Bilateral striopallidodentate calcinosis

Summary

Bilateral striopallidodentate calcinosis (MONDO:0008947) is a disease (an umbrella term covering 10 Mondo subtypes) with 6 cohort genes and 1 clinical trial. Top therapeutic interventions include etidronic acid.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Umbrella term: 10 Mondo subtypes
• Cohort genes: 6
• Phenotypes (HPO): 33
• Clinical trials: 1

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		200	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

33 HPO clinical features (Orphanet curated; top 33 by frequency):

HPO ID	Term	Frequency
HP:0000298	Mask-like facies	Frequent (30-79%)
HP:0000709	Psychosis	Frequent (30-79%)
HP:0000726	Dementia	Frequent (30-79%)
HP:0000739	Anxiety	Frequent (30-79%)
HP:0000751	Personality changes	Frequent (30-79%)
HP:0001250	Seizure	Frequent (30-79%)
HP:0001266	Choreoathetosis	Frequent (30-79%)
HP:0001337	Tremor	Frequent (30-79%)
HP:0002063	Rigidity	Frequent (30-79%)
HP:0002067	Bradykinesia	Frequent (30-79%)
HP:0002135	Basal ganglia calcification	Frequent (30-79%)
HP:0002315	Headache	Frequent (30-79%)
HP:0002321	Vertigo	Frequent (30-79%)
HP:0002344	Progressive neurologic deterioration	Frequent (30-79%)
HP:0007146	Bilateral basal ganglia lesions	Frequent (30-79%)
HP:0000012	Urinary urgency	Occasional (5-29%)
HP:0000802	Impotence	Occasional (5-29%)
HP:0000822	Hypertension	Occasional (5-29%)
HP:0001332	Dystonia	Occasional (5-29%)
HP:0001350	Slurred speech	Occasional (5-29%)
HP:0002015	Dysphagia	Occasional (5-29%)
HP:0002312	Clumsiness	Occasional (5-29%)
HP:0002317	Unsteady gait	Occasional (5-29%)
HP:0002354	Memory impairment	Occasional (5-29%)
HP:0003388	Easy fatigability	Occasional (5-29%)
HP:0100660	Dyskinesia	Occasional (5-29%)
HP:0003394	Muscle spasm	Occasional (5-29%)
HP:0004305	Involuntary movements	Occasional (5-29%)
HP:0007256	Abnormal pyramidal sign	Occasional (5-29%)
HP:0007352	Cerebellar calcifications	Occasional (5-29%)
HP:0031987	Diminished ability to concentrate	Occasional (5-29%)
HP:0011450	Unusual CNS infection	Excluded (0%)
HP:0032180	Abnormal circulating metabolite concentration	Excluded (0%)

Identifiers

Disease identifiers

Field	Value
Canonical name	bilateral striopallidodentate calcinosis
Mondo ID	MONDO:0008947
MeSH	C536275
OMIM	213600
Orphanet	1980
DOID	DOID:0060230
ICD-11	1081370436
SNOMED CT	110997000, 230311004
GARD	0006406
MedDRA	10059626
NORD	1127
Is cancer (heuristic)	no

Also known as: basal ganglia calcification · basal ganglia degeneration with calcification · BSPDC · cerebrovascular ferrocalcinosis · Fahr disease · idiopathic basal ganglia calcification · PFBC · Primary Familial Brain Calcification · primary familial brain calcification

Data availability: 6 GenCC gene-disease records · 1 HPO phenotype · 22 cell lines.

Disease family

An umbrella term covering 10 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › nervous system disorder › central nervous system disorder › brain disorder › basal ganglia disorder › bilateral striopallidodentate calcinosis

Related subtypes (3): basal ganglia cerebrovascular disorder, biotin-responsive basal ganglia disease, parkinsonian disorder

Subtypes (10): basal ganglia calcification, idiopathic, childhood-onset, basal ganglia calcification, idiopathic, 4, basal ganglia calcification, idiopathic, 5, basal ganglia calcification, idiopathic, 6, basal ganglia calcification, idiopathic, 1, basal ganglia calcification, idiopathic, 7, autosomal recessive, basal ganglia calcification, idiopathic, 8, autosomal recessive, basal ganglia calcification, idiopathic, 9, autosomal recessive, basal ganglia calcification, idiopathic, 10, autosomal recessive, basal ganglia calcification, idiopathic, 11, autosomal recessive

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

No tiered GWAS variants or ClinVar records for this disease.

