CLDN24

Summary

CLDN24 (claudin 24, HGNC:37200) is a protein-coding gene on chromosome 4q35.1, encoding Claudin-24 (A6NM45). 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. The protein encoded by this gene is 75% identical to the mouse homolog. This gene is upstream of the CLDN22 gene, which overlaps the WWC2 gene on the opposite strand in the genome.

Source: NCBI Gene 100132463 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 29 total
• MANE Select transcript: NM_001185149

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:37200
Approved symbol	CLDN24
Name	claudin 24
Location	4q35.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000185758
Ensembl biotype	protein_coding
Entrez	100132463

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000541814

RefSeq mRNA: 1 — MANE Select: NM_001185149 NM_001185149

CCDS: CCDS54824

Canonical transcript exons

ENST00000541814 — 1 exons

Exon	Start	End
ENSE00002266673	183321764	183322426

Expression profiles

Bgee: expression breadth broad, 61 present calls, max score 96.80.

Top tissues by expression

92 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	96.80	gold quality
granulocyte	CL:0000094	62.79	gold quality
adult mammalian kidney	UBERON:0000082	47.34	gold quality
cortical plate	UBERON:0005343	46.90	gold quality
sural nerve	UBERON:0015488	46.22	gold quality
kidney	UBERON:0002113	44.74	gold quality
apex of heart	UBERON:0002098	43.84	silver quality
liver	UBERON:0002107	41.92	silver quality
bone marrow cell	CL:0002092	41.53	gold quality
metanephros cortex	UBERON:0010533	41.52	gold quality
cortex of kidney	UBERON:0001225	40.39	gold quality
ganglionic eminence	UBERON:0004023	40.20	gold quality
tonsil	UBERON:0002372	39.22	silver quality
minor salivary gland	UBERON:0001830	39.13	gold quality
calcaneal tendon	UBERON:0003701	38.67	silver quality
saliva-secreting gland	UBERON:0001044	38.62	gold quality
hindlimb stylopod muscle	UBERON:0004252	38.59	gold quality
lung	UBERON:0002048	38.44	gold quality
esophagus mucosa	UBERON:0002469	38.31	gold quality
endometrium	UBERON:0001295	37.60	silver quality
upper lobe of left lung	UBERON:0008952	37.50	gold quality
bone marrow	UBERON:0002371	37.44	gold quality
colonic epithelium	UBERON:0000397	37.20	gold quality
ventricular zone	UBERON:0003053	36.48	gold quality
mucosa of stomach	UBERON:0001199	35.68	silver quality
right uterine tube	UBERON:0001302	35.19	gold quality
skeletal muscle tissue	UBERON:0001134	35.04	gold quality
muscle tissue	UBERON:0002385	34.72	gold quality
esophagus	UBERON:0001043	34.41	gold quality
islet of Langerhans	UBERON:0000006	34.06	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.82

Regulation

Is transcription factor: no

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

Protein

Protein identifiers

Claudin-24 — A6NM45 (reviewed: A6NM45)

Alternative names: Claudin-21

All UniProt accessions (1): A6NM45

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_001172078* (*=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 variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-A6NM45-F1	85.40	0.60

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 8 (showing top): chr4q35, GOCC_CELL_CELL_JUNCTION, GOCC_ANCHORING_JUNCTION, GOMF_STRUCTURAL_MOLECULE_ACTIVITY, GOCC_TIGHT_JUNCTION, WP_EPITHELIAL_TO_MESENCHYMAL_TRANSITION_IN_COLORECTAL_CANCER, GOCC_APICAL_JUNCTION_COMPLEX, KEGG_MEDICUS_REFERENCE_TIGHT_JUNCTION_ACTIN_SIGNALING_PATHWAY

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 (4): plasma membrane (GO:0005886), bicellular tight junction (GO:0005923), 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
cellular anatomical structure	1
cell junction	1

Protein interactions and networks

STRING

216 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CLDN24	CLDN34	H7C241	663
CLDN24	CLDN12	P56749	454
CLDN24	NBPF4	Q96M43	376
CLDN24	CLDN20	P56880	374
CLDN24	TJP3	O95049	348
CLDN24	GLIPR1L2	Q4G1C9	348
CLDN24	TJP1	Q07157	320
CLDN24	FSD2	A1L4K1	311
CLDN24	JAM3	Q9BX67	306
CLDN24	TJP2	Q9UDY2	297
CLDN24	CLDN1	O95832	292
CLDN24	N4BP2L1	Q5TBK1	279
CLDN24	OCLN	Q16625	275
CLDN24	CLDN23	Q96B33	274
CLDN24	MARVELD2	Q8N4S9	271

