CLDN1

Summary

CLDN1 (claudin 1, HGNC:2032) is a protein-coding gene on chromosome 3q28, encoding Claudin-1 (O95832). Claudins function as major constituents of the tight junction complexes that regulate the permeability of epithelia.

Tight junctions represent one mode of cell-to-cell adhesion in epithelial or endothelial cell sheets, forming continuous seals around cells and serving as a physical barrier to prevent solutes and water from passing freely through the paracellular space. These junctions are comprised of sets of continuous networking strands in the outwardly facing cytoplasmic leaflet, with complementary grooves in the inwardly facing extracytoplasmic leaflet. The protein encoded by this gene, a member of the claudin family, is an integral membrane protein and a component of tight junction strands. Loss of function mutations result in neonatal ichthyosis-sclerosing cholangitis syndrome.

Source: NCBI Gene 9076 — RefSeq curated summary.

At a glance

• Gene–disease (curated): neonatal ichthyosis-sclerosing cholangitis syndrome (Definitive, GenCC)
• GWAS associations: 2
• Clinical variants (ClinVar): 117 total — 5 pathogenic, 2 likely-pathogenic
• Phenotypes (HPO): 32
• MANE Select transcript: NM_021101

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2032
Approved symbol	CLDN1
Name	claudin 1
Location	3q28
Locus type	gene with protein product
Status	Approved
Aliases	SEMP1, ILVASC
Ensembl gene	ENSG00000163347
Ensembl biotype	protein_coding
OMIM	603718
Entrez	9076

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 1 protein_coding, 1 retained_intron

ENST00000295522, ENST00000490800

RefSeq mRNA: 1 — MANE Select: NM_021101 NM_021101

CCDS: CCDS3295

Canonical transcript exons

ENST00000295522 — 4 exons

Exon	Start	End
ENSE00001073597	190305707	190308439
ENSE00001073602	190312872	190313036
ENSE00001073604	190321984	190322446
ENSE00003492566	190310169	190310253

Expression profiles

Bgee: expression breadth ubiquitous, 221 present calls, max score 99.51.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 27.1564 / max 1453.5627, expressed in 1053 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
46085	26.9592	1053
46084	0.1032	47
46086	0.0738	22
46087	0.0201	5

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
upper leg skin	UBERON:0004262	99.51	gold quality
germinal epithelium of ovary	UBERON:0001304	99.43	gold quality
skin of hip	UBERON:0001554	99.43	gold quality
skin of abdomen	UBERON:0001416	99.08	gold quality
skin of leg	UBERON:0001511	98.63	gold quality
zone of skin	UBERON:0000014	98.30	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	98.01	gold quality
epithelium of nasopharynx	UBERON:0001951	97.35	gold quality
left uterine tube	UBERON:0001303	97.23	gold quality
right lobe of liver	UBERON:0001114	97.08	gold quality
nipple	UBERON:0002030	96.77	gold quality
gingival epithelium	UBERON:0001949	96.66	gold quality
gingiva	UBERON:0001828	96.53	gold quality
liver	UBERON:0002107	96.46	gold quality
mammalian vulva	UBERON:0000997	96.17	gold quality
parietal pleura	UBERON:0002400	96.11	gold quality
seminal vesicle	UBERON:0000998	95.72	gold quality
islet of Langerhans	UBERON:0000006	95.57	gold quality
nerve	UBERON:0001021	95.34	gold quality
tibial nerve	UBERON:0001323	95.34	gold quality
right adrenal gland cortex	UBERON:0035827	94.62	gold quality
oral cavity	UBERON:0000167	94.58	gold quality
right adrenal gland	UBERON:0001233	94.42	gold quality
bronchial epithelial cell	CL:0002328	94.12	gold quality
nasal cavity mucosa	UBERON:0001826	94.05	gold quality
lower esophagus mucosa	UBERON:0035834	93.97	gold quality
palpebral conjunctiva	UBERON:0001812	93.85	gold quality
upper arm skin	UBERON:0004263	93.63	gold quality
left adrenal gland	UBERON:0001234	93.38	gold quality
esophagus squamous epithelium	UBERON:0006920	93.36	gold quality

Single-cell (SCXA)

Detected in 13 experiment(s), a significant marker in 13.

