Hypercalcemia, infantile
disease diseaseOn this page
Also known as autosomal recessive hypercalcemia, infantileautosomal recessive infantile hypercalcemiafamilial infantile hypercalcemia with suppressed intact parathyroid hormonehypercalcemia disease of infancyhypercalcemia, idiopathic, of infancyhypercalcemia, infantile, autosomal recessiveidiopathic infantile hypercalcemiainfantile hypercalcemiainfantile hypercalcemia diseaseinfantile onset hypercalcemia disease
Summary
Hypercalcemia, infantile (MONDO:0000212) is a disease with 1 cohort gene and 1 clinical trial. Top therapeutic interventions include rifampin.
At a glance
- Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
- Cohort genes: 1
- ClinVar variants: 1
- Clinical trials: 1
Clinical features
Epidemiology
Prevalence records
2 prevalence record(s), Orphanet:
| Type | Class | Value | Geography | Validation |
|---|---|---|---|---|
| Cases/families | 12 | Worldwide | Validated | |
| Point prevalence | <1 / 1 000 000 | Worldwide | Validated |
Identifiers
Disease identifiers
| Field | Value |
|---|---|
| Canonical name | hypercalcemia, infantile |
| Mondo ID | MONDO:0000212 |
| MeSH | C562999 |
| OMIM | 143880 |
| Orphanet | 300547 |
| NCIT | C129734 |
| SNOMED CT | 276645004, 34225008 |
| UMLS | C4329374 |
| MedGen | 1380840 |
| GARD | 0017374 |
| Is cancer (heuristic) | no |
Also known as: autosomal recessive hypercalcemia, infantile · autosomal recessive infantile hypercalcemia · familial infantile hypercalcemia with suppressed intact parathyroid hormone · hypercalcemia disease of infancy · hypercalcemia, idiopathic, of infancy · hypercalcemia, infantile · hypercalcemia, infantile, autosomal recessive · idiopathic infantile hypercalcemia · infantile hypercalcemia · infantile hypercalcemia disease · infantile onset hypercalcemia disease
Data availability: 1 ClinVar variant.
Disease family
An umbrella term covering 2 Mondo subtypes.
Classification path: disease › human disease › disease by developmental or physiological process › metabolic disease › mineral metabolism disease › calcium metabolic disease › hypercalcemia disease › hypercalcemia, infantile
Related subtypes (2): familial hypocalciuric hypercalcemia, humoral hypercalcemia of malignancy
Subtypes (2): hypercalcemia, infantile, 2, hypercalcemia, infantile, 1
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
1 retrieved; paginated sample, class counts are floors:
1 pathogenic/likely pathogenic
| ClinVar | Variant (HGVS) | Gene | Classification | Review |
|---|---|---|---|---|
| 929955 | NM_003052.5(SLC34A1):c.745C>T (p.Arg249Ter) | SLC34A1 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
Genes & proteins
Mendelian disease overlap and somatic drivers
GenCC: 0 · Orphanet: 4 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0
Orphanet rare-disease linkage (cohort genes)
| Gene | Orphanet ID | Rare disease |
|---|---|---|
| SLC34A1 | Orphanet:157215 | Hereditary hypophosphatemic rickets with hypercalciuria |
| SLC34A1 | Orphanet:244305 | Dominant hypophosphatemia with nephrolithiasis or osteoporosis |
| SLC34A1 | Orphanet:300547 | Autosomal recessive infantile hypercalcemia |
| SLC34A1 | Orphanet:3337 | Primary Fanconi renotubular syndrome |
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 |
|---|---|---|---|---|---|
| SLC34A1 | HGNC:11019 | ENSG00000131183 | Q06495 | Sodium-dependent phosphate transport protein 2A | clinvar |
Cohort function summary
Lead sentence per gene, UniProt-curated.
| Symbol | Protein name | Function (lead sentence) |
|---|---|---|
| SLC34A1 | Sodium-dependent phosphate transport protein 2A | Involved in actively transporting phosphate into cells via Na(+) cotransport in the renal brush border membrane. |
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) |
|---|---|---|---|---|
| SLC34A1 | Other/Unknown | no | Na/Pi_transpt |
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 |
| kidney epithelium | 1 |
| nephron tubule | 1 |
Per-gene tissue summary (top 30)
| Symbol | Bgee breadth | FANTOM5 breadth | SCXA | Top tissues |
|---|---|---|---|---|
| SLC34A1 | 52 | tissue_specific | marker | nephron tubule, adult mammalian kidney, kidney epithelium |
Protein interactions among cohort
Intra-cohort edges: 0.
