CXCL12
Chr 10C-X-C motif chemokine ligand 12
Also known as: IRH, PBSF, SCYB12, SDF1, TLSF, TPAR1
The encoded protein is a chemokine that functions as a chemoattractant for T-lymphocytes and monocytes, activating the CXCR4 receptor to induce calcium mobilization and cell migration, and playing critical roles in immune cell trafficking, embryonic development, and B-cell lymphopoiesis. Mutations in this gene are associated with resistance to HIV-1 infection. The gene shows relatively low constraint to loss-of-function variation (pLI 0.12, LOEUF 1.18), suggesting tolerance to protein-truncating variants.
Primary Disease Associations & Inheritance
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly tolerant — LoF variants common in population
Tolerant to missense variation
The highest-scoring mechanism for this gene is dominant-negative.
Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
71 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 0 | 0 | 11 | 0 | 11 |
Likely Pathogenic | 0 | 0 | 2 | 0 | 2 |
VUS | 0 | 20 | 2 | 0 | 22 |
Likely Benign | 0 | 1 | 2 | 3 | 6 |
Benign | 0 | 0 | 24 | 1 | 25 |
| Total | 0 | 21 | 41 | 4 | 66 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
CXCL12 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
Role of Finerenone in African American Veterans With Diabetic Kidney Disease
NOT YET RECRUITINGThree Fraction Radiation to Induce Immuno-Oncologic Response
ACTIVE NOT RECRUITINGA-TANGO Phase 2 Study
NOT YET RECRUITINGPrognostic Value of Circulating Tumoral DNA After the First 6 Months of Treatment in Patients With Waldenström Macroglobulinemia
RECRUITINGNew Preclinical and Clinical Approaches to Mesothelioma
RECRUITINGBiomoleculars Markers of Sensitivity to Pre- and Post-operative Chemotherapy of Gastric and Cardia Adenocarcinomas: a Pilot Study
RECRUITINGBiomarkers in the Etiology of Idiopathic Intracranial Hypertension
RECRUITINGExternal Resources
Links to major genomics databases and tools