CLDND1

Summary

CLDND1 (claudin domain containing 1, HGNC:1322) is a protein-coding gene on chromosome 3q11.2, encoding Claudin domain-containing protein 1 (Q9NY35). Plays a role in negatively regulating the permeability of cells to small molecules.

Located in cell surface.

Source: NCBI Gene 56650 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 46 total
• MANE Select transcript: NM_001040181

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1322
Approved symbol	CLDND1
Name	claudin domain containing 1
Location	3q11.2
Locus type	gene with protein product
Status	Approved
Aliases	Z38
Ensembl gene	ENSG00000080822
Ensembl biotype	protein_coding
OMIM	619677
Entrez	56650

Gene structure

Transcript identifiers

Ensembl transcripts: 48 — 42 protein_coding, 4 retained_intron, 1 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000341181, ENST00000394180, ENST00000394181, ENST00000394185, ENST00000502288, ENST00000502299, ENST00000502980, ENST00000503004, ENST00000503621, ENST00000503799, ENST00000506575, ENST00000506885, ENST00000506927, ENST00000507411, ENST00000507874, ENST00000507944, ENST00000508071, ENST00000508503, ENST00000508659, ENST00000508902, ENST00000510541, ENST00000510545, ENST00000511081, ENST00000511667, ENST00000512147, ENST00000513287, ENST00000513452, ENST00000513873, ENST00000513988, ENST00000514537, ENST00000515620, ENST00000856826, ENST00000856827, ENST00000856828, ENST00000856829, ENST00000856830, ENST00000856831, ENST00000856832, ENST00000856833, ENST00000856834, ENST00000856835, ENST00000931201, ENST00000931202, ENST00000931203, ENST00000967077, ENST00000967078, ENST00000967079, ENST00000967080

RefSeq mRNA: 6 — MANE Select: NM_001040181 NM_001040181, NM_001040182, NM_001040183, NM_001040199, NM_001040200, NM_019895

CCDS: CCDS2930, CCDS43116, CCDS46877

Canonical transcript exons

ENST00000341181 — 5 exons

Exon	Start	End
ENSE00002048463	98522849	98522902
ENSE00002061271	98515483	98516879
ENSE00003584583	98518885	98518995
ENSE00003585189	98521133	98521442
ENSE00003788338	98517052	98517189

Expression profiles

Bgee: expression breadth ubiquitous, 291 present calls, max score 99.86.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 61.9878 / max 4016.2873, expressed in 1810 samples.

FANTOM5 promoters (10 alternative TSS)

Promoter ID	TPM avg	Samples expressed
43362	51.1191	1810
43363	4.3825	1495
43360	2.9686	447
43361	1.2138	207
43355	0.8961	294
43356	0.5322	92
43357	0.3996	143
43359	0.1974	74
43365	0.1410	75
43364	0.1377	59

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
corpus callosum	UBERON:0002336	99.86	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	99.84	gold quality
middle frontal gyrus	UBERON:0002702	99.78	gold quality
spinal cord	UBERON:0002240	99.75	gold quality
inferior vagus X ganglion	UBERON:0005363	99.75	gold quality
globus pallidus	UBERON:0001875	99.67	gold quality
medial globus pallidus	UBERON:0002477	99.67	gold quality
pons	UBERON:0000988	99.66	gold quality
subthalamic nucleus	UBERON:0001906	99.64	gold quality
lateral globus pallidus	UBERON:0002476	99.59	gold quality
substantia nigra pars reticulata	UBERON:0001966	99.57	gold quality
superior vestibular nucleus	UBERON:0007227	99.42	gold quality
substantia nigra pars compacta	UBERON:0001965	99.38	gold quality
medulla oblongata	UBERON:0001896	99.34	gold quality
dorsal plus ventral thalamus	UBERON:0001897	99.21	gold quality
hypothalamus	UBERON:0001898	99.16	gold quality
Ammon’s horn	UBERON:0001954	99.10	gold quality
putamen	UBERON:0001874	99.06	gold quality
ventral tegmental area	UBERON:0002691	99.05	gold quality
lateral nuclear group of thalamus	UBERON:0002736	99.00	gold quality
amygdala	UBERON:0001876	98.99	gold quality
inferior olivary complex	UBERON:0002127	98.88	gold quality
caudate nucleus	UBERON:0001873	98.81	gold quality
temporal lobe	UBERON:0001871	98.68	gold quality
nucleus accumbens	UBERON:0001882	98.59	gold quality
postcentral gyrus	UBERON:0002581	98.48	gold quality
parietal lobe	UBERON:0001872	98.36	gold quality
occipital lobe	UBERON:0002021	98.36	gold quality
prefrontal cortex	UBERON:0000451	98.35	gold quality
telencephalon	UBERON:0001893	98.31	gold quality

Single-cell (SCXA)

Detected in 9 experiment(s), a significant marker in 6.

