CLDN34

Summary

CLDN34 (claudin 34, HGNC:51259) is a protein-coding gene on chromosome Xp22.2, encoding Claudin-34 (H7C241). Plays a major role in tight junction-specific obliteration of the intercellular space, through calcium-independent cell-adhesion activity.

Predicted to enable structural molecule activity. Predicted to be involved in bicellular tight junction assembly and cell adhesion. Predicted to be active in bicellular tight junction and plasma membrane.

Source: NCBI Gene 100288814 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 28 total
• MANE Select transcript: NM_001195081

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:51259
Approved symbol	CLDN34
Name	claudin 34
Location	Xp22.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000234469
Ensembl biotype	protein_coding
Entrez	100288814

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000445307, ENST00000850986

RefSeq mRNA: 1 — MANE Select: NM_001195081 NM_001195081

CCDS: CCDS75951

Canonical transcript exons

ENST00000445307 — 1 exons

Exon	Start	End
ENSE00004283157	9967358	9968352

Expression profiles

Bgee: expression breadth broad, 42 present calls, max score 50.99.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
left testis	UBERON:0004533	50.99	gold quality
testis	UBERON:0000473	50.85	gold quality
right testis	UBERON:0004534	50.44	gold quality
right lobe of liver	UBERON:0001114	44.64	silver quality
islet of Langerhans	UBERON:0000006	43.93	gold quality
liver	UBERON:0002107	42.85	silver quality
colonic epithelium	UBERON:0000397	42.81	gold quality
lower esophagus mucosa	UBERON:0035834	41.82	silver quality
olfactory segment of nasal mucosa	UBERON:0005386	41.80	gold quality
skin of abdomen	UBERON:0001416	40.57	silver quality
esophagus mucosa	UBERON:0002469	39.84	silver quality
zone of skin	UBERON:0000014	38.57	silver quality
bone marrow cell	CL:0002092	38.32	gold quality
prostate gland	UBERON:0002367	37.64	gold quality
granulocyte	CL:0000094	37.57	gold quality
ganglionic eminence	UBERON:0004023	37.56	silver quality
upper lobe of left lung	UBERON:0008952	37.28	silver quality
urinary bladder	UBERON:0001255	37.11	gold quality
skin of leg	UBERON:0001511	37.09	silver quality
ectocervix	UBERON:0012249	36.57	gold quality
pancreas	UBERON:0001264	36.49	gold quality
ventricular zone	UBERON:0003053	36.48	gold quality
cortical plate	UBERON:0005343	36.47	gold quality
hindlimb stylopod muscle	UBERON:0004252	36.02	gold quality
placenta	UBERON:0001987	35.95	silver quality
kidney	UBERON:0002113	35.77	silver quality
lung	UBERON:0002048	35.74	silver quality
superior frontal gyrus	UBERON:0002661	35.25	silver quality
skeletal muscle tissue	UBERON:0001134	35.16	gold quality
uterine cervix	UBERON:0000002	34.62	silver 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

Cross-species orthologs

20 orthologs

Organism	Symbol	Gene ID
danio_rerio		ENSDARG00000087805
mus_musculus	Cldn34c4	ENSMUSG00000043569
mus_musculus	Cldn34b2	ENSMUSG00000057402
mus_musculus	Cldn34b3	ENSMUSG00000071738
mus_musculus	Cldn34b1	ENSMUSG00000072100
mus_musculus	Cldn34b4	ENSMUSG00000073085
mus_musculus	Cldn34c1	ENSMUSG00000079450
mus_musculus	Cldn34d	ENSMUSG00000079525
mus_musculus	Cldn34a	ENSMUSG00000091863
mus_musculus	Cldn34c2	ENSMUSG00000095474
mus_musculus	Cldn34c6	ENSMUSG00000118415
mus_musculus	Cldn34c3	ENSMUSG00000118430
mus_musculus	Cldn34c5	ENSMUSG00000118483
rattus_norvegicus	Cldn34a	ENSRNOG00000024350
rattus_norvegicus	Cldn34e	ENSRNOG00000026351
rattus_norvegicus	Cldn34b4	ENSRNOG00000029158
rattus_norvegicus	Cldn34c4	ENSRNOG00000031956
rattus_norvegicus	Cldn34d	ENSRNOG00000043402
rattus_norvegicus	Cldn34b	ENSRNOG00000065503
rattus_norvegicus	Cldn34b3	ENSRNOG00000071107

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), CLDN23 (ENSG00000253958)

Protein

Protein identifiers

Claudin-34 — H7C241 (reviewed: H7C241)

All UniProt accessions (1): H7C241

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.

Subunit / interactions. Can form homo- and heteropolymers with other CLDN.

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

Similarity. Belongs to the claudin family.

