CSF1R

Chr 5ARAD

colony stimulating factor 1 receptor

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

NCBI Gene: 1436 ENSG00000182578 UniProt: P07333 OMIM: 164770

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.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt, Mechanism

The protein encoded by this gene is the receptor for colony stimulating factor 1, a cytokine which controls the production, differentiation, and function of macrophages. This receptor mediates most if not all of the biological effects of this cytokine. Ligand binding activates the receptor kinase through a process of oligomerization and transphosphorylation. The encoded protein is a tyrosine kinase transmembrane receptor and member of the CSF1/PDGF receptor family of tyrosine-protein kinases. Mutations in this gene have been associated with a predisposition to myeloid malignancy. The first intron of this gene contains a transcriptionally inactive ribosomal protein L7 processed pseudogene oriented in the opposite direction. Alternative splicing results in multiple transcript variants. Expression of a splice variant from an LTR promoter has been found in Hodgkin lymphoma (HL), HL cell lines and anaplastic large cell lymphoma. [provided by RefSeq, Mar 2017]

GeneReviews OMIM ResearchGenerating clinical summary…

LOFmechanismAR/ADLOEUF 0.392 OMIM phenotypes

Clinical Summary— CSF1R

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Gene-Disease Validity (ClinGen)

leukoencephalopathy, diffuse hereditary, with spheroids 1 · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)

Constrained for loss-of-function variants (OE-LoF 0.24) despite low pLI — interpret in context.

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ClinVar Variants

83 unique Pathogenic / Likely Pathogenic· 414 VUS of 1030 total submissions

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Clinical Trials

7 active or recruiting trials — potential therapeutic options may be available

Explore recent and relevant literature in Research Assistant →

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GeneReview available — CSF1R

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.39LOEUF

pLI 0.133

Z-score 4.93

OE 0.24 (0.15–0.39)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

1.57Z-score

OE missense 0.81 (0.76–0.88)

466 obs / 571.8 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.24 (0.15–0.39)

0≤0.351.4

Missense OE?0.81 (0.76–0.88)

0≤0.61.4

Synonymous OE?1.04

0≤1.21.6

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

This gene — mechanism propensity

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

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.1

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.2

LOFWe sought to identify the role of microglial CSF1R haploinsufficiency in mediating pathogenesis.3

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

References

ClinVar Variant Classifications

1030 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic42

Likely Pathogenic41

VUS414

Likely Benign338

Benign105

Conflicting65

Pathogenic

Likely Pathogenic

414

VUS

338

Likely Benign

105

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	27	14	1	0	42
Likely Pathogenic	12	29	0	0	41
VUS	5	349	55	5	414
Likely Benign	0	52	102	184	338
Benign	0	18	67	20	105
Conflicting	—				65
Total	44	462	225	209	1,005

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

10 pathogenic / likely-pathogenic (of 14) ClinVar copy-number / structural variants overlap CSF1R — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →

Protein Context — Lollipop Plot

CSF1R · protein map & ClinVar variants

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

External Resources

Links to major genomics databases and tools

Franklin by Genoox

AI-powered variant curation and clinical analysis

DECIPHER

Genomic variants and phenotypes in rare disease patients

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GeneReview available — CSF1R

Authoritative clinical overview · NCBI Bookshelf · Recommended first read

Open GeneReview ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

Mesothelioma

New Preclinical and Clinical Approaches to Mesothelioma

RECRUITING

NCT06536179Marco Emilio BianchiStarted 2024-07-25

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)

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

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

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)

Clinical Literature

Open Research Assistant →

Landmark / reviewRecent case evidence

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