OCLN

protein-coding

occludin, the group of MARVEL domain containing|Tetraspan junctional complex superfamily|Protein phosphatase 1 regulatory subunits

Gene summary

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. [provided by RefSeq, Apr 2011]

MANE transcript

NM_001205254.2

Inheritance

ClinVar variants

P:24U:84B:29

Top phenotype

Pseudo-TORCH syndrome 1 (Band-like calcification with simplified gyration and polymicrogyria)

gnomAD constraint

pLI —, LoF o/e 0.6

Max pathogenic AF

—

Genomic locus

chr5:69,492,292-69,558,104

External References & Databases

Ensembl (ENSG00000197822)

NCBI Gene (100506658)

Transcript & Mutation Effects

hg38 • Region Span ~65.8 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

pseudo-TORCH syndrome 1DEFINITIVE

Inheritance Pattern: AR

Disease ID:MONDO:0020789

Submitter: G2P

pseudo-TORCH syndrome 1STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0020789

Submitter: PanelApp Australia

pseudo-TORCH syndromeSUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0009626

Submitter: Orphanet

pseudo-TORCH syndrome 1MODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0020789

Submitter: Ambry Genetics

pseudo-TORCH syndrome 1STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0020789

Submitter: Labcorp Genetics (formerly Invitae)

Clinical Genomic Database (CGD)

Pseudo-TORCH syndrome 1 (Band-like calcification with simplified gyration and polymicrogyria)AR

Manifestation: Neurologic

Intervention: General

Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing

Refs: 19012351; 19530192; 20727516

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to OCLN variants in ClinVar

8 Conditions Cataloged

not providedTotal: 74

Inborn genetic diseasesTotal: 54

Pseudo-TORCH syndrome 1Total: 29

not specifiedTotal: 12

OCLN-related disorderTotal: 3

Primary microcephalyTotal: 1

Global developmental delayTotal: 1

Cerebral calcificationTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001205254.2. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous		2 clinvar		17 clinvar	1 clinvar	20
missense	1 clinvar		79 clinvar	10 clinvar	1 clinvar	91
nonsense	5 clinvar	2 clinvar	1 clinvar			8
start loss						0
frameshift	5 clinvar	6 clinvar	3 clinvar			14
splice donor/acceptor (+/-2bp)		3 clinvar	1 clinvar			4
Total	11	13	84	27	2	137

Highest pathogenic variant AF is 0.00001950726

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 68 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001205254.2	RefSeq	NP_001192183.1	8	MANE Select
ENST00000396442.7	Ensembl	ENSP00000379719.2	8	MANE Select
NM_001205255.2	RefSeq	NP_001192184.1	6	Standard
NM_001410743.1	RefSeq	NP_001397672.1	7	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Cell adhesion molecules (CAMs) - Homo sapiens (human)
Tight junction - Homo sapiens (human)
Pathogenic Escherichia coli infection - Homo sapiens (human)
Hepatitis C - Homo sapiens (human)
Leukocyte transendothelial migration - Homo sapiens (human)

Biological Process

cell-cell junction organization
protein-containing complex assembly
response to interleukin-18
bicellular tight junction assembly
cellular response to tumor necrosis factor

Molecular Function

protein binding
protein domain specific binding

Cellular Component

plasma membrane
cell-cell junction
bicellular tight junction
integral component of membrane
apical plasma membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000355237
Coding exons: 8
Length: 65813
Individuals with no LoFs: 125697
Homozygous LoFs: 1
Heterozygous LoFs: 50
Defined: 125748
p: 0.000203

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.322	239	253	0.943	0.0000128	3405
Missense (PolyPhen)		80	87.457	0.91474		1228
Synonymous	2.29	63	90.7	0.694	0.00000510	971
Loss of Function	1.74	13	21.7	0.598	0.00000116	325

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00055	0.00055	rare
Latino/Admixed American	0.00032	0.00032	rare
Ashkenazi Jewish	0.00021	0.00020	rare
East Asian	0.00011	0.00011	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00022	0.00020	rare
South Asian	0.000098	0.000098	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: 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. {ECO:0000269|PubMed:19114660}.;
Disease: DISEASE: 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. {ECO:0000269|PubMed:20727516}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Recessive Scores

pRec: 0.395

Intolerance Scores

RVIS EVS: 0.48
RVIS percentile EVS: 79.25

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.932

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium