Microvillus inclusion disease

Summary

Microvillus inclusion disease (MONDO:0009635) is a disease caused by MYO5B (GenCC Definitive), with 4 cohort genes and 1 clinical trial.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Causal gene: MYO5B (GenCC Definitive)
• Cohort genes: 4
• ClinVar variants: 387
• Phenotypes (HPO): 11
• Clinical trials: 1

Clinical features

Epidemiology

Prevalence records

3 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		137	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated
Point prevalence	<1 / 1 000 000		Europe	Validated

Signs & symptoms

Clinical features (HPO)

11 HPO clinical features (Orphanet curated; top 11 by frequency):

HPO ID	Term	Frequency
HP:0000121	Nephrocalcinosis	Frequent (30-79%)
HP:0000989	Pruritus	Frequent (30-79%)
HP:0001263	Global developmental delay	Frequent (30-79%)
HP:0001942	Metabolic acidosis	Frequent (30-79%)
HP:0001944	Dehydration	Frequent (30-79%)
HP:0002014	Diarrhea	Frequent (30-79%)
HP:0003270	Abdominal distention	Frequent (30-79%)
HP:0011106	Hypovolemia	Frequent (30-79%)
HP:0011472	Abnormality of small intestinal villus morphology	Frequent (30-79%)
HP:0011473	Villous atrophy	Frequent (30-79%)
HP:0012211	Abnormal renal physiology	Frequent (30-79%)

Identifiers

Disease identifiers

Field	Value
Canonical name	microvillus inclusion disease
Mondo ID	MONDO:0009635
OMIM	251850
Orphanet	2290
DOID	DOID:0060775
ICD-11	2137578537
SNOMED CT	235729009
UMLS	C0341306
MedGen	137954
GARD	0007039
MedDRA	10068494
NORD	1446
Is cancer (heuristic)	no

Also known as: congenital familial protracted diarrhea · congenital familial protracted diarrhea with enterocyte brush-border abnormalities · congenital familial protracted diarrhoea · congenital familial protracted diarrhoea with enterocyte Brush-border abnormalities · congenital familial protracted diarrhoea with enterocyte brush-border abnormalities · congenital microvillous atrophy · congenital microvillus atrophy · Davidson disease · Davidson’s disease · DIAR2 · diarrhea 2, with microvillus atrophy · diarrhoea 2 with microvillus atrophy · diarrhoea 2, with microvillus atrophy · familial enteropathy, microvillus · intractable diarrhoea of infancy · microvillous inclusion disease · microvillus inclusion disease · MVID · MYO5B secretory diarrhea · MYO5B secretory diarrhoea (+2 more)

Data availability: 387 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 › secretory diarrhea › congenital secretory diarrhea › microvillus inclusion disease

Related subtypes (4): congenital secretory chloride diarrhea 1, congenital secretory sodium diarrhea 3, congenital diarrhea 5 with tufting enteropathy, congenital secretory sodium diarrhea 8

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

387 retrieved; paginated sample, class counts are floors:

