Congenital diarrhea 7 with exudative enteropathy

Summary

Congenital diarrhea 7 with exudative enteropathy (MONDO:0014375) is a disease caused by DGAT1 (GenCC Strong), with 2 cohort genes.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Causal gene: DGAT1 (GenCC Strong)
• Cohort genes: 2
• ClinVar variants: 44

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		2	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Identifiers

Disease identifiers

Field	Value
Canonical name	congenital diarrhea 7 with exudative enteropathy
Mondo ID	MONDO:0014375
OMIM	615863
Orphanet	329242
DOID	DOID:0060778
UMLS	C4014516
MedGen	862953
GARD	0017500
Is cancer (heuristic)	no

Also known as: congenital chronic diarrhea with exudative enteropathy · congenital chronic diarrhea with protein-losing enteropathy · congenital diarrhea caused by mutation in DGAT1 · congenital diarrhoea caused by mutation in DGAT1 · DGAT1 congenital diarrhea · DGAT1 congenital diarrhoea · DIAR7 · diarrhea 7 · diarrhea 7, protein-losing enteropathy type · diarrhea type 7 · diarrhoea 7 · diarrhoea 7, protein-losing enteropathy type · diarrhoea type 7

Data availability: 44 ClinVar variants · 6 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › digestive system disorder › diarrheal disease › congenital diarrhea › congenital diarrhea 7 with exudative enteropathy

Related subtypes (11): congenital malabsorptive diarrhea 4, congenital diarrhea 6, congenital sodium diarrhea, diarrhea 12, with microvillus atrophy, diarrhea 9, diarrhea 10, protein-losing enteropathy type, 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

44 retrieved; paginated sample, class counts are floors:

14 likely pathogenic, 11 uncertain significance, 9 pathogenic, 6 conflicting classifications of pathogenicity, 4 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1338779	NM_012079.6(DGAT1):c.805_*341del (p.Arg269fs)	DGAT1	Pathogenic	criteria provided, single submitter
139512	NM_012079.6(DGAT1):c.751+2T>C	DGAT1	Pathogenic	criteria provided, multiple submitters, no conflicts
1685693	NM_012079.6(DGAT1):c.1183C>T (p.Arg395Ter)	DGAT1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1685694	NM_012079.6(DGAT1):c.719_737dup (p.Leu247fs)	DGAT1	Pathogenic	criteria provided, single submitter
2636390	NM_012079.6(DGAT1):c.1094+2T>C	DGAT1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2834092	NM_012079.6(DGAT1):c.355C>T (p.Gln119Ter)	DGAT1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2842666	NM_012079.6(DGAT1):c.1190del (p.Gly397fs)	DGAT1	Pathogenic	criteria provided, multiple submitters, no conflicts
3255347	NM_012079.6(DGAT1):c.1202G>A (p.Trp401Ter)	DGAT1	Pathogenic	criteria provided, single submitter
4532092	NM_012079.6(DGAT1):c.796_809del (p.Asn266fs)	DGAT1	Pathogenic	criteria provided, single submitter
548013	NM_012079.6(DGAT1):c.629_631del (p.Ser210del)	DGAT1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
802448	NM_012079.6(DGAT1):c.889del (p.Gln297fs)	DGAT1	Pathogenic	criteria provided, single submitter
802449	NM_012079.6(DGAT1):c.838C>T (p.Arg280Ter)	DGAT1	Pathogenic	criteria provided, multiple submitters, no conflicts
816919	NM_012079.6(DGAT1):c.5del (p.Gly2fs)	DGAT1	Pathogenic	criteria provided, multiple submitters, no conflicts
1705597	NM_012079.6(DGAT1):c.140del (p.Pro47fs)	DGAT1	Likely pathogenic	criteria provided, single submitter
1801378	NM_012079.6(DGAT1):c.314T>C (p.Leu105Pro)	DGAT1	Likely pathogenic	criteria provided, single submitter
217459	NM_012079.6(DGAT1):c.884T>C (p.Leu295Pro)	DGAT1	Likely pathogenic	criteria provided, single submitter
2573105	NM_012079.6(DGAT1):c.1049C>T (p.Ala350Val)	DGAT1	Likely pathogenic	no assertion criteria provided
2573110	NM_012079.6(DGAT1):c.1215_1216del (p.Phe408fs)	DGAT1	Likely pathogenic	no assertion criteria provided
3255348	NM_012079.6(DGAT1):c.1072C>T (p.Arg358Trp)	DGAT1	Likely pathogenic	criteria provided, single submitter
3355242	NM_012079.6(DGAT1):c.1208_1217dup (p.Val407fs)	DGAT1	Likely pathogenic	criteria provided, single submitter
3595436	NM_012079.6(DGAT1):c.1393C>T (p.Gln465Ter)	DGAT1	Likely pathogenic	criteria provided, single submitter
3595437	NM_012079.6(DGAT1):c.777dup (p.Thr260fs)	DGAT1	Likely pathogenic	criteria provided, single submitter
421742	NM_012079.6(DGAT1):c.676+1G>A	DGAT1	Likely pathogenic	criteria provided, single submitter
489286	NM_012079.6(DGAT1):c.1311+1G>A	DGAT1	Likely pathogenic	criteria provided, single submitter
504005	NM_012079.6(DGAT1):c.1462del (p.Ala488fs)	DGAT1	Likely pathogenic	criteria provided, single submitter
684435	NM_012079.6(DGAT1):c.981+1G>T	DGAT1	Likely pathogenic	criteria provided, single submitter
684436	NM_012079.6(DGAT1):c.1310A>G (p.Gln437Arg)	DGAT1	Likely pathogenic	no assertion criteria provided
1053416	NM_012079.6(DGAT1):c.1374G>A (p.Trp458Ter)	DGAT1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1352679	NM_012079.6(DGAT1):c.1270C>T (p.Arg424Ter)	DGAT1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1422658	NM_012079.6(DGAT1):c.540_542dup (p.Ala181dup)	DGAT1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 9 · Orphanet: 2 · 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
DGAT1	Strong	Autosomal recessive	congenital diarrhea 7 with exudative enteropathy	5
PLVAP	Strong	Autosomal recessive	diarrhea 10, protein-losing enteropathy type	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
DGAT1	Orphanet:329242	Congenital chronic diarrhea with protein-losing enteropathy
PLVAP	Orphanet:329242	Congenital chronic diarrhea with protein-losing enteropathy

