CSF1R

colony stimulating factor 1 receptor, the group of Immunoglobulin like domain containing|CD molecules|Receptor tyrosine kinases

Basic information

Region (hg38): 5:150053290-150113372

Previous symbols: [ "FMS" ]

Links

ENSG00000182578 ∙ NCBI:1436 ∙ OMIM:164770 ∙ HGNC:2433 ∙ Uniprot:P07333 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• brain abnormalities, neurodegeneration, and dysosteosclerosis (Definitive), mode of inheritance: AR
• hereditary diffuse leukoencephalopathy with axonal spheroids and pigmented glia (Strong), mode of inheritance: AD
• hereditary diffuse leukoencephalopathy with axonal spheroids and pigmented glia (Definitive), mode of inheritance: AD
• hereditary diffuse leukoencephalopathy with axonal spheroids and pigmented glia (Supportive), mode of inheritance: AD
• early-onset calcifying leukoencephalopathy-skeletal dysplasia (Supportive), mode of inheritance: AR
• leukoencephalopathy, diffuse hereditary, with spheroids 1 (Strong), mode of inheritance: AD
• brain abnormalities, neurodegeneration, and dysosteosclerosis (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Leukoencephalopathy, diffuse hereditary, with spheroids 1; Brain abnormalities, neurodegeneration, and dysosteosclerosis	AD/AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Craniofacial; Musculoskeletal; Neurologic	16523341; 19153373; 22197934; 22843259; 23698128; 30982608; 30982609

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CSF1R gene.

• not provided (548 variants)
• Hereditary diffuse leukoencephalopathy with spheroids (179 variants)
• Inborn genetic diseases (36 variants)
• Brain abnormalities, neurodegeneration, and dysosteosclerosis (20 variants)
• not specified (12 variants)
• Leukoencephalopathy, diffuse hereditary, with spheroids 1 (8 variants)
• CSF1R-related condition (8 variants)
• Brain abnormalities, neurodegeneration, and dysosteosclerosis;Leukoencephalopathy, diffuse hereditary, with spheroids 1 (7 variants)
• Alzheimer disease (2 variants)
• CSF1R-Related Adult-Onset Leukoencephalopathy (1 variants)
• Leukoencephalopathy, diffuse hereditary, with spheroids 1;Brain abnormalities, neurodegeneration, and dysosteosclerosis (1 variants)
• See cases (1 variants)
• Parkinsonism (1 variants)
• Brain abnormalities, neurodegeneration, and dysosteosclerosis;Hereditary diffuse leukoencephalopathy with spheroids (1 variants)
• Frontotemporal dementia (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CSF1R gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			6	102	21	129
missense	8	18	183	47	17	273
nonsense	6	3	3			12
start loss						0
frameshift	2	2	6			10
inframe indel			15			15
splice donor/acceptor (+/-2bp)	1	3				4
splice region			15	16	5	36
non coding	1		33	47	64	145
Total	18	26	246	196	102

