pseudo-TORCH syndrome 1

Summary

pseudo-TORCH syndrome 1 (MONDO:0020789) is a disease caused by OCLN (GenCC Definitive), with 1 cohort gene.

At a glance

• Causal gene: OCLN (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 28

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	pseudo-TORCH syndrome 1
Mondo ID	MONDO:0020789
OMIM	251290
UMLS	C4552078
MedGen	1639355
GARD	0025250
Is cancer (heuristic)	no

Also known as: pseudo-TORCH syndrome · pseudo-TORCH syndrome 1 · pseudo-TORCH syndrome type 1 · PTORCH1

Data availability: 28 ClinVar variants · 4 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › autosomal genetic disease › autosomal recessive disease › pseudo-TORCH syndrome › pseudo-TORCH syndrome 1

Related subtypes (2): pseudo-TORCH syndrome 2, pseudo-TORCH syndrome 3

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

28 retrieved; paginated sample, class counts are floors:

8 pathogenic, 8 uncertain significance, 7 likely pathogenic, 3 conflicting classifications of pathogenicity, 1 benign/likely benign, 1 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1029457	NM_001205254.2(OCLN):c.106C>T (p.Arg36Ter)	OCLN	Pathogenic	criteria provided, multiple submitters, no conflicts
1065616	NM_001205254.2(OCLN):c.52_891del840 (p.Lys18_Trp297del)	OCLN	Pathogenic	no assertion criteria provided
1323383	NM_001205254.2(OCLN):c.513C>A (p.Tyr171Ter)	OCLN	Pathogenic	criteria provided, single submitter
1526118	NM_001205254.2(OCLN):c.1324G>T (p.Glu442Ter)	OCLN	Pathogenic	criteria provided, single submitter
211774	NM_001205254.2(OCLN):c.1037+5G>A	OCLN	Pathogenic	criteria provided, single submitter
436101	NM_001205254.2(OCLN):c.1037+1G>A	OCLN	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
6750	NM_001205254.2(OCLN):c.171_193del (p.Lys57fs)	OCLN	Pathogenic	no assertion criteria provided
6751	NM_001205254.2(OCLN):c.512dup (p.Tyr171Ter)	OCLN	Pathogenic	no assertion criteria provided
6752	NM_001205254.2(OCLN):c.656T>C (p.Phe219Ser)	OCLN	Pathogenic	no assertion criteria provided
1029458	NM_001205254.2(OCLN):c.50+2T>C	OCLN	Likely pathogenic	criteria provided, single submitter
217516	NM_001205254.2(OCLN):c.252del (p.Ser85fs)	OCLN	Likely pathogenic	no assertion criteria provided
2446043	NM_001205254.2(OCLN):c.1542del (p.Gly515fs)	OCLN	Likely pathogenic	criteria provided, single submitter
2664921	NM_001205254.2(OCLN):c.1254-1G>A	OCLN	Likely pathogenic	criteria provided, single submitter
2690659	NM_001205254.2(OCLN):c.630_645del (p.Gln211fs)	OCLN	Likely pathogenic	criteria provided, single submitter
3384093	NM_001205254.2(OCLN):c.981del (p.Asn328fs)	OCLN	Likely pathogenic	criteria provided, single submitter
800964	NM_001205254.2(OCLN):c.546G>C (p.Leu182=)	OCLN	Likely pathogenic	no assertion criteria provided
159459	NM_001205254.2(OCLN):c.384C>T (p.Tyr128=)	OCLN	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
159460	NM_001205254.2(OCLN):c.452C>T (p.Ala151Val)	OCLN	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
211775	NM_001205254.2(OCLN):c.173_194del (p.Trp58fs)	OCLN	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
159461	NM_001205254.2(OCLN):c.4T>C (p.Ser2Pro)	OCLN	Uncertain significance	criteria provided, single submitter
183322	NM_001205254.2(OCLN):c.514dup (p.Tyr172fs)	OCLN	Uncertain significance	criteria provided, single submitter
2434483	NM_001205254.2(OCLN):c.472A>G (p.Thr158Ala)	OCLN	Uncertain significance	criteria provided, multiple submitters, no conflicts
2434484	NM_001205254.2(OCLN):c.215T>G (p.Ile72Ser)	OCLN	Uncertain significance	criteria provided, single submitter
2434485	NM_001205254.2(OCLN):c.811A>G (p.Met271Val)	OCLN	Uncertain significance	criteria provided, single submitter
2434486	NM_001205254.2(OCLN):c.944A>T (p.Tyr315Phe)	OCLN	Uncertain significance	criteria provided, single submitter
2585630	NM_001205254.2(OCLN):c.1216G>A (p.Gly406Ser)	OCLN	Uncertain significance	criteria provided, single submitter
2585631	NM_001205254.2(OCLN):c.175A>C (p.Thr59Pro)	OCLN	Uncertain significance	criteria provided, single submitter
159462	NM_001205254.2(OCLN):c.70C>G (p.Pro24Ala)	OCLN	Benign/Likely benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · Orphanet: 1 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
OCLN	Definitive	Autosomal recessive	pseudo-TORCH syndrome 1	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
OCLN	Orphanet:1229	Pseudo-TORCH syndrome type 1

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
OCLN	HGNC:8104	ENSG00000197822	Q16625	Occludin	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
OCLN	Occludin	May play a role in the formation and regulation of the tight junction (TJ) paracellular permeability barrier.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Transporter	1	77.8×	0.013

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
OCLN	Transporter	yes		Occludin, Marvel, Occludin_ELL

Expression context

Cohort genes with no expression data: 0.

1 cohort gene are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
ileal mucosa	1
islet of Langerhans	1
pancreatic ductal cell	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
OCLN	195	broad	marker	islet of Langerhans, ileal mucosa, pancreatic ductal cell

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
OCLN	4,533

Structural data

PDB: 1 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
OCLN	Q16625	3

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 3. Enrichment computed across 1 evidence-associated genes (1 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
RUNX1 regulates expression of components of tight junctions	1	2284.0×	1e-03	OCLN
Epithelial-Mesenchymal Transition (EMT) during gastrulation	1	1427.5×	1e-03	OCLN
Apoptotic cleavage of cell adhesion proteins	1	1038.2×	1e-03	OCLN

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
protein localization to cell leading edge	1	4213.0×	0.002	OCLN
positive regulation of blood-brain barrier permeability	1	3370.4×	0.002	OCLN
regulation of D-glucose transmembrane transport	1	2106.5×	0.002	OCLN
epithelial cell migration	1	936.2×	0.003	OCLN
positive regulation of microtubule polymerization	1	674.1×	0.003	OCLN
cell-cell junction organization	1	624.1×	0.003	OCLN
positive regulation of lamellipodium assembly	1	601.9×	0.003	OCLN
positive regulation of wound healing	1	526.6×	0.003	OCLN
maintenance of blood-brain barrier	1	481.5×	0.003	OCLN
positive regulation of D-glucose import across plasma membrane	1	455.5×	0.003	OCLN
bicellular tight junction assembly	1	330.4×	0.004	OCLN
protein-containing complex assembly	1	113.9×	0.010	OCLN
negative regulation of gene expression	1	69.1×	0.016	OCLN
positive regulation of gene expression	1	38.7×	0.026	OCLN

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 1

Druggability breadth: 0 of 1 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
OCLN	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

0 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	1	OCLN
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

Undrugged target profiles

1 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
OCLN	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.