Tumoral calcinosis, hyperphosphatemic, familial, 3
diseaseOn this page
Also known as HFTC3
Summary
Tumoral calcinosis, hyperphosphatemic, familial, 3 (MONDO:0060715) is a disease with 1 cohort gene.
At a glance
- Cohort genes: 1
- ClinVar variants: 146
Clinical features
No curated clinical features (Orphanet) for this disease.
Identifiers
Disease identifiers
| Field | Value |
|---|---|
| Canonical name | tumoral calcinosis, hyperphosphatemic, familial, 3 |
| Mondo ID | MONDO:0060715 |
| EFO | EFO:0009384 |
| OMIM | 617994 |
| UMLS | C4693864 |
| MedGen | 1638917 |
| GARD | 0016282 |
| Is cancer (heuristic) | no |
Also known as: HFTC3 · tumoral calcinosis, hyperphosphatemic, familial, 3
Data availability: 146 ClinVar variants · 3 GenCC gene-disease records.
Disease family
Classification path: disease › human disease › disease by body system or component › integumentary system disorder › familial tumoral calcinosis › tumoral calcinosis, hyperphosphatemic, familial, 3
Related subtypes (4): normophosphatemic familial tumoral calcinosis, tumoral calcinosis, hyperphosphatemic, familial, 2, familial hyperphosphatemic tumoral calcinosis/hyperphosphatemic hyperostosis syndrome, tumoral calcinosis, hyperphosphatemic, familial, 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
146 retrieved; paginated sample, class counts are floors:
81 uncertain significance, 19 benign, 19 conflicting classifications of pathogenicity, 15 likely benign, 12 benign/likely benign
| ClinVar | Variant (HGVS) | Gene | Classification | Review |
|---|---|---|---|---|
| 311684 | NM_004795.4(KL):c.511C>A (p.Arg171Ser) | KL | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 311687 | NM_004795.4(KL):c.911A>G (p.Asn304Ser) | KL | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 311702 | NM_004795.4(KL):c.2259G>A (p.Leu753=) | KL | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 311706 | NM_004795.4(KL):c.2626G>A (p.Asp876Asn) | KL | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 5346 | NM_004795.4(KL):c.578A>G (p.His193Arg) | KL | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 64548 | NM_004795.4(KL):c.2862G>A (p.Pro954=) | KL | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 881364 | NM_004795.4(KL):c.15C>T (p.Ala5=) | KL | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 881482 | NM_004795.4(KL):c.2298C>G (p.Gly766=) | KL | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 881861 | NM_004795.4(KL):c.1188A>G (p.Gln396=) | KL | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 882962 | NM_004795.4(KL):c.450C>A (p.Ser150=) | KL | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 883027 | NM_004795.4(KL):c.1419G>A (p.Arg473=) | KL | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 883029 | NM_004795.4(KL):c.1626C>T (p.Thr542=) | KL | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 883105 | NM_004795.4(KL):c.2874T>G (p.Thr958=) | KL | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 883106 | NM_004795.4(KL):c.2904C>T (p.Thr968=) | KL | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 883759 | NM_004795.4(KL):c.614G>A (p.Gly205Asp) | KL | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 883761 | NM_004795.4(KL):c.747C>T (p.Ala249=) | KL | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 883811 | NM_004795.4(KL):c.1860C>A (p.Arg620=) | KL | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 883812 | NM_004795.4(KL):c.1873G>A (p.Glu625Lys) | KL | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 883813 | NM_004795.4(KL):c.1945C>T (p.Arg649Cys) | KL | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 1344758 | NM_004795.4(KL):c.2251A>G (p.Arg751Gly) | KL | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 1345701 | NM_004795.4(KL):c.254A>G (p.Lys85Arg) | KL | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 1361567 | NM_004795.4(KL):c.1462TTG[1] (p.Leu489del) | KL | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 1367439 | NM_004795.4(KL):c.398T>A (p.Phe133Tyr) | KL | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 1403649 | NM_004795.4(KL):c.1882C>T (p.Arg628Cys) | KL | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 1409686 | NM_004795.4(KL):c.1764G>T (p.Met588Ile) | KL | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 1417990 | NM_004795.4(KL):c.944A>G (p.Glu315Gly) | KL | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 1426214 | NM_004795.4(KL):c.2069C>T (p.Pro690Leu) | KL | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 1439474 | NM_004795.4(KL):c.257G>A (p.Gly86Asp) | KL | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 1485727 | NM_004795.4(KL):c.4C>T (p.Pro2Ser) | KL | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 1493920 | NM_004795.4(KL):c.2513G>C (p.Trp838Ser) | KL | Uncertain significance | criteria provided, multiple submitters, no conflicts |
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 |
|---|---|---|---|---|
| KL | Supportive | Autosomal recessive | tumoral calcinosis, hyperphosphatemic, familial, 1 | 4 |
Orphanet rare-disease linkage (cohort genes)
| Gene | Orphanet ID | Rare disease |
|---|---|---|
| KL | Orphanet:306661 | Familial hyperphosphatemic tumoral calcinosis/Hyperphosphatemic hyperostosis 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 |
|---|---|---|---|---|---|
| KL | HGNC:6344 | ENSG00000133116 | Q9UEF7 | Klotho | gencc,clinvar |
Cohort function summary
Lead sentence per gene, UniProt-curated.
