Brain abnormalities, neurodegeneration, and dysosteosclerosis

Summary

Brain abnormalities, neurodegeneration, and dysosteosclerosis (MONDO:0032772) is a disease caused by CSF1R (GenCC Definitive), with 1 cohort gene.

At a glance

• Causal gene: CSF1R (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 42

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	brain abnormalities, neurodegeneration, and dysosteosclerosis
Mondo ID	MONDO:0032772
OMIM	618476
UMLS	C5193117
MedGen	1678789
Is cancer (heuristic)	no

Also known as: BANDDOS

Data availability: 42 ClinVar variants · 2 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › CSF1R-related disorder › brain abnormalities, neurodegeneration, and dysosteosclerosis

Related subtypes (1): leukoencephalopathy, diffuse hereditary, with spheroids 1

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

42 retrieved; paginated sample, class counts are floors:

15 uncertain significance, 8 benign, 6 pathogenic, 5 conflicting classifications of pathogenicity, 5 likely pathogenic, 2 benign/likely benign, 1 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1029946	NM_001288705.3(CSF1R):c.1620T>A (p.Tyr540Ter)	CSF1R	Pathogenic	criteria provided, multiple submitters, no conflicts
2575888	NM_001288705.3(CSF1R):c.2471C>T (p.Pro824Leu)	CSF1R	Pathogenic	criteria provided, single submitter
3069042	NM_001288705.3(CSF1R):c.2549C>A (p.Ser850Ter)	CSF1R	Pathogenic	criteria provided, single submitter
38378	NM_001288705.3(CSF1R):c.2345G>A (p.Arg782His)	CSF1R	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
520697	NM_001288705.3(CSF1R):c.1441C>T (p.Gln481Ter)	CSF1R	Pathogenic	criteria provided, multiple submitters, no conflicts
635123	NM_001288705.3(CSF1R):c.1969+115_1969+116del	CSF1R	Pathogenic	criteria provided, single submitter
635124	NM_001288705.3(CSF1R):c.1754-1G>C	CSF1R	Pathogenic	no assertion criteria provided
2443077	NM_001288705.3(CSF1R):c.69dup (p.Glu24fs)	CSF1R	Likely pathogenic	criteria provided, single submitter
3064487	NM_001288705.3(CSF1R):c.828C>G (p.Tyr276Ter)	CSF1R	Likely pathogenic	criteria provided, single submitter
3251449	NM_001288705.3(CSF1R):c.2545T>A (p.Phe849Ile)	CSF1R	Likely pathogenic	criteria provided, single submitter
3779550	NM_001288705.3(CSF1R):c.931C>T (p.Gln311Ter)	CSF1R	Likely pathogenic	criteria provided, single submitter
4277572	NM_001288705.3(CSF1R):c.2405A>G (p.Asp802Gly)	CSF1R	Likely pathogenic	criteria provided, single submitter
1420666	NM_001288705.3(CSF1R):c.2073G>C (p.Gln691His)	CSF1R	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1567619	NM_001288705.3(CSF1R):c.110C>T (p.Thr37Met)	CSF1R	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
162128	NM_001288705.3(CSF1R):c.2350G>A (p.Val784Met)	CSF1R	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2415792	NM_001288705.3(CSF1R):c.2797G>A (p.Gly933Ser)	CSF1R	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1465714	NM_001288705.3(CSF1R):c.656C>A (p.Ala219Asp)	LOC111188154	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1341872	NM_001288705.3(CSF1R):c.410G>T (p.Gly137Val)	CSF1R	Uncertain significance	criteria provided, single submitter
162129	NM_001288705.3(CSF1R):c.2562T>A (p.Asn854Lys)	CSF1R	Uncertain significance	criteria provided, multiple submitters, no conflicts
2270770	NM_001288705.3(CSF1R):c.2308G>A (p.Ala770Thr)	CSF1R	Uncertain significance	criteria provided, multiple submitters, no conflicts
2441972	NM_001288705.3(CSF1R):c.740C>T (p.Pro247Leu)	CSF1R	Uncertain significance	criteria provided, single submitter
2441995	NM_001288705.3(CSF1R):c.604C>T (p.Pro202Ser)	CSF1R	Uncertain significance	criteria provided, single submitter
2682172	NM_001288705.3(CSF1R):c.2809A>G (p.Ser937Gly)	CSF1R	Uncertain significance	criteria provided, single submitter
3591897	NM_001288705.3(CSF1R):c.719A>G (p.Asn240Ser)	CSF1R	Uncertain significance	criteria provided, single submitter
452495	NM_001288705.3(CSF1R):c.1879_1881del (p.Lys627del)	CSF1R	Uncertain significance	criteria provided, single submitter
635119	NM_001288705.3(CSF1R):c.395C>T (p.Pro132Leu)	CSF1R	Uncertain significance	criteria provided, single submitter
635121	NM_001288705.3(CSF1R):c.1859-119G>A	CSF1R	Uncertain significance	criteria provided, single submitter
635125	NM_001288705.3(CSF1R):c.1929C>A (p.His643Gln)	CSF1R	Uncertain significance	criteria provided, single submitter
930387	NM_001288705.3(CSF1R):c.1402G>T (p.Val468Leu)	CSF1R	Uncertain significance	criteria provided, multiple submitters, no conflicts
930578	NM_001288705.3(CSF1R):c.349G>A (p.Val117Met)	CSF1R	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 7 · Orphanet: 2 · 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
CSF1R	Definitive	Autosomal recessive	brain abnormalities, neurodegeneration, and dysosteosclerosis	7

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
CSF1R	Orphanet:313808	Adult-onset leukoencephalopathy with axonal spheroids and pigmented glia
CSF1R	Orphanet:556985	Early-onset calcifying leukoencephalopathy-skeletal dysplasia

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
CSF1R	HGNC:2433	ENSG00000182578	P07333	Macrophage colony-stimulating factor 1 receptor	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CSF1R	Macrophage colony-stimulating factor 1 receptor	Tyrosine-protein kinase that acts as a cell-surface receptor for CSF1 and IL34 and plays an essential role in the regulation of survival, proliferation and differentiation of hematopoietic precursor cells, especially mononuclear phagocytes…

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)
CSF1R	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
granulocyte	1
leukocyte	1
monocyte	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CSF1R	245	broad	marker	granulocyte, monocyte, leukocyte

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CSF1R	4,392

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
CSF1R	P07333	26

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 3. 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
Other interleukin signaling	1	475.8×	0.004	CSF1R
Signaling by CSF1 (M-CSF) in myeloid cells	1	346.1×	0.004	CSF1R
Transcriptional Regulation by VENTX	1	265.6×	0.004	CSF1R

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
forebrain neuron differentiation	1	5617.3×	0.003	CSF1R
macrophage colony-stimulating factor signaling pathway	1	5617.3×	0.003	CSF1R
regulation of macrophage migration	1	4213.0×	0.003	CSF1R
cellular response to macrophage colony-stimulating factor stimulus	1	3370.4×	0.003	CSF1R
positive regulation of macrophage proliferation	1	3370.4×	0.003	CSF1R
mammary gland duct morphogenesis	1	2407.4×	0.003	CSF1R
positive regulation of protein tyrosine kinase activity	1	2106.5×	0.003	CSF1R
cell-cell junction maintenance	1	1872.4×	0.003	CSF1R
microglial cell proliferation	1	1872.4×	0.003	CSF1R
regulation of bone resorption	1	1532.0×	0.003	CSF1R
host-mediated activation of viral process	1	1404.3×	0.003	CSF1R
ruffle organization	1	1296.3×	0.003	CSF1R
positive regulation of macrophage chemotaxis	1	802.5×	0.003	CSF1R
monocyte differentiation	1	802.5×	0.003	CSF1R
olfactory bulb development	1	766.0×	0.003	CSF1R
positive regulation of cell motility	1	766.0×	0.003	CSF1R
positive regulation of tyrosine phosphorylation of STAT protein	1	732.7×	0.003	CSF1R
