Renal hypomagnesemia 3
diseaseOn this page
Also known as CLDN16 familial primary hypomagnesemiaCLDN16 primary hypomagnesemiafamilial primary hypomagnesemia caused by mutation in CLDN16FHHNC without severe ocular involvementHOMG3hypomagnesemia 3, renalhypomagnesemia, familial, with hypercalciuria and nephrocalcinosishypomagnesemia, familial, with hypercalciuria and nephrocalcinosis hypercalciuria, childhood, self-limiting, includedhypomagnesemia, isolated renalhypomagnesemia, primary, due to defect in renal tubular Transport Of magnesiummagnesium, defect in renal tubular transport ofprimary hypomagnesemia caused by mutation in CLDN16renal hypomagnesemia type 3
Summary
Renal hypomagnesemia 3 (MONDO:0009550) is a disease caused by CLDN16 (GenCC Strong), with 1 cohort gene.
At a glance
- Prevalence: (Worldwide) [Orphanet-validated]
- Causal gene: CLDN16 (GenCC Strong)
- Cohort genes: 1
- ClinVar variants: 163
Clinical features
Epidemiology
Prevalence records
2 prevalence record(s), Orphanet:
| Type | Class | Value | Geography | Validation |
|---|---|---|---|---|
| Cases/families | 110 | Worldwide | Validated | |
| Point prevalence | <1 / 1 000 000 | Europe | Not yet validated |
Identifiers
Disease identifiers
| Field | Value |
|---|---|
| Canonical name | renal hypomagnesemia 3 |
| Mondo ID | MONDO:0009550 |
| MeSH | C537153 |
| OMIM | 248250 |
| Orphanet | 31043 |
| DOID | DOID:0060880 |
| SNOMED CT | 725033008 |
| UMLS | C0268448 |
| MedGen | 120640 |
| GARD | 0002906 |
| Is cancer (heuristic) | no |
Also known as: CLDN16 familial primary hypomagnesemia · CLDN16 primary hypomagnesemia · familial primary hypomagnesemia caused by mutation in CLDN16 · FHHNC without severe ocular involvement · HOMG3 · hypomagnesemia 3, renal · hypomagnesemia, familial, with hypercalciuria and nephrocalcinosis · hypomagnesemia, familial, with hypercalciuria and nephrocalcinosis hypercalciuria, childhood, self-limiting, included · hypomagnesemia, isolated renal · hypomagnesemia, primary, due to defect in renal tubular Transport Of magnesium · magnesium, defect in renal tubular transport of · primary hypomagnesemia caused by mutation in CLDN16 · renal hypomagnesemia type 3
Data availability: 163 ClinVar variants · 2 GenCC gene-disease records.
Disease family
Classification path: disease › human disease › disease by developmental or physiological process › metabolic disease › mineral metabolism disease › calcium metabolic disease › calcinosis › nephrocalcinosis › renal hypomagnesemia 3
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
163 retrieved; paginated sample, class counts are floors:
80 uncertain significance, 22 pathogenic, 18 likely pathogenic, 16 benign, 11 conflicting classifications of pathogenicity, 5 pathogenic/likely pathogenic, 5 likely benign, 4 benign/likely benign, 2 not provided
| ClinVar | Variant (HGVS) | Gene | Classification | Review |
|---|---|---|---|---|
| 1199406 | NM_006580.4(CLDN16):c.236G>A (p.Arg79Gln) | CLDN16 | Pathogenic | no assertion criteria provided |
| 30405 | NM_006580.4(CLDN16):c.613A>T (p.Lys205Ter) | CLDN16 | Pathogenic | no assertion criteria provided |
| 3250410 | NM_006580.4(CLDN16):c.374T>C (p.Leu125Pro) | CLDN16 | Pathogenic | criteria provided, single submitter |
| 3359186 | NM_006580.4(CLDN16):c.165del (p.Phe55fs) | CLDN16 | Pathogenic | no assertion criteria provided |
| 3362772 | NM_006580.4(CLDN16):c.436C>T (p.Arg146Cys) | CLDN16 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 3390939 | NM_006580.4(CLDN16):c.152T>G (p.Val51Gly) | CLDN16 | Pathogenic | criteria provided, single submitter |
| 3779533 | NM_006580.4(CLDN16):c.130C>T (p.Arg44Ter) | CLDN16 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 438693 | NM_006580.4(CLDN16):c.468del (p.Gly157fs) | CLDN16 | Pathogenic | no assertion criteria provided |
| 545703 | NM_006580.4(CLDN16):c.335_338dup (p.Lys113delinsAsnTer) | CLDN16 | Pathogenic | criteria provided, single submitter |
| 560390 | NM_006580.4(CLDN16):c.392G>A (p.Gly131Glu) | CLDN16 | Pathogenic | no assertion criteria provided |
| 5925 | NM_006580.4(CLDN16):c.235C>T (p.Arg79Ter) | CLDN16 | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 5926 | NM_006580.4(CLDN16):c.505G>A (p.Gly169Arg) | CLDN16 | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 5927 | NM_006580.4(CLDN16):c.361G>A (p.Gly121Arg) | CLDN16 | Pathogenic | criteria provided, single submitter |
| 5928 | NM_006580.4(CLDN16):c.383G>A (p.Gly128Asp) | CLDN16 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 5929 | NM_006580.4(CLDN16):c.2T>G (p.Met1Arg) | CLDN16 | Pathogenic | no assertion criteria provided |
| 5930 | NM_006580.4(CLDN16):c.290T>C (p.Leu97Pro) | CLDN16 | Pathogenic | no assertion criteria provided |
| 5932 | NM_006580.4(CLDN16):c.488G>A (p.Gly163Asp) | CLDN16 | Pathogenic | no assertion criteria provided |