Highest pathogenic variant AF is 0.00000657

Variants in CSF1R

This is a list of pathogenic ClinVar variants found in the CSF1R region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
5-150053295-T-C		Hereditary diffuse leukoencephalopathy with spheroids	Benign (Jan 13, 2018)
5-150053300-T-C		Hereditary diffuse leukoencephalopathy with spheroids	Benign (Jan 13, 2018)
5-150053301-A-C		Hereditary diffuse leukoencephalopathy with spheroids	Uncertain significance (Jan 12, 2018)
5-150053320-G-A		Hereditary diffuse leukoencephalopathy with spheroids	Uncertain significance (Jan 13, 2018)
5-150053336-C-T		Hereditary diffuse leukoencephalopathy with spheroids	Uncertain significance (Jan 12, 2018)
5-150053344-CTGTT-C		Hereditary diffuse leukoencephalopathy with spheroids	Likely benign (Jun 14, 2016)
5-150053354-G-A		Hereditary diffuse leukoencephalopathy with spheroids	Uncertain significance (Jan 12, 2018)
5-150053450-C-A		Hereditary diffuse leukoencephalopathy with spheroids	Uncertain significance (Jan 12, 2018)
5-150053465-T-C		Hereditary diffuse leukoencephalopathy with spheroids	Benign (Jan 12, 2018)
5-150053508-G-A		Hereditary diffuse leukoencephalopathy with spheroids	Uncertain significance (Jan 13, 2018)
5-150053530-G-T		Hereditary diffuse leukoencephalopathy with spheroids	Uncertain significance (Jan 13, 2018)
5-150053537-C-T		Hereditary diffuse leukoencephalopathy with spheroids	Benign (Jan 13, 2018)
5-150053538-G-A		Hereditary diffuse leukoencephalopathy with spheroids	Uncertain significance (Jan 13, 2018)
5-150053539-G-T		Hereditary diffuse leukoencephalopathy with spheroids	Uncertain significance (Jan 13, 2018)
5-150053557-A-G		Hereditary diffuse leukoencephalopathy with spheroids	Benign (Jan 13, 2018)
5-150053569-G-A		Hereditary diffuse leukoencephalopathy with spheroids	Benign (Jan 12, 2018)
5-150053664-C-G		Hereditary diffuse leukoencephalopathy with spheroids	Benign (Jan 12, 2018)
5-150053759-G-T		Hereditary diffuse leukoencephalopathy with spheroids	Benign (Jan 12, 2018)
5-150053806-C-G		Hereditary diffuse leukoencephalopathy with spheroids	Uncertain significance (Jan 13, 2018)
5-150053820-T-C		Hereditary diffuse leukoencephalopathy with spheroids	Uncertain significance (Jan 12, 2018)
5-150053834-GA-G		Hereditary diffuse leukoencephalopathy with spheroids	Uncertain significance (Jun 14, 2016)
5-150053836-G-T		Hereditary diffuse leukoencephalopathy with spheroids	Uncertain significance (Jan 12, 2018)
5-150053835-A-AGG		Hereditary diffuse leukoencephalopathy with spheroids	Uncertain significance (Jun 14, 2016)
5-150053837-G-C		Hereditary diffuse leukoencephalopathy with spheroids	Uncertain significance (Jan 13, 2018)
5-150053837-G-GC		Hereditary diffuse leukoencephalopathy with spheroids	Benign (Jun 14, 2016)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CSF1R	protein_coding	protein_coding	ENST00000286301	21	60082

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.133	0.867	125718	0	30	125748	0.000119

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.57	466	572	0.815	0.0000337	6356
Missense in Polyphen		126	217.78	0.57857		2550
Synonymous	-0.485	252	242	1.04	0.0000157	1917
Loss of Function	4.93	12	49.4	0.243	0.00000240	550

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000243	0.000242
Ashkenazi Jewish	0.000101	0.0000992
East Asian	0.0000546	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.000168	0.000167
Middle Eastern	0.0000546	0.0000544
South Asian	0.000131	0.000131
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Tyrosine-protein kinase that acts as 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, such as macrophages and monocytes. Promotes the release of proinflammatory chemokines in response to IL34 and CSF1, and thereby plays an important role in innate immunity and in inflammatory processes. Plays an important role in the regulation of osteoclast proliferation and differentiation, the regulation of bone resorption, and is required for normal bone and tooth development. Required for normal male and female fertility, and for normal development of milk ducts and acinar structures in the mammary gland during pregnancy. Promotes reorganization of the actin cytoskeleton, regulates formation of membrane ruffles, cell adhesion and cell migration, and promotes cancer cell invasion. Activates several signaling pathways in response to ligand binding. Phosphorylates PIK3R1, PLCG2, GRB2, SLA2 and CBL. Activation of PLCG2 leads to the production of the cellular signaling molecules diacylglycerol and inositol 1,4,5- trisphosphate, that then lead to the activation of protein kinase C family members, especially PRKCD. Phosphorylation of PIK3R1, the regulatory subunit of phosphatidylinositol 3-kinase, leads to activation of the AKT1 signaling pathway. Activated CSF1R also mediates activation of the MAP kinases MAPK1/ERK2 and/or MAPK3/ERK1, and of the SRC family kinases SRC, FYN and YES1. Activated CSF1R transmits signals both via proteins that directly interact with phosphorylated tyrosine residues in its intracellular domain, or via adapter proteins, such as GRB2. Promotes activation of STAT family members STAT3, STAT5A and/or STAT5B. Promotes tyrosine phosphorylation of SHC1 and INPP5D/SHIP- 1. Receptor signaling is down-regulated by protein phosphatases, such as INPP5D/SHIP-1, that dephosphorylate the receptor and its downstream effectors, and by rapid internalization of the activated receptor. {ECO:0000269|PubMed:12882960, ECO:0000269|PubMed:15117969, ECO:0000269|PubMed:16170366, ECO:0000269|PubMed:16337366, ECO:0000269|PubMed:16648572, ECO:0000269|PubMed:17121910, ECO:0000269|PubMed:18467591, ECO:0000269|PubMed:18814279, ECO:0000269|PubMed:19193011, ECO:0000269|PubMed:19934330, ECO:0000269|PubMed:20489731, ECO:0000269|PubMed:20504948, ECO:0000269|PubMed:20829061, ECO:0000269|PubMed:7683918}.
• Disease: DISEASE: Note=Aberrant expression of CSF1 or CSF1R can promote cancer cell proliferation, invasion and formation of metastases. Overexpression of CSF1 or CSF1R is observed in a significant percentage of breast, ovarian, prostate, and endometrial cancers.; DISEASE: Note=Aberrant expression of CSF1 or CSF1R may play a role in inflammatory diseases, such as rheumatoid arthritis, glomerulonephritis, atherosclerosis, and allograft rejection.; DISEASE: Leukoencephalopathy, diffuse hereditary, with spheroids (HDLS) [MIM:221820]: An autosomal dominant adult-onset rapidly progressive neurodegenerative disorder characterized by variable behavioral, cognitive, and motor changes. Patients often die of dementia within 6 years of onset. Brain imaging shows patchy abnormalities in the cerebral white matter, predominantly affecting the frontal and parietal lobes. {ECO:0000269|PubMed:22197934, ECO:0000269|PubMed:24532199}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: PI3K-Akt signaling pathway - Homo sapiens (human);Acute myeloid leukemia - Homo sapiens (human);Rap1 signaling pathway - Homo sapiens (human);Ras signaling pathway - Homo sapiens (human);MAPK signaling pathway - Homo sapiens (human);Pathways in cancer - Homo sapiens (human);Transcriptional misregulation in cancer - Homo sapiens (human);Osteoclast differentiation - Homo sapiens (human);Hematopoietic cell lineage - Homo sapiens (human);Cytokine-cytokine receptor interaction - Homo sapiens (human);Differentiation Pathway;Imatinib and Chronic Myeloid Leukemia;Focal Adhesion-PI3K-Akt-mTOR-signaling pathway;PI3K-Akt Signaling Pathway;Ras Signaling;Other interleukin signaling;Signaling by Interleukins;mets affect on macrophage differentiation;Cytokine Signaling in Immune system;Immune System;Signaling events mediated by TCPTP;C-MYB transcription factor network;Signaling events mediated by PTP1B;Integrins in angiogenesis (Consensus)

