CX3CL1

C-X3-C motif chemokine ligand 1, the group of Chemokine ligands

Basic information

Region (hg38): 16:57372476-57385044

Previous symbols: [ "SCYD1" ]

Links

ENSG00000006210 ∙ NCBI:6376 ∙ OMIM:601880 ∙ HGNC:10647 ∙ Uniprot:P78423 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CX3CL1 gene.

• Inborn genetic diseases (24 variants)
• not provided (11 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CX3CL1 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				3	4	7
missense			22	3	1	26
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding					2	2
Total	0	0	22	6	7

Variants in CX3CL1

This is a list of pathogenic ClinVar variants found in the CX3CL1 region.

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

Position	Type	Phenotype	Significance	ClinVar
16-57372600-G-T		not specified	Uncertain significance (Apr 07, 2022)
16-57372636-C-A		not specified	Uncertain significance (Feb 28, 2023)
16-57376022-T-G			Benign (Jul 15, 2020)
16-57379667-C-T		not specified	Uncertain significance (Oct 10, 2023)
16-57379748-C-T			Benign (Aug 29, 2018)
16-57379763-T-C			Benign (Jul 09, 2018)
16-57382055-T-C		not specified	Uncertain significance (May 30, 2023)
16-57382091-G-A		not specified	Uncertain significance (Jan 05, 2022)
16-57382093-G-A			Benign (Dec 31, 2019)
16-57382139-G-A		not specified	Uncertain significance (Aug 02, 2021)
16-57382163-G-A		not specified	Uncertain significance (Oct 06, 2021)
16-57382188-C-T		not specified	Uncertain significance (Apr 28, 2022)
16-57382189-C-T			Likely benign (May 15, 2018)
16-57382192-C-T			Benign (Feb 17, 2018)
16-57382193-G-A		not specified	Likely benign (Jul 09, 2021)
16-57382257-C-A		not specified	Uncertain significance (Oct 20, 2023)
16-57382314-C-T		not specified	Uncertain significance (Jul 13, 2021)
16-57382315-G-A			Likely benign (Mar 06, 2018)
16-57382344-T-C		not specified	Uncertain significance (Nov 08, 2022)
16-57382350-C-T		not specified	Uncertain significance (Jan 04, 2024)
16-57382353-C-T		not specified	Uncertain significance (Jun 29, 2022)
16-57382375-G-T			Likely benign (Apr 01, 2023)
16-57382386-C-T		not specified	Uncertain significance (Jan 26, 2022)
16-57382398-G-A		not specified	Uncertain significance (Aug 12, 2021)
16-57382414-C-T			Benign (Jun 18, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CX3CL1	protein_coding	protein_coding	ENST00000006053	3	12591

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.608	0.390	125742	0	4	125746	0.0000159

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.843	211	248	0.849	0.0000156	2520
Missense in Polyphen		32	51.12	0.62597		581
Synonymous	-1.95	141	114	1.23	0.00000822	867
Loss of Function	2.61	2	11.6	0.173	6.41e-7	106

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000905	0.0000905
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000178	0.0000176
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Acts as a ligand for both CX3CR1 and integrins. Binds to CX3CR1 (PubMed:23125415, PubMed:9931005, PubMed:21829356). Binds to integrins ITGAV:ITGB3 and ITGA4:ITGB1. Can activate integrins in both a CX3CR1-dependent and CX3CR1-independent manner. In the presence of CX3CR1, activates integrins by binding to the classical ligand-binding site (site 1) in integrins. In the absence of CX3CR1, binds to a second site (site 2) in integrins which is distinct from site 1 and enhances the binding of other integrin ligands to site 1 (PubMed:23125415, PubMed:24789099). The soluble form is chemotactic for T-cells and monocytes and not for neutrophils. The membrane-bound form promotes adhesion of those leukocytes to endothelial cells. May play a role in regulating leukocyte adhesion and migration processes at the endothelium (PubMed:9024663, PubMed:9177350). {ECO:0000269|PubMed:21829356, ECO:0000269|PubMed:23125415, ECO:0000269|PubMed:24789099, ECO:0000269|PubMed:9024663, ECO:0000269|PubMed:9177350, ECO:0000269|PubMed:9931005}.
• Pathway: TNF signaling pathway - Homo sapiens (human);Chemokine signaling pathway - Homo sapiens (human);Cytokine-cytokine receptor interaction - Homo sapiens (human);Chemokine signaling pathway;Signaling by GPCR;Signal Transduction;Chemokine receptors bind chemokines;Peptide ligand-binding receptors;Class A/1 (Rhodopsin-like receptors);GPCR ligand binding;Direct p53 effectors;G alpha (i) signalling events;GPCR downstream signalling (Consensus)

