Congenital secretory sodium diarrhea 3
diseaseOn this page
Also known as congenital secretory sodium diarrhea type 3congenital secretory sodium diarrhoea type 3DIAR3diarrhea 3, secretory sodium, congenital, with or without other congenital anomaliesdiarrhoea 3, secretory sodium, congenital, syndromicdiarrhoea 3, secretory sodium, congenital, with or without other congenital anomaliessecretory diarrhea caused by mutation in SPINT2secretory diarrhoea caused by mutation in SPINT2SPINT2 secretory diarrheaSPINT2 secretory diarrhoea
Summary
Congenital secretory sodium diarrhea 3 (MONDO:0010036) is a disease caused by SPINT2 (GenCC Strong), with 1 cohort gene.
At a glance
- Causal gene: SPINT2 (GenCC Strong)
- Cohort genes: 1
- ClinVar variants: 15
Clinical features
No curated clinical features (Orphanet) for this disease.
Identifiers
Disease identifiers
| Field | Value |
|---|---|
| Canonical name | congenital secretory sodium diarrhea 3 |
| Mondo ID | MONDO:0010036 |
| OMIM | 270420 |
| DOID | DOID:0060781 |
| UMLS | C5441927 |
| MedGen | 1778108 |
| GARD | 0018260 |
| Is cancer (heuristic) | no |
Also known as: congenital secretory sodium diarrhea type 3 · congenital secretory sodium diarrhoea type 3 · DIAR3 · diarrhea 3, secretory sodium, congenital, with or without other congenital anomalies · diarrhoea 3, secretory sodium, congenital, syndromic · diarrhoea 3, secretory sodium, congenital, with or without other congenital anomalies · secretory diarrhea caused by mutation in SPINT2 · secretory diarrhoea caused by mutation in SPINT2 · SPINT2 secretory diarrhea · SPINT2 secretory diarrhoea
Data availability: 15 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 › congenital sodium diarrhea › congenital secretory sodium diarrhea 3
Related subtypes (2): congenital secretory sodium diarrhea 8, syndromic congenital sodium diarrhea
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
15 retrieved; paginated sample, class counts are floors:
8 pathogenic, 4 uncertain significance, 2 likely pathogenic, 1 pathogenic/likely pathogenic
| ClinVar | Variant (HGVS) | Gene | Classification | Review |
|---|---|---|---|---|
| 157607 | NM_021102.4(SPINT2):c.502G>A (p.Gly168Ser) | SPINT2 | Pathogenic | no assertion criteria provided |
| 1810622 | NM_021102.4(SPINT2):c.342del (p.Arg115fs) | SPINT2 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 3062101 | NM_021102.4(SPINT2):c.166_167dup (p.Asn57fs) | SPINT2 | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 5204 | NM_021102.4(SPINT2):c.593-1G>A | SPINT2 | Pathogenic | no assertion criteria provided |
| 5205 | NM_021102.4(SPINT2):c.488A>G (p.Tyr163Cys) | SPINT2 | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 5206 | NM_021102.4(SPINT2):c.337+2T>C | SPINT2 | Pathogenic | no assertion criteria provided |
| 5207 | NM_021102.4(SPINT2):c.553+2T>A | SPINT2 | Pathogenic | no assertion criteria provided |
| 5208 | NM_021102.4(SPINT2):c.1A>T (p.Met1Leu) | SPINT2 | Pathogenic | no assertion criteria provided |
| 635284 | NM_021102.4(SPINT2):c.447G>A (p.Trp149Ter) | SPINT2 | Pathogenic | no assertion criteria provided |
| 1321871 | NM_021102.4(SPINT2):c.386A>G (p.Tyr129Cys) | SPINT2 | Likely pathogenic | no assertion criteria provided |
| 2500740 | NM_021102.4(SPINT2):c.421C>G (p.Pro141Ala) | SPINT2 | Likely pathogenic | criteria provided, single submitter |
| 1028719 | NM_021102.4(SPINT2):c.553C>T (p.Arg185Cys) | SPINT2 | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 1481882 | NM_021102.4(SPINT2):c.593-2_593del | SPINT2 | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 2690070 | NM_021102.4(SPINT2):c.122C>T (p.Ser41Leu) | SPINT2 | Uncertain significance | criteria provided, single submitter |
| 4080191 | NM_021102.4(SPINT2):c.749_750del (p.Tyr250fs) | SPINT2 | Uncertain significance | criteria provided, single submitter |
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 |
|---|---|---|---|---|
| SPINT2 | Definitive | Autosomal recessive | syndromic congenital sodium diarrhea | 4 |
Orphanet rare-disease linkage (cohort genes)
| Gene | Orphanet ID | Rare disease |
|---|---|---|
| SPINT2 | Orphanet:563708 | Syndromic congenital sodium diarrhea |
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 |
|---|---|---|---|---|---|
| SPINT2 | HGNC:11247 | ENSG00000167642 | O43291 | Kunitz-type protease inhibitor 2 | gencc,clinvar |
Cohort function summary
Lead sentence per gene, UniProt-curated.