| Symbol | Protein name | Function (lead sentence) |
|---|---|---|
| KL | Klotho | May have weak glycosidase activity towards glucuronylated steroids. |
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) |
|---|---|---|---|---|
| KL | Other/Unknown | no | Glyco_hydro_1, GH_hydrolase_sf, GH_1_N_CS |
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 |
|---|---|
| choroid plexus epithelium | 1 |
| kidney epithelium | 1 |
| nephron tubule | 1 |
Per-gene tissue summary (top 30)
| Symbol | Bgee breadth | FANTOM5 breadth | SCXA | Top tissues |
|---|---|---|---|---|
| KL | 188 | tissue_specific | marker | choroid plexus epithelium, nephron tubule, kidney epithelium |
Protein interactions among cohort
Intra-cohort edges: 0.
Hub genes (top 10 by interactor count)
| Symbol | Interactor count |
|---|---|
| KL | 1,494 |
Structural data
PDB: 1 · AlphaFold-only: 0 · No structure: 0
Cohort genes with PDB structures (top 30)
| Symbol | UniProt | PDB entries |
|---|---|---|
| KL | Q9UEF7 | 6 |
Function
Pathway analysis
Distinct Reactome pathways touched by cohort: 12. 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 |
|---|---|---|---|---|
| FGFR1c and Klotho ligand binding and activation | 1 | 2855.0× | 0.004 | KL |
| Phospholipase C-mediated cascade: FGFR1 | 1 | 671.8× | 0.004 | KL |
| Downstream signaling of activated FGFR1 | 1 | 543.8× | 0.004 | KL |
| PI-3K cascade:FGFR1 | 1 | 519.1× | 0.004 | KL |
| SHC-mediated cascade:FGFR1 | 1 | 496.5× | 0.004 | KL |
| FRS-mediated FGFR1 signaling | 1 | 456.8× | 0.004 | KL |
| Negative regulation of FGFR1 signaling | 1 | 368.4× | 0.005 | KL |
| PI3K Cascade | 1 | 271.9× | 0.006 | KL |
| Constitutive Signaling by Aberrant PI3K in Cancer | 1 | 126.9× | 0.011 | KL |
| PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling | 1 | 96.8× | 0.012 | KL |
| PIP3 activates AKT signaling | 1 | 66.8× | 0.016 | KL |
| RAF/MAP kinase cascade | 1 | 61.1× | 0.016 | KL |
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 |
|---|---|---|---|---|
| positive regulation of MAPKKK cascade by fibroblast growth factor receptor signaling pathway | 1 | 2808.7× | 0.002 | KL |
| norepinephrine biosynthetic process | 1 | 2106.5× | 0.002 | KL |
| response to angiotensin | 1 | 1872.4× | 0.002 | KL |
| negative regulation of systemic arterial blood pressure | 1 | 1053.2× | 0.002 | KL |
| energy reserve metabolic process | 1 | 1053.2× | 0.002 | KL |
| response to vitamin D | 1 | 802.5× | 0.002 | KL |
| calcium ion homeostasis | 1 | 443.5× | 0.003 | KL |
| determination of adult lifespan | 1 | 432.1× | 0.003 | KL |
| positive regulation of bone mineralization | 1 | 391.9× | 0.003 | KL |
| response to activity | 1 | 324.1× | 0.004 | KL |
| fibroblast growth factor receptor signaling pathway | 1 | 285.6× | 0.004 | KL |
| carbohydrate metabolic process | 1 | 135.9× | 0.007 | KL |
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 |
|---|---|---|
| KL | 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 |
|---|---|---|
| KL | 1 | ADMET: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 | KL |
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) |
|---|---|---|
| KL | 1 | — |
Clinical trials & evidence
Clinical trials
Clinical trials: 0.
Related Atlas pages
- Cohort genes: KL