RefSeq proteins (1): NP_001182010* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR006187	Claudin	Family

UniProt features (10 total): topological domain 5, transmembrane region 4, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-H7C241-F1	86.14	0.60

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, chrXp22, BRUINS_UVC_RESPONSE_VIA_TP53_GROUP_A, LEE_BMP2_TARGETS_UP, GOCC_TIGHT_JUNCTION, BREDEMEYER_RAG_SIGNALING_VIA_ATM_NOT_VIA_NFKB_UP, GLI1_TARGET_GENES, 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

92 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CLDN34	CLDN24	A6NM45	663
CLDN34	CLDN25	C9JDP6	582
CLDN34	CLDN15	P56746	520
CLDN34	CLDN17	P56750	453
CLDN34	CLDN22	Q8N7P3	446
CLDN34	CLDN18	P56856	413
CLDN34	CLDN23	Q96B33	376
CLDN34	CLDN9	O95484	358
CLDN34	CLDN12	P56749	323
CLDN34	CLDN16	Q9Y5I7	321
CLDN34	RGS1	Q08116	304
CLDN34	CLDN8	P56748	304
CLDN34	CLDN6	P56747	302
CLDN34	CLDN11	O75508	296
CLDN34	CLDN5	O00501	294

IntAct

0 interactions, top by confidence:

ESM2 similar proteins: A6NFC5, A6NM45, A8MUP6, B1AQL3, C3VMW3, C9JDP6, D3Z7H4, D3ZK93, H7C241, O75204, O88552, P0DP42, P56750, P57739, Q16617, Q2KIY2, Q2KJ11, Q32KQ5, Q3SZT1, Q3UUA0, Q497B3, Q4V922, Q5CZV0, Q5M962, Q5R9K1, Q6AYL2, Q6GV28, Q6ICI0, Q6UXU4, Q765P1, Q7T392, Q7YQI4, Q7Z7N9, Q8BGP5, Q8BXA6, Q8C6V3, Q8N7P3, Q8NHS1, Q8VHW1, Q8WXS4

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	24
Likely benign	4
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

345 predictions. Top by Δscore:

Variant	Effect	Δscore
X:9967956:A:G	acceptor_gain	0.8100
X:9967667:A:T	donor_gain	0.8000
X:9967579:A:G	donor_gain	0.7400
X:9967665:G:GT	donor_gain	0.7400
X:9967475:A:T	donor_gain	0.7000
X:9967577:C:A	acceptor_gain	0.6900
X:9967585:C:G	donor_gain	0.6900
X:9967955:A:AG	acceptor_gain	0.6700
X:9967877:G:GT	donor_gain	0.6600
X:9967463:ATATG:A	donor_loss	0.6500
X:9967464:TATG:T	donor_loss	0.6500
X:9967465:ATG:A	donor_loss	0.6500
X:9967466:TGGT:T	donor_loss	0.6500
X:9967467:GGTAC:G	donor_loss	0.6500
X:9967468:G:C	donor_loss	0.6500
X:9967469:T:A	donor_loss	0.6500
X:9967666:G:GT	donor_gain	0.6400
X:9967954:C:G	acceptor_gain	0.6300
X:9967468:G:GG	donor_gain	0.6200
X:9967419:G:GT	donor_gain	0.6100
X:9967470:A:C	donor_loss	0.6100
X:9967592:G:GT	donor_gain	0.6100
X:9967666:G:T	donor_gain	0.6100
X:9967958:T:G	acceptor_gain	0.6100
X:9967718:G:GT	donor_gain	0.6000
X:9967680:T:G	donor_gain	0.5900
X:9967619:AT:A	acceptor_gain	0.5800
X:9967656:G:GT	donor_gain	0.5800
X:9967459:GCGAA:G	donor_gain	0.5700
X:9967526:G:GG	donor_gain	0.5700

AlphaMissense

1405 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:9967835:T:C	F160L	0.875
X:9967837:C:A	F160L	0.875
X:9967837:C:G	F160L	0.875
X:9967457:T:A	W34R	0.854
X:9967457:T:C	W34R	0.854
X:9967520:T:C	F55L	0.844
X:9967522:T:A	F55L	0.844
X:9967522:T:G	F55L	0.844
X:9967459:G:C	W34C	0.833
X:9967459:G:T	W34C	0.833
X:9967598:T:C	F81L	0.814
X:9967600:T:A	F81L	0.814
X:9967600:T:G	F81L	0.814
X:9967421:T:A	W22R	0.803
X:9967421:T:C	W22R	0.803
X:9967646:A:C	S97R	0.769
X:9967648:C:A	S97R	0.769
X:9967648:C:G	S97R	0.769
X:9967736:T:C	F127L	0.765
X:9967738:C:A	F127L	0.765
X:9967738:C:G	F127L	0.765
X:9967876:G:C	Q173H	0.764
X:9967876:G:T	Q173H	0.764
X:9967466:T:A	W37R	0.754
X:9967466:T:C	W37R	0.754
X:9967461:G:C	R35P	0.751
X:9967400:T:C	F15L	0.746
X:9967402:C:A	F15L	0.746
X:9967402:C:G	F15L	0.746
X:9967568:T:C	F71L	0.712

dbSNP variants (sampled 300 via entrez): RS1001418516 (X:9968398 A>C), RS1002662249 (X:9965415 C>G), RS1003616920 (X:9967607 T>C,G), RS1004163797 (X:9965379 A>T), RS1004870941 (X:9966948 A>G), RS1005149743 (X:9967409 A>G), RS1005562414 (X:9967302 T>TC), RS1006207881 (X:9968624 A>C), RS1009068533 (X:9965894 G>A), RS1010009787 (X:9968351 C>T), RS1010906361 (X:9966294 C>T), RS1012476641 (X:9967445 G>A), RS1014369076 (X:9965865 A>C,G), RS1015242721 (X:9967413 C>T), RS1015296548 (X:9967065 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

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs5934731	CLDN34		0.00	0

CTD chemical–gene interactions

3 total (human), top 3 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Copper	affects cotreatment, decreases expression	1

Clinical trials (associated diseases)

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