205 uncertain significance, 57 benign, 56 conflicting classifications of pathogenicity, 25 pathogenic, 18 benign/likely benign, 17 likely pathogenic, 5 likely benign, 4 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1031041	NM_001080467.3(MYO5B):c.2641C>T (p.Gln881Ter)	MYO5B	Pathogenic	criteria provided, multiple submitters, no conflicts
1301570	NM_001080467.3(MYO5B):c.2062C>T (p.Arg688Ter)	MYO5B	Pathogenic	criteria provided, multiple submitters, no conflicts
1679140	NM_001080467.3(MYO5B):c.4090C>T (p.Gln1364Ter)	MYO5B	Pathogenic	criteria provided, single submitter
1686950	NM_001080467.3(MYO5B):c.2259_2262dup (p.Tyr755fs)	MYO5B	Pathogenic	no assertion criteria provided
1686963	NM_001080467.3(MYO5B):c.28-2A>G	MYO5B	Pathogenic	no assertion criteria provided
1686964	NM_001080467.3(MYO5B):c.4366C>T (p.Gln1456Ter)	MYO5B	Pathogenic	no assertion criteria provided
1686965	NM_001080467.3(MYO5B):c.4460-1G>C	MYO5B	Pathogenic	no assertion criteria provided
1686966	NM_001080467.3(MYO5B):c.1540T>C (p.Cys514Arg)	MYO5B	Pathogenic	no assertion criteria provided
1686967	NM_001080467.3(MYO5B):c.2330del (p.Gly777fs)	MYO5B	Pathogenic	criteria provided, single submitter
2138152	NM_001080467.3(MYO5B):c.3046C>T (p.Arg1016Ter)	MYO5B	Pathogenic	criteria provided, multiple submitters, no conflicts
2152298	NM_001080467.3(MYO5B):c.4168C>T (p.Gln1390Ter)	MYO5B	Pathogenic	criteria provided, multiple submitters, no conflicts
2431612	NM_001080467.3(MYO5B):c.1110_1113del (p.Ser370fs)	MYO5B	Pathogenic	criteria provided, single submitter
3068174	NM_001080467.3(MYO5B):c.2723_2726dup (p.Glu909delinsAspTer)	MYO5B	Pathogenic	criteria provided, single submitter
3255321	NM_001080467.3(MYO5B):c.4036C>T (p.Gln1346Ter)	MYO5B	Pathogenic	criteria provided, single submitter
3255322	NM_001080467.3(MYO5B):c.1906-1G>A	MYO5B	Pathogenic	criteria provided, single submitter
3255326	NM_001080467.3(MYO5B):c.1462del (p.Ile488fs)	MYO5B	Pathogenic	criteria provided, multiple submitters, no conflicts
4247	NM_001080467.3(MYO5B):c.1363_1364insGTTCTGTAA (p.Cys454_Ile455insSerSerVal)	MYO5B	Pathogenic	no assertion criteria provided
4249	NM_001080467.3(MYO5B):c.323T>G (p.Val108Gly)	MYO5B	Pathogenic	no assertion criteria provided
4250	NM_001080467.3(MYO5B):c.1125G>A (p.Trp375Ter)	MYO5B	Pathogenic	criteria provided, single submitter
4252	NM_001080467.3(MYO5B):c.1979C>T (p.Pro660Leu)	MYO5B	Pathogenic	criteria provided, single submitter
4277796	NM_001080467.3(MYO5B):c.1411T>C (p.Phe471Leu)	MYO5B	Pathogenic	criteria provided, single submitter
4537421	NM_001080467.3(MYO5B):c.660del (p.Phe220fs)	MYO5B	Pathogenic	criteria provided, single submitter
4814142	NM_001080467.3(MYO5B):c.1346del (p.Ser449fs)	MYO5B	Pathogenic	criteria provided, single submitter
4845331	NM_001080467.3(MYO5B):c.1350dup (p.Glu451Ter)	MYO5B	Pathogenic	criteria provided, single submitter
666977	NM_001080467.3(MYO5B):c.1347del (p.Phe450fs)	MYO5B	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
803491	NM_001080467.3(MYO5B):c.656G>A (p.Arg219His)	MYO5B	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
973894	NM_001080467.3(MYO5B):c.3277-2A>G	MYO5B	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
986347	NM_001080467.3(MYO5B):c.947G>T (p.Gly316Val)	MYO5B	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
488385	NM_001080467.3(MYO5B):c.4905del (p.Thr1636fs)	SNHG22	Pathogenic	criteria provided, multiple submitters, no conflicts
1184992	NM_001080467.3(MYO5B):c.2090+3A>T	MYO5B	Likely pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 18 · Orphanet: 5 · 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
MYO5B	Definitive	Autosomal recessive	microvillus inclusion disease	6
STX3	Strong	Autosomal recessive	retinal dystrophy and microvillus inclusion disease	5
STXBP2	Limited	Autosomal recessive	microvillus inclusion disease	7

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
MYO5B	Orphanet:2290	Microvillus inclusion disease
MYO5B	Orphanet:480491	MYO5B-related progressive familial intrahepatic cholestasis
MYO5B	Orphanet:79306	Progressive familial intrahepatic cholestasis type 1
STX3	Orphanet:2290	Microvillus inclusion disease
STXBP2	Orphanet:540	Familial hemophagocytic lymphohistiocytosis

Cohort genes → proteins

4 cohort genes, 3 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	4

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
MYO5B	HGNC:7603	ENSG00000167306	Q9ULV0	Unconventional myosin-Vb	gencc,clinvar
STX3	HGNC:11438	ENSG00000166900	Q13277	Syntaxin-3	gencc
STXBP2	HGNC:11445	ENSG00000076944	Q15833	Syntaxin-binding protein 2	gencc
SNHG22	HGNC:50285	ENSG00000267322		small nucleolar RNA host gene 22	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
MYO5B	Unconventional myosin-Vb	May be involved in vesicular trafficking via its association with the CART complex.
STX3	Syntaxin-3	Potentially involved in docking of synaptic vesicles at presynaptic active zones.
STXBP2	Syntaxin-binding protein 2	Involved in intracellular vesicle trafficking and vesicle fusion with membranes.

Protein-family classification

Druggable: 0 · Difficult: 1 · Unknown: 3 · 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	4.3×	0.404
Other/Unknown	3	1.3×	0.404

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
MYO5B	Scaffold/PPI	no		IQ_motif_EF-hand-BS, Myosin_head_motor_dom-like, Dilute_dom
STX3	Other/Unknown	no		T_SNARE_dom, Syntaxin_N, Syntaxin/epimorphin_CS
STXBP2	Other/Unknown	no		Sec1-like, Sec1-like_dom2, Sec1-like_sf
SNHG22	Other/Unknown	no

Expression context

Cohort genes with no expression data: 0.