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 43 · Orphanet: 15 · 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
JAM2	Supportive	Autosomal dominant	bilateral striopallidodentate calcinosis	4
MYORG	Supportive	Autosomal dominant	bilateral striopallidodentate calcinosis	5
PDGFB	Supportive	Autosomal dominant	bilateral striopallidodentate calcinosis	7
PDGFRB	Supportive	Autosomal dominant	bilateral striopallidodentate calcinosis	17
SLC20A2	Supportive	Autosomal dominant	bilateral striopallidodentate calcinosis	4
XPR1	Supportive	Autosomal dominant	bilateral striopallidodentate calcinosis	6

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SLC20A2	Orphanet:1980	Bilateral striopallidodentate calcinosis
XPR1	Orphanet:1980	Bilateral striopallidodentate calcinosis
JAM2	Orphanet:1980	Bilateral striopallidodentate calcinosis
MYORG	Orphanet:1980	Bilateral striopallidodentate calcinosis
PDGFB	Orphanet:1980	Bilateral striopallidodentate calcinosis
PDGFB	Orphanet:2495	Meningioma
PDGFB	Orphanet:263662	Familial multiple meningioma
PDGFB	Orphanet:31112	Dermatofibrosarcoma protuberans
PDGFRB	Orphanet:168950	Myeloid/lymphoid neoplasm associated with PDGFRB rearrangement
PDGFRB	Orphanet:1980	Bilateral striopallidodentate calcinosis
PDGFRB	Orphanet:2591	Infantile myofibromatosis
PDGFRB	Orphanet:314950	Primary hypereosinophilic syndrome
PDGFRB	Orphanet:363665	Acroosteolysis-keloid-like lesions-premature aging syndrome
PDGFRB	Orphanet:477831	Kosaki overgrowth syndrome
PDGFRB	Orphanet:86830	Chronic myeloproliferative disease, unclassifiable

Cohort genes → proteins

6 cohort genes, 6 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	6

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
SLC20A2	HGNC:10947	ENSG00000168575	Q08357	Sodium-dependent phosphate transporter 2	gencc
XPR1	HGNC:12827	ENSG00000143324	Q9UBH6	Solute carrier family 53 member 1	gencc
JAM2	HGNC:14686	ENSG00000154721	P57087	Junctional adhesion molecule B	gencc
MYORG	HGNC:19918	ENSG00000164976	Q6NSJ0	Alpha-galactosidase MYORG	gencc
PDGFB	HGNC:8800	ENSG00000100311	P01127	Platelet-derived growth factor subunit B	gencc
PDGFRB	HGNC:8804	ENSG00000113721	P09619	Platelet-derived growth factor receptor beta	gencc

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SLC20A2	Sodium-dependent phosphate transporter 2	Sodium-phosphate symporter which preferentially transports the monovalent form of phosphate with a stoichiometry of two sodium ions per phosphate ion.
XPR1	Solute carrier family 53 member 1	Inorganic ion transporter that mediates phosphate ion export across the plasma membrane.
JAM2	Junctional adhesion molecule B	Junctional adhesion protein that mediates heterotypic cell-cell interactions with its cognate receptor JAM3 to regulate different cellular processes.
MYORG	Alpha-galactosidase MYORG	Alpha-galactosidase with unusual specificity for the Gal-alpha1,4-Glc structure, whose in vivo substrate is still unknown.
PDGFB	Platelet-derived growth factor subunit B	Growth factor that plays an essential role in the regulation of embryonic development, cell proliferation, cell migration, survival and chemotaxis.
PDGFRB	Platelet-derived growth factor receptor beta	Tyrosine-protein kinase that acts as a cell-surface receptor for homodimeric PDGFB and PDGFD and for heterodimers formed by PDGFA and PDGFB, and plays an essential role in the regulation of embryonic development, cell proliferation, surviv…

