CXCL14

Chr 5

C-X-C motif chemokine ligand 14

Also known as: BMAC, BRAK, KEC, KS1, MIP-2g, MIP2G, NJAC, SCYB14

NCBI Gene: 9547ENSG00000145824UniProt: O95715

This antimicrobial gene belongs to the cytokine gene family which encode secreted proteins involved in immunoregulatory and inflammatory processes. The protein encoded by this gene is structurally related to the CXC (Cys-X-Cys) subfamily of cytokines. Members of this subfamily are characterized by two cysteines separated by a single amino acid. This cytokine displays chemotactic activity for monocytes but not for lymphocytes, dendritic cells, neutrophils or macrophages. It has been implicated that this cytokine is involved in the homeostasis of monocyte-derived macrophages rather than in inflammation. [provided by RefSeq, Sep 2014]

36
ClinVar variants
13
Pathogenic / LP
0.04
pLI score
1
Active trials
Clinical Summary— CXCL14
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.04) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
13 Pathogenic / Likely Pathogenic· 21 VUS of 36 total submissions
💊
Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
1.20LOEUF
pLI 0.037
Z-score 1.26
OE 0.47 (0.21–1.20)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.69Z-score
OE missense 0.76 (0.61–0.96)
50 obs / 65.7 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.47 (0.21–1.20)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.76 (0.61–0.96)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.87
0≤1.21.6
LoF obs/exp: 3 / 6.4Missense obs/exp: 50 / 65.7Syn Z: 0.55

ClinVar Variant Classifications

36 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic12
Likely Pathogenic1
VUS21
Likely Benign2
12
Pathogenic
1
Likely Pathogenic
21
VUS
2
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
12
0
12
Likely Pathogenic
0
0
1
0
1
VUS
0
16
5
0
21
Likely Benign
0
1
1
0
2
Benign
0
0
0
0
0
Total01719036

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

CXCL14 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
p21 produces a bioactive secretome that places stressed cells under immunosurveillance.
Sturmlechner I et al.·Science
2021
Proteomic and metabolomic profiling of urine uncovers immune responses in patients with COVID-19.
Bi X et al.·Cell Rep
2022Cohort
Osteosarcoma Cells Secrete CXCL14 That Activates Integrin α11β1 on Fibroblasts to Form a Lung Metastatic Niche.
Xu Y et al.·Cancer Res
2024
CALB2 drives pancreatic cancer metastasis through inflammatory reprogramming of the tumor microenvironment.
Tao J et al.·J Exp Clin Cancer Res
2024
Overcoming immunotherapy resistance in bladder cancer with a novel antibody-drug conjugate RC48.
Xiao J et al.·J Immunother Cancer
2025
Cancer-associated fibroblast derived CXCL14 drives cisplatin chemoresistance by enhancing nucleotide excision repair in bladder cancer.
Li T et al.·J Exp Clin Cancer Res
2025
Transitional CXCL14(+) cancer-associated fibroblasts enhance tumour metastasis and confer resistance to EGFR-TKIs, revealing therapeutic vulnerability to filgotinib in lung adenocarcinoma.
Xu W et al.·Clin Transl Med
2025
Fibroblast-derived CXCL14 aggravates crystalline silica-induced pulmonary fibrosis by mediating polarization and recruitment of interstitial macrophages.
You Y et al.·J Hazard Mater
2023
C-X-C domain ligand 14-mediated stromal cell-macrophage interaction as a therapeutic target for hand dermal fibrosis.
Goto A et al.·Commun Biol
2023
Insulin-like growth factor 1 reduces coronary atherosclerosis in pigs with familial hypercholesterolemia.
Sukhanov S et al.·JCI Insight
2023
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Multi-omics analysis reveals CXCL14+ inhibitory neuron dysfunction in major depressive disorder.
Zhang L et al.·J Affect Disord
2026
AF6 knockout-induced upregulation of bile acid production promotes CXCL14-mediated antitumor immunity in HCC.
Xu K et al.·J Hepatol
2026
CXCL14 Promotes Ovarian Cancer Progression and Autophagy Through the IKBKE/NF-κB Pathway.
Lingling Y et al.·J Gene Med
2026
Immunohistochemically-detected differential localization of CXCL14 in mouse cerebellum suggesting the presence of neuronal and glial forms of CXCL14.
Suzuki H et al.·Neurosci Lett
2026Functional
CXCL14 Promotes Skeletal Muscle Mass Growth and Attenuates Lipopolysaccharide- and Dexamethasone-Induced Muscle Atrophy in Cultured Myotubes and Mouse Models.
Sarmito B et al.·J Cachexia Sarcopenia Muscle
2025🔓 Open AccessFunctional
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
Metastatic Colorectal CancerMetastatic Cancer to Liver

FAPI Molecular Imaging for Diagnosis of the CMS4 Unfavorable Colorectal Cancer Subtype

NOT YET RECRUITING
NCT06191120Phase NAUMC UtrechtStarted 2024-04
[18F]-ALF-FAPI-74 PET/CT scan

External Resources

Links to major genomics databases and tools