN20	ITGA2	P17301	414
CLDN20	TJP3	O95049	376
CLDN20	CLDN24	A6NM45	374
CLDN20	CDC50A	Q9NV96	365
CLDN20	NOX3	Q9HBY0	322
CLDN20	TJP2	Q9UDY2	317
CLDN20	NHLRC2	Q8NBF2	301

IntAct

141 interactions, top by confidence:

A	B	Type	Score
CNIH3	CLDN20	psi-mi:“MI:0915”(physical association)	0.560
ANKRD46	CLDN20	psi-mi:“MI:0915”(physical association)	0.560
IGFBP5	CLDN20	psi-mi:“MI:0915”(physical association)	0.560
TMEM239	CLDN20	psi-mi:“MI:0915”(physical association)	0.560
MAL	CLDN20	psi-mi:“MI:0915”(physical association)	0.560
PLP1	CLDN20	psi-mi:“MI:0915”(physical association)	0.560
CLDN20	CNIH3	psi-mi:“MI:0915”(physical association)	0.560
CLDN20	TMEM239	psi-mi:“MI:0915”(physical association)	0.560
CLDN20	ANKRD46	psi-mi:“MI:0915”(physical association)	0.560
CLDN20	PLP1	psi-mi:“MI:0915”(physical association)	0.560
CLDN20	PDZD2	psi-mi:“MI:0407”(direct interaction)	0.440
CLDN20	PDZK1	psi-mi:“MI:0407”(direct interaction)	0.440
CLDN20	LNX2	psi-mi:“MI:0407”(direct interaction)	0.440
CLDN20	HTRA3	psi-mi:“MI:0407”(direct interaction)	0.440
APBA3	CLDN20	psi-mi:“MI:0407”(direct interaction)	0.440
CLDN20	MAST2	psi-mi:“MI:0407”(direct interaction)	0.440
CLDN20	NHERF4	psi-mi:“MI:0407”(direct interaction)	0.440
CLDN20	PICK1	psi-mi:“MI:0407”(direct interaction)	0.440
CLDN20	MAGI1	psi-mi:“MI:0407”(direct interaction)	0.440
CLDN20	PTPN13	psi-mi:“MI:0407”(direct interaction)	0.440
CLDN20	LIN7C	psi-mi:“MI:0407”(direct interaction)	0.440
CLDN20	MPP2	psi-mi:“MI:0407”(direct interaction)	0.440

BioGRID (11): HIF1AN (Affinity Capture-MS), CLDN20 (Two-hybrid), CLDN20 (Two-hybrid), CLDN20 (Two-hybrid), MAL (Two-hybrid), ANKRD46 (Two-hybrid), TMEM239 (Two-hybrid), HIF1AN (Affinity Capture-MS), ACTA1 (Affinity Capture-MS), FYN (Affinity Capture-MS), APP (Reconstituted Complex)

ESM2 similar proteins: A1A5C7, A5D7H1, A6H7A0, A6NJW4, A6QLN9, A8MUP2, A8MXK1, B0BMW8, B0BNL6, O35393, O62657, O75078, P52875, P55244, P56880, P57791, Q08334, Q0V881, Q15768, Q16557, Q2M1K6, Q3SZQ2, Q3UHH2, Q4V899, Q5E9H2, Q5FYB0, Q5M7U7, Q5R6I6, Q5RCI5, Q5SQ64, Q642A6, Q6PCB0, Q7TPB4, Q8BM89, Q8BZH0, Q8N431, Q8N5I2, Q8R2R5, Q8R2Z5, Q8VE98

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.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 86 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	50.1×	2e-06
Unblocking of NMDA receptors, glutamate binding and activation	5	47.7×	2e-06
Negative regulation of NMDA receptor-mediated neuronal transmission	5	47.7×	2e-06
Assembly and cell surface presentation of NMDA receptors	10	44.5×	1e-12
Dopamine Neurotransmitter Release Cycle	5	43.5×	3e-06
Long-term potentiation	5	41.7×	3e-06
Neurexins and neuroligins	11	38.0×	8e-13
Protein-protein interactions at synapses	7	32.6×	1e-07

GO biological processes:

GO term	Partners	Fold	FDR
establishment or maintenance of epithelial cell apical/basal polarity	11	78.9×	3e-16
protein localization to synapse	6	56.7×	1e-07
receptor clustering	7	53.9×	1e-08
regulation of postsynaptic membrane neurotransmitter receptor levels	7	42.8×	4e-08
protein-containing complex assembly	9	12.7×	3e-06
cell-cell adhesion	9	11.3×	6e-06
chemical synaptic transmission	8	7.6×	5e-04
actin cytoskeleton organization	6	5.9×	1e-02

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	30
Likely benign	0
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

314 predictions. Top by Δscore:

