CLDN22

Summary

CLDN22 (claudin 22, HGNC:2044) is a protein-coding gene on chromosome 4q35.1, encoding Claudin-22 (Q8N7P3). 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. This gene is intronless and overlaps the 3’ UTR of the WWC2 gene (GeneID: 80014) on the opposite strand.

Source: NCBI Gene 53842 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 40 total — 2 pathogenic
• MANE Select transcript: NM_001111319

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2044
Approved symbol	CLDN22
Name	claudin 22
Location	4q35.1
Locus type	gene with protein product
Status	Approved
Aliases	CLDN21
Ensembl gene	ENSG00000177300
Ensembl biotype	protein_coding
OMIM	620566
Entrez	53842

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000323319

RefSeq mRNA: 1 — MANE Select: NM_001111319 NM_001111319

CCDS: CCDS43286

Canonical transcript exons

ENST00000323319 — 1 exons

Exon	Start	End
ENSE00001225814	183318100	183320276

Expression profiles

Bgee: expression breadth ubiquitous, 111 present calls, max score 87.22.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0194 / max 6.1592, expressed in 9 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
55088	0.0194	9

Top tissues by expression

128 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	87.22	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	73.86	gold quality
minor salivary gland	UBERON:0001830	63.71	gold quality
saliva-secreting gland	UBERON:0001044	62.38	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	61.89	gold quality
granulocyte	CL:0000094	55.82	gold quality
right lobe of liver	UBERON:0001114	54.85	gold quality
apex of heart	UBERON:0002098	54.21	gold quality
cortical plate	UBERON:0005343	51.90	gold quality
lower esophagus mucosa	UBERON:0035834	51.14	gold quality
primary visual cortex	UBERON:0002436	49.74	gold quality
endometrium	UBERON:0001295	47.45	gold quality
ventricular zone	UBERON:0003053	46.73	gold quality
skeletal muscle tissue	UBERON:0001134	45.71	silver quality
ganglionic eminence	UBERON:0004023	45.63	gold quality
mucosa of transverse colon	UBERON:0004991	43.85	silver quality
fallopian tube	UBERON:0003889	43.72	gold quality
liver	UBERON:0002107	43.60	gold quality
muscle tissue	UBERON:0002385	43.24	silver quality
prefrontal cortex	UBERON:0000451	42.82	gold quality
sural nerve	UBERON:0015488	41.97	gold quality
upper lobe of left lung	UBERON:0008952	41.74	gold quality
colonic epithelium	UBERON:0000397	41.43	gold quality
superior frontal gyrus	UBERON:0002661	40.80	gold quality
body of pancreas	UBERON:0001150	40.79	gold quality
adult mammalian kidney	UBERON:0000082	40.66	gold quality
adenohypophysis	UBERON:0002196	40.31	gold quality
Brodmann (1909) area 9	UBERON:0013540	40.13	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	39.71	gold quality
frontal cortex	UBERON:0001870	39.63	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

85 targeting CLDN22, 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-656-3P	100.00	72.15	2788
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-6748-5P	100.00	65.81	1057
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-6759-5P	99.99	66.54	785
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-568	99.98	69.86	2084
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-6835-3P	99.93	70.49	2904
HSA-MIR-3671	99.90	73.04	3897
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-3681-3P	99.88	70.46	2254
HSA-MIR-6124	99.87	69.78	3551
HSA-MIR-137-3P	99.87	74.74	2401
HSA-MIR-544A	99.84	68.66	1965
HSA-MIR-944	99.82	70.85	3042
HSA-MIR-577	99.78	69.13	2479
HSA-MIR-3934-3P	99.76	65.51	1351
HSA-MIR-4517	99.76	69.19	1867
HSA-MIR-6745	99.74	65.33	1321
HSA-MIR-8084	99.73	69.57	1760
HSA-MIR-548AU-3P	99.70	68.22	1373
HSA-MIR-33A-3P	99.70	70.27	3362

Literature-anchored findings (GeneRIF, showing 1)

• CLDN21, clustered with CLDN22 at human chromosome 4q35.1, is a four-transmembrane protein with WWCC motif, defined by W-X(17-22)-W-X(2)-C-X(8-10)-C. (PMID:12736707)

Cross-species orthologs

0 orthologs

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

Protein

Protein identifiers

Claudin-22 — Q8N7P3 (reviewed: Q8N7P3)

All UniProt accessions (1): Q8N7P3

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_001104789* (*=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 (11 total): topological domain 5, transmembrane region 4, chain 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8N7P3-F1	86.41	0.54

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-420029	Tight junction interactions

