Basal ganglia calcification, idiopathic, 4

Summary

Basal ganglia calcification, idiopathic, 4 (MONDO:0014004) is a disease caused by PDGFRB (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: PDGFRB (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 468

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	basal ganglia calcification, idiopathic, 4
Mondo ID	MONDO:0014004
OMIM	615007
UMLS	C3554321
MedGen	767235
GARD	0015893
Is cancer (heuristic)	no

Also known as: basal ganglia calcification, idiopathic, 4 · basal ganglia calcification, idiopathic, type 4 · IBGC4

Data availability: 468 ClinVar variants · 4 GenCC gene-disease records.

Disease family

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 › basal ganglia calcification, idiopathic, 4

Related subtypes (9): basal ganglia calcification, idiopathic, childhood-onset, 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

ClinVar germline variants

468 retrieved; paginated sample, class counts are floors:

202 likely benign, 135 uncertain significance, 59 benign, 40 conflicting classifications of pathogenicity, 25 benign/likely benign, 4 pathogenic, 2 pathogenic/likely pathogenic, 1 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
208692	NM_002609.4(PDGFRB):c.1996A>C (p.Asn666His)	PDGFRB	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2096300	NM_002609.4(PDGFRB):c.2483C>A (p.Ala828Glu)	PDGFRB	Pathogenic	criteria provided, single submitter
2925384	NM_002609.4(PDGFRB):c.1679C>T (p.Pro560Leu)	PDGFRB	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
375682	NM_002609.4(PDGFRB):c.1696T>C (p.Trp566Arg)	PDGFRB	Pathogenic	criteria provided, multiple submitters, no conflicts
39588	NM_002609.4(PDGFRB):c.1973T>C (p.Leu658Pro)	PDGFRB	Pathogenic	no assertion criteria provided
55848	NM_002609.4(PDGFRB):c.1681C>T (p.Arg561Cys)	PDGFRB	Pathogenic	criteria provided, multiple submitters, no conflicts
4794434	NM_002609.4(PDGFRB):c.1A>G (p.Met1Val)	PDGFRB	Likely pathogenic	criteria provided, single submitter
1304805	NM_002609.4(PDGFRB):c.419C>T (p.Thr140Met)	PDGFRB	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
135650	NM_002609.4(PDGFRB):c.2083C>T (p.Arg695Cys)	PDGFRB	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1486244	NM_002609.4(PDGFRB):c.2905-8G>A	PDGFRB	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1518353	NM_002609.4(PDGFRB):c.1526C>T (p.Thr509Met)	PDGFRB	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
194497	NM_002609.4(PDGFRB):c.2126G>A (p.Arg709His)	PDGFRB	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1946074	NM_002609.4(PDGFRB):c.938G>A (p.Ser313Asn)	PDGFRB	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1960043	NM_002609.4(PDGFRB):c.2164G>A (p.Val722Ile)	PDGFRB	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1961685	NM_002609.4(PDGFRB):c.2122C>T (p.Arg708Cys)	PDGFRB	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1975317	NM_002609.4(PDGFRB):c.3275C>T (p.Ser1092Leu)	PDGFRB	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2042019	NM_002609.4(PDGFRB):c.1535A>G (p.Asn512Ser)	PDGFRB	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2054278	NM_002609.4(PDGFRB):c.338G>A (p.Arg113Gln)	PDGFRB	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2056802	NM_002609.4(PDGFRB):c.3181G>A (p.Asp1061Asn)	PDGFRB	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2065779	NM_002609.4(PDGFRB):c.2971C>T (p.Arg991Cys)	PDGFRB	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2144767	NM_002609.4(PDGFRB):c.542G>C (p.Gly181Ala)	PDGFRB	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2146418	NM_002609.4(PDGFRB):c.1399G>A (p.Gly467Arg)	PDGFRB	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2151826	NM_002609.4(PDGFRB):c.1487G>A (p.Arg496His)	PDGFRB	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2178345	NM_002609.4(PDGFRB):c.2243C>T (p.Ser748Leu)	PDGFRB	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2190056	NM_002609.4(PDGFRB):c.2635C>A (p.Leu879Ile)	PDGFRB	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2228308	NM_002609.4(PDGFRB):c.2791G>A (p.Asp931Asn)	PDGFRB	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2262363	NM_002609.4(PDGFRB):c.2281G>A (p.Val761Ile)	PDGFRB	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2367685	NM_002609.4(PDGFRB):c.1106C>T (p.Thr369Met)	PDGFRB	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2635001	NM_002609.4(PDGFRB):c.11C>A (p.Pro4Gln)	PDGFRB	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2927478	NM_002609.4(PDGFRB):c.370A>G (p.Thr124Ala)	PDGFRB	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 17 · Orphanet: 7 · 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
PDGFRB	Strong	Autosomal dominant	basal ganglia calcification, idiopathic, 4	17

