CLDN23

Summary

CLDN23 (claudin 23, HGNC:17591) is a protein-coding gene on chromosome 8p23.1, encoding Claudin-23 (Q96B33). 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 expressed in germinal center B-cells, placenta and stomach as well as in colon tumor. This gene is down-regulated in intestinal type gastric cancer.

Source: NCBI Gene 137075 — RefSeq curated summary.

At a glance

• GWAS associations: 37
• Clinical variants (ClinVar): 86 total — 2 pathogenic, 1 likely-pathogenic
• MANE Select transcript: NM_194284

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17591
Approved symbol	CLDN23
Name	claudin 23
Location	8p23.1
Locus type	gene with protein product
Status	Approved
Aliases	CLDNL
Ensembl gene	ENSG00000253958
Ensembl biotype	protein_coding
OMIM	609203
Entrez	137075

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000519106

RefSeq mRNA: 1 — MANE Select: NM_194284 NM_194284

CCDS: CCDS55195

Canonical transcript exons

ENST00000519106 — 1 exons

Exon	Start	End
ENSE00002113555	8701937	8704096

Expression profiles

Bgee: expression breadth ubiquitous, 121 present calls, max score 91.61.

FANTOM5 (CAGE): breadth broad, TPM avg 2.3925 / max 91.3627, expressed in 780 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
87274	1.9362	748
87275	0.4563	170

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
mucosa of transverse colon	UBERON:0004991	91.61	gold quality
rectum	UBERON:0001052	82.99	gold quality
duodenum	UBERON:0002114	80.65	gold quality
transverse colon	UBERON:0001157	80.39	gold quality
body of stomach	UBERON:0001161	80.17	gold quality
skin of abdomen	UBERON:0001416	78.50	gold quality
skin of leg	UBERON:0001511	78.42	gold quality
zone of skin	UBERON:0000014	78.22	gold quality
right lobe of liver	UBERON:0001114	78.17	gold quality
stomach	UBERON:0000945	77.84	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	77.66	gold quality
mucosa of stomach	UBERON:0001199	76.35	gold quality
placenta	UBERON:0001987	75.16	gold quality
small intestine Peyer’s patch	UBERON:0003454	75.15	gold quality
small intestine	UBERON:0002108	74.85	gold quality
liver	UBERON:0002107	74.51	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	74.45	gold quality
fundus of stomach	UBERON:0001160	74.18	gold quality
omental fat pad	UBERON:0010414	73.82	gold quality
minor salivary gland	UBERON:0001830	73.71	gold quality
saliva-secreting gland	UBERON:0001044	73.53	gold quality
adipose tissue	UBERON:0001013	73.36	gold quality
subcutaneous adipose tissue	UBERON:0002190	73.00	gold quality
upper lobe of left lung	UBERON:0008952	71.57	gold quality
intestine	UBERON:0000160	71.44	gold quality
right lobe of thyroid gland	UBERON:0001119	71.44	gold quality
left lobe of thyroid gland	UBERON:0001120	71.35	gold quality
adult mammalian kidney	UBERON:0000082	71.24	gold quality
thoracic mammary gland	UBERON:0005200	71.03	gold quality
islet of Langerhans	UBERON:0000006	70.91	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.36

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): E2F1, SOX8

miRNA regulators (miRDB)

43 targeting CLDN23, 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-5692A	100.00	74.40	6850
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-4282	99.99	75.36	6408
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-590-3P	99.96	74.34	6478
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-218-5P	99.93	72.22	2103
HSA-MIR-1305	99.91	71.43	3443
HSA-MIR-4517	99.76	69.19	1867
HSA-MIR-6745	99.74	65.33	1321
HSA-MIR-4666B	99.64	68.69	1282
HSA-MIR-587	99.64	70.86	2611
HSA-MIR-190A-5P	99.54	71.45	933
HSA-MIR-190B-5P	99.54	71.40	925
HSA-MIR-106A-3P	99.53	67.58	995
HSA-MIR-363-5P	99.46	64.51	1015
HSA-MIR-6878-3P	99.24	64.23	920
HSA-MIR-6744-3P	99.22	64.41	972
HSA-MIR-4291	99.20	68.88	2969
HSA-MIR-4279	99.19	66.70	2437
HSA-MIR-6809-5P	99.13	68.45	1223
HSA-MIR-6815-3P	99.13	68.98	1530
HSA-MIR-548AS-3P	99.12	69.12	2294
HSA-MIR-4757-5P	99.12	64.51	981
HSA-MIR-3619-5P	99.00	68.87	2308
HSA-MIR-4424	98.91	70.33	1145
HSA-MIR-491-3P	98.88	68.86	1224