| Symbol | Protein name | Function (lead sentence) |
|---|---|---|
| SPINT2 | Kunitz-type protease inhibitor 2 | Inhibitor of HGFAC. |
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) |
|---|---|---|---|---|
| SPINT2 | Other/Unknown | no | Kunitz_BPTI, Prtase_inh_Kunz-CS, Kunitz_BPTI_sf |
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 |
|---|---|
| mucosa of transverse colon | 1 |
| parotid gland | 1 |
| type B pancreatic cell | 1 |
Per-gene tissue summary (top 30)
| Symbol | Bgee breadth | FANTOM5 breadth | SCXA | Top tissues |
|---|---|---|---|---|
| SPINT2 | 288 | ubiquitous | marker | type B pancreatic cell, mucosa of transverse colon, parotid gland |
Protein interactions among cohort
Intra-cohort edges: 0.
Hub genes (top 10 by interactor count)
| Symbol | Interactor count |
|---|---|
| SPINT2 | 1,426 |
Structural data
PDB: 1 · AlphaFold-only: 0 · No structure: 0
Cohort genes with PDB structures (top 30)
| Symbol | UniProt | PDB entries |
|---|---|---|
| SPINT2 | O43291 | 1 |
Function
Pathway analysis
Distinct Reactome pathways touched by cohort: 5. Enrichment computed across 1 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 |
|---|---|---|---|---|
| Signaling by MST1 | 1 | 2284.0× | 0.001 | SPINT2 |
| MET Receptor Activation | 1 | 1903.3× | 0.001 | SPINT2 |
| Signaling by MET | 1 | 317.2× | 0.005 | SPINT2 |
| Signaling by Receptor Tyrosine Kinases | 1 | 51.7× | 0.024 | SPINT2 |
| Signal Transduction | 1 | 10.2× | 0.098 | SPINT2 |
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 |
|---|---|---|---|---|
| epithelial cell morphogenesis involved in placental branching | 1 | 5617.3× | 0.001 | SPINT2 |
| negative regulation of neural precursor cell proliferation | 1 | 1532.0× | 0.002 | SPINT2 |
| negative regulation of cell motility | 1 | 1296.3× | 0.002 | SPINT2 |
| negative regulation of cell-cell adhesion | 1 | 991.3× | 0.002 | SPINT2 |
| cellular response to BMP stimulus | 1 | 561.7× | 0.003 | SPINT2 |
| basement membrane organization | 1 | 510.7× | 0.003 | SPINT2 |
| establishment or maintenance of cell polarity | 1 | 401.2× | 0.003 | SPINT2 |
| neural tube closure | 1 | 187.2× | 0.005 | SPINT2 |
Therapeutics
Drug target analysis
Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 1
Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).
Top cohort targets by molecule count
| Symbol | Molecules | Max phase |
|---|---|---|
| SPINT2 | 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 |
|---|---|---|
| SPINT2 | 1 | Binding:1 |
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 | SPINT2 |
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) |
|---|---|---|
| SPINT2 | 1 | — |
Clinical trials & evidence
Clinical trials
Clinical trials: 0.
Related Atlas pages
- Cohort genes: SPINT2