| 5933 | NM_006580.4(CLDN16):c.494C>T (p.Ser165Phe) | CLDN16 | Pathogenic | no assertion criteria provided |
| 5934 | NM_006580.4(CLDN16):c.243G>T (p.Leu81Phe) | CLDN16 | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 5935 | NM_006580.4(CLDN16):c.242T>G (p.Leu81Trp) | CLDN16 | Pathogenic | no assertion criteria provided |
| 5936 | NM_006580.4(CLDN16):c.224T>C (p.Leu75Pro) | CLDN16 | Pathogenic | criteria provided, single submitter |
| 5937 | NM_006580.4(CLDN16):c.140G>A (p.Trp47Ter) | CLDN16 | Pathogenic | no assertion criteria provided |
| 5938 | NM_006580.4(CLDN16):c.453G>T (p.Leu151Phe) | CLDN16 | Pathogenic | no assertion criteria provided |
| 5940 | NM_006580.4(CLDN16):c.621T>G (p.Tyr207Ter) | CLDN16 | Pathogenic | no assertion criteria provided |
| 692157 | NM_006580.4(CLDN16):c.217+5G>A | CLDN16 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 872664 | NM_006580.4(CLDN16):c.437G>A (p.Arg146His) | CLDN16 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 932893 | NM_006580.4:c.(?598)(900_?)del | CLDN16 | Pathogenic | no assertion criteria provided |
| 1202637 | NM_006580.4(CLDN16):c.137T>C (p.Leu46Pro) | CLDN16 | Likely pathogenic | criteria provided, single submitter |
| 1202638 | NM_006580.4(CLDN16):c.103G>A (p.Asp35Asn) | CLDN16 | Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 1324089 | NM_006580.4(CLDN16):c.494C>A (p.Ser165Tyr) | CLDN16 | Likely pathogenic | criteria provided, single submitter |
Genes & proteins
Mendelian disease overlap and somatic drivers
GenCC: 2 · 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 |
|---|---|---|---|---|
| CLDN16 | Strong | Autosomal recessive | renal hypomagnesemia 3 | 2 |
Orphanet rare-disease linkage (cohort genes)
| Gene | Orphanet ID | Rare disease |
|---|---|---|
| CLDN16 | Orphanet:31043 | Primary hypomagnesemia with hypercalciuria and nephrocalcinosis without severe ocular involvement |
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 |
|---|---|---|---|---|---|
| CLDN16 | HGNC:2037 | ENSG00000113946 | Q9Y5I7 | Claudin-16 | gencc,clinvar |
Cohort function summary
Lead sentence per gene, UniProt-curated.
| Symbol | Protein name | Function (lead sentence) |
|---|---|---|
| CLDN16 | Claudin-16 | Forms paracellular channels: coassembles with CLDN19 into tight junction strands with cation-selective channels through the strands, conveying epithelial permeability in a process known as paracellular tight junction permeability. |
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) |
|---|---|---|---|---|
| CLDN16 | Other/Unknown | no | Claudin16, PMP22/EMP/MP20/Claudin, Claudin |
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 |
|---|---|
| adult mammalian kidney | 1 |
| male germ line stem cell (sensu Vertebrata) in testis | 1 |
| olfactory segment of nasal mucosa | 1 |
Per-gene tissue summary (top 30)
| Symbol | Bgee breadth | FANTOM5 breadth | SCXA | Top tissues |
|---|---|---|---|---|
| CLDN16 | 127 | tissue_specific | marker | male germ line stem cell (sensu Vertebrata) in testis, olfactory segment of nasal mucosa, adult mammalian kidney |
Protein interactions among cohort
Intra-cohort edges: 0.
Hub genes (top 10 by interactor count)
| Symbol | Interactor count |
|---|---|
| CLDN16 | 637 |
Structural data
PDB: 0 · AlphaFold-only: 1 · No structure: 0
AlphaFold-only cohort genes (top 30 by pLDDT)
| Symbol | UniProt | pLDDT |
|---|---|---|
| CLDN16 | Q9Y5I7 | 76.74 |
Function
Pathway analysis
Distinct Reactome pathways touched by cohort: 1. 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 |
|---|---|---|---|---|
| Tight junction interactions | 1 | 368.4× | 0.003 | CLDN16 |
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 |
|---|---|---|---|---|
| intercellular transport | 1 | 16852.0× | 5e-04 | CLDN16 |
| paracellular transport | 1 | 2407.4× | 0.001 | CLDN16 |
| metal ion transport | 1 | 1872.4× | 0.001 | CLDN16 |
| renal absorption | 1 | 1685.2× | 0.001 | CLDN16 |
| intracellular monoatomic cation homeostasis | 1 | 1123.5× | 0.001 | CLDN16 |
| calcium-independent cell-cell adhesion | 1 | 802.5× | 0.002 | CLDN16 |
| bicellular tight junction assembly | 1 | 330.4× | 0.003 | CLDN16 |
| cell adhesion | 1 | 37.5× | 0.027 | CLDN16 |
Therapeutics
Drug target analysis
Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 1
Druggability breadth: 0 of 1 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 |
|---|---|---|
| CLDN16 | 0 | 0 |
Bioactivity and enzyme data
Enzyme cohort genes (≥1 EC): 0.
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 | CLDN16 |
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) |
|---|---|---|
| CLDN16 | 0 | — |
Clinical trials & evidence
Clinical trials
Clinical trials: 0.
Related Atlas pages
- Cohort genes: CLDN16