Basal ganglia calcification, idiopathic, 8, autosomal recessive

Summary

Basal ganglia calcification, idiopathic, 8, autosomal recessive (MONDO:0032938) is a disease caused by JAM2 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: JAM2 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 8

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	basal ganglia calcification, idiopathic, 8, autosomal recessive
Mondo ID	MONDO:0032938
OMIM	618824
UMLS	C5394199
MedGen	1713414
GARD	0016384
Is cancer (heuristic)	no

Also known as: IBGC8

Data availability: 8 ClinVar variants · 3 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, 8, autosomal recessive

Related subtypes (9): 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, 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

8 retrieved; paginated sample, class counts are floors:

8 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
829531	NM_021219.4(JAM2):c.143del (p.Ile47_Leu48insTer)	JAM2	Pathogenic	no assertion criteria provided
829533	NM_021219.4(JAM2):c.1A>G (p.Met1Val)	JAM2	Pathogenic	no assertion criteria provided
829535	NM_021219.4(JAM2):c.504G>C (p.Trp168Cys)	JAM2	Pathogenic	no assertion criteria provided
829537	NM_021219.4:c.(67+1_68-1)_(394+1_395-1)del	JAM2	Pathogenic	no assertion criteria provided
829539	NM_021219.4(JAM2):c.323G>A (p.Arg108His)	JAM2	Pathogenic	no assertion criteria provided
829541	NM_021219.4(JAM2):c.685C>T (p.Arg229Ter)	JAM2	Pathogenic	criteria provided, multiple submitters, no conflicts
829543	NM_021219.4(JAM2):c.395-1dup	JAM2	Pathogenic	no assertion criteria provided
829545	NM_021219.4(JAM2):c.177_180del (p.Ser59_Arg60insTer)	JAM2	Pathogenic	no assertion criteria provided

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 4 · 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
JAM2	Strong	Autosomal recessive	basal ganglia calcification, idiopathic, 8, autosomal recessive	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
JAM2	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
JAM2	HGNC:14686	ENSG00000154721	P57087	Junctional adhesion molecule B	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
JAM2	Junctional adhesion molecule B	Junctional adhesion protein that mediates heterotypic cell-cell interactions with its cognate receptor JAM3 to regulate different cellular processes.

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
Antibody/Immunoglobulin	1	29.2×	0.034

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
JAM2	Antibody/Immunoglobulin	yes		Ig_sub2, Ig_sub, Ig-like_dom

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
tendon of biceps brachii	1
vena cava	1
ventricular zone	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
JAM2	277	ubiquitous	marker	ventricular zone, tendon of biceps brachii, vena cava

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
JAM2	651

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
JAM2	P57087	82.91

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 4. 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
Integrin cell surface interactions	1	134.3×	0.021	JAM2
Cell surface interactions at the vascular wall	1	95.2×	0.021	JAM2
Extracellular matrix organization	1	63.1×	0.021	JAM2
Hemostasis	1	36.0×	0.028	JAM2

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
positive regulation of lymphocyte migration	1	8426.0×	7e-04	JAM2
lymphocyte aggregation	1	5617.3×	7e-04	JAM2
cellular extravasation	1	4213.0×	7e-04	JAM2
hematopoietic stem cell migration to bone marrow	1	3370.4×	7e-04	JAM2
negative regulation of myelination	1	1872.4×	0.001	JAM2
leukocyte tethering or rolling	1	842.6×	0.002	JAM2
maintenance of blood-brain barrier	1	481.5×	0.003	JAM2
leukocyte cell-cell adhesion	1	468.1×	0.003	JAM2
spermatid development	1	145.3×	0.008	JAM2
cell-cell adhesion	1	101.5×	0.010	JAM2

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
JAM2	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
JAM2	1	Binding:1

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	1	JAM2
E	Difficult family or no structure, no drug	0

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)
JAM2	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.