OCLN

Summary

OCLN (occludin, HGNC:8104) is a protein-coding gene on chromosome 5q13.2, encoding Occludin (Q16625). May play a role in the formation and regulation of the tight junction (TJ) paracellular permeability barrier.

This gene encodes an integral membrane protein that is required for cytokine-induced regulation of the tight junction paracellular permeability barrier. Mutations in this gene are thought to be a cause of band-like calcification with simplified gyration and polymicrogyria (BLC-PMG), an autosomal recessive neurologic disorder that is also known as pseudo-TORCH syndrome. Alternative splicing results in multiple transcript variants. A related pseudogene is present 1.5 Mb downstream on the q arm of chromosome 5.

Source: NCBI Gene 100506658 — RefSeq curated summary.

At a glance

• Gene–disease (curated): pseudo-TORCH syndrome 1 (Definitive, GenCC) — +1 more curated relationship
• GWAS associations: 2
• Clinical variants (ClinVar): 165 total — 12 pathogenic, 10 likely-pathogenic
• Phenotypes (HPO): 43
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity unscored
• MANE Select transcript: NM_001205254

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:8104
Approved symbol	OCLN
Name	occludin
Location	5q13.2
Locus type	gene with protein product
Status	Approved
Aliases	PPP1R115
Ensembl gene	ENSG00000197822
Ensembl biotype	protein_coding
OMIM	602876
Entrez	100506658

Gene structure

Transcript identifiers

Ensembl transcripts: 32 — 28 protein_coding, 2 retained_intron, 1 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000355237, ENST00000396442, ENST00000510666, ENST00000514370, ENST00000538151, ENST00000680027, ENST00000680098, ENST00000680496, ENST00000680784, ENST00000681041, ENST00000681586, ENST00000681588, ENST00000681889, ENST00000681895, ENST00000901825, ENST00000901826, ENST00000901827, ENST00000901828, ENST00000901829, ENST00000901830, ENST00000901831, ENST00000901832, ENST00000901833, ENST00000901834, ENST00000935161, ENST00000935162, ENST00000935163, ENST00000955763, ENST00000955764, ENST00000955765, ENST00000955766, ENST00000955767

RefSeq mRNA: 4 — MANE Select: NM_001205254 NM_001205254, NM_001205255, NM_001410743, NM_002538

CCDS: CCDS4006, CCDS54864, CCDS93725

Canonical transcript exons

ENST00000396442 — 9 exons

Exon	Start	End
ENSE00001007952	69504177	69504294
ENSE00001486184	69509141	69509819
ENSE00002074220	69492790	69492900
ENSE00003495716	69551544	69551585
ENSE00003521232	69544904	69545119
ENSE00003549833	69513948	69514109
ENSE00003560198	69534694	69534839
ENSE00003668008	69547930	69548101
ENSE00003911614	69553570	69558104

Expression profiles

Bgee: expression breadth ubiquitous, 195 present calls, max score 92.33.

FANTOM5 (CAGE): breadth broad, TPM avg 11.0534 / max 188.7642, expressed in 909 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
56859	10.0108	899
56856	0.8339	315
56855	0.2087	115

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
islet of Langerhans	UBERON:0000006	92.33	gold quality
ileal mucosa	UBERON:0000331	91.20	gold quality
pancreatic ductal cell	CL:0002079	89.91	gold quality
pancreas	UBERON:0001264	89.15	gold quality
right lobe of thyroid gland	UBERON:0001119	89.07	gold quality
body of pancreas	UBERON:0001150	88.75	gold quality
left lobe of thyroid gland	UBERON:0001120	88.60	gold quality
thyroid gland	UBERON:0002046	88.50	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	88.49	gold quality
sural nerve	UBERON:0015488	88.07	gold quality
rectum	UBERON:0001052	87.98	gold quality
right lung	UBERON:0002167	86.61	gold quality
upper lobe of left lung	UBERON:0008952	86.09	gold quality
upper lobe of lung	UBERON:0008948	85.66	gold quality
lung	UBERON:0002048	85.38	gold quality
epithelial cell of pancreas	CL:0000083	85.09	silver quality
right lobe of liver	UBERON:0001114	84.75	gold quality
mucosa of transverse colon	UBERON:0004991	84.68	gold quality
endothelial cell	CL:0000115	84.52	silver quality
colonic mucosa	UBERON:0000317	84.27	gold quality
lower esophagus mucosa	UBERON:0035834	84.20	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	84.04	gold quality
liver	UBERON:0002107	84.03	gold quality
gall bladder	UBERON:0002110	84.00	gold quality
esophagus mucosa	UBERON:0002469	83.26	gold quality
body of stomach	UBERON:0001161	83.10	gold quality
mucosa of sigmoid colon	UBERON:0004993	83.07	gold quality
skin of leg	UBERON:0001511	82.72	gold quality
stomach	UBERON:0000945	82.53	gold quality
colonic epithelium	UBERON:0000397	82.28	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-MTAB-9388	yes	13.49
E-MTAB-7249	yes	11.06
E-MTAB-6379	no	6.36
E-ANND-3	no	0.00

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

4 targets.

