Diarrhea 12, with microvillus atrophy

Summary

Diarrhea 12, with microvillus atrophy (MONDO:0030335) is a disease caused by STX3 (GenCC Strong), with 2 cohort genes.

At a glance

• Causal gene: STX3 (GenCC Strong)
• Cohort genes: 2
• ClinVar variants: 3

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	diarrhea 12, with microvillus atrophy
Mondo ID	MONDO:0030335
OMIM	619445
UMLS	C5561942
MedGen	1794152
Is cancer (heuristic)	no

Also known as: DIAR12 · diarrhea 12, with microvillus atrophy · microvillus inclusion disease 2

Data availability: 3 ClinVar variants · 1 GenCC gene-disease record.

Disease family

Classification path: disease › human disease › disease by body system or component › digestive system disorder › diarrheal disease › congenital diarrhea › diarrhea 12, with microvillus atrophy

Related subtypes (11): congenital malabsorptive diarrhea 4, congenital diarrhea 6, congenital diarrhea 7 with exudative enteropathy, congenital sodium diarrhea, 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

3 retrieved; paginated sample, class counts are floors:

2 pathogenic, 1 conflicting classifications of pathogenicity

ClinVar	Variant (HGVS)	Gene	Classification	Review
1434000	NM_213607.3(DNAAF19):c.328C>T (p.Arg110Ter)	DNAAF19	Pathogenic	criteria provided, multiple submitters, no conflicts
1069027	NM_004177.5(STX3):c.739C>T (p.Arg247Ter)	STX3	Pathogenic	criteria provided, single submitter
915320	NM_004177.5(STX3):c.589C>T (p.Arg197Ter)	STX3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · 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
STX3	Strong	Autosomal recessive	retinal dystrophy and microvillus inclusion disease	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
STX3	Orphanet:2290	Microvillus inclusion disease
DNAAF19	Orphanet:244	Primary ciliary dyskinesia

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
STX3	HGNC:11438	ENSG00000166900	Q13277	Syntaxin-3	gencc,clinvar
DNAAF19	HGNC:32700	ENSG00000167131	Q8IW40	Dynein axonemal assembly factor 19	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
STX3	Syntaxin-3	Potentially involved in docking of synaptic vesicles at presynaptic active zones.
DNAAF19	Dynein axonemal assembly factor 19	Dynein-attachment factor required for cilia motility.

Protein-family classification

Druggable: 0 · Difficult: 0 · 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
Other/Unknown	2	1.8×	0.312

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
STX3	Other/Unknown	no		T_SNARE_dom, Syntaxin_N, Syntaxin/epimorphin_CS
DNAAF19	Other/Unknown	no		RPAP3-like_C, Dynein_attach_N, CC103

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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
blood	1
rectum	1
right lung	1
left testis	1
male germ line stem cell (sensu Vertebrata) in testis	1
testis	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
STX3	263	ubiquitous	marker	rectum, right lung, blood
DNAAF19	130	broad	yes	male germ line stem cell (sensu Vertebrata) in testis, left testis, testis

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
STX3	1,869
DNAAF19	764

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
STX3	Q13277	83.60
DNAAF19	Q8IW40	80.42

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 4. 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
Other interleukin signaling	1	475.8×	0.008	STX3
Signaling by Interleukins	1	64.2×	0.031	STX3
Cytokine Signaling in Immune system	1	40.8×	0.033	STX3
Immune System	1	13.0×	0.077	STX3

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
organelle membrane fusion	1	8426.0×	0.003	STX3
exocytic insertion of neurotransmitter receptor to postsynaptic membrane	1	4213.0×	0.003	STX3
determination of digestive tract left/right asymmetry	1	1404.3×	0.005	DNAAF19
vesicle-mediated transport in synapse	1	766.0×	0.005	STX3
epithelial cilium movement involved in determination of left/right asymmetry	1	648.1×	0.005	DNAAF19
axonemal dynein complex assembly	1	526.6×	0.005	DNAAF19
inner dynein arm assembly	1	443.5×	0.005	DNAAF19
positive regulation of chemotaxis	1	421.3×	0.005	STX3
epithelial cilium movement involved in extracellular fluid movement	1	383.0×	0.005	DNAAF19
obsolete vesicle docking	1	383.0×	0.005	STX3
positive regulation of protein localization to cell surface	1	383.0×	0.005	STX3
outer dynein arm assembly	1	366.4×	0.005	DNAAF19
vesicle fusion	1	300.9×	0.006	STX3
neurotransmitter transport	1	210.7×	0.008	STX3
cilium movement	1	195.9×	0.008	DNAAF19
long-term synaptic potentiation	1	140.4×	0.009	STX3
positive regulation of cell adhesion	1	135.9×	0.009	STX3
positive regulation of protein localization to plasma membrane	1	135.9×	0.009	STX3
heart looping	1	133.8×	0.009	DNAAF19
determination of left/right symmetry	1	127.7×	0.009	DNAAF19
neuron projection development	1	61.1×	0.019	STX3
regulation of gene expression	1	41.7×	0.026	STX3
intracellular protein transport	1	32.4×	0.032	STX3
positive regulation of cell population proliferation	1	16.8×	0.059	STX3

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 2

Druggability breadth: 0 of 2 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
STX3	0	0
DNAAF19	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

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	2	STX3, DNAAF19

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
STX3	0	—
DNAAF19	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.