Experiment	Marker?	Max mean expression
E-GEOD-81547	yes	4369.33
E-MTAB-8142	yes	3557.31
E-GEOD-130473	yes	2340.29
E-HCAD-38	yes	1443.41
E-MTAB-5061	yes	1082.73
E-MTAB-10885	yes	638.24
E-GEOD-83139	yes	464.53
E-GEOD-124472	yes	372.79
E-GEOD-75688	yes	343.94
E-MTAB-10553	yes	23.97
E-CURD-119	yes	16.50
E-ENAD-27	yes	6.50
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ATF3, CDX1, CDX2, CLDN5, CTNNB1, GATA4, HOXB7, IL1B, KDM5B, MECOM, RAMP2, RUNX1, SMAD4, SNAI1, SNAI2, SP1, SP3, TCF7L2, TFAP4, TP63, TTF1

miRNA regulators (miRDB)

135 targeting CLDN1, 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-190A-3P	100.00	80.35	5520
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-MIR-98-3P	100.00	74.08	3907
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-6856-5P	100.00	65.47	1298
HSA-MIR-6758-5P	100.00	66.21	1470
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-10401-5P	99.99	65.79	948
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-8068	99.98	73.85	2376
HSA-LET-7F-5P	99.98	72.56	1784
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-4789-5P	99.98	70.76	2721
HSA-LET-7A-5P	99.98	72.29	1790
HSA-LET-7B-5P	99.98	72.31	1790

Literature-anchored findings (GeneRIF, showing 40)

