CSF1R

Chr 5ARAD

colony stimulating factor 1 receptor

Also known as: BANDDOS, C-FMS, CD115, CSF-1R, CSFR, FIM2, FMS, GPSC

The protein is a tyrosine kinase transmembrane receptor for colony stimulating factor 1 that controls macrophage production, differentiation, and function through ligand-induced oligomerization and transphosphorylation. Mutations cause brain abnormalities with neurodegeneration and dysosteosclerosis, as well as diffuse hereditary leukoencephalopathy with spheroids, inherited in both autosomal dominant and autosomal recessive patterns. The pathogenic mechanism involves gain-of-function effects that disrupt normal macrophage regulation in the central nervous system.

OMIMResearchSummary from RefSeq, OMIM, UniProt, Mechanism
LOFmechanismAR/ADLOEUF 0.392 OMIM phenotypes
Clinical SummaryCSF1R
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Gene-Disease Validity (ClinGen)
leukoencephalopathy, diffuse hereditary, with spheroids 1 · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.24) despite low pLI — interpret in context.
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Clinical Trials
7 active or recruiting trials — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.39LOEUF
pLI 0.133
Z-score 4.93
OE 0.24 (0.150.39)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
1.57Z-score
OE missense 0.81 (0.760.88)
466 obs / 571.8 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.24 (0.150.39)
00.351.4
Missense OE0.81 (0.760.88)
00.61.4
Synonymous OE1.04
01.21.6
LoF obs/exp: 12 / 49.4Missense obs/exp: 466 / 571.8Syn Z: -0.48
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveCSF1R-related brain abnormalities, neurodegeneration, and dysosteosclerosisLOFAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.76top 25%
GOF
0.78top 25%
LOF
0.2677th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Literature Evidence

DNA novel dominant-negative mutation of the CSF1R gene causes adult-onset leukoencephalopathy with axonal spheroids and pigmented glia.PMID:31632577
GOFMono-allelic gain-of-function mutations in CSF1R in humans are associated with an autosomal-dominant leukodystrophy and bi-allelic loss-of-function mutations with recessive skeletal dysplasia, brain disorders, and developmental anomalies.PMID:31330095
LOFWe sought to identify the role of microglial CSF1R haploinsufficiency in mediating pathogenesis.PMID:34433559

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

CSF1R · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

Lymphoma, Non-HodgkinMultiple MyelomaAdvanced Solid Tumors

Canadian Profiling and Targeted Agent Utilization Trial (CAPTUR)

RECRUITING
NCT03297606Phase PHASE2Canadian Cancer Trials GroupStarted 2018-03-23
OlaparibDasatinibNivolumab plus Ipilimumab
Non-Small Cell Carcinoma of Lung, TNM Stage 4Non-Small Cell Lung CancerEGFR Gene Mutation

Early Rebiopsy to Identify Biomarkers of Tumor Cell Survival Following EGFR, ALK, ROS1 or BRAF TKI Therapy

RECRUITING
NCT03042221University of Colorado, DenverStarted 2016-05-10
LeukodystrophyWhite Matter DiseaseLeukoencephalopathies

The Myelin Disorders Biorepository Project

RECRUITING
NCT03047369Children's Hospital of PhiladelphiaStarted 2016-12-08
Malignant Solid Neoplasms

Adapting Treatment to the Tumor Molecular Alterations for Patients With Advanced Solid Tumors: MyOwnSpecificTreatment

RECRUITING
NCT02029001Phase PHASE2Centre Leon BerardStarted 2014-03
Nilotinib (400 mg BID)Everolimus (10 mg QD)Sorafenib (400 mg BID)
Mesothelioma

New Preclinical and Clinical Approaches to Mesothelioma

RECRUITING
NCT06536179Marco Emilio BianchiStarted 2024-07-25
Lymphoma, Non-HodgkinMultiple MyelomaAdvanced Solid Tumors

TAPUR: Testing the Use of Food and Drug Administration (FDA) Approved Drugs That Target a Specific Abnormality in a Tumor Gene in People With Advanced Stage Cancer

RECRUITING
NCT02693535Phase PHASE2American Society of Clinical OncologyStarted 2016-03-14
PalbociclibSunitinibTemsirolimus
Advanced Solid TumorMetastatic Solid TumorsMET Gene Alterations

Study of TPX-0022 in Patients With Advanced NSCLC, Gastric Cancer or Solid Tumors Harboring Genetic Alterations in MET

ACTIVE NOT RECRUITING
NCT03993873Phase PHASE1Turning Point Therapeutics, Inc.Started 2019-09-05
elzovantinib (TPX-0022)
Clinical Literature
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Full-Text Mentions
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