Experiment	Marker?	Max mean expression
E-GEOD-84465	yes	10524.85
E-HCAD-35	yes	83.60
E-HCAD-25	yes	61.75
E-CURD-122	yes	36.18
E-CURD-112	yes	3.83
E-CURD-97	no	1980.98
E-MTAB-7606	no	486.22
E-CURD-120	no	10.86
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

110 targeting CLDND1, 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-3163	100.00	77.23	8605
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-511-3P	99.99	68.85	1467
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-568	99.98	69.86	2084
HSA-MIR-6888-3P	99.97	65.95	1170
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-6835-3P	99.93	70.49	2904
HSA-MIR-329-3P	99.91	66.56	1234
HSA-MIR-362-3P	99.91	66.38	1267
HSA-MIR-1297	99.91	73.41	3162
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-221-3P	99.86	71.56	1329
HSA-MIR-222-3P	99.86	71.35	1337

Literature-anchored findings (GeneRIF, showing 6)

• A cDNA library consisting of 220 upregulated genes in tumour tissue was established and named as LSCC. Differential expression was confirmed in five of these genes, including IGFBP5, SQLE, RAP2B, CLDN1, and TBL1XR1. (PMID:17316888)
• CLDND1 as a novel survival factor in basal-like breast cancer cell lines (PMID:26083392)
• findings strongly suggest that CLDND1 is a direct RORalpha target (PMID:28130419)
• suggest that the transient decrease of CLDND1 after cerebellar hemorrhage is responsible for low-molecular-weight selective vascular hyperpermeability (PMID:28244141)
• Z38 was overexpressed in clinical patients with RCC and was associated with RCC stage. Knockdown of Z38 in A498 and ACHIN cells inhibited cell proliferation and metastasis (PMID:28849012)
• Transcription of CLDND1 in human brain endothelial cells is regulated by the myeloid zinc finger 1. (PMID:33037622)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	cldnd1b	ENSDARG00000052386
danio_rerio	cldnd1a	ENSDARG00000104439
mus_musculus	Cldnd1	ENSMUSG00000022744
rattus_norvegicus	Cldnd1	ENSRNOG00000001657

Protein

Protein identifiers

Claudin domain-containing protein 1 — Q9NY35 (reviewed: Q9NY35)

Alternative names: Claudin-25, Membrane protein GENX-3745

All UniProt accessions (20): Q9NY35, A0A0R4J2F2, D6R9K1, D6R9S8, D6RA76, D6RAZ7, D6RB31, D6RC11, D6RCE6, D6RCP3, D6RCR8, D6RD48, D6RDI6, D6RDP6, D6RDY1, D6RFX6, D6RHU6, D6RIU2, H0Y8T9, H0YA53

UniProt curated annotations — full annotation on UniProt →

Function. Plays a role in negatively regulating the permeability of cells to small molecules.

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

Tissue specificity. Widely distributed in the adult CNS with highest expression in the corpus callosum, caudate nucleus, cerebral cortex, medulla, putamen, spinal cord, substantia nigra and subthalamic nucleus. Weak expression was detected in the adult heart.

Domain organisation. The C-terminal region is required for localization to tight junctions which occurs in a TJP1/ZO1-independent manner.

Similarity. Belongs to the PMP-22/EMP/MP20 family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q9NY35-1	1	yes
Q9NY35-2	2
Q9NY35-3	3

RefSeq proteins (6): NP_001035271, NP_001035272, NP_001035273, NP_001035289, NP_001035290, NP_063948 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004031	PMP22/EMP/MP20/Claudin	Family
IPR042356	CLDN1	Family

Pfam: PF13903

UniProt features (12 total): transmembrane region 4, splice variant 3, glycosylation site 2, chain 1, sequence variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NY35-F1	86.73	0.56

Functional residue map

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

Glycosylation sites (2): 42, 72

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 227 (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, GCM_MAP4K4, GGTGTGT_MIR329, ASTON_MAJOR_DEPRESSIVE_DISORDER_DN, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GOCC_CELL_SURFACE, RACCACAR_AML_Q6, TGACCTY_ERR1_Q2, GTGCCTT_MIR506, SCHAEFFER_PROSTATE_DEVELOPMENT_6HR_DN, SCHAEFFER_PROSTATE_DEVELOPMENT_AND_CANCER_BOX1_DN, NKX22_01, GOCC_APICAL_PLASMA_MEMBRANE

GO Biological Process (0):