Hub genes (top 10 by interactor count)
| Symbol | Interactor count |
|---|---|
| SLC34A1 | 3,362 |
Structural data
PDB: 0 · AlphaFold-only: 1 · No structure: 0
AlphaFold-only cohort genes (top 30 by pLDDT)
| Symbol | UniProt | pLDDT |
|---|---|---|
| SLC34A1 | Q06495 | 72.24 |
Function
Pathway analysis
Distinct Reactome pathways touched by cohort: 3. 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 |
|---|---|---|---|---|
| Defective SLC34A1 causes hypophosphatemic nephrolithiasis/osteoporosis 1 (NPHLOP1) | 1 | 5710.0× | 5e-04 | SLC34A1 |
| Type II Na+/Pi cotransporters | 1 | 2855.0× | 5e-04 | SLC34A1 |
| Surfactant metabolism | 1 | 368.4× | 0.003 | SLC34A1 |
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 |
|---|---|---|---|---|
| indole metabolic process | 1 | 8426.0× | 9e-04 | SLC34A1 |
| gentamycin metabolic process | 1 | 8426.0× | 9e-04 | SLC34A1 |
| arsenate ion transmembrane transport | 1 | 8426.0× | 9e-04 | SLC34A1 |
| positive regulation of phosphate transmembrane transport | 1 | 8426.0× | 9e-04 | SLC34A1 |
| cellular response to phosphate starvation | 1 | 4213.0× | 0.001 | SLC34A1 |
| cellular response to metal ion | 1 | 4213.0× | 0.001 | SLC34A1 |
| positive regulation of sodium-dependent phosphate transport | 1 | 4213.0× | 0.001 | SLC34A1 |
| cellular response to staurosporine | 1 | 3370.4× | 0.001 | SLC34A1 |
| positive regulation of membrane potential | 1 | 2808.7× | 0.001 | SLC34A1 |
| tricarboxylic acid metabolic process | 1 | 2808.7× | 0.001 | SLC34A1 |
| response to mercury ion | 1 | 2407.4× | 0.001 | SLC34A1 |
| response to potassium ion | 1 | 2106.5× | 0.001 | SLC34A1 |
| response to thyroid hormone | 1 | 2106.5× | 0.001 | SLC34A1 |
| dentinogenesis | 1 | 2106.5× | 0.001 | SLC34A1 |
| phosphate ion transport | 1 | 1872.4× | 0.001 | SLC34A1 |
| sodium-dependent phosphate transport | 1 | 1872.4× | 0.001 | SLC34A1 |
| intracellular phosphate ion homeostasis | 1 | 1532.0× | 0.001 | SLC34A1 |
| response to magnesium ion | 1 | 1404.3× | 0.001 | SLC34A1 |
| cellular response to parathyroid hormone stimulus | 1 | 1404.3× | 0.001 | SLC34A1 |
| phosphate ion transmembrane transport | 1 | 1203.7× | 0.001 | SLC34A1 |
| glycoprotein metabolic process | 1 | 1123.5× | 0.001 | SLC34A1 |
| response to growth hormone | 1 | 1123.5× | 0.001 | SLC34A1 |
| response to peptide | 1 | 1123.5× | 0.001 | SLC34A1 |
| response to vitamin A | 1 | 1053.2× | 0.001 | SLC34A1 |
| phosphate ion homeostasis | 1 | 1053.2× | 0.001 | SLC34A1 |
| response to lead ion | 1 | 936.2× | 0.001 | SLC34A1 |
| response to cadmium ion | 1 | 732.7× | 0.002 | SLC34A1 |
| sodium ion import across plasma membrane | 1 | 624.1× | 0.002 | SLC34A1 |
| ossification | 1 | 227.7× | 0.005 | SLC34A1 |
| response to estradiol | 1 | 198.3× | 0.005 | SLC34A1 |
Therapeutics
Drug target analysis
Approved (phase 4): 1 · Phase ≥3: 1 · Phased (≥1): 1 · Undrugged: 0
Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).
Genes with an approved drug
The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.
| Symbol | Example approved molecule |
|---|---|
| SLC34A1 | SODIUM PHOSPHATE, DIBASIC, ANHYDROUS |
Top cohort targets by molecule count
| Symbol | Molecules | Max phase |
|---|---|---|
| SLC34A1 | 2 | 4 |
Drugs targeting cohort genes (top 30)
| Molecule | Max phase | Targets in cohort |
|---|---|---|
| SODIUM PHOSPHATE, DIBASIC, ANHYDROUS | 4 | SLC34A1 |
| POTASSIUM PHOSPHATE, MONOBASIC | 4 | SLC34A1 |
Bioactivity and enzyme data
Enzyme cohort genes (≥1 EC): 0.
Cohort genes with ChEMBL bioactivity (full, sorted by assay count)
| Symbol | Assays | Type breakdown |
|---|---|---|
| SLC34A1 | 8 | Binding:7, Functional: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
2 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.
| Compound | Max phase | Cohort target (bioactivity) |
|---|---|---|
| SODIUM PHOSPHATE, DIBASIC, ANHYDROUS | 4 | SLC34A1 |
| POTASSIUM PHOSPHATE, MONOBASIC | 4 | SLC34A1 |
Druggability pyramid
Cohort genes binned by druggability tier (high → low):
| Tier | Definition | Genes | Symbols |
|---|---|---|---|
| A | Approved (phase 4 drug) | 1 | SLC34A1 |
| 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 | 0 |
Undrugged target profiles
0 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).
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 |
|---|---|---|---|
| NCT03301038 | PHASE2 | RECRUITING | Rifampin in CYP24A1-related Hypercalcemia and Hypercalciuria |
Drugs tested across these trials (top 30)
| Molecule | Max phase | Trials referencing |
|---|---|---|
| RIFAMPIN | 4 | 1 |