CXCL12

C-X-C motif chemokine ligand 12, the group of Chemokine ligands

Basic information

Region (hg38): 10:44370164-44386493

Previous symbols: [ "SDF1A", "SDF1B", "SDF1" ]

Links

ENSG00000107562 ∙ NCBI:6387 ∙ OMIM:600835 ∙ HGNC:10672 ∙ Uniprot:P48061 ∙ 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 CXCL12 gene.

• not provided (24 variants)
• Inborn genetic diseases (8 variants)
• Susceptibility to HIV infection (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CXCL12 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				1		1
missense			8			8
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding			1	1	22	24
Total	0	0	9	2	22

Variants in CXCL12

This is a list of pathogenic ClinVar variants found in the CXCL12 region.

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

Position	Type	Phenotype	Significance	ClinVar
10-44372809-C-T			Benign (Nov 12, 2018)
10-44373017-C-T		CXCL12-related disorder	Benign (Jun 19, 2021)
10-44373096-T-C		CXCL12-related disorder	Likely benign (Feb 19, 2019)
10-44373408-A-C			Benign (Nov 11, 2018)
10-44373416-C-T			Benign (Nov 10, 2018)
10-44373578-C-T			Benign (Nov 10, 2018)
10-44375898-G-A			Benign (Jun 19, 2021)
10-44376100-G-A			Benign (Nov 10, 2018)
10-44377749-T-C		CXCL12-related disorder	Likely benign (Oct 18, 2022)
10-44377752-C-A		CXCL12-related disorder	Benign/Likely benign (Jan 01, 2023)
10-44377754-C-A		not specified	Uncertain significance (Sep 14, 2021)
10-44377772-A-G		not specified	Uncertain significance (Dec 01, 2022)
10-44377786-G-A		not specified	Uncertain significance (Dec 28, 2023)
10-44377808-A-G		not specified	Uncertain significance (Mar 02, 2023)
10-44377816-C-T		not specified	Likely benign (Aug 02, 2021)
10-44377840-G-A		not specified	Uncertain significance (Feb 28, 2024)
10-44377876-C-T		not specified	Uncertain significance (Jun 06, 2023)
10-44377884-G-A		CXCL12-related disorder	Likely benign (Feb 21, 2019)
10-44378102-C-T		Susceptibility to HIV infection	protective (Jan 16, 1998)
10-44378401-A-G			Benign (Jun 18, 2021)
10-44378544-C-CCT			Benign (Nov 10, 2018)
10-44378631-G-A		Susceptibility to HIV infection	Uncertain significance (Mar 30, 2021)
10-44378768-G-A			Benign (Nov 10, 2018)
10-44378805-C-T			Benign (Jun 18, 2021)
10-44378861-G-T			Benign (Nov 10, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CXCL12	protein_coding	protein_coding	ENST00000395794	4	88904

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.119	0.788	125744	0	4	125748	0.0000159

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.253	87	80.6	1.08	0.00000468	893
Missense in Polyphen		20	28.116	0.71135		331
Synonymous	0.158	31	32.1	0.965	0.00000195	285
Loss of Function	1.33	2	5.30	0.377	3.11e-7	59

