CX3CL1

protein-coding

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

Gene summary

This gene belongs to the CX3C subgroup of chemokines, characterized by the number of amino acids located between the conserved cysteine residues. This is the only member of the CX3C subgroup, which contains three amino acids between cysteine residues, resulting in a Cys-X-X-X-Cys configuration. The encoded protein contains an extended mucin-like stalk with a chemokine domain on top, and exists in both a membrane-anchored form where it acts as a binding molecule, or, in soluble form, as a chemotactic cytokine. The mature form of this protein can be cleaved at the cell surface, yielding different soluble forms that can interact with the G-protein coupled receptor, C-X3-C motif chemokine receptor 1 gene product. This gene plays a role in a wide range of diseases, including cancer, vasculitis, neuropathies, atherosclerosis, inflammatory diseases, and in human immunodeficiency virus infections. [provided by RefSeq, Sep 2017]

Previous symbols:

SCYD1

MANE transcript

NM_002996.6

Inheritance

—

ClinVar variants

U:71B:15

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.17

Max pathogenic AF

—

Genomic locus

chr16:57,372,477-57,385,044

External References & Databases

Ensembl (ENSG00000006210)

Transcript & Mutation Effects

hg38 • Region Span ~12.6 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to CX3CL1 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 73

not providedTotal: 10

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_002996.6. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous				3 clinvar	4 clinvar	7
missense			68 clinvar	7 clinvar	1 clinvar	76
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			3 clinvar			3
Total	0	0	71	10	5	86

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 10 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_002996.6	RefSeq	NP_002987.1	3	MANE Select
ENST00000006053.7	Ensembl	ENSP00000006053.6	3	MANE Select
NM_001304392.3	RefSeq	NP_001291321.1	1	Standard
ENST00000563383.1	Ensembl	ENSP00000456830.1	3	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

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

Biological Process

microglial cell activation
positive regulation of cell-matrix adhesion
positive regulation of neuroblast proliferation
leukocyte migration involved in inflammatory response
monocyte chemotaxis

Molecular Function

signaling receptor binding
integrin binding
protein binding
chemokine activity
CX3C chemokine receptor binding

Cellular Component

extracellular region
extracellular space
plasma membrane
cell surface
membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000006053
Coding exons: 3
Length: 12591
Individuals with no LoFs: 125742
Homozygous LoFs: 0
Heterozygous LoFs: 4
Defined: 125746
p: 0.0000159

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.843	211	248	0.849	0.0000156	2520
Missense (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

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.000018	0.000018	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

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}.;

Recessive Scores

pRec: 0.319

Intolerance Scores

LoFtool: 0.227
RVIS EVS: -0.51
RVIS percentile EVS: 21.65

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.815

Gene Damage Prediction

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