MSigDB gene sets: 37 (showing top): GSE45365_CTRL_VS_MCMV_INFECTION_NK_CELL_UP, KEGG_TIGHT_JUNCTION, GOBP_CELL_CELL_ADHESION, chr4q35, GOCC_CELL_CELL_JUNCTION, KEGG_CELL_ADHESION_MOLECULES_CAMS, GOCC_ANCHORING_JUNCTION, REACTOME_TIGHT_JUNCTION_INTERACTIONS, GOMF_STRUCTURAL_MOLECULE_ACTIVITY, CHEN_METABOLIC_SYNDROM_NETWORK, REACTOME_CELL_JUNCTION_ORGANIZATION, KEGG_LEUKOCYTE_TRANSENDOTHELIAL_MIGRATION, GOCC_TIGHT_JUNCTION, SOX10_TARGET_GENES, MIR3671

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 (4): plasma membrane (GO:0005886), bicellular tight junction (GO:0005923), 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
cellular process	1
cell-cell adhesion	1
apical junction assembly	1
tight junction assembly	1
molecular_function	1
protein binding	1
binding	1
membrane	1
cell periphery	1
apical junction complex	1
tight junction	1
cellular anatomical structure	1
cell junction	1

Protein interactions and networks

STRING

268 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CLDN22	CLDN23	Q96B33	559
CLDN22	CLDN12	P56749	485
CLDN22	CLDN34	H7C241	446
CLDN22	CDKN2AIP	Q9NXV6	404
CLDN22	TJP3	O95049	348
CLDN22	JAM3	Q9BX67	343
CLDN22	NBPF4	Q96M43	308
CLDN22	DIPK1B	Q5VUD6	295
CLDN22	VSIG1	Q86XK7	285
CLDN22	TJP2	Q9UDY2	270
CLDN22	CCDC102B	Q68D86	269
CLDN22	SMIM5	Q71RC9	263
CLDN22	PATJ	Q8NI35	260
CLDN22	F11R	Q9Y624	260
CLDN22	FSD2	A1L4K1	247
CLDN22	MARVELD2	Q8N4S9	247

IntAct

22 interactions, top by confidence:

A	B	Type	Score
CLDN22	CLEC4C	psi-mi:“MI:0915”(physical association)	0.560
TMBIM6	CLDN22	psi-mi:“MI:0915”(physical association)	0.560
CLDN22	SPG21	psi-mi:“MI:0915”(physical association)	0.560
CXCR2	CLDN22	psi-mi:“MI:0915”(physical association)	0.560
OPRM1	CLDN22	psi-mi:“MI:0915”(physical association)	0.560
CLDN22	LHFPL5	psi-mi:“MI:0915”(physical association)	0.560
CLDN22	TREX1	psi-mi:“MI:0915”(physical association)	0.560
CLDN22	CXCR2	psi-mi:“MI:0915”(physical association)	0.000
CLDN22	OPRM1	psi-mi:“MI:0915”(physical association)	0.000
CLDN22	CLEC4C	psi-mi:“MI:0915”(physical association)	0.000
TMBIM6	CLDN22	psi-mi:“MI:0915”(physical association)	0.000
SPG21	CLDN22	psi-mi:“MI:0915”(physical association)	0.000
CLDN22	LHFPL5	psi-mi:“MI:0915”(physical association)	0.000
TREX1	CLDN22	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (7): CLDN22 (Two-hybrid), CLDN22 (Two-hybrid), CLDN22 (Two-hybrid), CXCR2 (Two-hybrid), LHFPL5 (Two-hybrid), CLEC4C (Two-hybrid), TREX1 (Two-hybrid)

ESM2 similar proteins: A6NFC5, A6NM45, A8MUP6, B1AQL3, C3VMW3, C9JDP6, O35912, O75204, O88551, O88552, O95500, O95832, P56745, P56746, P56748, P56750, P57739, Q08DE1, Q0V9E0, Q0VCN0, Q16617, Q2KIY2, Q2KJ11, Q3UUA0, Q4V922, Q5CZV0, Q5M962, Q5QT56, Q6ICI0, Q765P1, Q7T392, Q7TQI0, Q7Z7N9, Q8BGP5, Q8BXA6, Q8N7P3, Q8NHS1, Q8VHW3, Q95KM6, Q96B33

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

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	0
Uncertain significance	32
Likely benign	4
Benign	0

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
1527133	GRCh37/hg19 4q32.1-35.2(chr4:159755174-190225765)	Pathogenic
1527139	GRCh37/hg19 4q34.1-35.2(chr4:175855408-190957473)	Pathogenic

SpliceAI

60 predictions. Top by Δscore:

Variant	Effect	Δscore
4:183319624:A:AG	acceptor_gain	0.4900
4:183319625:G:GG	acceptor_gain	0.4900
4:183319558:A:T	acceptor_gain	0.4300
4:183319704:G:GT	acceptor_gain	0.4300
4:183320137:T:TC	acceptor_gain	0.4000
4:183319780:CCTGA:C	donor_gain	0.3800
4:183319682:TCCTA:T	acceptor_gain	0.3700
4:183319709:C:T	acceptor_gain	0.3700
4:183319556:TTAG:T	acceptor_gain	0.3600
4:183319557:TAGT:T	acceptor_gain	0.3600
4:183318544:A:AG	acceptor_gain	0.3500
4:183318545:G:GG	acceptor_gain	0.3500
4:183320137:T:C	acceptor_gain	0.3500
4:183320163:A:T	acceptor_gain	0.3500
4:183318543:CAGTG:C	acceptor_gain	0.3400
4:183319587:A:AG	acceptor_gain	0.3400
4:183319588:G:GG	acceptor_gain	0.3400
4:183318844:G:GA	acceptor_gain	0.3300
4:183318845:C:A	acceptor_gain	0.3300
4:183319589:T:G	acceptor_gain	0.3300
4:183319679:CCCTC:C	acceptor_gain	0.3200
4:183319680:CCTCC:C	acceptor_gain	0.3200
4:183318544:A:T	acceptor_gain	0.3100
4:183319621:CGT:C	acceptor_gain	0.3000
4:183319705:C:T	acceptor_gain	0.3000
4:183318542:TCAG:T	acceptor_gain	0.2900
4:183318831:A:T	acceptor_gain	0.2900
4:183319624:AGT:A	acceptor_gain	0.2900
4:183319625:GTG:G	acceptor_gain	0.2900
4:183318545:GTGTC:G	acceptor_gain	0.2800

AlphaMissense

1406 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:183319775:G:C	F148L	0.993
4:183319775:G:T	F148L	0.993
4:183319777:A:G	F148L	0.993
4:183320120:C:A	W33C	0.975
4:183320120:C:G	W33C	0.975
4:183319739:C:A	W160C	0.966
4:183319739:C:G	W160C	0.966
4:183320066:C:A	W51C	0.965
4:183320066:C:G	W51C	0.965
4:183319776:A:C	F148C	0.963
4:183319718:A:C	F167L	0.959
4:183319718:A:T	F167L	0.959
4:183319720:A:G	F167L	0.959
4:183319731:C:A	G163V	0.959
4:183320081:C:A	W46C	0.957
4:183320081:C:G	W46C	0.957
4:183320117:C:A	K34N	0.953
4:183320117:C:G	K34N	0.953
4:183319711:A:G	W170R	0.951
4:183319711:A:T	W170R	0.951
4:183320158:A:G	W21R	0.948
4:183320158:A:T	W21R	0.948
4:183320018:A:C	F67L	0.947
4:183320018:A:T	F67L	0.947
4:183320020:A:G	F67L	0.947
4:183319812:G:C	P136R	0.945
4:183320074:C:G	G49R	0.939
4:183320074:C:T	G49R	0.939
4:183319812:G:T	P136H	0.933
4:183319809:A:T	V137D	0.932

dbSNP variants (sampled 300 via entrez): RS1000040175 (4:183317850 G>C,T), RS1000706899 (4:183318362 T>C), RS1001042453 (4:183319114 T>C), RS1001078414 (4:183318691 A>G), RS1003180672 (4:183320052 A>G), RS1004417019 (4:183321066 A>G), RS1005705028 (4:183320409 T>A), RS1006298490 (4:183319067 A>G), RS1006638260 (4:183319422 T>C), RS1006749696 (4:183321035 G>C), RS1007516388 (4:183318856 C>T), RS1007754885 (4:183318652 G>C), RS1008451095 (4:183322160 C>A,T), RS1009059136 (4:183321521 A>G), RS1010138780 (4:183317785 T>A)

Disease associations

OMIM: gene MIM:620566 | 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

11 total (human), top 11 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
propionaldehyde	decreases expression	1
2-methyl-4-isothiazolin-3-one	increases expression	1
pentanal	increases expression	1
CGP 52608	affects binding, increases reaction	1
Grape Seed Proanthocyanidins	affects cotreatment, decreases expression	1
jinfukang	affects cotreatment, decreases expression	1
Sunitinib	increases expression	1
Catechin	affects cotreatment, decreases expression	1
Cisplatin	affects cotreatment, decreases expression	1
Malathion	decreases expression	1
Tobacco Smoke Pollution	affects expression	1

Clinical trials (associated diseases)

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