Target	Regulation
CLDN2	Repression
SLC2A1	Activation
SLC2A4	Activation
SP1	Activation

Upstream regulators (CollecTRI, top): CUX1, HEY1, HNF4A, NKX2-1, NONO, NR3C1, NR3C2, RUNX1, SH3GL2, SMAD3, SMAD4, SNAI1, SNAI2, SP3, TTF1, YY1, ZHX2

miRNA regulators (miRDB)

173 targeting OCLN, 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-3613-3P	100.00	76.36	7965
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-126-5P	100.00	72.71	3180
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-340-5P	100.00	72.50	4437
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-4455	100.00	65.48	1587
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-9-3P	99.96	70.88	2068
HSA-LET-7C-3P	99.95	73.42	2862

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity Not yet evaluated (unscored). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 40)

• The transmembrane domain TM4(-) isoform of Occludin may be translated at low levels in specific conditions and may contribute to regulation of Occludin function. (PMID:12118072)
• oxidative stress induces tyrosine phosphorylation and cellular redistribution of occludin-ZO-1 and E-cadherin-beta-catenin complexes by a tyrosine-kinase-dependent mechanism. (PMID:12169098)
• a cyclic peptide with the sequence LYHY, in the second extracellular domain, inhibits endothelial cell barriers and prevents aggregation of fibroblasts transfected with cDNA encoding occludin. LYHY motif is an occludin cell adhesion recognition sequence. (PMID:12184633)
• different occludin variants were identified on the mRNA level (PMID:12419305)
• Occludin mRNA, being mainly located in epithelial cells and its expression correlated with tumor differentiation, may be involved in the development of multi-drug resistance in gastric cancer. (PMID:12667324)
• E-cadherin and claudins/occludin have roles in the regulation of tight junctions during the epithelium-mesenchyme transition, but are repressed by snail (PMID:12668723)
• Occludin expression decreased progressively in parallel with the increase in carcinoma grade, and the decreased occludin expression correlated with myometrial invasion and lymph node metastasis (PMID:14991532)
• MEK/ERK signaling pathway probably regulates the cell dissociation status of pancreatic cancer through influencing the intracellular localization and expression of occludin. (PMID:15069537)
• occludin 50-kDa form is an estrogen-specific-induced occludin isoform and that the mechanism of estrogen-abrogation of transcervical R(TJ) involves occludin modulation. (PMID:15472219)
• The occludin present in the tight junctions in HepG2 cells . (PMID:15500294)
• Activation of PKC by the phorbol ester TPA induced ZO-1 and occludin transcription, whereas PKC inhibition lead to decreased expression levels (PMID:15622522)
• distinct properties for these two extracellular segments of the occludin protein and provide an improved understanding of how specific domains of occludin may interact with proteins present at tight junction structures (PMID:15659655)
• Tight junction protein occludin has a potent inhibitory effect on the Raf1-mediated tumorigenesis (PMID:15806147)
• high-resolution crystal structure of its C-terminal distal cytoplasmic domain; identified a large positively charged surface that contains the binding site for ZO-1; this surface is required for proper localization of occludin to cell-cell junctions (PMID:16081103)
• ERK interacts with the C-terminal region of occludin and mediates the prevention of H2O2-induced disruption of TJs by EGF. (PMID:16134968)
• modulation of tight-junction function by H. pylori is ammonium-dependent and linked to the accumulation of a low-molecular-weight and detergent-soluble form of occludin. (PMID:16207910)
• CKI epsilon is a novel occludin kinase that may be important for the regulation of occludin (PMID:16616143)
• These findings support a role of Slug in mediating Raf 1-induced transcriptional repression of occludin and subsequent epithelial to mesenchymal transition. (PMID:16924233)
• Na-K-ATPase is required for controlling the tight junction gate function through phosphorylation of occlusion. (PMID:16959951)
• Estrogen modulates tight junctional resistance through estrogen receptor-alpha-mediated remodeling of occludin (PMID:17038551)
• OCLN accumulated at cell-to-cell junctions of the breast neoplasm cell line. (PMID:17243118)
• Expression of cytoplasmic occludin was decreased in acute acalculous cholecystitis. (PMID:17283368)
• Tight junction proteins contribute to the permeability barrier in epidermal keratinocytes (PMID:17359339)
• Rhesus monkey rotavirus infection of Caco-2 cells induced the disappearance of occludin. (PMID:17553883)
• Selected neurons, astrocytes and oligodendrocytes expressed occludin, in all cases studied. (PMID:17635647)
• Complete/partial truncation of the COOH-terminal tail of occludin did not prevent targeting to epithelial cell tight junctions. TM4 deletions abolished tight junction targeting. (PMID:17855770)
• Occludin expression was determined in thyroid neoplasms. (PMID:17962811)
• B coxsackievirus entry depends on occludin and require the activity of Rab34, Ras, and Rab5, GTPases known to regulate macropinocytosis. (PMID:18005733)
• Heat stress-induced increase in occludin protein expression is mediated by HSF-1 activation and subsequent binding of HSF-1 to the occludin promoter. (PMID:18276783)
• Hepatocellular carcinomas and metastases are characterized by markedly different protein expression pattern of occludin and ZO-1, which phenomenon might be attributed to the different histogenesis of these tumors. (PMID:18386163)
• study of correlation between mutations & expression of E-cadherin, beta-catenin, occludin & claudin & complexity of colon carcinoma growth; perturbed expression & distribution of these proteins was found, but could not be linked to complexity of growth (PMID:18397460)
• These data demonstrate that the tight junction undergoes constant remodeling and suggest that this dynamic behavior may contribute to tight junction assembly and regulation. (PMID:18474622)
• Occludin mediates apoptosis and invasion by elevating the cytoplasmic calcium concentration and that exon 9 of occludin is an important region that mediates these effects. (PMID:18489585)
• neither occludin nor claudin-7 expression was associated with clinicopathologic findings in patients with urothelial carcinoma of the upper urinary tract. (PMID:18550469)
• Claudin-1 plays a crucial role in recruiting occludin to tight junctions, and occludin is involved in intercellular barrier function. (PMID:18560860)
• Glucocorticoids regulate the human occludin gene through a single imperfect palindromic glucocorticoid response element. (PMID:18782596)
• 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)
• a unique motif in the occludin sequence that is involved in the regulation of ZO-1 binding by reversible phosphorylation of specific Tyr residues. (PMID:19017651)
• The authors show that in addition to claudin-1 another tight junction protein, occludin, is also required for HCV 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)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	oclnb	ENSDARG00000003091
danio_rerio	oclna	ENSDARG00000005108
mus_musculus	Ocln	ENSMUSG00000021638
rattus_norvegicus	Ocln	ENSRNOG00000071323
drosophila_melanogaster	Su(Tpl)	FBGN0014037
caenorhabditis_elegans		WBGENE00021281