Protein-family classification

Druggable: 3 · Difficult: 0 · Unknown: 3 · Druggable fraction: 0.5

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
Transporter	1	13.0×	0.264
Antibody/Immunoglobulin	1	4.9×	0.264
Kinase	1	4.6×	0.264
Other/Unknown	3	0.9×	0.758

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
SLC20A2	Transporter	yes		Phos_transporter
XPR1	Other/Unknown	no		SPX_dom, EXS_C
JAM2	Antibody/Immunoglobulin	yes		Ig_sub2, Ig_sub, Ig-like_dom
MYORG	Other/Unknown	no		Glyco_hydro_31_TIM, Glyco_hydro_b, GH_hydrolase_sf
PDGFB	Other/Unknown	no		PDGF/VEGF_dom, PDGF_N, PD_growth_factor_CS
PDGFRB	Kinase	yes	2.7.10.1	Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom, Tyr_kinase_rcpt_3_CS

Expression context

Cohort genes with no expression data: 0.

6 cohort genes 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)	6
unknown	0

Top tissues across cohort

Tissue	Cohort genes
ventricular zone	2
left lobe of thyroid gland	1
right lobe of thyroid gland	1
thyroid gland	1
cortical plate	1
kidney epithelium	1
left ventricle myocardium	1
tendon of biceps brachii	1
vena cava	1
gastrocnemius	1
hindlimb stylopod muscle	1
apex of heart	1
olfactory bulb	1
type B pancreatic cell	1
endocervix	1
right coronary artery	1
stromal cell of endometrium	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SLC20A2	276	ubiquitous	marker	left lobe of thyroid gland, right lobe of thyroid gland, thyroid gland
XPR1	254	ubiquitous	marker	cortical plate, kidney epithelium, left ventricle myocardium
JAM2	277	ubiquitous	marker	ventricular zone, tendon of biceps brachii, vena cava
MYORG	185	ubiquitous	marker	ventricular zone, gastrocnemius, hindlimb stylopod muscle
PDGFB	259	ubiquitous	marker	olfactory bulb, type B pancreatic cell, apex of heart
PDGFRB	270	ubiquitous	marker	stromal cell of endometrium, right coronary artery, endocervix

Protein interactions among cohort

Intra-cohort edges: 8.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
PDGFRB	5,111
XPR1	2,863
PDGFB	2,424
SLC20A2	1,923
MYORG	1,675
JAM2	651

Intra-cohort edges

A	B	Sources
MYORG	PDGFB	string_interaction
MYORG	PDGFRB	string_interaction
MYORG	SLC20A2	string_interaction
MYORG	XPR1	intact, string_interaction
PDGFB	PDGFRB	biogrid_interaction, intact, string_interaction
PDGFB	SLC20A2	string_interaction
PDGFRB	SLC20A2	string_interaction
SLC20A2	XPR1	string_interaction

Structural data

PDB: 4 · AlphaFold-only: 2 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
XPR1	Q9UBH6	51
PDGFRB	P09619	8
PDGFB	P01127	6
MYORG	Q6NSJ0	3

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
JAM2	P57087	82.91
SLC20A2	Q08357	72.63

