Basal ganglia calcification, idiopathic, 6

Summary

Basal ganglia calcification, idiopathic, 6 (MONDO:0014628) is a disease caused by XPR1 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: XPR1 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 18

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	basal ganglia calcification, idiopathic, 6
Mondo ID	MONDO:0014628
OMIM	616413
UMLS	C4225335
MedGen	901404
GARD	0016107
Is cancer (heuristic)	no

Also known as: basal ganglia calcification, idiopathic, 6 · basal ganglia calcification, idiopathic, type 6 · bilateral striopallidodentate calcinosis caused by mutation in XPR1 · IBGC6 · XPR1 bilateral striopallidodentate calcinosis

Data availability: 18 ClinVar variants · 5 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, 6

Related subtypes (9): basal ganglia calcification, idiopathic, childhood-onset, basal ganglia calcification, idiopathic, 4, basal ganglia calcification, idiopathic, 5, 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

18 retrieved; paginated sample, class counts are floors:

9 uncertain significance, 4 pathogenic, 2 conflicting classifications of pathogenicity, 1 benign, 1 likely pathogenic, 1 likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
192303	NM_004736.4(XPR1):c.434T>C (p.Leu145Pro)	XPR1	Pathogenic	no assertion criteria provided
192304	NM_004736.4(XPR1):c.407G>A (p.Ser136Asn)	XPR1	Pathogenic	no assertion criteria provided
192305	NM_004736.4(XPR1):c.419T>C (p.Leu140Pro)	XPR1	Pathogenic	no assertion criteria provided
192306	NM_004736.4(XPR1):c.653T>C (p.Leu218Ser)	XPR1	Pathogenic	no assertion criteria provided
3065743	NM_004736.4(XPR1):c.863A>G (p.Asn288Ser)	XPR1	Likely pathogenic	criteria provided, single submitter
1937231	NM_004736.4(XPR1):c.66T>C (p.Tyr22=)	XPR1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2053888	NM_004736.4(XPR1):c.1964G>A (p.Arg655His)	XPR1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1199197	NM_004736.4(XPR1):c.1811G>A (p.Arg604Gln)	XPR1	Uncertain significance	criteria provided, multiple submitters, no conflicts
1367752	NM_004736.4(XPR1):c.762C>T (p.Ala254=)	XPR1	Uncertain significance	criteria provided, multiple submitters, no conflicts
1398547	NM_004736.4(XPR1):c.1158C>G (p.Phe386Leu)	XPR1	Uncertain significance	criteria provided, multiple submitters, no conflicts
3572878	NM_004736.4(XPR1):c.1229T>A (p.Leu410Gln)	XPR1	Uncertain significance	criteria provided, single submitter
3780807	NM_004736.4(XPR1):c.2041C>T (p.Arg681Cys)	XPR1	Uncertain significance	criteria provided, multiple submitters, no conflicts
3897997	NM_004736.4(XPR1):c.2003C>G (p.Ser668Cys)	XPR1	Uncertain significance	criteria provided, single submitter
634593	NM_004736.4(XPR1):c.1954G>A (p.Val652Ile)	XPR1	Uncertain significance	criteria provided, multiple submitters, no conflicts
978145	NM_004736.4(XPR1):c.1093A>T (p.Thr365Ser)	XPR1	Uncertain significance	criteria provided, single submitter
982909	NM_004736.4(XPR1):c.2018G>A (p.Arg673His)	XPR1	Uncertain significance	criteria provided, multiple submitters, no conflicts
1281645	NM_004736.4(XPR1):c.1135-8dup	XPR1	Benign	criteria provided, multiple submitters, no conflicts
744559	NM_004736.4(XPR1):c.1887C>A (p.Ile629=)	XPR1	Likely benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 6 · 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
XPR1	Strong	Autosomal dominant	basal ganglia calcification, idiopathic, 6	6

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
XPR1	Orphanet:1980	Bilateral striopallidodentate calcinosis

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
XPR1	HGNC:12827	ENSG00000143324	Q9UBH6	Solute carrier family 53 member 1	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
XPR1	Solute carrier family 53 member 1	Inorganic ion transporter that mediates phosphate ion export across the plasma membrane.

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)
XPR1	Other/Unknown	no		SPX_dom, EXS_C

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
cortical plate	1
kidney epithelium	1
left ventricle myocardium	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
XPR1	254	ubiquitous	marker	cortical plate, kidney epithelium, left ventricle myocardium

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
XPR1	2,863

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
XPR1	Q9UBH6	51

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
cellular response to phosphate starvation	1	4213.0×	0.001	XPR1
phosphate ion transport	1	1872.4×	0.001	XPR1
intracellular phosphate ion homeostasis	1	1532.0×	0.001	XPR1
phosphate ion transmembrane transport	1	1203.7×	0.001	XPR1
response to virus	1	144.0×	0.007	XPR1

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
XPR1	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	XPR1

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)
XPR1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.