Paralogs (5): OCEL1 (ENSG00000099330), ELL (ENSG00000105656), ELL2 (ENSG00000118985), ELL3 (ENSG00000128886), MARVELD2 (ENSG00000152939)

Protein

Protein identifiers

Occludin — Q16625 (reviewed: Q16625)

All UniProt accessions (4): A0A0G2JPF2, A0A7P0T9T6, A0A7P0TB95, Q16625

UniProt curated annotations — full annotation on UniProt →

Function. May play a role in the formation and regulation of the tight junction (TJ) paracellular permeability barrier. It is able to induce adhesion when expressed in cells lacking tight junctions. (Microbial infection) Acts as a coreceptor for hepatitis C virus (HCV) in hepatocytes.

Subunit / interactions. Interacts with TJP1/ZO1. Interacts with VAPA. Interacts with CLDN1, CLDN6, CLDN9, CLDN11, CLDN12 and CLDN17. Interacts with PLSCR1. Interacts with LSR, ILDR1 and ILDR2. Interacts with TJP2/ZO2.

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

Tissue specificity. Localized at tight junctions of both epithelial and endothelial cells. Highly expressed in kidney. Not detected in testis.

Post-translational modifications. Dephosphorylated by PTPRJ. The tyrosine phosphorylation on Tyr-398 and Tyr-402 reduces its ability to interact with TJP1. Phosphorylation at Ser-490 also attenuates the interaction with TJP1. (Microbial infection) Cleaved by S.pyogenes SpeB protease; leading to its degradation. Degradation by SpeB promotes bacterial translocation across the host epithelial barrier.

