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GeneBe

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

ENSG00000107562NCBI:6387OMIM:600835HGNC:10672Uniprot:P48061AlphaFoldGenCCjaxSfariGnomADPubmedClinVar

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
clinvar
1
missense
8
clinvar
8
nonsense
0
start loss
0
frameshift
0
inframe indel
0
splice donor/acceptor (+/-2bp)
0
splice region
0
non coding
1
clinvar
1
clinvar
22
clinvar
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)1291069
10-44373017-C-T CXCL12-related condition Benign (Jun 19, 2021)1233193
10-44373096-T-C CXCL12-related condition Likely benign (Feb 19, 2019)3037442
10-44373408-A-C Benign (Nov 11, 2018)1280296
10-44373416-C-T Benign (Nov 10, 2018)1237787
10-44373578-C-T Benign (Nov 10, 2018)1272932
10-44375898-G-A Benign (Jun 19, 2021)1220639
10-44376100-G-A Benign (Nov 10, 2018)1250974
10-44377749-T-C CXCL12-related condition Likely benign (Oct 18, 2022)3044678
10-44377752-C-A CXCL12-related condition Benign/Likely benign (Jan 01, 2023)2640421
10-44377754-C-A not specified Uncertain significance (Sep 14, 2021)2249000
10-44377772-A-G not specified Uncertain significance (Dec 01, 2022)2330339
10-44377786-G-A not specified Uncertain significance (Dec 28, 2023)3079169
10-44377808-A-G not specified Uncertain significance (Mar 02, 2023)2493358
10-44377816-C-T not specified Likely benign (Aug 02, 2021)3079168
10-44377840-G-A not specified Uncertain significance (Feb 28, 2024)3079167
10-44377876-C-T not specified Uncertain significance (Jun 06, 2023)2523174
10-44377884-G-A CXCL12-related condition Likely benign (Feb 21, 2019)3058031
10-44378102-C-T Susceptibility to HIV infection protective (Jan 16, 1998)8762
10-44378401-A-G Benign (Jun 18, 2021)1251315
10-44378544-C-CCT Benign (Nov 10, 2018)1274726
10-44378631-G-A Susceptibility to HIV infection Uncertain significance (Mar 30, 2021)625926
10-44378768-G-A Benign (Nov 10, 2018)1246518
10-44378805-C-T Benign (Jun 18, 2021)1284236
10-44378861-G-T Benign (Nov 10, 2018)1234302

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
CXCL12protein_codingprotein_codingENST00000395794 488904
pLI Probability
LOF Intolerant
pRec Probability
LOF Recessive
Individuals with
no LOFs
Individuals with
Homozygous LOFs
Individuals with
Heterozygous LOFs
Defined p
0.1190.788125744041257480.0000159
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense-0.2538780.61.080.00000468893
Missense in Polyphen2028.1160.71135331
Synonymous0.1583132.10.9650.00000195285
Loss of Function1.3325.300.3773.11e-759

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.000.00
Ashkenazi Jewish0.000.00
East Asian0.00005440.0000544
Finnish0.000.00
European (Non-Finnish)0.00001760.0000176
Middle Eastern0.00005440.0000544
South Asian0.00003270.0000327
Other0.000.00

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

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium

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