Normophosphatemic familial tumoral calcinosis
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Also known as NFTCtumoral calcinosis, familial, normophosphatemictumoral calcinosis, normophosphatemic, familial
Summary
Normophosphatemic familial tumoral calcinosis (MONDO:0012502) is a disease caused by SAMD9 (GenCC Strong), with 1 cohort gene.
At a glance
- Causal gene: SAMD9 (GenCC Strong)
- Cohort genes: 1
- ClinVar variants: 44
Clinical features
No curated clinical features (Orphanet) for this disease.
Identifiers
Disease identifiers
| Field | Value |
|---|---|
| Canonical name | normophosphatemic familial tumoral calcinosis |
| Mondo ID | MONDO:0012502 |
| MeSH | C566473 |
| OMIM | 610455 |
| Orphanet | 306658 |
| DOID | DOID:0080170 |
| UMLS | C1864861 |
| MedGen | 355311 |
| GARD | 0010878 |
| Is cancer (heuristic) | no |
Also known as: NFTC · normophosphatemic familial tumoral calcinosis · tumoral calcinosis, familial, normophosphatemic · tumoral calcinosis, normophosphatemic, familial
Data availability: 44 ClinVar variants · 5 GenCC gene-disease records.
Disease family
Classification path: disease › human disease › disease by body system or component › integumentary system disorder › familial tumoral calcinosis › normophosphatemic familial tumoral calcinosis
Related subtypes (4): tumoral calcinosis, hyperphosphatemic, familial, 2, tumoral calcinosis, hyperphosphatemic, familial, 3, 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
44 retrieved; paginated sample, class counts are floors:
21 uncertain significance, 8 benign/likely benign, 8 conflicting classifications of pathogenicity, 2 likely benign, 1 benign, 1 pathogenic, 1 not provided, 1 likely pathogenic, 1 pathogenic/likely pathogenic
| ClinVar | Variant (HGVS) | Gene | Classification | Review |
|---|---|---|---|---|
| 1229 | NM_017654.4(SAMD9):c.4483A>G (p.Lys1495Glu) | SAMD9 | Pathogenic | criteria provided, single submitter |
| 985307 | NM_017654.4(SAMD9):c.2944C>T (p.Arg982Cys) | SAMD9 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 556683 | NM_017654.4(SAMD9):c.132del (p.Val45fs) | SAMD9 | Likely pathogenic | no assertion criteria provided |
| 1174761 | NM_017654.4(SAMD9):c.2686T>C (p.Tyr896His) | SAMD9 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 1299393 | NM_017654.4(SAMD9):c.1171G>T (p.Gly391Ter) | SAMD9 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 1648073 | NM_017654.4(SAMD9):c.4413G>A (p.Met1471Ile) | SAMD9 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 225463 | NM_017654.4(SAMD9):c.460C>T (p.Gln154Ter) | SAMD9 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 552976 | NM_017654.4(SAMD9):c.3381C>A (p.Tyr1127Ter) | SAMD9 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 554815 | NM_017654.4(SAMD9):c.1800_1801del (p.Glu600fs) | SAMD9 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 709973 | NM_017654.4(SAMD9):c.4724G>A (p.Gly1575Glu) | SAMD9 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 992633 | NM_017654.4(SAMD9):c.3878G>A (p.Arg1293Gln) | SAMD9 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 1336034 | NM_017654.4(SAMD9):c.4001G>T (p.Arg1334Ile) | SAMD9 | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 1337200 | NM_017654.4(SAMD9):c.2611G>T (p.Glu871Ter) | SAMD9 | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 1337472 | NM_017654.4(SAMD9):c.3403A>G (p.Ile1135Val) | SAMD9 | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 1347521 | NM_017654.4(SAMD9):c.1460A>G (p.His487Arg) | SAMD9 | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 1497031 | NM_017654.4(SAMD9):c.83T>C (p.Ile28Thr) | SAMD9 | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 1506133 | NM_017654.4(SAMD9):c.29del (p.Asn10fs) | SAMD9 | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 1521693 | NM_017654.4(SAMD9):c.2581_2582insT (p.Glu861fs) | SAMD9 | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 1675124 | NM_017654.4(SAMD9):c.1252A>G (p.Asn418Asp) | SAMD9 | Uncertain significance | criteria provided, single submitter |