Disease relevance. Pseudo-TORCH syndrome 1 (PTORCH1) [MIM:251290] An autosomal recessive neurologic disorder with characteristic clinical and neuroradiologic features that mimic intrauterine TORCH infection in the absence of evidence of infection. Affected individuals have congenital microcephaly, intracranial calcifications, and severe developmental delay. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. The C-terminal is cytoplasmic and is important for interaction with ZO-1. Sufficient for the tight junction localization. Involved in the regulation of the permeability barrier function of the tight junction. The first extracellular loop participates in an adhesive interaction.

Similarity. Belongs to the ELL/occludin family.

Isoforms (7)

UniProt ID	Names	Canonical?
Q16625-1	1, WT-OCLN, TM4(+)	yes
Q16625-2	2, OCLN-ex4del, TM4(-)
Q16625-3	3, OCLN-ex7ext
Q16625-4	4, OCLN-ex3del, OCLN-ex3pdel
Q16625-5	5, OCLN-ex3-4del
Q16625-6	6, OCLN-ex3p-9pdel
Q16625-7	7, OCLN-ex3p-7pdel

RefSeq proteins (4): NP_001192183, NP_001192184, NP_001397672, NP_002529 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002958	Occludin	Family
IPR008253	Marvel	Domain
IPR010844	Occludin_ELL	Domain
IPR031176	ELL/occludin	Family
IPR036259	MFS_trans_sf	Homologous_superfamily

Pfam: PF01284, PF07303

UniProt features (54 total): modified residue 14, splice variant 8, mutagenesis site 7, topological domain 5, transmembrane region 4, compositionally biased region 3, helix 3, domain 2, region of interest 2, chain 1, coiled-coil region 1, disulfide bond 1, sequence variant 1, sequence conflict 1, turn 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
1XAW	X-RAY DIFFRACTION	1.45
1WPA	X-RAY DIFFRACTION	1.5
3G7C	X-RAY DIFFRACTION	2

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q16625-F1	65.82	0.29

Functional residue map

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

Post-translational modifications (14): 302, 305, 313, 321, 340, 368, 369, 370, 398, 402, 403, 404, 408, 490

Disulfide bonds (1): 216–237

Mutagenesis-validated functional residues (7):

Position	Phenotype
398	loss of phosphorylation and loss of regulation of tjp1 binding; when associated with a-402.
398	loss of phosphorylation, almost complete loss of binding to tjp1, loss of regulation of tjp1 binding and loss of localiz
398	loss of phosphorylation, decrease in binding to tjp1 and significant loss of regulation of tjp1 binding; when associated
402	loss of phosphorylation and loss of regulation of tjp1 binding; when associated with a-398.
402	loss of phosphorylation, almost complete loss of binding to tjp1, loss of regulation of tjp1 binding and loss of localiz
402	loss of phosphorylation, decrease in binding to tjp1 and significant loss of regulation of tjp1 binding; when associated
404	loss of localization to the tight junctions.

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-351906	Apoptotic cleavage of cell adhesion proteins
R-HSA-8935964	RUNX1 regulates expression of components of tight junctions
R-HSA-9758919	Epithelial-Mesenchymal Transition (EMT) during gastrulation

MSigDB gene sets: 332 (showing top): MODULE_52, GOBP_CARBOHYDRATE_TRANSPORT, GOBP_REGULATION_OF_PROTEIN_POLYMERIZATION, GOBP_REGULATION_OF_MICROTUBULE_BASED_PROCESS, GOBP_REGULATION_OF_WOUND_HEALING, GOBP_CIRCULATORY_SYSTEM_PROCESS, GOCC_VACUOLAR_MEMBRANE, GOBP_APICAL_JUNCTION_ASSEMBLY, KEGG_TIGHT_JUNCTION, GOBP_POSITIVE_REGULATION_OF_ORGANELLE_ORGANIZATION, GOBP_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, GOBP_REGULATION_OF_LAMELLIPODIUM_ASSEMBLY, GOBP_POSITIVE_REGULATION_OF_TRANSMEMBRANE_TRANSPORT, GOBP_AMEBOIDAL_TYPE_CELL_MIGRATION, SENESE_HDAC1_AND_HDAC2_TARGETS_DN

GO Biological Process (15): positive regulation of lamellipodium assembly (GO:0010592), positive regulation of gene expression (GO:0010628), negative regulation of gene expression (GO:0010629), epithelial cell migration (GO:0010631), regulation of D-glucose transmembrane transport (GO:0010827), positive regulation of microtubule polymerization (GO:0031116), maintenance of blood-brain barrier (GO:0035633), cell-cell junction organization (GO:0045216), positive regulation of D-glucose import across plasma membrane (GO:0046326), protein-containing complex assembly (GO:0065003), bicellular tight junction assembly (GO:0070830), positive regulation of wound healing (GO:0090303), protein localization to cell leading edge (GO:1902463), positive regulation of blood-brain barrier permeability (GO:1905605), tight junction organization (GO:0120193)