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (6): bicellular tight junction (GO:0005923), cell surface (GO:0009986), apical plasma membrane (GO:0016324), plasma membrane (GO:0005886), membrane (GO:0016020), anchoring junction (GO:0070161)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
binding	1
apical junction complex	1
tight junction	1
apical part of cell	1
plasma membrane region	1
membrane	1
cell periphery	1
cell junction	1

Protein interactions and networks

STRING

386 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CLDND1	GPR15	P49685	574
CLDND1	LRRN3	Q9H3W5	507
CLDND1	FXYD1	O00168	483
CLDND1	FLOT2	Q14254	474
CLDND1	LRRC8A	Q8IWT6	449
CLDND1	CFAP44	Q96MT7	445
CLDND1	FYN	P06241	438
CLDND1	OCEL1	Q9H607	429
CLDND1	PIF1	Q9H611	418
CLDND1	LRIT2	A6NDA9	409
CLDND1	LRIT1	Q9P2V4	399
CLDND1	CLDN25	C9JDP6	342
CLDND1	CDH20	Q9HBT6	335
CLDND1	CLDN12	P56749	331
CLDND1	TATDN1	Q6P1N9	321
CLDND1	ACKR5	O15218	321

IntAct

43 interactions, top by confidence:

A	B	Type	Score
ENTREP1	WWP2	psi-mi:“MI:0914”(association)	0.850
GOLGA7	ZDHHC5	psi-mi:“MI:0914”(association)	0.710
STX7	SNAP23	psi-mi:“MI:0914”(association)	0.640
GYPA	TCAF2	psi-mi:“MI:0914”(association)	0.640
CLDND1	ZDHHC4	psi-mi:“MI:0915”(physical association)	0.560
CXCR1	CLDND1	psi-mi:“MI:0915”(physical association)	0.560
GPR61	CLDND1	psi-mi:“MI:0915”(physical association)	0.560
ZDHHC4	CLDND1	psi-mi:“MI:0915”(physical association)	0.560
HAVCR2	TCAF2	psi-mi:“MI:0914”(association)	0.530
FAM241A	NRP1	psi-mi:“MI:0914”(association)	0.530
SLC44A5	NME2P1	psi-mi:“MI:0914”(association)	0.530
CD93	RARS1	psi-mi:“MI:0914”(association)	0.530
ANKRD22	ESYT2	psi-mi:“MI:0914”(association)	0.530
LPAR1	TMEM223	psi-mi:“MI:0914”(association)	0.530
CLDND1	MTNR1B	psi-mi:“MI:0915”(physical association)	0.370
CLDND1	DRD2	psi-mi:“MI:0915”(physical association)	0.370
	NPC1	psi-mi:“MI:0914”(association)	0.350
RUSF1	TMEM120B	psi-mi:“MI:0914”(association)	0.350
STX7	TYW5	psi-mi:“MI:0914”(association)	0.350
SIDT2	KLRG2	psi-mi:“MI:0914”(association)	0.350
RXFP1	UPK3BL1	psi-mi:“MI:0914”(association)	0.350
LYPD3	TNPO2	psi-mi:“MI:0914”(association)	0.350
VNN2	ATP2A1	psi-mi:“MI:0914”(association)	0.350
ITGA8	SUSD5	psi-mi:“MI:0914”(association)	0.350
CLDND1	MAN1A2	psi-mi:“MI:0914”(association)	0.350
TMEFF1	FGF2	psi-mi:“MI:0914”(association)	0.350
LDLRAD1	ZNF316	psi-mi:“MI:0914”(association)	0.350
CLDND1	TNFRSF10B	psi-mi:“MI:0914”(association)	0.350

BioGRID (102): GOLGA7 (Affinity Capture-MS), KIAA2013 (Affinity Capture-MS), MAN1A1 (Affinity Capture-MS), MAN1A2 (Affinity Capture-MS), ZDHHC8 (Affinity Capture-MS), ZDHHC5 (Affinity Capture-MS), B4GALT4 (Affinity Capture-MS), BMPR1A (Affinity Capture-MS), ALG3 (Affinity Capture-MS), CLDND1 (Affinity Capture-MS), CLDND1 (Affinity Capture-MS), CLDND1 (Affinity Capture-MS), CLDND1 (Affinity Capture-MS), ZDHHC5 (Affinity Capture-MS), ZDHHC8 (Affinity Capture-MS)