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
DGAT1	HGNC:2843	ENSG00000185000	O75907	Diacylglycerol O-acyltransferase 1	gencc,clinvar
PLVAP	HGNC:13635	ENSG00000130300	Q9BX97	Plasmalemma vesicle-associated protein	gencc

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
DGAT1	Diacylglycerol O-acyltransferase 1	Catalyzes the terminal and only committed step in triacylglycerol synthesis by using diacylglycerol and fatty acyl CoA as substrates.
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: 1 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.5

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
Enzyme (other)	1	6.0×	0.320
Other/Unknown	1	0.9×	0.805

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
DGAT1	Enzyme (other)	yes	2.3.1.20	MBOAT_fam, Oat_ACAT_DAG_ARE, Diacylglycerol_acylTrfase1
PLVAP	Other/Unknown	no		PV-1

Expression context

Cohort genes with no expression data: 0.

2 cohort genes 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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
duodenum	1
mucosa of transverse colon	1
right adrenal gland cortex	1
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
DGAT1	134	ubiquitous	marker	duodenum, mucosa of transverse colon, right adrenal gland cortex
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
DGAT1	2,407
PLVAP	1,546

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
DGAT1	O75907	5

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
PLVAP	Q9BX97	82.39

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 3. Enrichment computed across 2 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
Acyl chain remodeling of DAG and TAG	1	1631.4×	0.002	DGAT1
Triglyceride biosynthesis	1	671.8×	0.002	DGAT1
Neutrophil degranulation	1	23.1×	0.043	DGAT1

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 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	1685.2×	0.004	PLVAP
long-chain fatty-acyl-CoA metabolic process	1	1203.7×	0.004	DGAT1
monoacylglycerol biosynthetic process	1	766.0×	0.004	DGAT1
very-low-density lipoprotein particle assembly	1	601.9×	0.004	DGAT1
diacylglycerol metabolic process	1	601.9×	0.004	DGAT1
regulation of vascular permeability	1	561.7×	0.004	PLVAP
fatty acid homeostasis	1	468.1×	0.004	DGAT1
triglyceride biosynthetic process	1	366.4×	0.004	DGAT1
developmental process	1	337.0×	0.004	PLVAP
lipid storage	1	271.8×	0.005	DGAT1
triglyceride metabolic process	1	221.7×	0.005	DGAT1
tumor necrosis factor-mediated signaling pathway	1	165.2×	0.007	PLVAP
MAPK cascade	1	76.6×	0.013	PLVAP

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 2 evidence-associated genes (50%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
DGAT1	3	3
PLVAP	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
PRADIGASTAT	3	DGAT1
PF-04620110	1	DGAT1
AZD-7687	1	DGAT1

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
DGAT1	130	Binding:130

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
DGAT1	2.3.1.20	diacylglycerol O-acyltransferase

Cohort genes with high screening signal

≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.

Symbol	ChEMBL assays
DGAT1	130

Pharmacogenomics

Cohort genes with a PharmGKB record: 2; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

3 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.

Compound	Max phase	Cohort target (bioactivity)
PRADIGASTAT	3	DGAT1
PF-04620110	1	DGAT1
AZD-7687	1	DGAT1

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	1	DGAT1
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.