GO Molecular Function (2): protein domain specific binding (GO:0019904), protein binding (GO:0005515)

GO Cellular Component (14): lysosomal membrane (GO:0005765), plasma membrane (GO:0005886), cell-cell junction (GO:0005911), bicellular tight junction (GO:0005923), apical plasma membrane (GO:0016324), apicolateral plasma membrane (GO:0016327), cell junction (GO:0030054), endocytic vesicle (GO:0030139), cell leading edge (GO:0031252), cytoplasmic vesicle (GO:0031410), protein-containing complex (GO:0032991), tight junction (GO:0070160), membrane (GO:0016020), anchoring junction (GO:0070161)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Apoptotic cleavage of cellular proteins	1
Transcriptional regulation by RUNX1	1
Gastrulation	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
gene expression	2
regulation of gene expression	2
plasma membrane region	2
regulation of lamellipodium assembly	1
lamellipodium assembly	1
positive regulation of plasma membrane bounded cell projection assembly	1
positive regulation of lamellipodium organization	1
positive regulation of macromolecule biosynthetic process	1
negative regulation of macromolecule biosynthetic process	1
ameboidal-type cell migration	1
epithelium migration	1
regulation of transmembrane transport	1
D-glucose transmembrane transport	1
positive regulation of microtubule polymerization or depolymerization	1
regulation of microtubule polymerization	1
positive regulation of protein polymerization	1
microtubule polymerization	1
positive regulation of supramolecular fiber organization	1
tissue homeostasis	1
cell junction organization	1
positive regulation of D-glucose transmembrane transport	1
regulation of D-glucose import across plasma membrane	1
D-glucose import across plasma membrane	1
cellular component assembly	1
protein-containing complex organization	1
apical junction assembly	1
tight junction assembly	1
wound healing	1
regulation of wound healing	1
positive regulation of response to wounding	1
intracellular protein localization	1
positive regulation of vascular permeability	1
regulation of blood-brain barrier permeability	1
cell-cell junction organization	1
protein binding	1
binding	1
lysosome	1
lytic vacuole membrane	1
membrane	1

Protein interactions and networks

STRING

3780 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
OCLN	CLDN1	O95832	999
OCLN	CLDN5	O00501	999
OCLN	CLDN7	O95471	999
OCLN	TJP1	Q07157	999
OCLN	TJP2	Q9UDY2	999
OCLN	TJP3	O95049	998
OCLN	F11R	Q9Y624	998
OCLN	CLDN3	O15551	997
OCLN	CGN	Q9P2M7	995
OCLN	CDH1	P12830	992
OCLN	MARVELD2	Q8N4S9	989
OCLN	CLDN4	O14493	988
OCLN	CDH5	P33151	980
OCLN	CD81	P18582	974
OCLN	ESAM	Q96AP7	970

IntAct

139 interactions, top by confidence:

A	B	Type	Score
CSNK1E	OCLN	psi-mi:“MI:2364”(proximity)	0.830
CSNK1E	OCLN	psi-mi:“MI:0915”(physical association)	0.830
OCLN	CSNK1E	psi-mi:“MI:0915”(physical association)	0.830
OCLN	CSNK1E	psi-mi:“MI:0403”(colocalization)	0.830
CSNK1E	OCLN	psi-mi:“MI:0217”(phosphorylation reaction)	0.830
CD9	ADAM10	psi-mi:“MI:0914”(association)	0.750
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
OCLN	SYNE4	psi-mi:“MI:0915”(physical association)	0.670
SYNE4	OCLN	psi-mi:“MI:0915”(physical association)	0.670
TNFSF8	TOR1B	psi-mi:“MI:0914”(association)	0.640
STX12	SNAP23	psi-mi:“MI:0914”(association)	0.640
OCLN	CLEC7A	psi-mi:“MI:0915”(physical association)	0.560
CLEC7A	OCLN	psi-mi:“MI:0915”(physical association)	0.560
OCLN	GPX8	psi-mi:“MI:0915”(physical association)	0.560
OCLN	DNM2	psi-mi:“MI:0915”(physical association)	0.560
OCLN	NDUFV2	psi-mi:“MI:0915”(physical association)	0.560
TMEM30B	KLRG2	psi-mi:“MI:0914”(association)	0.530
OCLN	DNAJC13	psi-mi:“MI:0914”(association)	0.530
SYT12	B4GALT5	psi-mi:“MI:0914”(association)	0.530