Literature-anchored findings (GeneRIF, showing 7)

• Human CLDN23, showing 79.5% total-amino-acid identity with mouse Cldn23, is a four-transmembrane protein with WWCC motif, defined by W-X(17-22)-W-X(2)-C-X(8-10)-C. (PMID:12736707)
• characterization of CLDN23 gene, a candidate tumor suppressor gene implicated in intestinal-type gastric cancer (PMID:12736707)
• Down-regulation of CLDN23 is associated with colorectal cancer. (PMID:24222123)
• The present study demonstrated an epigenetic link between the activity of the EZH2 methyltransferase at the CLDN23 locus and the expression of CLDN23 in CRC tissue. (PMID:25695204)
• The expression of claudin-11, -23 was remarkably downregulated in gastric cancer. (PMID:28350854)
• claudin-23 facilitates the migration ability of colorectal cancer cells and may participate in the metastasis of colorectal cancer (PMID:30014629)
• Claudin-23 reshapes epithelial tight junction architecture to regulate barrier function. (PMID:37798277)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	cldn23.1	ENSDARG00000028096
danio_rerio	cldn23.2	ENSDARG00000103703
mus_musculus	Cldn23	ENSMUSG00000055976
rattus_norvegicus	Cldn23	ENSRNOG00000011424

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), CLDN25 (ENSG00000228607), CLDN34 (ENSG00000234469)

Protein

Protein identifiers

Claudin-23 — Q96B33 (reviewed: Q96B33)

All UniProt accessions (1): Q96B33

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.

Tissue specificity. Expressed in germinal center B-cells, placenta, stomach as well as in colon tumor.

Similarity. Belongs to the claudin family.

RefSeq proteins (1): NP_919260* (*=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 (13 total): topological domain 5, transmembrane region 4, chain 1, region of interest 1, compositionally biased region 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96B33-F1	76.64	0.40

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-420029	Tight junction interactions

MSigDB gene sets: 92 (showing top): GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, KEGG_TIGHT_JUNCTION, GOBP_CELL_CELL_ADHESION, SENGUPTA_NASOPHARYNGEAL_CARCINOMA_DN, SCHAEFFER_PROSTATE_DEVELOPMENT_48HR_UP, SABATES_COLORECTAL_ADENOMA_DN, FREAC7_01, GOCC_CELL_CELL_JUNCTION, KEGG_CELL_ADHESION_MOLECULES_CAMS, GOCC_ANCHORING_JUNCTION, REACTOME_TIGHT_JUNCTION_INTERACTIONS, DODD_NASOPHARYNGEAL_CARCINOMA_DN, MMEF2_Q6, GOMF_STRUCTURAL_MOLECULE_ACTIVITY, REACTOME_CELL_JUNCTION_ORGANIZATION

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

566 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CLDN23	MFHAS1	Q9Y4C4	970
CLDN23	PPP1R3B	Q86XI6	891
CLDN23	CLDN16	Q9Y5I7	630
CLDN23	CLDN22	Q8N7P3	559
CLDN23	CLDN11	O75508	539
CLDN23	CLDN12	P56749	511
CLDN23	CLDN4	O14493	492
CLDN23	CLDN10	P78369	491
CLDN23	CDH15	P55291	490
CLDN23	CLDN20	P56880	484
CLDN23	FAM90A7	A6NKC0	477
CLDN23	CLDN8	P56748	452
CLDN23	SVOPL	Q8N434	447
CLDN23	ANO10	Q9NW15	435
CLDN23	CADPS2	Q86UW7	422

IntAct

4 interactions, top by confidence:

A	B	Type	Score
CLDN23	SUSD3	psi-mi:“MI:0915”(physical association)	0.560
CLDN23	SUSD3	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (4): CLDN23 (Two-hybrid), CLDN23 (Positive Genetic), CLDN23 (Proximity Label-MS), CLDN23 (Affinity Capture-RNA)