ESM2 similar proteins: A0A1D5NY17, A4IF75, B2RVY9, B3SHH9, F6V1J6, O42281, O70578, P19518, P97707, Q06432, Q08CE6, Q08DE1, Q0D289, Q0V9E0, Q14714, Q2MJQ7, Q4R4Z3, Q4V922, Q5CZV0, Q5PRC1, Q5RDV7, Q5XGU1, Q62147, Q66IV3, Q68FV0, Q6AZD1, Q6P0C6, Q6R5J2, Q6ZP80, Q6ZUX7, Q7ZZL8, Q86WI0, Q8BGA2, Q8NBL3, Q8VHW3, Q8VHW4, Q8VHW7, Q8VHW8, Q91Y55, Q925N4

Diamond homologs: Q4R4Z3, Q5RDV7, Q9CQX5, Q9NY35

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	42
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1068 predictions. Top by Δscore:

Variant	Effect	Δscore
3:98518883:A:AC	donor_gain	1.0000
3:98518884:C:CC	donor_gain	1.0000
3:98518884:CAGGT:C	donor_gain	1.0000
3:98521438:CTGCT:C	acceptor_gain	1.0000
3:98521439:TGCT:T	acceptor_gain	1.0000
3:98521441:CT:C	acceptor_gain	1.0000
3:98521442:TC:T	acceptor_loss	1.0000
3:98521443:C:CA	acceptor_loss	1.0000
3:98521443:C:CC	acceptor_gain	1.0000
3:98521447:T:C	acceptor_gain	1.0000
3:98521447:T:TC	acceptor_gain	1.0000
3:98521454:T:TC	acceptor_gain	1.0000
3:98521800:CAGA:C	donor_gain	1.0000
3:98517197:T:C	acceptor_gain	0.9900
3:98517197:T:TC	acceptor_gain	0.9900
3:98518884:CAG:C	donor_gain	0.9900
3:98518991:TGACT:T	acceptor_gain	0.9900
3:98518994:CT:C	acceptor_gain	0.9900
3:98518996:C:CC	acceptor_gain	0.9900
3:98521440:GCT:G	acceptor_gain	0.9900
3:98521441:CTC:C	acceptor_gain	0.9900
3:98521442:TCT:T	acceptor_gain	0.9900
3:98521443:C:G	acceptor_gain	0.9900
3:98521444:T:C	acceptor_loss	0.9900
3:98521445:G:C	acceptor_gain	0.9900
3:98521453:G:C	acceptor_gain	0.9900
3:98521453:G:GC	acceptor_gain	0.9900
3:98521454:T:C	acceptor_gain	0.9900
3:98521803:A:AC	donor_gain	0.9900
3:98521804:C:CC	donor_gain	0.9900

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000142068 (3:98517753 C>G), RS1000180428 (3:98522687 C>G), RS1000249989 (3:98515072 C>A), RS1000257217 (3:98522973 C>A,G,T), RS1000514714 (3:98521497 G>A,C,T), RS1000589734 (3:98521841 T>C), RS1001263606 (3:98520624 AG>A), RS1002259269 (3:98520108 C>T), RS1002588448 (3:98518699 A>T), RS1003205473 (3:98524737 G>A), RS1003280851 (3:98517829 A>C), RS1003909972 (3:98523389 T>C), RS1004193830 (3:98516849 T>G), RS1004267968 (3:98517121 C>T), RS1004491109 (3:98515766 T>C)

Disease associations

OMIM: gene MIM:619677 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST003264_768	Post bronchodilator FEV1/FVC ratio	3.000000e-07

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004713	FEV/FVC ratio

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Air Pollutants	increases abundance, increases oxidation, increases expression, affects cotreatment, decreases expression	2
Benzo(a)pyrene	increases expression	2
dicrotophos	decreases expression	1
alpha-pinene	decreases expression, increases oxidation, increases abundance, affects cotreatment	1
trichostatin A	affects expression	1
beta-lapachone	increases expression	1
sodium arsenite	increases expression	1
cobaltous chloride	increases expression	1
cupric chloride	increases expression	1
methacrylaldehyde	affects cotreatment, decreases expression, increases oxidation, increases abundance	1
beta-methylcholine	affects expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
K 7174	increases expression	1
NSC 689534	increases expression, affects binding	1
(+)-JQ1 compound	increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Acetaminophen	increases expression	1
Acrolein	decreases expression, increases oxidation, increases abundance, affects cotreatment	1
Copper	affects binding, increases expression	1
Dimethyl Sulfoxide	increases expression	1
Doxorubicin	decreases expression	1
Hydrogen Peroxide	affects expression	1
Ivermectin	decreases expression	1
Ozone	affects cotreatment, decreases expression, increases oxidation, increases abundance	1
Plant Extracts	affects cotreatment, increases expression	1
Tobacco Smoke Pollution	increases expression	1
Urethane	increases expression	1
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	increases expression	1
Aflatoxin B1	decreases methylation	1

Clinical trials (associated diseases)

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