BioGRID (614): CLEC7A (Two-hybrid), SYNE4 (Two-hybrid), SNW1 (Two-hybrid), CSNK1E (Two-hybrid), ULK1 (Two-hybrid), CSNK1E (Reconstituted Complex), CSNK1A1 (Reconstituted Complex), OCLN (Affinity Capture-Western), OCLN (Biochemical Activity), OCLN (Affinity Capture-MS), OCLN (Affinity Capture-MS), OCLN (Affinity Capture-MS), OCLN (Affinity Capture-MS), OCLN (Affinity Capture-MS), OCLN (Affinity Capture-MS)

ESM2 similar proteins: A0JPA1, A4GG66, A4GVD1, A4IG66, A7YWH9, A9L8T6, B0VX73, B1MT31, F1NVK6, G5EBQ8, P18861, P28228, P28229, P36383, P91682, Q00M95, Q0IHQ3, Q0P5V9, Q11186, Q16625, Q28269, Q2HJ66, Q3UZP0, Q499S9, Q5BKX6, Q5RFS5, Q5YLM1, Q61146, Q62847, Q66IE4, Q6GMF8, Q6NZH5, Q6P6T5, Q6PIX5, Q6PJF5, Q6PYT3, Q6R4A8, Q6WQJ1, Q7TMB7, Q7ZXS7

Diamond homologs: Q16625, Q28269, Q28793, Q5RFS5, Q61146, Q6P6T5, Q91049, Q9PUN1, O00472, O08856, P55199, Q3UKU1, Q3UZP0, Q8N4S9, Q0IHQ3

SIGNOR signaling

11 interactions.

A	Effect	B	Mechanism
PRKCE	up-regulates	OCLN	phosphorylation
CSNK2B	unknown	OCLN	phosphorylation
ITCH	“down-regulates quantity by destabilization”	OCLN	ubiquitination
SNAI1	“down-regulates quantity by repression”	OCLN	“transcriptional regulation”
OCLN	down-regulates	Epithelial-mesenchymal_transition
PRKCA	“up-regulates activity”	OCLN	phosphorylation
PRKCB	“up-regulates activity”	OCLN	phosphorylation
PRKCG	“up-regulates activity”	OCLN	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 154 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
GRB2 events in EGFR signaling	5	37.0×	4e-05
SHC1 events in EGFR signaling	5	34.6×	4e-05
GRB2 events in ERBB2 signaling	5	30.8×	6e-05
SHC1 events in ERBB2 signaling	5	23.1×	1e-04
Signaling by ERBB2 TMD/JMD mutants	5	23.1×	1e-04
Signaling by ERBB2 KD Mutants	5	20.5×	2e-04
NCAM signaling for neurite out-growth	5	13.2×	9e-04
RAF/MAP kinase cascade	8	4.7×	5e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	12
Likely pathogenic	10
Uncertain significance	85
Likely benign	31
Benign	9

Top pathogenic / likely-pathogenic (22)

Variant ID	HGVS	Classification
1029457	NM_001205254.2(OCLN):c.106C>T (p.Arg36Ter)	Pathogenic
1065616	NM_001205254.2(OCLN):c.52_891del840 (p.Lys18_Trp297del)	Pathogenic
1323383	NM_001205254.2(OCLN):c.513C>A (p.Tyr171Ter)	Pathogenic
1526118	NM_001205254.2(OCLN):c.1324G>T (p.Glu442Ter)	Pathogenic
211774	NM_001205254.2(OCLN):c.1037+5G>A	Pathogenic
2125619	NM_001205254.2(OCLN):c.138_139del (p.Phe46fs)	Pathogenic
2711780	NM_001205254.2(OCLN):c.35dup (p.Tyr12Ter)	Pathogenic
3246503	NC_000005.9:g.(?68800072)(68809956_?)del	Pathogenic
503999	NM_001205254.2(OCLN):c.1016_1017del (p.Glu339fs)	Pathogenic
6750	NM_001205254.2(OCLN):c.171_193del (p.Lys57fs)	Pathogenic
6751	NM_001205254.2(OCLN):c.512dup (p.Tyr171Ter)	Pathogenic
6752	NM_001205254.2(OCLN):c.656T>C (p.Phe219Ser)	Pathogenic
1029458	NM_001205254.2(OCLN):c.50+2T>C	Likely pathogenic
217516	NM_001205254.2(OCLN):c.252del (p.Ser85fs)	Likely pathogenic
2446043	NM_001205254.2(OCLN):c.1542del (p.Gly515fs)	Likely pathogenic
2664921	NM_001205254.2(OCLN):c.1254-1G>A	Likely pathogenic
2690659	NM_001205254.2(OCLN):c.630_645del (p.Gln211fs)	Likely pathogenic
3384093	NM_001205254.2(OCLN):c.981del (p.Asn328fs)	Likely pathogenic
451555	NM_001205254.2(OCLN):c.724C>T (p.Gln242Ter)	Likely pathogenic
800964	NM_001205254.2(OCLN):c.546G>C (p.Leu182=)	Likely pathogenic
817656	NM_001205254.2(OCLN):c.23del (p.Ser8fs)	Likely pathogenic
987167	NM_001205254.2(OCLN):c.1054C>T (p.Gln352Ter)	Likely pathogenic