Recessive Scores

• pRec: 0.319

Intolerance Scores

• loftool: 0.227
• rvis_EVS: -0.51
• rvis_percentile_EVS: 21.65

Haploinsufficiency Scores

• pHI: 0.133
• hipred: N
• hipred_score: 0.326
• ghis: 0.492

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.815

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Cx3cl1
• Phenotype: cellular phenotype; homeostasis/metabolism phenotype; immune system 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); hematopoietic system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan)

Gene ontology

• Biological process: microglial cell activation;positive regulation of cell-matrix adhesion;positive regulation of neuroblast proliferation;leukocyte migration involved in inflammatory response;monocyte chemotaxis;response to ischemia;chemotaxis;defense response;inflammatory response;immune response;cell adhesion;G protein-coupled receptor signaling pathway;cell-cell signaling;aging;regulation of signaling receptor activity;negative regulation of cell-substrate adhesion;positive regulation of neuron projection development;neuron remodeling;cytokine-mediated signaling pathway;negative regulation of cell migration;neutrophil chemotaxis;leukocyte chemotaxis;regulation of lipopolysaccharide-mediated signaling pathway;positive regulation of actin filament bundle assembly;negative regulation of interleukin-1 alpha production;negative regulation of interleukin-1 beta production;negative regulation of interleukin-6 production;negative regulation of tumor necrosis factor production;positive regulation of transforming growth factor beta1 production;integrin activation;autocrine signaling;positive regulation of I-kappaB kinase/NF-kappaB signaling;positive regulation of MAPK cascade;positive regulation of GTPase activity;positive regulation of angiogenesis;positive regulation of transcription by RNA polymerase II;regulation of synaptic plasticity;eosinophil chemotaxis;macrophage chemotaxis;lymphocyte chemotaxis;positive regulation of smooth muscle cell proliferation;positive regulation of inflammatory response;regulation of neurogenesis;leukocyte adhesive activation;positive chemotaxis;positive regulation of calcium-independent cell-cell adhesion;positive regulation of NF-kappaB transcription factor activity;positive regulation of release of sequestered calcium ion into cytosol;positive regulation of protein kinase B signaling;angiogenesis involved in wound healing;microglial cell proliferation;neuron cellular homeostasis;chemokine-mediated signaling pathway;positive regulation of ERK1 and ERK2 cascade;cellular response to interferon-gamma;cellular response to interleukin-1;cellular response to tumor necrosis factor;cell-cell adhesion;synapse pruning;negative regulation of hippocampal neuron apoptotic process;negative regulation of glutamate receptor signaling pathway;positive regulation of I-kappaB phosphorylation;negative regulation of microglial cell activation;negative regulation of tumor necrosis factor secretion;negative regulation of neuron migration;negative regulation of apoptotic signaling pathway;negative regulation of extrinsic apoptotic signaling pathway in absence of ligand
• Cellular component: extracellular region;extracellular space;plasma membrane;cell surface;membrane;integral component of membrane;cell projection;neuron projection;neuronal cell body;perinuclear region of cytoplasm
• Molecular function: signaling receptor binding;integrin binding;protein binding;chemokine activity;CX3C chemokine receptor binding;chemoattractant activity;CXCR1 chemokine receptor binding;CCR chemokine receptor binding