| 1675125 | NM_017654.4(SAMD9):c.2960T>C (p.Leu987Ser) | SAMD9 | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 225462 | NM_017654.4(SAMD9):c.95del (p.His32fs) | SAMD9 | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 2893962 | NM_017654.4(SAMD9):c.2641G>A (p.Asp881Asn) | SAMD9 | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 3687542 | NM_017654.4(SAMD9):c.2009del (p.Asn670fs) | SAMD9 | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 3780578 | NM_017654.4(SAMD9):c.1507del (p.Glu503fs) | SAMD9 | Uncertain significance | criteria provided, single submitter |
| 3892349 | NM_017654.4(SAMD9):c.2907A>C (p.Lys969Asn) | SAMD9 | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 553658 | NM_017654.4(SAMD9):c.2T>C (p.Met1Thr) | SAMD9 | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 554312 | NM_017654.4(SAMD9):c.4558G>T (p.Glu1520Ter) | SAMD9 | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 555093 | NM_017654.4(SAMD9):c.4331AAC[1] (p.Gln1445del) | SAMD9 | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 557138 | NM_017654.4(SAMD9):c.3505C>T (p.Gln1169Ter) | SAMD9 | Uncertain significance | no assertion criteria provided |
| 558150 | NM_017654.4(SAMD9):c.2509dup (p.Arg837fs) | SAMD9 | Uncertain significance | no assertion criteria provided |
Genes & proteins
Mendelian disease overlap and somatic drivers
GenCC: 14 · 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 |
|---|---|---|---|---|
| SAMD9 | Strong | Autosomal recessive | normophosphatemic familial tumoral calcinosis | 14 |
Orphanet rare-disease linkage (cohort genes)
| Gene | Orphanet ID | Rare disease |
|---|---|---|
| SAMD9 | Orphanet:306658 | Familial normophosphatemic tumoral calcinosis |
| SAMD9 | Orphanet:494433 | MIRAGE 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 |
|---|---|---|---|---|---|
| SAMD9 | HGNC:1348 | ENSG00000205413 | Q5K651 | Sterile alpha motif domain-containing protein 9 | gencc,clinvar |
Cohort function summary
Lead sentence per gene, UniProt-curated.
| Symbol | Protein name | Function (lead sentence) |
|---|---|---|
| SAMD9 | Sterile alpha motif domain-containing protein 9 | Double-stranded nucleic acid binding that acts as an antiviral factor by playing an essential role in the formation of cytoplasmic antiviral granules. |
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) |
|---|---|---|---|---|
| SAMD9 | Other/Unknown | no | SAM, SAM/pointed_sf, P-loop_NTPase |
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 |
|---|---|
| amniotic fluid | 1 |
| epithelium of esophagus | 1 |
| esophagus squamous epithelium | 1 |
Per-gene tissue summary (top 30)
| Symbol | Bgee breadth | FANTOM5 breadth | SCXA | Top tissues |
|---|---|---|---|---|
| SAMD9 | 247 | ubiquitous | marker | esophagus squamous epithelium, amniotic fluid, epithelium of esophagus |
Protein interactions among cohort
Intra-cohort edges: 0.
Hub genes (top 10 by interactor count)
| Symbol | Interactor count |
|---|---|
| SAMD9 | 1,316 |
Structural data
PDB: 1 · AlphaFold-only: 0 · No structure: 0
Cohort genes with PDB structures (top 30)
| Symbol | UniProt | PDB entries |
|---|---|---|
| SAMD9 | Q5K651 | 7 |
Function
Pathway analysis
Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 1 evidence-associated genes (0 with Reactome annotation).
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 |
|---|---|---|---|---|
| endosomal vesicle fusion | 1 | 1123.5× | 0.002 | SAMD9 |
| innate immune response | 1 | 33.6× | 0.030 | SAMD9 |
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 |
|---|---|---|
| SAMD9 | 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 | SAMD9 |
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) |
|---|---|---|
| SAMD9 | 0 | — |
Clinical trials & evidence
Clinical trials
Clinical trials: 0.
Related Atlas pages
- Cohort genes: SAMD9