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 20. Enrichment computed across 6 evidence-associated genes (4 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 4 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Downstream signal transduction	2	190.3×	8e-04	PDGFB, PDGFRB
Signaling by PDGF	2	126.9×	9e-04	PDGFB, PDGFRB
Defective SLC20A2 causes idiopathic basal ganglia calcification 1 (IBGC1)	1	2855.0×	0.002	SLC20A2
Constitutive Signaling by Aberrant PI3K in Cancer	2	63.4×	0.002	PDGFB, PDGFRB
PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling	2	48.4×	0.003	PDGFB, PDGFRB
Sodium-coupled phosphate cotransporters	1	951.7×	0.004	SLC20A2
PIP3 activates AKT signaling	2	33.4×	0.004	PDGFB, PDGFRB
RAF/MAP kinase cascade	2	30.5×	0.004	PDGFB, PDGFRB
SLC transporter disorders	1	51.0×	0.043	SLC20A2
Non-integrin membrane-ECM interactions	1	38.6×	0.047	PDGFB
Disorders of transmembrane transporters	1	34.8×	0.047	SLC20A2
Integrin cell surface interactions	1	33.6×	0.047	JAM2
R-HSA-425393	1	32.4×	0.047	SLC20A2
Cell surface interactions at the vascular wall	1	23.8×	0.059	JAM2
Platelet degranulation	1	22.0×	0.060	PDGFB
Extracellular matrix organization	1	15.8×	0.077	JAM2
SLC-mediated transmembrane transport	1	14.8×	0.078	SLC20A2
Hemostasis	1	9.0×	0.118	JAM2
Transport of small molecules	1	6.3×	0.158	SLC20A2
Disease	1	3.3×	0.273	SLC20A2

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 6 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 metanephric mesenchymal cell migration by platelet-derived growth factor receptor-beta signaling pathway	2	1872.4×	3e-05	PDGFB, PDGFRB
smooth muscle adaptation	2	1404.3×	3e-05	PDGFB, PDGFRB
phosphate ion transmembrane transport	2	401.2×	2e-04	SLC20A2, XPR1
positive regulation of DNA biosynthetic process	2	374.5×	2e-04	PDGFB, PDGFRB
positive regulation of smooth muscle cell migration	2	330.4×	2e-04	PDGFB, PDGFRB
positive regulation of calcium ion import	2	312.1×	2e-04	PDGFB, PDGFRB
positive regulation of chemotaxis	2	280.9×	3e-04	PDGFB, PDGFRB
positive regulation of MAP kinase activity	2	216.1×	4e-04	PDGFB, PDGFRB
positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	3	39.2×	4e-04	MYORG, PDGFB, PDGFRB
platelet-derived growth factor receptor signaling pathway	2	187.2×	4e-04	PDGFB, PDGFRB
positive regulation of mitotic nuclear division	2	181.2×	4e-04	PDGFB, PDGFRB
positive regulation of reactive oxygen species metabolic process	2	170.2×	4e-04	PDGFB, PDGFRB
peptidyl-tyrosine phosphorylation	2	140.4×	6e-04	PDGFB, PDGFRB
positive regulation of smooth muscle cell proliferation	2	110.1×	8e-04	PDGFB, PDGFRB
cell migration involved in coronary angiogenesis	1	2808.7×	0.002	PDGFRB
metanephric glomerular mesangial cell development	1	2808.7×	0.002	PDGFB
metanephric glomerular mesangial cell proliferation involved in metanephros development	1	2808.7×	0.002	PDGFRB
positive regulation of vascular associated smooth muscle cell dedifferentiation	1	2808.7×	0.002	PDGFB
positive regulation of metanephric mesenchymal cell migration	1	2808.7×	0.002	PDGFB
cell chemotaxis	2	61.7×	0.002	PDGFB, PDGFRB
negative regulation of phosphatidylinositol biosynthetic process	1	1404.3×	0.003	PDGFB
cell migration involved in vasculogenesis	1	1404.3×	0.003	PDGFRB
cellular response to mycophenolic acid	1	1404.3×	0.003	PDGFB
smooth muscle cell chemotaxis	1	1404.3×	0.003	PDGFRB
positive regulation of lymphocyte migration	1	1404.3×	0.003	JAM2
positive regulation of glomerular filtration	1	936.2×	0.003	PDGFB
positive regulation of cell proliferation by VEGF-activated platelet derived growth factor receptor signaling pathway	1	936.2×	0.003	PDGFRB
lymphocyte aggregation	1	936.2×	0.003	JAM2
metanephric glomerular capillary formation	1	936.2×	0.003	PDGFRB
cellular response to phosphate starvation	1	702.2×	0.004	XPR1

