Congenital diarrhea

Summary

Congenital diarrhea (MONDO:0000824) is a disease (an umbrella term covering 12 Mondo subtypes) with 3 cohort genes.

At a glance

• Umbrella term: 12 Mondo subtypes
• Cohort genes: 3
• ClinVar variants: 5

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	congenital diarrhea
Mondo ID	MONDO:0000824
OMIM	214700
DOID	DOID:0060774
UMLS	C6013449
MedGen	1877146
Is cancer (heuristic)	no

Also known as: diarrhea, congenital

Data availability: 5 ClinVar variants · 1 GenCC gene-disease record.

Disease family

An umbrella term covering 12 Mondo subtypes.

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

Related subtypes (6): secretory diarrhea, diarrheal disease secondary to altered bowel motility, inflammatory diarrhea, acute diarrhea, chronic diarrheal disease, non-infectious diarrheal disease

Subtypes (12): congenital malabsorptive diarrhea 4, congenital diarrhea 6, congenital diarrhea 7 with exudative enteropathy, 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

5 retrieved; paginated sample, class counts are floors:

4 likely pathogenic, 1 conflicting classifications of pathogenicity

ClinVar	Variant (HGVS)	Gene	Classification	Review
3252071	NM_031485.4(GRWD1):c.920A>G (p.His307Arg)	GRWD1	Likely pathogenic	criteria provided, single submitter
3252072	NM_031485.4(GRWD1):c.1102G>T (p.Val368Phe)	GRWD1	Likely pathogenic	criteria provided, single submitter
3252073	NM_032355.4(MON1A):c.454C>T (p.Arg152Cys)	MON1A	Likely pathogenic	criteria provided, single submitter
3252074	NM_005379.4(MYO1A):c.718G>A (p.Asp240Asn)	MYO1A	Likely pathogenic	criteria provided, single submitter
164588	NM_005379.4(MYO1A):c.2032A>T (p.Ile678Phe)	MYO1A	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 1 · 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
GRWD1	Limited	Autosomal recessive	congenital diarrhea

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
MYO1A	Orphanet:90635	Rare autosomal dominant non-syndromic sensorineural deafness type DFNA

Cohort genes → proteins

3 cohort genes, 3 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	3

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
GRWD1	HGNC:21270	ENSG00000105447	Q9BQ67	Glutamate-rich WD repeat-containing protein 1	gencc,clinvar
MON1A	HGNC:28207	ENSG00000164077	Q86VX9	Vacuolar fusion protein MON1 homolog A	clinvar
MYO1A	HGNC:7595	ENSG00000166866	Q9UBC5	Unconventional myosin-Ia	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
GRWD1	Glutamate-rich WD repeat-containing protein 1	Histone binding-protein that regulates chromatin dynamics and loading of minichromosome maintenance (MCM) complex at replication origins, possibly by promoting chromatin openness.
MON1A	Vacuolar fusion protein MON1 homolog A	Plays an important role in membrane trafficking through the secretory apparatus.
MYO1A	Unconventional myosin-Ia	Involved in directing the movement of organelles along actin filaments.

Protein-family classification

Druggable: 0 · Difficult: 1 · Unknown: 2 · 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
Scaffold/PPI	1	5.8×	0.327
Other/Unknown	2	1.2×	0.587

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
GRWD1	Scaffold/PPI	no		WD40_rpt, WD40/YVTN_repeat-like_dom_sf, WD40_repeat_CS
MON1A	Other/Unknown	no		Mon1, FUZ/MON1/HPS1_longin_3, FUZ/MON1/HPS1_longin_2
MYO1A	Other/Unknown	no		IQ_motif_EF-hand-BS, Myosin_head_motor_dom-like, Myosin_TH1

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)	3
unknown	0

Top tissues across cohort

Tissue	Cohort genes
gastrocnemius	1
muscle of leg	1
tongue squamous epithelium	1
kidney epithelium	1
prefrontal cortex	1
upper arm skin	1
ileal mucosa	1
jejunal mucosa	1
mucosa of transverse colon	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
GRWD1	285	ubiquitous	marker	tongue squamous epithelium, gastrocnemius, muscle of leg
MON1A	226	ubiquitous	yes	upper arm skin, kidney epithelium, prefrontal cortex
MYO1A	165	tissue_specific	marker	jejunal mucosa, mucosa of transverse colon, ileal mucosa

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
GRWD1	3,065
MON1A	1,124
MYO1A	989

Structural data

PDB: 1 · AlphaFold-only: 2 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
MON1A	Q86VX9	2

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
GRWD1	Q9BQ67	89.21
MYO1A	Q9UBC5	85.11

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 4. Enrichment computed across 3 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
Rab regulation of trafficking	1	368.4×	0.011	MON1A
RAB GEFs exchange GTP for GDP on RABs	1	124.1×	0.016	MON1A
Membrane Trafficking	1	37.1×	0.029	MON1A
Vesicle-mediated transport	1	34.8×	0.029	MON1A

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 3 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
vesicle localization	1	1872.4×	0.007	MYO1A
microvillus assembly	1	624.1×	0.010	MYO1A
protein targeting to vacuole	1	432.1×	0.010	MON1A
nucleosome disassembly	1	267.5×	0.010	GRWD1
actin filament-based movement	1	267.5×	0.010	MYO1A
ribosome biogenesis	1	208.1×	0.010	GRWD1
protein secretion	1	87.8×	0.021	MON1A
DNA replication	1	55.1×	0.029	GRWD1
nucleosome assembly	1	46.8×	0.031	GRWD1
actin filament organization	1	39.6×	0.031	MYO1A
sensory perception of sound	1	33.6×	0.031	MYO1A
vesicle-mediated transport	1	32.1×	0.031	MON1A
endocytosis	1	31.7×	0.031	MYO1A

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 3 evidence-associated genes (33%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
GRWD1	0	0
MON1A	0	0
MYO1A	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
GRWD1	6	Binding:6

Pharmacogenomics

Cohort genes with a PharmGKB record: 3; 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	3	GRWD1, MON1A, MYO1A

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
GRWD1	6	—
MON1A	0	—
MYO1A	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.