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
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

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
PDGFRB	HGNC:8804	ENSG00000113721	P09619	Platelet-derived growth factor receptor beta	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
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: 1 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

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
Kinase	1	27.7×	0.036

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
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.

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
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
PDGFRB	270	ubiquitous	marker	stromal cell of endometrium, right coronary artery, endocervix

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
PDGFRB	5,111

Structural data

PDB: 1 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
PDGFRB	P09619	8

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 6. 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
Downstream signal transduction	1	380.7×	0.012	PDGFRB
Signaling by PDGF	1	253.8×	0.012	PDGFRB
Constitutive Signaling by Aberrant PI3K in Cancer	1	126.9×	0.015	PDGFRB
PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling	1	96.8×	0.015	PDGFRB
PIP3 activates AKT signaling	1	66.8×	0.016	PDGFRB
RAF/MAP kinase cascade	1	61.1×	0.016	PDGFRB

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
cell migration involved in coronary angiogenesis	1	16852.0×	8e-04	PDGFRB
metanephric glomerular mesangial cell proliferation involved in metanephros development	1	16852.0×	8e-04	PDGFRB
cell migration involved in vasculogenesis	1	8426.0×	8e-04	PDGFRB
smooth muscle cell chemotaxis	1	8426.0×	8e-04	PDGFRB
positive regulation of metanephric mesenchymal cell migration by platelet-derived growth factor receptor-beta signaling pathway	1	5617.3×	8e-04	PDGFRB
positive regulation of cell proliferation by VEGF-activated platelet derived growth factor receptor signaling pathway	1	5617.3×	8e-04	PDGFRB
metanephric glomerular capillary formation	1	5617.3×	8e-04	PDGFRB
smooth muscle adaptation	1	4213.0×	1e-03	PDGFRB
platelet-derived growth factor receptor-beta signaling pathway	1	3370.4×	0.001	PDGFRB
retina vasculature development in camera-type eye	1	1685.2×	0.002	PDGFRB
cardiac myofibril assembly	1	1296.3×	0.002	PDGFRB
positive regulation of DNA biosynthetic process	1	1123.5×	0.002	PDGFRB
positive regulation of smooth muscle cell migration	1	991.3×	0.002	PDGFRB
positive regulation of calcium ion import	1	936.2×	0.002	PDGFRB
aorta morphogenesis	1	887.0×	0.002	PDGFRB
positive regulation of chemotaxis	1	842.6×	0.002	PDGFRB
positive regulation of MAP kinase activity	1	648.1×	0.003	PDGFRB
platelet-derived growth factor receptor signaling pathway	1	561.7×	0.003	PDGFRB
positive regulation of mitotic nuclear division	1	543.6×	0.003	PDGFRB
positive regulation of reactive oxygen species metabolic process	1	510.7×	0.003	PDGFRB
peptidyl-tyrosine phosphorylation	1	421.3×	0.004	PDGFRB
positive regulation of calcium-mediated signaling	1	421.3×	0.004	PDGFRB
positive regulation of smooth muscle cell proliferation	1	330.4×	0.004	PDGFRB
cell chemotaxis	1	185.2×	0.007	PDGFRB
cell surface receptor protein tyrosine kinase signaling pathway	1	173.7×	0.008	PDGFRB
regulation of actin cytoskeleton organization	1	157.5×	0.008	PDGFRB
protein autophosphorylation	1	145.3×	0.008	PDGFRB
positive regulation of ERK1 and ERK2 cascade	1	85.1×	0.014	PDGFRB
positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	1	78.4×	0.015	PDGFRB
angiogenesis	1	62.4×	0.017	PDGFRB

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
PDGFRB	PONATINIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
PDGFRB	102	4

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

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: 1; 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	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: 0.