• Claudin-based tight junctions occur in the epidermis and they are crucial for the barrier function of the mammalian skin. (PMID:11889141)
• Involvement in the beta-catenin/Tcf signaling pathway and its frequent upregulation in human colorectal cancers (PMID:11939410)
• CLDN1, clustered with CLDN16 at human chromosome 3q28, is a four-transmembrane protein with WWCC motif, defined by W-X(17-22)-W-X(2)-C-X(8-10)-C. (PMID:12736707)
• Airway tight junctions are regulated by claudin interactions that confer the selectivity of the junction. (PMID:12909588)
• Showed that residues located C-terminal to the last transmembrane domain of claudin 1 are required for the proper targeting to apical TJ.s. (PMID:15260435)
• Lack of claudin-1 in neonatal sclerosing cholangitis syndrome may lead to increased paracellular permeability between epithelial cells and bile duct disease. (PMID:15521008)
• Arrangement of expression and distribution of claudin-1 is closely related to cell dissociation status in pancreatic cancer cells through MEK2 activation (PMID:15547692)
• significant loss of CLDN1 protein in breast cancer cells suggests that CLDN1 may play a role in invasion and metastasis (PMID:15743508)
• This review summarizes the role of claudins in cancer and points out that claudin 1 (CLDN1) may support tumor suppressive functions in tissues such as the brain, where dramatic loss of CLDN1 expression has been demonstrated in glioblastoma multiforme. (PMID:15820559)
• Genetic manipulations of claudin-1 expression in colon cancer cell lines induced changes in cellular phenotype, with structural and functional changes in markers of epithelial-mesenchymal transition. (PMID:15965503)
• Claudin-1 was downregulated by Snail and Slug in MDCK and human breast neoplasm cells. (PMID:16232121)
• The expression of claudin-1, -3 and -4 was upregulated 5.7-, 1.5- and 2.4-fold, respectively, in colorectal tumor tissues in comparison to the normal ones. (PMID:16253248)
• Differential expression of genes encoding claudins in colorectal cancer suggests that these tight junction proteins may be associated to and involved in tumorigenesis. (PMID:17047970)
• Claudin1 gene shows increased expression in papillary thyroid cancer. (PMID:17091452)
• Expression of cytoplasmic claudin-1 was decreased in acute acalculous cholecystitis. (PMID:17283368)
• CLDN1 is required for HCV infection of human hepatoma cell lines and is the first factor to confer susceptibility to HCV when ectopically expressed in non-hepatic cells (PMID:17325668)
• Tight junction proteins contribute to the permeability barrier in epidermal keratinocytes (PMID:17359339)
• Squamous cell carcinomas and carcinoids showed different CLDN1 expression. (PMID:17418912)
• Claudin-1 immunohistochemistry should be considered for use as a new diagnostic tool for distinguishing malignant from benign lesions of the prostate. (PMID:17440968)
• Squamous cell carcinomas were positive for CLDN-1 and negative for CLDN-5, whereas adenocarcinomas were positive for CLDN-5 and negative for CLDN-1. (PMID:17585317)
• CLDN1 expression correlated with the recurrence status and malignant potential of breast cancer. (PMID:17611630)
• Nine potential tetraspanin CD9 partners, including claudin-1, were identified. (PMID:17644758)
• Cell-cell transmission of hepatitis C virus is dependent on CLDN1 expression. (PMID:17941058)
• The expression of claudin-1 and claudin-2 in cancer tissues was upregulated 40- and 49.2-fold, respectively, at the mRNA level, as compared with that in normal tissues (PMID:17970035)
• CLDN1 is unlikely to play a critical role in migration of Langerhans cells (or their precursors) to the epidermis or their positioning within the epidermis. (PMID:18095941)
• Inhibition of claudin-1 expression may represent a novel mechanism that contributes to RON-mediated invasive activities, leading to increased tumor malignancy (PMID:18204077)
• specific localization pattern of CLDN1 may be crucial in the regulation of hepatitis C virus cellular tropism (PMID:18211898)
• in 5 cases of follicular dendritic cell sarcoma, study found diffuse intense positivity of the tumor cells for Glut-1 in all 5 cases and focal and weak immunoreaction for Claudin-1 in 3 cases (PMID:18227718)
• Here, we confirm the role of claudin-1 in HCV entry. (PMID:18234789)
• fluorescent protein-tagged forms of CD81 and CLDN1 colocalized. (PMID:18337570)
• Claudin-1 expression is correlated with recurrence status and poor prognosis in esophageal cancer. (PMID:18480547)
• claudins 1 and 3 had a significant effect on overall survival in patients with urothelial carcinoma of the upper urinary tract. (PMID:18550469)
• Claudin-1 and claudin-2 expression was elevated in active inflammatory bowel disease (IBD), adenomas, and IBD-associated dysplasia, but not acute self limiting colitis (PMID:18711353)
• Suggest that claudin-1 participates in the transformation of biological behaviors in gastric adenocarcinomas. (PMID:18756604)
• Hepatocyte tight junctions-associated proteins occludin, claudin-1, and Zonula Occludens protein-1 (ZO-1) disappeared from the borders of adjacent cells in hepatoma cells harboring genomic hepatitis c virus replicons. (PMID:18802961)
• For the first time this study proves the presence of Claudin-1, Claudin-3 and Claudin-5 in ECV304 (obtained from ECACC) cell layers and the inducibility of their expression by glioma-conditioned media. (PMID:18817843)
• claudin-1 expression is responsible for TNF-alpha-dependent growth signals and the proliferation of pancreatic cancer cells. (PMID:18949385)
• Mutational study of CLDN1 revealed that its tight junctional distribution plays an important role in mediating hepatitis C virus entry. (PMID:19052094)
• VHL loss-of-function also has striking effects on the expression of the tight junction (TJ) components occludin and claudin 1 in vitro in VHL-defective clear cell renal cell carcinoma (CCRCC) cells and in vivo in VHL-defective sporadic CCRCCs. (PMID:19073886)
• We investigated common genetic variation in CLDN1 in four self-described ethnically distinct U.S. populations to look for genetic variation and signatures of selection and compared CLDN1 with CLDN7, the most similar of the claudin genes. (PMID:19077439)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	cldn1	ENSDARG00000040045
danio_rerio		ENSDARG00000115608
mus_musculus	Cldn1	ENSMUSG00000022512
rattus_norvegicus	Cldn1	ENSRNOG00000001926

Paralogs (22): CLDN11 (ENSG00000013297), CLDN18 (ENSG00000066405), CLDN15 (ENSG00000106404), CLDN16 (ENSG00000113946), CLDN10 (ENSG00000134873), CLDN17 (ENSG00000156282), CLDN8 (ENSG00000156284), CLDN14 (ENSG00000159261), 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), CLDN23 (ENSG00000253958)

Protein

Protein identifiers

Claudin-1 — O95832 (reviewed: O95832)