IntAct

0 interactions, top by confidence:

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

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	26
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

230 predictions. Top by Δscore:

Variant	Effect	Δscore
4:183322251:T:TA	donor_gain	0.9500
4:183322189:AGAC:A	donor_gain	0.8600
4:183322179:AAGAT:A	donor_gain	0.8500
4:183322248:A:AC	donor_gain	0.8500
4:183322249:C:CC	donor_gain	0.8500
4:183322308:AAGT:A	donor_gain	0.8500
4:183322296:T:TA	donor_gain	0.8300
4:183322248:ACTT:A	donor_gain	0.8200
4:183322249:CTTC:C	donor_gain	0.8200
4:183322191:AC:A	donor_gain	0.8100
4:183322192:CC:C	donor_gain	0.8100
4:183322252:C:A	donor_gain	0.8100
4:183322176:A:C	donor_gain	0.8000
4:183322183:T:A	donor_gain	0.8000
4:183322226:AAAGT:A	donor_gain	0.8000
4:183322327:T:TA	donor_gain	0.7900
4:183322228:AGT:A	donor_gain	0.7800
4:183322230:T:A	donor_gain	0.7800
4:183321988:CCTGA:C	donor_gain	0.7700
4:183322058:T:TA	donor_gain	0.7600
4:183322180:AGAT:A	donor_gain	0.7600
4:183322062:C:CA	donor_gain	0.7500
4:183321977:AT:A	donor_gain	0.7300
4:183322227:AAGT:A	donor_gain	0.7300
4:183322243:T:TA	donor_gain	0.7300
4:183322250:T:C	donor_gain	0.7200
4:183322244:C:A	donor_gain	0.7100
4:183322266:CAGGT:C	donor_gain	0.7000
4:183321977:ATC:A	donor_gain	0.6900
4:183322061:T:TA	donor_gain	0.6800

AlphaMissense

1412 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:183321983:G:C	F148L	0.994
4:183321983:G:T	F148L	0.994
4:183321985:A:G	F148L	0.994
4:183322328:C:A	W33C	0.990
4:183322328:C:G	W33C	0.990
4:183322274:C:A	W51C	0.982
4:183322274:C:G	W51C	0.982
4:183321919:A:G	W170R	0.978
4:183321919:A:T	W170R	0.978
4:183321947:C:A	W160C	0.978
4:183321947:C:G	W160C	0.978
4:183322289:C:A	W46C	0.978
4:183322289:C:G	W46C	0.978
4:183321939:C:A	G163V	0.976
4:183322282:C:G	G49R	0.975
4:183322282:C:T	G49R	0.975
4:183322330:A:G	W33R	0.974
4:183322330:A:T	W33R	0.974
4:183321984:A:C	F148C	0.971
4:183322020:G:C	P136R	0.970
4:183322038:C:T	G130E	0.969
4:183322369:C:G	G20R	0.969
4:183322369:C:T	G20R	0.969
4:183322236:C:G	C64S	0.968
4:183322237:A:T	C64S	0.968
4:183322368:C:T	G20E	0.968
4:183322325:C:A	K34N	0.965
4:183322325:C:G	K34N	0.965
4:183322276:A:G	W51R	0.964
4:183322276:A:T	W51R	0.964

dbSNP variants (sampled 300 via entrez): RS1000315005 (4:183323896 G>A), RS1000759988 (4:183324351 C>T), RS1004768762 (4:183323564 A>C), RS1006938950 (4:183323000 C>T), RS1007150398 (4:183323271 C>T), RS1008416572 (4:183322562 G>A), RS1008451095 (4:183322160 C>A,T), RS1009059136 (4:183321521 A>G), RS1010321468 (4:183323528 G>A,T), RS1010351213 (4:183323357 C>T), RS1012681422 (4:183322065 A>G), RS1013212102 (4:183322916 C>G,T), RS1015467183 (4:183322567 T>C), RS1018705732 (4:183321522 T>G), RS1018874991 (4:183323572 G>A)

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

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

2 total (human), top 2 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Sunitinib	increases expression	1
Lactic Acid	increases expression	1

Clinical trials (associated diseases)

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