Therapeutics

Drug target analysis

Approved (phase 4): 1 · Phase ≥3: 1 · Phased (≥1): 1 · Undrugged: 5

Druggability breadth: 4 of 6 evidence-associated genes (67%) 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
PDGFRB	PONATINIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
PDGFRB	102	4
SLC20A2	0	0
XPR1	0	0
JAM2	0	0
MYORG	0	0
PDGFB	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
PONATINIB	4	PDGFRB
FEDRATINIB	4	PDGFRB
TIVOZANIB	4	PDGFRB
LENVATINIB	4	PDGFRB
AXITINIB	4	PDGFRB
SORAFENIB	4	PDGFRB
SUNITINIB MALATE	4	PDGFRB
REGORAFENIB	4	PDGFRB
PACRITINIB	4	PDGFRB
VANDETANIB	4	PDGFRB
NILOTINIB	4	PDGFRB
BOSUTINIB	4	PDGFRB
NINTEDANIB ESYLATE	4	PDGFRB
GILTERITINIB	4	PDGFRB
TOVORAFENIB	4	PDGFRB
PEXIDARTINIB	4	PDGFRB
PAZOPANIB	4	PDGFRB
NINTEDANIB	4	PDGFRB
SUNITINIB	4	PDGFRB
DASATINIB	4	PDGFRB
ERLOTINIB	4	PDGFRB
LAPATINIB	4	PDGFRB
QUIZARTINIB	4	PDGFRB
MIDOSTAURIN	4	PDGFRB
IMATINIB	4	PDGFRB
VATALANIB	3	PDGFRB
FAMITINIB	3	PDGFRB
MASITINIB	3	PDGFRB
CRENOLANIB	3	PDGFRB
SARACATINIB	3	PDGFRB

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
PDGFRB	1,237	Binding:1213, Functional:16, ADMET:8
PDGFB	3	Binding:3
SLC20A2	1	Binding:1
JAM2	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
PDGFRB	2.7.10.1	receptor protein-tyrosine kinase

Cohort genes with high screening signal

≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.

Symbol	ChEMBL assays
PDGFRB	1,237

Pharmacogenomics

Cohort genes with a PharmGKB record: 6; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

30 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)
PONATINIB	4	PDGFRB
FEDRATINIB	4	PDGFRB
TIVOZANIB	4	PDGFRB
LENVATINIB	4	PDGFRB
AXITINIB	4	PDGFRB
SORAFENIB	4	PDGFRB
SUNITINIB MALATE	4	PDGFRB
REGORAFENIB	4	PDGFRB
PACRITINIB	4	PDGFRB
VANDETANIB	4	PDGFRB
NILOTINIB	4	PDGFRB
BOSUTINIB	4	PDGFRB
NINTEDANIB ESYLATE	4	PDGFRB
GILTERITINIB	4	PDGFRB
TOVORAFENIB	4	PDGFRB
PEXIDARTINIB	4	PDGFRB
PAZOPANIB	4	PDGFRB
NINTEDANIB	4	PDGFRB
SUNITINIB	4	PDGFRB
DASATINIB	4	PDGFRB
ERLOTINIB	4	PDGFRB
LAPATINIB	4	PDGFRB
QUIZARTINIB	4	PDGFRB
MIDOSTAURIN	4	PDGFRB
IMATINIB	4	PDGFRB
VATALANIB	3	PDGFRB
FAMITINIB	3	PDGFRB
MASITINIB	3	PDGFRB
CRENOLANIB	3	PDGFRB
SARACATINIB	3	PDGFRB

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	PDGFRB
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	2	SLC20A2, JAM2
E	Difficult family or no structure, no drug	3	XPR1, MYORG, PDGFB

Undrugged target profiles

5 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
MYORG	0	PDGFRB
PDGFB	3	PDGFRB
SLC20A2	1	—
XPR1	0	—
JAM2	1	—

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
NCT05662111	PHASE2	RECRUITING	Treatment of Ectopic Calcification in Fahr’s Disease or Syndrome

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
ETIDRONIC ACID	4	1