SpliceAI

1726 predictions. Top by Δscore:

Variant	Effect	Δscore
5:69504173:TTAG:T	acceptor_loss	1.0000
5:69504175:A:AG	acceptor_gain	1.0000
5:69504175:AGATT:A	acceptor_gain	1.0000
5:69504176:G:GG	acceptor_gain	1.0000
5:69504176:GA:G	acceptor_gain	1.0000
5:69504176:GATT:G	acceptor_gain	1.0000
5:69504176:GATTG:G	acceptor_gain	1.0000
5:69504290:GAATT:G	donor_gain	1.0000
5:69504291:AATT:A	donor_gain	1.0000
5:69504292:ATT:A	donor_gain	1.0000
5:69504293:TT:T	donor_gain	1.0000
5:69504293:TTG:T	donor_loss	1.0000
5:69504294:TG:T	donor_loss	1.0000
5:69504295:G:GC	donor_loss	1.0000
5:69504295:G:GG	donor_gain	1.0000
5:69504296:T:A	donor_loss	1.0000
5:69504299:G:GG	donor_gain	1.0000
5:69509139:A:AG	acceptor_gain	1.0000
5:69509140:G:GG	acceptor_gain	1.0000
5:69509140:GC:G	acceptor_gain	1.0000
5:69509140:GCA:G	acceptor_gain	1.0000
5:69513942:TTTTA:T	acceptor_loss	1.0000
5:69513943:TTTAG:T	acceptor_loss	1.0000
5:69513944:TTAG:T	acceptor_loss	1.0000
5:69513945:TA:T	acceptor_loss	1.0000
5:69513946:A:AG	acceptor_gain	1.0000
5:69513947:G:GA	acceptor_loss	1.0000
5:69513947:G:GG	acceptor_gain	1.0000
5:69514106:GTGG:G	donor_gain	1.0000
5:69514108:GG:G	donor_gain	1.0000

AlphaMissense

3423 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:69509736:T:A	C216S	0.999
5:69509737:G:A	C216Y	0.999
5:69509737:G:C	C216S	0.999
5:69509738:C:G	C216W	0.999
5:69509736:T:C	C216R	0.998
5:69509799:T:A	C237S	0.998
5:69509799:T:C	C237R	0.998
5:69509800:G:A	C237Y	0.998
5:69509800:G:C	C237S	0.998
5:69509801:T:G	C237W	0.998
5:69509334:T:C	C82R	0.997
5:69509737:G:T	C216F	0.997
5:69514109:G:C	W297C	0.997
5:69514109:G:T	W297C	0.997
5:69509332:C:A	A81D	0.996
5:69509357:G:C	W89C	0.996
5:69509357:G:T	W89C	0.996
5:69509676:G:A	G196R	0.996
5:69509676:G:C	G196R	0.996
5:69547963:A:C	R429S	0.996
5:69547963:A:T	R429S	0.996
5:69509316:T:C	C76R	0.995
5:69509341:C:A	A84D	0.995
5:69509800:G:T	C237F	0.995
5:69513966:G:A	G250R	0.995
5:69513966:G:C	G250R	0.995
5:69514107:T:A	W297R	0.995
5:69514107:T:C	W297R	0.995
5:69551550:G:C	A478P	0.995
5:69509625:A:C	S179R	0.994

dbSNP variants (sampled 300 via entrez): RS1000084798 (5:69527260 G>C), RS1000100740 (5:69501887 G>A,C), RS1000175050 (5:69522822 G>A,T), RS1000186477 (5:69521461 A>G), RS1000206297 (5:69522529 C>G), RS1000420746 (5:69536893 G>A,C,T), RS1000502780 (5:69524277 C>G), RS1000551170 (5:69492241 A>G), RS1000562158 (5:69507568 C>T), RS1000665847 (5:69518397 G>C,T), RS1000694856 (5:69528717 A>G), RS1000755702 (5:69514718 T>A,C), RS1000771041 (5:69492909 TGGGCGCGGCGTCAG>T), RS1000782934 (5:69533446 C>A,T), RS1000858125 (5:69511231 C>T)