Recessive Scores

• pRec: 0.525

Intolerance Scores

• loftool: 0.150
• rvis_EVS: 0.61
• rvis_percentile_EVS: 82.96

Haploinsufficiency Scores

• pHI: 0.424
• hipred: Y
• hipred_score: 0.699
• ghis: 0.405

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.652

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Csf1r
• Phenotype: cellular phenotype; homeostasis/metabolism phenotype; craniofacial phenotype; endocrine/exocrine gland phenotype; taste/olfaction phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); growth/size/body region phenotype; skeleton phenotype; immune system phenotype; limbs/digits/tail phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); hearing/vestibular/ear phenotype; normal phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); reproductive system phenotype; hematopoietic system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan)

Zebrafish Information Network

• Gene name: csf1ra
• Affected structure: retinal ganglion cell
• Phenotype tag: abnormal
• Phenotype quality: undifferentiated

Gene ontology

• Biological process: positive regulation of protein phosphorylation;hematopoietic progenitor cell differentiation;inflammatory response;signal transduction;transmembrane receptor protein tyrosine kinase signaling pathway;multicellular organism development;axon guidance;cell population proliferation;positive regulation of cell population proliferation;negative regulation of cell population proliferation;regulation of cell shape;peptidyl-tyrosine phosphorylation;cytokine-mediated signaling pathway;olfactory bulb development;forebrain neuron differentiation;hemopoiesis;monocyte differentiation;macrophage differentiation;osteoclast differentiation;positive regulation of cell migration;ruffle organization;cellular response to macrophage colony-stimulating factor stimulus;macrophage colony-stimulating factor signaling pathway;positive regulation of tyrosine phosphorylation of STAT protein;positive regulation of MAPK cascade;innate immune response;regulation of bone resorption;cell-cell junction maintenance;phosphatidylinositol metabolic process;protein autophosphorylation;phosphatidylinositol-mediated signaling;mammary gland duct morphogenesis;positive regulation of protein tyrosine kinase activity;positive regulation of ERK1 and ERK2 cascade;cellular response to cytokine stimulus;positive regulation of protein serine/threonine kinase activity;positive regulation of chemokine secretion;positive regulation of cell motility;regulation of actin cytoskeleton reorganization
• Cellular component: nucleoplasm;plasma membrane;integral component of plasma membrane;cell surface;intracellular membrane-bounded organelle;receptor complex;CSF1-CSF1R complex
• Molecular function: transmembrane receptor protein tyrosine kinase activity;macrophage colony-stimulating factor receptor activity;protein binding;ATP binding;protein phosphatase binding;cytokine binding;protein homodimerization activity