Alternative names: Senescence-associated epithelial membrane protein

All UniProt accessions (2): A5JSJ9, O95832

UniProt curated annotations — full annotation on UniProt →

Function. Claudins function as major constituents of the tight junction complexes that regulate the permeability of epithelia. While some claudin family members play essential roles in the formation of impermeable barriers, others mediate the permeability to ions and small molecules. Often, several claudin family members are coexpressed and interact with each other, and this determines the overall permeability. CLDN1 is required to prevent the paracellular diffusion of small molecules through tight junctions in the epidermis and is required for the normal barrier function of the skin. Required for normal water homeostasis and to prevent excessive water loss through the skin, probably via an indirect effect on the expression levels of other proteins, since CLDN1 itself seems to be dispensable for water barrier formation in keratinocyte tight junctions. (Microbial infection) Acts as a co-receptor for hepatitis C virus (HCV) in hepatocytes. Associates with CD81 and the CLDN1-CD81 receptor complex is essential for HCV entry into host cell. Acts as a receptor for dengue virus.

Subunit / interactions. Homopolymers interact with CLDN3, but not CLDN2, homopolymers. Can form homo- and heteropolymers with other claudin family members. Directly interacts with TJP1/ZO-1, TJP2/ZO-2 and TJP3/ZO-3. Interacts with MPDZ and PATJ. Interacts with OCLN, CLDN4, CLDN6 and CLDN9. Interacts with CD81. (Microbial infection) Interacts with hepatitis c virus heterodimer E1/E2. (Microbial infection) Interacts with dengue virus small envelope protein M.

Subcellular location. Cell junction. Tight junction. Cell membrane. Basolateral cell membrane.

Tissue specificity. Strongly expressed in liver and kidney. Expressed in heart, brain, spleen, lung and testis.

Disease relevance. Ichthyosis-sclerosing cholangitis neonatal syndrome (NISCH) [MIM:607626] A rare autosomal recessive complex ichthyosis syndrome characterized by scalp hypotrichosis, scarring alopecia, mild diffuse ichthyosis, sclerosing cholangitis and leukocyte vacuolization. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the claudin family.

RefSeq proteins (1): NP_066924* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003548	Claudin1	Family
IPR004031	PMP22/EMP/MP20/Claudin	Family
IPR006187	Claudin	Family
IPR017974	Claudin_CS	Conserved_site

Pfam: PF00822

UniProt features (17 total): topological domain 5, transmembrane region 4, region of interest 2, mutagenesis site 2, sequence conflict 2, chain 1, disulfide bond 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O95832-F1	84.57	0.54

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Disulfide bonds (1): 54–64

Mutagenesis-validated functional residues (2):

Position	Phenotype
32	loss of hcv receptor activity. significant loss of interaction with cd81. reduced interaction with ocln.
48	loss of hcv receptor activity. significant loss of interaction with cd81. reduced interaction with ocln. according to pu

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-420029	Tight junction interactions
R-HSA-9918485	Dengue Virus Attachment and Entry

MSigDB gene sets: 413 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_UP, GSE45365_NK_CELL_VS_CD8A_DC_MCMV_INFECTION_DN, GSE37336_LY6C_POS_VS_NEG_NAIVE_CD4_TCELL_UP, GOBP_ENDOTHELIAL_CELL_DEVELOPMENT, TGGTGCT_MIR29A_MIR29B_MIR29C, LEE_SP4_THYMOCYTE, GOBP_RESPONSE_TO_ETHANOL, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, GOBP_HEPATICOBILIARY_SYSTEM_DEVELOPMENT, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_REGULATION_OF_WOUND_HEALING, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, GOBP_RESPONSE_TO_PEPTIDE, GOBP_CELLULAR_RESPONSE_TO_LIPID, GOBP_EPITHELIAL_CELL_DEVELOPMENT