cellular response to cytokine stimulus	1	543.6×	0.004	CSF1R
macrophage differentiation	1	468.1×	0.005	CSF1R
regulation of MAPK cascade	1	455.5×	0.005	CSF1R
peptidyl-tyrosine phosphorylation	1	421.3×	0.005	CSF1R
positive regulation of chemokine production	1	374.5×	0.005	CSF1R
osteoclast differentiation	1	343.9×	0.005	CSF1R
positive regulation of protein phosphorylation	1	276.3×	0.006	CSF1R
hemopoiesis	1	267.5×	0.006	CSF1R
response to ischemia	1	251.5×	0.007	CSF1R
cell surface receptor protein tyrosine kinase signaling pathway	1	173.7×	0.009	CSF1R
regulation of actin cytoskeleton organization	1	157.5×	0.010	CSF1R
protein autophosphorylation	1	145.3×	0.010	CSF1R
cytokine-mediated signaling pathway	1	130.6×	0.011	CSF1R

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
CSF1R	PONATINIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
CSF1R	79	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
PONATINIB	4	CSF1R
FEDRATINIB	4	CSF1R
AXITINIB	4	CSF1R
SORAFENIB	4	CSF1R
DASATINIB ANHYDROUS	4	CSF1R
SUNITINIB MALATE	4	CSF1R
NERATINIB	4	CSF1R
IBRUTINIB	4	CSF1R
ENTRECTINIB	4	CSF1R
PACRITINIB	4	CSF1R
VANDETANIB	4	CSF1R
NILOTINIB	4	CSF1R
BOSUTINIB	4	CSF1R
FILGOTINIB	4	CSF1R
BRIGATINIB	4	CSF1R
PEXIDARTINIB	4	CSF1R
PAZOPANIB	4	CSF1R
NINTEDANIB	4	CSF1R
SUNITINIB	4	CSF1R
DASATINIB	4	CSF1R
QUIZARTINIB	4	CSF1R
CRIZOTINIB	4	CSF1R
MIDOSTAURIN	4	CSF1R
IMATINIB	4	CSF1R
VATALANIB	3	CSF1R
DACTOLISIB	3	CSF1R
MASITINIB	3	CSF1R
LINIFANIB	3	CSF1R
SEMAXANIB	3	CSF1R
BRIVANIB	3	CSF1R

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
CSF1R	897	Binding:879, Functional:17, ADMET:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
CSF1R	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
CSF1R	897

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	CSF1R
FEDRATINIB	4	CSF1R
AXITINIB	4	CSF1R
SORAFENIB	4	CSF1R
DASATINIB ANHYDROUS	4	CSF1R
SUNITINIB MALATE	4	CSF1R
NERATINIB	4	CSF1R
IBRUTINIB	4	CSF1R
ENTRECTINIB	4	CSF1R
PACRITINIB	4	CSF1R
VANDETANIB	4	CSF1R
NILOTINIB	4	CSF1R
BOSUTINIB	4	CSF1R
FILGOTINIB	4	CSF1R
BRIGATINIB	4	CSF1R
PEXIDARTINIB	4	CSF1R
PAZOPANIB	4	CSF1R
NINTEDANIB	4	CSF1R
SUNITINIB	4	CSF1R
DASATINIB	4	CSF1R
QUIZARTINIB	4	CSF1R
CRIZOTINIB	4	CSF1R
MIDOSTAURIN	4	CSF1R
IMATINIB	4	CSF1R
VATALANIB	3	CSF1R
DACTOLISIB	3	CSF1R
MASITINIB	3	CSF1R
LINIFANIB	3	CSF1R
SEMAXANIB	3	CSF1R
BRIVANIB	3	CSF1R

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	CSF1R
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.