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

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	1
Uncertain significance	79
Likely benign	4
Benign	0

Top pathogenic / likely-pathogenic (3)

Variant ID	HGVS	Classification
154448	GRCh38/hg38 8p23.1(chr8:8273108-9687019)x1	Pathogenic
60347	GRCh38/hg38 8p23.1(chr8:8336212-9953226)x1	Pathogenic
563525	GRCh37/hg19 8p23.1(chr8:6999219-8881836)x3	Likely pathogenic

SpliceAI

24 predictions. Top by Δscore:

Variant	Effect	Δscore
8:8703888:C:CA	acceptor_gain	0.9700
8:8703889:G:A	acceptor_gain	0.8800
8:8703886:T:TA	acceptor_gain	0.5200
8:8703689:T:A	acceptor_gain	0.4500
8:8702119:C:A	donor_gain	0.4200
8:8703877:A:AG	acceptor_gain	0.4100
8:8703882:T:G	acceptor_gain	0.3700
8:8703881:A:AG	acceptor_gain	0.3500
8:8703878:C:G	acceptor_gain	0.3300
8:8701966:TG:T	donor_gain	0.3200
8:8701967:GG:G	donor_gain	0.3200
8:8701968:GG:G	donor_gain	0.3200
8:8701969:GG:G	donor_gain	0.3200
8:8703692:T:A	acceptor_gain	0.3200
8:8702358:G:GT	donor_gain	0.2800
8:8703696:T:G	acceptor_gain	0.2800
8:8703063:A:G	donor_gain	0.2700
8:8703064:G:GG	donor_gain	0.2600
8:8703066:ACTAC:A	donor_gain	0.2500
8:8702121:G:GT	donor_gain	0.2400
8:8701970:G:T	donor_gain	0.2100
8:8703067:C:CG	donor_gain	0.2100
8:8703180:TGG:T	donor_gain	0.2100
8:8702363:C:T	donor_gain	0.2000

AlphaMissense

1864 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:8702548:G:C	W50C	0.996
8:8702548:G:T	W50C	0.996
8:8702488:G:C	W30C	0.995
8:8702488:G:T	W30C	0.995
8:8702897:A:C	S167R	0.994
8:8702899:C:A	S167R	0.994
8:8702899:C:G	S167R	0.994
8:8702486:T:A	W30R	0.993
8:8702486:T:C	W30R	0.993
8:8702540:G:C	G48R	0.989
8:8702444:T:C	C16R	0.988
8:8702540:G:T	G48C	0.988
8:8702873:A:C	S159R	0.987
8:8702875:C:A	S159R	0.987
8:8702875:C:G	S159R	0.987
8:8702900:T:C	C168R	0.987
8:8702610:A:G	Y71C	0.986
8:8702555:T:A	C53S	0.985
8:8702556:G:C	C53S	0.985
8:8702585:T:A	C63S	0.985
8:8702586:G:C	C63S	0.985
8:8702546:T:A	W50R	0.984
8:8702546:T:C	W50R	0.984
8:8702751:G:A	G118D	0.983
8:8702894:G:C	G166R	0.980
8:8702490:G:C	R31P	0.978
8:8702505:T:G	F36C	0.978
8:8702919:G:A	G174D	0.978
8:8702678:G:A	G94R	0.977
8:8702678:G:C	G94R	0.977

dbSNP variants (sampled 300 via entrez): RS1000039358 (8:8701764 G>A,C), RS1001756684 (8:8701037 T>G), RS1001889892 (8:8700044 G>A), RS1002360727 (8:8700190 G>A,C), RS1003170758 (8:8703472 C>A), RS1003223177 (8:8703723 A>G), RS1003369397 (8:8699954 A>G), RS1004001122 (8:8700346 G>A), RS1004922341 (8:8701395 A>T), RS1004977943 (8:8701644 G>A,C,T), RS1005398837 (8:8701061 G>C), RS1005678106 (8:8703215 G>A,T), RS1005926342 (8:8700462 G>A), RS1006226957 (8:8703401 G>A), RS1006589706 (8:8702860 G>A,T)