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000544	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.0000176	0.0000176
Middle Eastern	0.0000544	0.0000544
South Asian	0.0000327	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Chemoattractant active on T-lymphocytes and monocytes but not neutrophils. Activates the C-X-C chemokine receptor CXCR4 to induce a rapid and transient rise in the level of intracellular calcium ions and chemotaxis. SDF-1-beta(3-72) and SDF-1-alpha(3- 67) show a reduced chemotactic activity. Binding to cell surface proteoglycans seems to inhibit formation of SDF-1-alpha(3-67) and thus to preserve activity on local sites. Also binds to atypical chemokine receptor ACKR3, which activates the beta-arrestin pathway and acts as a scavenger receptor for SDF-1. Binds to the allosteric site (site 2) of integrins and activates integrins ITGAV:ITGB3, ITGA4:ITGB1 and ITGA5:ITGB1 in a CXCR4-independent manner (PubMed:29301984). Acts as a positive regulator of monocyte migration and a negative regulator of monocyte adhesion via the LYN kinase. Stimulates migration of monocytes and T-lymphocytes through its receptors, CXCR4 and ACKR3, and decreases monocyte adherence to surfaces coated with ICAM-1, a ligand for beta-2 integrins. SDF1A/CXCR4 signaling axis inhibits beta-2 integrin LFA-1 mediated adhesion of monocytes to ICAM-1 through LYN kinase. Inhibits CXCR4-mediated infection by T-cell line-adapted HIV-1. Plays a protective role after myocardial infarction. Induces down- regulation and internalization of ACKR3 expressed in various cells. Has several critical functions during embryonic development; required for B-cell lymphopoiesis, myelopoiesis in bone marrow and heart ventricular septum formation. Stimulates the proliferation of bone marrow-derived B-cell progenitors in the presence of IL7 as well as growth of stromal cell-dependent pre-B- cells (By similarity). {ECO:0000250|UniProtKB:P40224, ECO:0000269|PubMed:11069075, ECO:0000269|PubMed:11859124, ECO:0000269|PubMed:16107333, ECO:0000269|PubMed:18802065, ECO:0000269|PubMed:19255243, ECO:0000269|PubMed:29301984, ECO:0000269|PubMed:8752281}.
• Pathway: Chemokine signaling pathway - Homo sapiens (human);Axon guidance - Homo sapiens (human);Pathways in cancer - Homo sapiens (human);Rheumatoid arthritis - Homo sapiens (human);NF-kappa B signaling pathway - Homo sapiens (human);Cytokine-cytokine receptor interaction - Homo sapiens (human);Intestinal immune network for IgA production - Homo sapiens (human);Leukocyte transendothelial migration - Homo sapiens (human);miR-targeted genes in lymphocytes - TarBase;miR-targeted genes in muscle cell - TarBase;Allograft Rejection;Signaling by ERBB4;EV release from cardiac cells and their functional effects;RIG-I-like Receptor Signaling;Chemokine signaling pathway;Developmental Biology;Signaling by GPCR;Signal Transduction;pertussis toxin-insensitive ccr5 signaling in macrophage;g-protein signaling through tubby proteins;cxcr4 signaling pathway;corticosteroids and cardioprotection;cystic fibrosis transmembrane conductance regulator (cftr) and beta 2 adrenergic receptor (b2ar) pathway;ion channels and their functional role in vascular endothelium;activation of csk by camp-dependent protein kinase inhibits signaling through the t cell receptor;chrebp regulation by carbohydrates and camp;role of -arrestins in the activation and targeting of map kinases;activation of camp-dependent protein kinase pka;Chemokine receptors bind chemokines;Peptide ligand-binding receptors;Class A/1 (Rhodopsin-like receptors);roles of arrestin dependent recruitment of src kinases in gpcr signaling;GPCR ligand binding;activation of pkc through g-protein coupled receptors;CXCR4-mediated signaling events;-arrestins in gpcr desensitization;Signaling by Nuclear Receptors;Signaling by ROBO receptors;G alpha (i) signalling events;Axon guidance;Estrogen-dependent gene expression;Nuclear signaling by ERBB4;Signaling by ERBB4;Signaling by Receptor Tyrosine Kinases;GPCR downstream signalling;ESR-mediated signaling;HIF-1-alpha transcription factor network;Syndecan-4-mediated signaling events (Consensus)

Intolerance Scores

• loftool: 0.756
• rvis_EVS: 0.01
• rvis_percentile_EVS: 54.95

Haploinsufficiency Scores

• pHI: 0.610
• hipred: N
• hipred_score: 0.310
• ghis: 0.566

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.858

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Cxcl12
• 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; 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); hematopoietic system phenotype; liver/biliary system 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); cellular phenotype; muscle phenotype

Zebrafish Information Network

• Gene name: cxcl12b
• Affected structure: endodermal cell
• Phenotype tag: abnormal
• Phenotype quality: mislocalised anteriorly

Gene ontology

• Biological process: response to hypoxia;neuron migration;positive regulation of endothelial cell proliferation;cellular calcium ion homeostasis;chemotaxis;defense response;immune response;cell adhesion;signal transduction;G protein-coupled receptor signaling pathway;axon guidance;blood circulation;regulation of actin polymerization or depolymerization;adult locomotory behavior;response to radiation;response to heat;response to virus;regulation of signaling receptor activity;viral process;telencephalon cell migration;positive regulation of cell migration;animal organ regeneration;positive regulation of dopamine secretion;integrin activation;chemokine (C-X-C motif) ligand 12 signaling pathway;response to peptide hormone;positive regulation of cell adhesion;positive regulation of axon extension involved in axon guidance;induction of positive chemotaxis;detection of temperature stimulus involved in sensory perception of pain;detection of mechanical stimulus involved in sensory perception of pain;cell chemotaxis;chemokine-mediated signaling pathway;positive regulation of monocyte chemotaxis;positive regulation of calcium ion import;negative regulation of intrinsic apoptotic signaling pathway in response to DNA damage;negative regulation of leukocyte tethering or rolling;response to ultrasound;cellular response to chemokine;positive regulation of T cell migration;negative regulation of dendritic cell apoptotic process
• Cellular component: extracellular region;nucleus;cytoplasm;external side of plasma membrane;extracellular exosome
• Molecular function: signaling receptor binding;integrin binding;protein binding;chemokine activity;growth factor activity;chemokine receptor binding;CXCR chemokine receptor binding