4 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)	4
unknown	0

Top tissues across cohort

Tissue	Cohort genes
ileal mucosa	1
jejunal mucosa	1
lower esophagus mucosa	1
blood	1
rectum	1
right lung	1
granulocyte	1
leukocyte	1
monocyte	1
bone marrow cell	1
colonic epithelium	1
sural nerve	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
MYO5B	228	broad	marker	ileal mucosa, lower esophagus mucosa, jejunal mucosa
STX3	263	ubiquitous	marker	rectum, right lung, blood
STXBP2	227	ubiquitous	marker	granulocyte, monocyte, leukocyte
SNHG22	167	ubiquitous	marker	colonic epithelium, sural nerve, bone marrow cell

Protein interactions among cohort

Intra-cohort edges: 2.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
MYO5B	3,604
STX3	1,869
STXBP2	1,556
SNHG22	0

Intra-cohort edges

A	B	Sources
MYO5B	STX3	string_interaction
STX3	STXBP2	biogrid_interaction, intact, string_interaction

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
MYO5B	Q9ULV0	4
STXBP2	Q15833	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
STX3	Q13277	83.60

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 11. Enrichment computed across 4 evidence-associated genes (3 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 3 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Other interleukin signaling	2	317.2×	1e-04	STX3, STXBP2
Signaling by Interleukins	2	42.8×	0.004	STX3, STXBP2
Cytokine Signaling in Immune system	2	27.2×	0.006	STX3, STXBP2
Aquaporin-mediated transport	1	122.8×	0.022	MYO5B
Vasopressin regulates renal water homeostasis via Aquaporins	1	88.5×	0.025	MYO5B
Response to elevated platelet cytosolic Ca2+	1	54.4×	0.029	STXBP2
Immune System	2	8.6×	0.029	STX3, STXBP2
Platelet activation, signaling and aggregation	1	35.2×	0.039	STXBP2
Platelet degranulation	1	29.3×	0.041	STXBP2
Hemostasis	1	12.0×	0.089	STXBP2
Transport of small molecules	1	8.4×	0.115	MYO5B

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
leukocyte mediated cytotoxicity	1	5617.3×	0.002	STXBP2
organelle membrane fusion	1	5617.3×	0.002	STX3
exocytic insertion of neurotransmitter receptor to postsynaptic membrane	1	2808.7×	0.003	STX3
presynaptic dense core vesicle exocytosis	1	1404.3×	0.004	STXBP2
intracellular protein transport	2	43.2×	0.004	STX3, STXBP2
neutrophil degranulation	1	1123.5×	0.004	STXBP2
regulation of mast cell degranulation	1	624.1×	0.006	STXBP2
vesicle-mediated transport in synapse	1	510.7×	0.007	STX3
positive regulation of chemotaxis	1	280.9×	0.010	STX3
obsolete vesicle docking	1	255.3×	0.010	STX3
positive regulation of protein localization to cell surface	1	255.3×	0.010	STX3
obsolete vesicle docking involved in exocytosis	1	224.7×	0.010	STXBP2
vesicle fusion	1	200.6×	0.010	STX3
renal water homeostasis	1	170.2×	0.011	MYO5B
neurotransmitter transport	1	140.4×	0.013	STX3
long-term synaptic potentiation	1	93.6×	0.016	STX3
positive regulation of cell adhesion	1	90.6×	0.016	STX3
positive regulation of protein localization to plasma membrane	1	90.6×	0.016	STX3
endosomal transport	1	81.4×	0.017	MYO5B
cellular response to type II interferon	1	69.3×	0.019	STXBP2
neuron projection development	1	40.7×	0.031	STX3
actin filament organization	1	39.6×	0.031	MYO5B
vesicle-mediated transport	1	32.1×	0.035	MYO5B
endocytosis	1	31.7×	0.035	MYO5B
regulation of gene expression	1	27.8×	0.038	STX3
protein transport	1	14.6×	0.069	MYO5B
positive regulation of cell population proliferation	1	11.2×	0.087	STX3

Therapeutics

Drug target analysis

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

Druggability breadth: 0 of 4 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
MYO5B	0	0
STX3	0	0
STXBP2	0	0
SNHG22	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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	4	MYO5B, STX3, STXBP2, SNHG22

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
MYO5B	0	—
STX3	0	—
STXBP2	0	—
SNHG22	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 1.

Phase distribution (across all retrieved trials)

Phase	Trials
PHASE2	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT06721871	PHASE2	RECRUITING	Ascending Doses of Crofelemer Powder for Oral Solution in Pediatric Microvillus Inclusion Disease (MVID)