Disease associations

OMIM: gene MIM:609203 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

37 associations (top):

Study	Trait	p-value
GCST001762_175	Obesity-related traits	3.000000e-06
GCST002343_5	Response to cytidine analogues (gemcitabine)	2.000000e-06
GCST003151_7	White matter lesion progression	8.000000e-06
GCST004351_13	Bone ultrasound measurement (broadband ultrasound attenuation)	4.000000e-07
GCST004833_4	Cervical cancer	4.000000e-06
GCST005232_114	Neuroticism	2.000000e-29
GCST005232_129	Neuroticism	3.000000e-31
GCST005237_1	Mood instability	5.000000e-09
GCST005238_1	Mood instability	2.000000e-09
GCST006628_9	Systolic blood pressure	5.000000e-09
GCST007325_116	General risk tolerance (MTAG)	2.000000e-11
GCST007325_245	General risk tolerance (MTAG)	2.000000e-09
GCST007565_38	Morning person	6.000000e-14
GCST007565_41	Morning person	4.000000e-14
GCST007576_89	Chronotype	4.000000e-14
GCST007709_169	General factor of neuroticism	9.000000e-10
GCST007709_61	General factor of neuroticism	3.000000e-11
GCST007709_74	General factor of neuroticism	3.000000e-13
GCST007709_80	General factor of neuroticism	1.000000e-12
GCST008971_11	Urate levels	6.000000e-07
GCST008972_194	Urate levels	7.000000e-10
GCST009724_12	Vertical cup-disc ratio (multi-trait analysis)	8.000000e-14
GCST010002_269	Refractive error	1.000000e-24
GCST010142_4	Fish- and plant-related diet	2.000000e-12
GCST010142_6	Fish- and plant-related diet	3.000000e-12
GCST010142_89	Fish- and plant-related diet	4.000000e-16
GCST010142_90	Fish- and plant-related diet	7.000000e-15
GCST010653_66	Thyroid stimulating hormone levels	4.000000e-11
GCST010703_306	Brain morphology (MOSTest)	5.000000e-26
GCST010989_132	Body size at age 10	8.000000e-14

EFO canonical traits (15, from GWAS)

EFO ID	Trait name
EFO:0004626	IGFBP-3 measurement
EFO:0007746	white matter lesion progression measurement
EFO:0004514	bone quantitative ultrasound measurement
EFO:0007660	neuroticism measurement
EFO:0008475	mood instability measurement
EFO:0006335	systolic blood pressure
EFO:0008579	risk-taking behaviour
EFO:0008328	chronotype measurement
EFO:0004531	urate measurement
EFO:0006939	cup-to-disc ratio measurement
EFO:0008111	diet measurement
EFO:0004346	neuroimaging measurement
EFO:0009819	comparative body size at age 10, self-reported
EFO:0007789	BMI-adjusted waist circumference
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

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression, increases methylation	7
trichostatin A	affects cotreatment, increases expression	3
Benzo(a)pyrene	affects methylation, increases expression	3
entinostat	affects cotreatment, increases expression	2
Decitabine	affects expression, decreases expression, decreases reaction	2
Panobinostat	affects cotreatment, increases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
ammonium 2,3,3,3-tetrafluoro-2-(heptafluoropropoxy)-propanoate	affects cotreatment, decreases expression	1
methylmercuric chloride	increases expression	1
sodium arsenate	decreases expression, increases abundance	1
quercitrin	affects expression	1
perfluorooctanoic acid	affects cotreatment, decreases expression	1
ochratoxin A	decreases expression	1
ferrous chloride	decreases expression	1
cupric oxide	decreases expression	1
perfluorooctane sulfonic acid	affects cotreatment, decreases expression	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, increases expression	1
perfluorobutanesulfonic acid	decreases expression, affects cotreatment	1
jinfukang	increases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Acetaminophen	increases expression	1
Arsenic	decreases expression, increases abundance	1
Caffeine	decreases phosphorylation	1
Cisplatin	affects expression	1
Hydrogen Peroxide	affects expression	1
Methotrexate	increases expression	1
Plant Extracts	affects cotreatment, decreases expression	1

Clinical trials (associated diseases)

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