GO Biological Process (27): cell adhesion (GO:0007155), establishment of blood-nerve barrier (GO:0008065), response to toxic substance (GO:0009636), calcium-independent cell-cell adhesion (GO:0016338), positive regulation of cell migration (GO:0030335), response to lipopolysaccharide (GO:0032496), cell junction maintenance (GO:0034331), maintenance of blood-brain barrier (GO:0035633), cell-cell junction organization (GO:0045216), response to ethanol (GO:0045471), protein complex oligomerization (GO:0051259), positive regulation of epithelial cell proliferation involved in wound healing (GO:0060054), establishment of skin barrier (GO:0061436), xenobiotic transport across blood-nerve barrier (GO:0061772), response to interleukin-18 (GO:0070673), bicellular tight junction assembly (GO:0070830), cellular response to lead ion (GO:0071284), cellular response to type II interferon (GO:0071346), cellular response to tumor necrosis factor (GO:0071356), response to dexamethasone (GO:0071548), cellular response to transforming growth factor beta stimulus (GO:0071560), positive regulation of wound healing (GO:0090303), establishment of endothelial intestinal barrier (GO:0090557), liver regeneration (GO:0097421), positive regulation of bicellular tight junction assembly (GO:1903348), cellular response to butyrate (GO:1903545), symbiont entry into host cell (GO:0046718)

GO Molecular Function (4): virus receptor activity (GO:0001618), structural molecule activity (GO:0005198), identical protein binding (GO:0042802), protein binding (GO:0005515)

GO Cellular Component (11): plasma membrane (GO:0005886), bicellular tight junction (GO:0005923), membrane (GO:0016020), basolateral plasma membrane (GO:0016323), apical plasma membrane (GO:0016324), lateral plasma membrane (GO:0016328), protein-containing complex (GO:0032991), tight junction (GO:0070160), cell-cell junction (GO:0005911), cell junction (GO:0030054), anchoring junction (GO:0070161)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Cell-cell junction organization	1
Dengue Virus Infection	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
cell junction organization	2
cellular response to cytokine stimulus	2
plasma membrane region	2
cellular process	1
endothelial cell development	1
peripheral nervous system development	1
response to chemical	1
cell-cell adhesion	1
cell migration	1
regulation of cell migration	1
positive regulation of cell motility	1
response to molecule of bacterial origin	1
response to lipid	1
response to oxygen-containing compound	1
cellular component maintenance	1
tissue homeostasis	1
response to alcohol	1
protein-containing complex assembly	1
wound healing	1
positive regulation of epithelial cell proliferation	1
skin epidermis development	1
xenobiotic transport	1
response to cytokine	1
apical junction assembly	1
tight junction assembly	1
response to lead ion	1
cellular response to metal ion	1
response to type II interferon	1
response to tumor necrosis factor	1
response to glucocorticoid	1
response to ketone	1
symbiont entry into host cell	1
exogenous protein binding	1
molecular_function	1
protein binding	1
binding	1
membrane	1
cell periphery	1
apical junction complex	1

Protein interactions and networks

STRING

2532 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CLDN1	CD81	P18582	999
CLDN1	TJP1	Q07157	999
CLDN1	OCLN	Q16625	999
CLDN1	TJP2	Q9UDY2	999
CLDN1	F11R	Q9Y624	991
CLDN1	TJP3	O95049	988
CLDN1	PATJ	Q8NI35	951
CLDN1	SCARB1	Q8WTV0	934
CLDN1	CLDN12	P56749	922
CLDN1	MARVELD2	Q8N4S9	887
CLDN1	CDH1	P12830	864
CLDN1	EFNB1	P98172	852
CLDN1	CLDN4	O14493	838
CLDN1	TACSTD2	P09758	822
CLDN1	CD9	P21926	812

IntAct

147 interactions, top by confidence:

