CSF1R

Chr 5

colony stimulating factor 1 receptor

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

NCBI Gene: 1436 ENSG00000182578 UniProt: P07333

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 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 ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtLeukoencephalopathy, hereditary diffuse, with spheroids 1

UniProtBrain abnormalities, neurodegeneration, and dysosteosclerosis

Clinical highlights

Gene-disease validity (ClinGen)

leukoencephalopathy, diffuse hereditary, with spheroids 1 · ADDefinitivesufficient evidence for diagnostic panels2 gene-disease associations curated in total

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype) and the gene is intolerant of it in the population — truncating, frameshift and canonical splice variants carry more prior weight here than missense.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

497

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.39

LOEUF

LOF

Mechanism· G2P

📖

GeneReview available — CSF1R

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

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

ClinVar Variant Classifications

0 submitted variants in ClinVar

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.

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

📖

GeneReview available — CSF1R

Authoritative clinical overview · NCBI Bookshelf · Recommended first read

Open GeneReview ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

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)

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

SunitinibTemsirolimusTrastuzumab and Pertuzumab

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)

Mesothelioma

New Preclinical and Clinical Approaches to Mesothelioma

RECRUITING

NCT06536179Marco Emilio BianchiStarted 2024-07-25