Disease associations

OMIM: gene MIM:602876 | disease phenotypes: MIM:251290

GenCC curated gene-disease

Disease	Classification	Inheritance
pseudo-TORCH syndrome 1	Definitive	Autosomal recessive
pseudo-TORCH syndrome	Supportive	Autosomal recessive

Mondo (2): pseudo-TORCH syndrome 1 (MONDO:0020789), pseudo-TORCH syndrome (MONDO:0009626)

Orphanet (1): Pseudo-TORCH syndrome type 1 (Orphanet:1229)

HPO phenotypes

43 total (30 of 43 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000083	Renal insufficiency
HP:0000218	High palate
HP:0000252	Microcephaly
HP:0000308	Microretrognathia
HP:0000340	Sloping forehead
HP:0000343	Long philtrum
HP:0000369	Low-set ears
HP:0000463	Anteverted nares
HP:0000518	Cataract
HP:0000639	Nystagmus
HP:0000952	Jaundice
HP:0000967	Petechiae
HP:0001250	Seizure
HP:0001252	Hypotonia
HP:0001257	Spasticity
HP:0001263	Global developmental delay
HP:0001302	Pachygyria
HP:0001321	Cerebellar hypoplasia
HP:0001332	Dystonia
HP:0001339	Lissencephaly
HP:0001347	Hyperreflexia
HP:0001410	Decreased liver function
HP:0001508	Failure to thrive
HP:0001537	Umbilical hernia
HP:0001643	Patent ductus arteriosus
HP:0001655	Patent foramen ovale
HP:0001744	Splenomegaly
HP:0001873	Thrombocytopenia
HP:0002119	Ventriculomegaly

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST004441_1	Interleukin-18 levels	2.000000e-11
GCST010278_5	Hand grip strength (Mahalanobis distance)	5.000000e-06

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004581	interleukin 18 measurement
EFO:0006941	grip strength measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Particulate Matter	decreases expression, decreases reaction, affects localization, affects reaction	8
sodium arsenite	increases abundance, affects expression, affects phosphorylation, increases expression, decreases expression (+1 more)	5
Acetylcysteine	decreases expression, decreases reaction, affects cotreatment	4
Glucose	decreases expression, decreases reaction, affects cotreatment	4
Lipopolysaccharides	affects cotreatment, decreases expression, decreases reaction, increases reaction	4
Valproic Acid	increases expression, affects cotreatment, decreases expression	4
Aflatoxin B1	decreases expression, decreases methylation, increases methylation	4
bisphenol A	affects cotreatment, increases methylation, decreases expression, increases expression	3
ochratoxin A	increases acetylation, affects reaction, decreases expression	3
perfluorooctane sulfonic acid	decreases reaction, increases expression, decreases expression	3
2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one	decreases expression, decreases reaction	3
Ethanol	decreases reaction, affects localization, decreases expression	3
Arsenic	increases abundance, affects methylation, affects phosphorylation, increases expression, decreases expression (+1 more)	3
Quercetin	affects localization, decreases expression, decreases reaction	3
deoxynivalenol	affects localization, increases expression	2
trichostatin A	decreases expression, increases expression	2
perfluorooctanoic acid	decreases expression, increases expression, affects cotreatment, increases abundance	2
2,3’,4,4’,5-pentachlorobiphenyl	affects cotreatment, decreases expression, decreases reaction	2
bisindolylmaleimide I	affects localization, decreases reaction, increases phosphorylation, increases expression	2
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one	affects localization, decreases expression, decreases reaction	2
SB 203580	decreases reaction, decreases expression	2
ethyl 6-(N-(2-chloro-4-fluorophenyl)sulfamoyl)cyclohex-1-ene-1-carboxylate	decreases expression, decreases reaction, affects cotreatment	2
Resveratrol	decreases expression, decreases reaction	2
Fulvestrant	affects cotreatment, increases methylation, decreases reaction, increases expression	2
Acetaldehyde	affects localization, decreases reaction, affects reaction	2
Benzo(a)pyrene	affects methylation, decreases expression	2
Cadmium	affects localization, decreases expression, affects expression, affects response to substance	2
Hydrogen Peroxide	affects expression, decreases expression, decreases reaction	2
Indomethacin	decreases expression, decreases reaction	2
Methotrexate	decreases expression, increases expression	2

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_TB58	HAP1 OCLN (-) 1	Cancer cell line	Male
CVCL_XR28	HAP1 OCLN (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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