A	B	Type	Score
PATJ	CLDN1	psi-mi:“MI:0407”(direct interaction)	0.610
CLDN1	PATJ	psi-mi:“MI:0407”(direct interaction)	0.610
PATJ	CLDN1	psi-mi:“MI:0915”(physical association)	0.610
TACSTD2	CLDN7	psi-mi:“MI:0914”(association)	0.570
CLDN1	MS4A3	psi-mi:“MI:0915”(physical association)	0.560
CLDN1	CD69	psi-mi:“MI:0915”(physical association)	0.560
CLDN1	TMEM9	psi-mi:“MI:0915”(physical association)	0.560
CLDN1	TMEM179B	psi-mi:“MI:0915”(physical association)	0.560
CLDN1	CD79A	psi-mi:“MI:0915”(physical association)	0.560
CLDN1	FNDC9	psi-mi:“MI:0915”(physical association)	0.560
CLDN1	PDZD2	psi-mi:“MI:0407”(direct interaction)	0.440
CLDN1	APBA1	psi-mi:“MI:0407”(direct interaction)	0.440
CLDN1	PDZK1	psi-mi:“MI:0407”(direct interaction)	0.440
CLDN1	LNX2	psi-mi:“MI:0407”(direct interaction)	0.440
CLDN1	NOS1	psi-mi:“MI:0407”(direct interaction)	0.440
CLDN1	RADIL	psi-mi:“MI:0407”(direct interaction)	0.440
CLDN1	HTRA3	psi-mi:“MI:0407”(direct interaction)	0.440
CLDN1	HTRA1	psi-mi:“MI:0407”(direct interaction)	0.440
CLDN1	APBA3	psi-mi:“MI:0407”(direct interaction)	0.440
CLDN1	PICK1	psi-mi:“MI:0407”(direct interaction)	0.440
CLDN1	HTRA4	psi-mi:“MI:0407”(direct interaction)	0.440
CLDN1	MPP2	psi-mi:“MI:0407”(direct interaction)	0.440
CLDN1	DLG3	psi-mi:“MI:0407”(direct interaction)	0.440
CLDN1	TIAM2	psi-mi:“MI:0407”(direct interaction)	0.440

BioGRID (30): CLDN1 (Proximity Label-MS), CLDN1 (Proximity Label-MS), CLDN3 (Affinity Capture-Western), CLDN1 (Affinity Capture-Western), CLDN1 (Two-hybrid), CLDN1 (Two-hybrid), CLDN1 (Two-hybrid), CLDN1 (Two-hybrid), FNDC9 (Two-hybrid), TMEM179B (Two-hybrid), CLDN1 (Affinity Capture-MS), INADL (Reconstituted Complex), CLDN1 (Proximity Label-MS), CLDN1 (Proximity Label-MS), CLDN1 (Proximity Label-MS)

ESM2 similar proteins: A0A8C0N7E5, C3VMW3, D3ZQJ0, O00501, O14493, O15551, O19005, O35054, O35912, O54942, O88551, O95471, O95484, O95832, P56745, P56746, P56747, P56748, P56750, P78369, Q2HJ22, Q2KIY2, Q3B7N4, Q5E9L0, Q5QT56, Q5R8E5, Q63400, Q6BBL6, Q6DHB5, Q6DHP1, Q6L708, Q765N9, Q8BXA6, Q8N6F1, Q95KM5, Q9D1D1, Q9ET38, Q9JKD6, Q9QYW5, Q9YH90

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 91 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	46.0×	3e-06
Unblocking of NMDA receptors, glutamate binding and activation	5	43.9×	3e-06
Negative regulation of NMDA receptor-mediated neuronal transmission	5	43.9×	3e-06
Assembly and cell surface presentation of NMDA receptors	10	40.9×	3e-12
Dopamine Neurotransmitter Release Cycle	5	40.0×	4e-06
Long-term potentiation	5	38.4×	4e-06
Neurexins and neuroligins	11	34.9×	2e-12
Protein-protein interactions at synapses	7	30.0×	2e-07

GO biological processes:

GO term	Partners	Fold	FDR
establishment or maintenance of epithelial cell apical/basal polarity	11	75.2×	5e-16
protein localization to synapse	6	54.1×	2e-07
receptor clustering	7	51.4×	1e-08
regulation of postsynaptic membrane neurotransmitter receptor levels	6	35.0×	2e-06
bicellular tight junction assembly	5	19.4×	3e-04
protein-containing complex assembly	8	10.7×	6e-05
cell-cell adhesion	8	9.6×	1e-04
regulation of small GTPase mediated signal transduction	5	8.5×	7e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	5
Likely pathogenic	2
Uncertain significance	57
Likely benign	25
Benign	16

Top pathogenic / likely-pathogenic (7)

Variant ID	HGVS	Classification
1322095	NM_021101.5(CLDN1):c.141C>A (p.Tyr47Ter)	Pathogenic
3247037	NC_000003.11:g.(?190026066)(190127825_?)del	Pathogenic
3600269	NM_021101.5(CLDN1):c.89G>A (p.Trp30Ter)	Pathogenic
6089	NM_021101.5(CLDN1):c.358del (p.Val120fs)	Pathogenic
625822	GRCh37/hg19 3q28(chr3:190039387-190040504)	Pathogenic
3062251	NM_021101.5(CLDN1):c.19C>T (p.Gln7Ter)	Likely pathogenic
3779532	NM_021101.5(CLDN1):c.453_460dup (p.Pro154delinsLeuTer)	Likely pathogenic

