Diarrhea 10, protein-losing enteropathy type

Summary

Diarrhea 10, protein-losing enteropathy type (MONDO:0032586) is a disease caused by PLVAP (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: PLVAP (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 9

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	diarrhea 10, protein-losing enteropathy type
Mondo ID	MONDO:0032586
OMIM	618183
UMLS	C4748579
MedGen	1648311
Is cancer (heuristic)	no

Also known as: DIAR10

Data availability: 9 ClinVar variants · 3 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › digestive system disorder › diarrheal disease › congenital diarrhea › diarrhea 10, protein-losing enteropathy type

Related subtypes (11): congenital malabsorptive diarrhea 4, congenital diarrhea 6, congenital diarrhea 7 with exudative enteropathy, congenital sodium diarrhea, diarrhea 12, with microvillus atrophy, diarrhea 9, diarrhea 11, malabsorptive, congenital, congenital secretory diarrhea, diarrhea 13, diarrhea 14, congenital, diarrhea 15, congenital

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

9 retrieved; paginated sample, class counts are floors:

3 uncertain significance, 3 pathogenic, 2 likely benign, 1 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
590326	NM_031310.3(PLVAP):c.1072C>T (p.Arg358Ter)	PLVAP	Pathogenic	criteria provided, multiple submitters, no conflicts
590327	NM_031310.3(PLVAP):c.988C>T (p.Gln330Ter)	PLVAP	Pathogenic	criteria provided, single submitter
590328	NM_031310.3(PLVAP):c.101T>C (p.Leu34Pro)	PLVAP	Pathogenic	no assertion criteria provided
2501702	NM_031310.3(PLVAP):c.1086del (p.Lys363fs)	PLVAP	Likely pathogenic	criteria provided, single submitter
2165325	NM_031310.3(PLVAP):c.1024C>T (p.Arg342Trp)	PLVAP	Uncertain significance	criteria provided, multiple submitters, no conflicts
4277301	NM_031310.3(PLVAP):c.712C>T (p.Arg238Cys)	PLVAP	Uncertain significance	criteria provided, single submitter
4846894	NM_031310.3(PLVAP):c.482T>C (p.Leu161Pro)	PLVAP	Uncertain significance	criteria provided, single submitter
1973330	NM_031310.3(PLVAP):c.1241-19C>T	PLVAP	Likely benign	criteria provided, multiple submitters, no conflicts
2079287	NM_031310.3(PLVAP):c.1040C>T (p.Ala347Val)	PLVAP	Likely benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 4 · 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
PLVAP	Strong	Autosomal recessive	diarrhea 10, protein-losing enteropathy type	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
PLVAP	Orphanet:329242	Congenital chronic diarrhea with protein-losing enteropathy

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
PLVAP	HGNC:13635	ENSG00000130300	Q9BX97	Plasmalemma vesicle-associated protein	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
PLVAP	Plasmalemma vesicle-associated protein	Endothelial cell-specific membrane protein involved in the formation of the diaphragms that bridge endothelial fenestrae.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.0

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
Other/Unknown	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
PLVAP	Other/Unknown	no		PV-1

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
left lobe of thyroid gland	1
right lobe of thyroid gland	1
thyroid gland	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
PLVAP	224	broad	marker	left lobe of thyroid gland, right lobe of thyroid gland, thyroid gland

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
PLVAP	1,546

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
PLVAP	Q9BX97	82.39

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 1 evidence-associated genes (0 with Reactome annotation).

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
positive regulation of cellular extravasation	1	3370.4×	0.001	PLVAP
regulation of vascular permeability	1	1123.5×	0.002	PLVAP
developmental process	1	674.1×	0.002	PLVAP
tumor necrosis factor-mediated signaling pathway	1	330.4×	0.004	PLVAP
MAPK cascade	1	153.2×	0.007	PLVAP

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
PLVAP	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	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	PLVAP

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)
PLVAP	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.