Variant	Effect	Δscore
6:155264284:CCCAG:C	donor_loss	0.9800
6:155264285:CCAG:C	donor_loss	0.9800
6:155264286:CAG:C	donor_loss	0.9800
6:155264289:GTAAG:G	donor_loss	0.9800
6:155268594:G:T	donor_gain	0.9700
6:155270039:TGG:T	donor_gain	0.9700
6:155264165:A:G	donor_gain	0.9100
6:155275614:A:AG	acceptor_gain	0.9100
6:155275615:G:GG	acceptor_gain	0.9100
6:155270040:G:GA	donor_gain	0.9000
6:155272797:CA:C	donor_gain	0.9000
6:155275709:A:C	donor_gain	0.9000
6:155272128:T:G	acceptor_gain	0.8800
6:155275600:T:TA	acceptor_loss	0.8700
6:155275610:CCTTA:C	acceptor_loss	0.8700
6:155275611:CTTAG:C	acceptor_loss	0.8700
6:155275612:TTAGG:T	acceptor_loss	0.8700
6:155275613:TA:T	acceptor_loss	0.8700
6:155275614:A:G	acceptor_loss	0.8700
6:155275615:G:A	acceptor_loss	0.8700
6:155264289:G:GG	donor_gain	0.8500
6:155268606:A:AG	donor_gain	0.8400
6:155265938:A:T	acceptor_gain	0.8000
6:155265943:G:C	acceptor_gain	0.8000
6:155264778:AATGT:A	donor_gain	0.7900
6:155270041:GAAG:G	donor_gain	0.7900
6:155275616:G:T	acceptor_loss	0.7800
6:155270095:G:T	donor_gain	0.7700
6:155272135:CTG:C	acceptor_gain	0.7700
6:155275596:GTTTT:G	acceptor_loss	0.7700

AlphaMissense

1424 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:155275809:G:C	W30C	0.986
6:155275809:G:T	W30C	0.986
6:155275872:G:C	W51C	0.978
6:155275872:G:T	W51C	0.978
6:155276089:T:C	C124R	0.974
6:155275999:G:A	G94R	0.973
6:155275999:G:C	G94R	0.973
6:155275999:G:T	G94W	0.973
6:155276000:G:A	G94E	0.972
6:155275870:T:A	W51R	0.971
6:155275870:T:C	W51R	0.971
6:155275807:T:A	W30R	0.970
6:155275807:T:C	W30R	0.970
6:155275865:G:A	G49E	0.970
6:155275909:T:A	C64S	0.963
6:155275910:G:C	C64S	0.963
6:155275879:T:A	C54S	0.961
6:155275880:G:C	C54S	0.961
6:155276252:G:A	G178D	0.961
6:155275981:T:C	C88R	0.960
6:155276158:T:C	F147L	0.958
6:155276160:T:A	F147L	0.958
6:155276160:T:G	F147L	0.958
6:155275864:G:A	G49R	0.957
6:155275864:G:C	G49R	0.957
6:155276102:C:A	A128E	0.957
6:155276113:A:C	S132R	0.957
6:155276115:T:A	S132R	0.957
6:155276115:T:G	S132R	0.957
6:155276104:G:A	G129R	0.956

dbSNP variants (sampled 300 via entrez): RS1000377841 (6:155276812 T>G), RS1000567928 (6:155265084 G>A), RS1000632714 (6:155263517 C>A), RS1000671858 (6:155271790 A>C,G), RS1000707015 (6:155272065 G>A), RS1000778025 (6:155265334 T>C), RS1001056052 (6:155271846 T>A), RS1001307611 (6:155268248 T>C), RS1001337139 (6:155268685 C>A), RS1001369439 (6:155268875 A>C), RS1001498534 (6:155268267 CA>C,CAA), RS1002327942 (6:155275448 T>C), RS1002431434 (6:155266508 T>C), RS1002895379 (6:155272107 G>A), RS1003012097 (6:155276948 A>G)

Disease associations

OMIM: gene `` | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST005756_4	Dimensional psychopathology (Negative)	1.000000e-06
GCST005758_3	Dimensional psychopathology (Arousal)	9.000000e-07
GCST008155_40	Waist-hip ratio	3.000000e-06
GCST008159_56	Waist-to-hip ratio adjusted for BMI	4.000000e-06

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0009096	negative domain measurement
EFO:0009099	arousal domain measurement
EFO:0004343	waist-hip ratio
EFO:0007788	BMI-adjusted waist-hip ratio

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

6 total (human), top 6 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
butyraldehyde	decreases expression	1
CGP 52608	affects binding, increases reaction	1
Lead	decreases expression	1
Valproic Acid	decreases expression	1
Aflatoxin B1	increases methylation	1
Lactic Acid	increases expression	1

Clinical trials (associated diseases)

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