SpliceAI

491 predictions. Top by Δscore:

Variant	Effect	Δscore
3:190310163:CGTTA:C	donor_loss	1.0000
3:190310164:GTTA:G	donor_loss	1.0000
3:190310165:TTAC:T	donor_loss	1.0000
3:190310166:TACC:T	donor_loss	1.0000
3:190310168:C:CA	donor_loss	1.0000
3:190312868:TTAC:T	donor_loss	1.0000
3:190312869:TACCT:T	donor_loss	1.0000
3:190312870:ACCTG:A	donor_loss	1.0000
3:190312871:CC:C	donor_loss	1.0000
3:190312908:T:TA	donor_gain	1.0000
3:190312914:T:C	donor_gain	1.0000
3:190313032:TGTGC:T	acceptor_gain	1.0000
3:190313034:TGC:T	acceptor_gain	1.0000
3:190313037:C:CC	acceptor_gain	1.0000
3:190313042:A:T	acceptor_gain	1.0000
3:190321982:A:AC	donor_gain	1.0000
3:190321983:C:CC	donor_gain	1.0000
3:190321983:CTG:C	donor_gain	1.0000
3:190321983:CTGCT:C	donor_gain	1.0000
3:190310249:CAGAC:C	acceptor_gain	0.9900
3:190312917:TCTGC:T	donor_gain	0.9900
3:190313033:GTGC:G	acceptor_gain	0.9900
3:190313035:GC:G	acceptor_gain	0.9900
3:190313036:CC:C	acceptor_gain	0.9900
3:190313041:C:CT	acceptor_gain	0.9900
3:190322013:TTGC:T	donor_gain	0.9900
3:190309489:T:TA	donor_gain	0.9800
3:190310254:C:CC	acceptor_gain	0.9800
3:190321982:ACTG:A	donor_gain	0.9800
3:190321983:CT:C	donor_gain	0.9800

AlphaMissense

1366 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:190310198:G:C	F148L	0.998
3:190310198:G:T	F148L	0.998
3:190310200:A:G	F148L	0.998
3:190308408:A:G	W169R	0.997
3:190308408:A:T	W169R	0.997
3:190322016:C:G	C64S	0.997
3:190322017:A:T	C64S	0.997
3:190322056:A:G	W51R	0.997
3:190322056:A:T	W51R	0.997
3:190322062:C:G	G49R	0.997
3:190322062:C:T	G49R	0.997
3:190322117:C:A	W30C	0.997
3:190322117:C:G	W30C	0.997
3:190322119:A:G	W30R	0.997
3:190322119:A:T	W30R	0.997
3:190322054:C:A	W51C	0.996
3:190322054:C:G	W51C	0.996
3:190322135:G:C	S24R	0.996
3:190322135:G:T	S24R	0.996
3:190322137:T:G	S24R	0.996
3:190308428:C:A	G162V	0.995
3:190322046:C:G	C54S	0.995
3:190322047:A:T	C54S	0.995
3:190322061:C:T	G49E	0.995
3:190322062:C:A	G49W	0.995
3:190322158:C:G	G17R	0.995
3:190322158:C:T	G17R	0.995
3:190322046:C:T	C54Y	0.994
3:190322157:C:T	G17E	0.994
3:190322179:C:G	G10R	0.994

dbSNP variants (sampled 300 via entrez): RS1000200686 (3:190309368 C>A), RS1000250529 (3:190316036 C>A,G), RS1000481420 (3:190307538 C>T), RS1000567677 (3:190307958 A>G), RS1000583110 (3:190314665 A>C), RS1000635933 (3:190309716 C>A,T), RS1000772729 (3:190314402 T>A), RS1000800997 (3:190319470 C>T), RS1000853452 (3:190319215 A>G), RS1000935262 (3:190307681 G>A,C), RS1001481709 (3:190305890 T>G), RS1001493860 (3:190315360 G>C), RS1001809356 (3:190313620 T>C), RS1002066181 (3:190323939 C>A,T), RS1002342396 (3:190319784 C>G,T)

