Basal ganglia calcification, idiopathic, 5

Summary

Basal ganglia calcification, idiopathic, 5 (MONDO:0014204) is a disease caused by PDGFB (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: PDGFB (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 15

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	basal ganglia calcification, idiopathic, 5
Mondo ID	MONDO:0014204
OMIM	615483
UMLS	C3809645
MedGen	815975
GARD	0015973
Is cancer (heuristic)	no

Also known as: basal ganglia calcification, idiopathic, 5 · basal ganglia calcification, idiopathic, type 5 · IBGC5

Data availability: 15 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, 5

Related subtypes (9): basal ganglia calcification, idiopathic, childhood-onset, basal ganglia calcification, idiopathic, 4, 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

15 retrieved; paginated sample, class counts are floors:

6 pathogenic, 3 uncertain significance, 3 conflicting classifications of pathogenicity, 3 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
4819278	NM_002608.4(PDGFB):c.64-50_160+533del	PDGFB	Pathogenic	criteria provided, single submitter
75237	NM_002608.4(PDGFB):c.433C>T (p.Gln145Ter)	PDGFB	Pathogenic	criteria provided, single submitter
75239	NM_002608.4(PDGFB):c.356T>C (p.Leu119Pro)	PDGFB	Pathogenic	no assertion criteria provided
75241	NM_002608.4(PDGFB):c.726G>C (p.Ter242Tyr)	PDGFB	Pathogenic	no assertion criteria provided
75243	NM_002608.4(PDGFB):c.445C>T (p.Arg149Ter)	PDGFB	Pathogenic	criteria provided, multiple submitters, no conflicts
75245	NM_002608.4(PDGFB):c.3G>A (p.Met1Ile)	PDGFB	Pathogenic	no assertion criteria provided
2920727	NM_002608.4(PDGFB):c.-373C>G	PDGFB	Likely pathogenic	criteria provided, single submitter
2920728	NM_002608.4(PDGFB):c.-318C>T	PDGFB	Likely pathogenic	criteria provided, single submitter
976390	NM_002608.4(PDGFB):c.1A>G (p.Met1Val)	PDGFB	Likely pathogenic	criteria provided, single submitter
1626703	NM_002608.4(PDGFB):c.647G>A (p.Arg216His)	PDGFB	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1679380	NM_002608.4(PDGFB):c.298C>T (p.Arg100Cys)	PDGFB	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1690643	NM_002608.4(PDGFB):c.598C>T (p.Arg200Ter)	PDGFB	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1029462	NM_002608.4(PDGFB):c.71C>A (p.Pro24His)	PDGFB	Uncertain significance	criteria provided, single submitter
1806159	NM_002608.4(PDGFB):c.70C>A (p.Pro24Thr)	PDGFB	Uncertain significance	criteria provided, single submitter
4278275	NM_002608.4(PDGFB):c.370T>C (p.Cys124Arg)	PDGFB	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 7 · Orphanet: 4 · 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
PDGFB	Strong	Autosomal dominant	basal ganglia calcification, idiopathic, 5	7

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
PDGFB	Orphanet:1980	Bilateral striopallidodentate calcinosis
PDGFB	Orphanet:2495	Meningioma
PDGFB	Orphanet:263662	Familial multiple meningioma
PDGFB	Orphanet:31112	Dermatofibrosarcoma protuberans

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
PDGFB	HGNC:8800	ENSG00000100311	P01127	Platelet-derived growth factor subunit B	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
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.

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)
PDGFB	Other/Unknown	no		PDGF/VEGF_dom, PDGF_N, PD_growth_factor_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
apex of heart	1
olfactory bulb	1
type B pancreatic cell	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
PDGFB	259	ubiquitous	marker	olfactory bulb, type B pancreatic cell, apex of heart

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
PDGFB	2,424

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
PDGFB	P01127	6

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 8. 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×	0.015	PDGFB
Signaling by PDGF	1	253.8×	0.015	PDGFB
Non-integrin membrane-ECM interactions	1	154.3×	0.015	PDGFB
Constitutive Signaling by Aberrant PI3K in Cancer	1	126.9×	0.015	PDGFB
PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling	1	96.8×	0.015	PDGFB
Platelet degranulation	1	87.8×	0.015	PDGFB
PIP3 activates AKT signaling	1	66.8×	0.016	PDGFB
RAF/MAP kinase cascade	1	61.1×	0.016	PDGFB

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
metanephric glomerular mesangial cell development	1	16852.0×	0.001	PDGFB
positive regulation of vascular associated smooth muscle cell dedifferentiation	1	16852.0×	0.001	PDGFB
positive regulation of metanephric mesenchymal cell migration	1	16852.0×	0.001	PDGFB
negative regulation of phosphatidylinositol biosynthetic process	1	8426.0×	0.001	PDGFB
cellular response to mycophenolic acid	1	8426.0×	0.001	PDGFB
positive regulation of glomerular filtration	1	5617.3×	0.001	PDGFB
positive regulation of metanephric mesenchymal cell migration by platelet-derived growth factor receptor-beta signaling pathway	1	5617.3×	0.001	PDGFB
smooth muscle adaptation	1	4213.0×	0.001	PDGFB
positive regulation of hyaluronan biosynthetic process	1	4213.0×	0.001	PDGFB
negative regulation of vascular associated smooth muscle cell differentiation	1	3370.4×	0.001	PDGFB
interleukin-18-mediated signaling pathway	1	2808.7×	0.001	PDGFB
paracrine signaling	1	2808.7×	0.001	PDGFB
positive regulation of glomerular mesangial cell proliferation	1	2808.7×	0.001	PDGFB
negative regulation of platelet activation	1	1872.4×	0.002	PDGFB
positive regulation of DNA biosynthetic process	1	1123.5×	0.003	PDGFB
positive regulation of smooth muscle cell migration	1	991.3×	0.003	PDGFB
positive regulation of vascular associated smooth muscle cell migration	1	991.3×	0.003	PDGFB
positive regulation of calcium ion import	1	936.2×	0.003	PDGFB
positive regulation of chemotaxis	1	842.6×	0.003	PDGFB
embryonic placenta development	1	766.0×	0.004	PDGFB
cellular response to platelet-derived growth factor stimulus	1	648.1×	0.004	PDGFB
positive regulation of MAP kinase activity	1	648.1×	0.004	PDGFB
negative regulation of miRNA transcription	1	624.1×	0.004	PDGFB
monocyte chemotaxis	1	581.1×	0.004	PDGFB
platelet-derived growth factor receptor signaling pathway	1	561.7×	0.004	PDGFB
positive regulation of mitotic nuclear division	1	543.6×	0.004	PDGFB
positive regulation of reactive oxygen species metabolic process	1	510.7×	0.004	PDGFB
positive regulation of cell-substrate adhesion	1	495.6×	0.004	PDGFB
reactive oxygen species metabolic process	1	468.1×	0.004	PDGFB
positive regulation of vascular associated smooth muscle cell proliferation	1	432.1×	0.004	PDGFB

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
PDGFB	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
PDGFB	3	Binding:3

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	PDGFB

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)
PDGFB	3	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.