Disease associations

OMIM: gene MIM:603718 | disease phenotypes: MIM:607626

GenCC curated gene-disease

Disease	Classification	Inheritance
neonatal ichthyosis-sclerosing cholangitis syndrome	Definitive	Autosomal recessive

Mondo (1): neonatal ichthyosis-sclerosing cholangitis syndrome (MONDO:0011874)

Orphanet (1): Neonatal ichthyosis-sclerosing cholangitis syndrome (Orphanet:59303)

HPO phenotypes

32 total (30 of 32 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000653	Sparse eyelashes
HP:0000668	Hypodontia
HP:0000677	Oligodontia
HP:0000682	Abnormal dental enamel morphology
HP:0000952	Jaundice
HP:0000956	Acanthosis nigricans
HP:0000958	Dry skin
HP:0000989	Pruritus
HP:0001036	Parakeratosis
HP:0001249	Intellectual disability
HP:0001395	Hepatic fibrosis
HP:0001396	Cholestasis
HP:0001399	Hepatic failure
HP:0001408	Bile duct proliferation
HP:0001409	Portal hypertension
HP:0001596	Alopecia
HP:0001744	Splenomegaly
HP:0002209	Sparse scalp hair
HP:0002231	Sparse body hair
HP:0002240	Hepatomegaly
HP:0003623	Neonatal onset
HP:0004552	Scarring alopecia of scalp
HP:0005248	Intrahepatic biliary atresia
HP:0006297	Enamel hypoplasia
HP:0008064	Ichthyosis
HP:0008070	Sparse hair
HP:0025092	Epidermal acanthosis
HP:0030991	Sclerosing cholangitis
HP:0040162	Orthokeratosis

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST000883_9	Response to antipsychotic treatment in schizophrenia (working memory)	2.000000e-06
GCST009462_26	Optic disc size	3.000000e-08

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004335	short-term memory

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C564365	Ichthyosis, Leukocyte Vacuoles, Alopecia, And Sclerosing Cholangitis (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Particulate Matter	affects cotreatment, decreases expression, decreases reaction, increases abundance, increases expression	9
sodium arsenite	decreases reaction, increases abundance, increases expression, decreases expression	5
Benzo(a)pyrene	decreases expression, decreases methylation	5
Estradiol	decreases expression, decreases reaction, affects cotreatment, increases expression	5
Valproic Acid	decreases expression, increases expression	5
deoxynivalenol	affects cotreatment, decreases expression, affects localization, increases expression	3
Acetylcysteine	decreases reaction, decreases expression	3
Air Pollutants	increases expression, increases abundance, decreases expression	3
Doxorubicin	increases expression, decreases abundance, increases reaction, decreases expression	3
Lipopolysaccharides	affects expression, affects response to substance, affects cotreatment, decreases expression, increases expression	3
Asbestos, Crocidolite	affects expression, increases expression	3
trichostatin A	decreases expression, increases expression	2
diallyl trisulfide	decreases expression, increases expression	2
perfluorooctane sulfonic acid	decreases expression, increases expression	2
Resveratrol	increases expression, affects cotreatment, decreases expression	2
Arsenic Trioxide	decreases reaction, increases expression, decreases expression	2
Acetaminophen	decreases expression, increases expression	2
Arsenic	decreases expression, decreases reaction, increases abundance	2
Copper	affects binding, increases expression	2
Disulfiram	decreases reaction, affects binding, increases expression	2
Hydrogen Peroxide	increases expression, affects expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Quercetin	affects localization, decreases expression	2
Silicon Dioxide	increases expression	2
Tobacco Smoke Pollution	decreases expression	2
Zearalenone	decreases expression, affects cotreatment	2
Cadmium Chloride	decreases expression, increases expression	2
Genistein	increases expression, increases reaction	2
aristolochic acid I	decreases expression	1
bisphenol F	affects cotreatment, decreases expression	1

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B1BX	Abcam A-431 CLDN1 KO	Cancer cell line	Female
CVCL_C3V7	HT-1080/hCLDN-1	Cancer cell line	Male

Clinical trials (associated diseases)

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