CXCL14

Summary

CXCL14 (C-X-C motif chemokine ligand 14, HGNC:10640) is a protein-coding gene on chromosome 5q31.1, encoding C-X-C motif chemokine 14 (O95715). Potent chemoattractant for neutrophils, and weaker for dendritic cells.

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.

Source: NCBI Gene 9547 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 29 total
• MANE Select transcript: NM_004887

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10640
Approved symbol	CXCL14
Name	C-X-C motif chemokine ligand 14
Location	5q31.1
Locus type	gene with protein product
Status	Approved
Aliases	BRAK, NJAC, bolekine, Kec, MIP-2g, BMAC, KS1
Ensembl gene	ENSG00000145824
Ensembl biotype	protein_coding
OMIM	604186
Entrez	9547

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 3 protein_coding

ENST00000337225, ENST00000512158, ENST00000867030

RefSeq mRNA: 1 — MANE Select: NM_004887 NM_004887

CCDS: CCDS4188

Canonical transcript exons

ENST00000512158 — 4 exons

Exon	Start	End
ENSE00001362860	135570679	135571868
ENSE00001362876	135578434	135578539
ENSE00002068642	135578715	135578991
ENSE00002207769	135574572	135574685

Expression profiles

Bgee: expression breadth ubiquitous, 269 present calls, max score 99.89.

FANTOM5 (CAGE): breadth broad, TPM avg 16.8978 / max 6733.5205, expressed in 545 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
63560	16.2638	535
63559	0.5658	189
63558	0.0251	5
63557	0.0234	6
63561	0.0198	2

Top tissues by expression

285 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
skin of hip	UBERON:0001554	99.89	gold quality
upper arm skin	UBERON:0004263	99.82	gold quality
nipple	UBERON:0002030	99.80	gold quality
upper leg skin	UBERON:0004262	99.73	gold quality
nephron tubule	UBERON:0001231	99.68	gold quality
periodontal ligament	UBERON:0008266	99.59	gold quality
pylorus	UBERON:0001166	99.52	gold quality
mammalian vulva	UBERON:0000997	99.51	gold quality
skin of abdomen	UBERON:0001416	99.44	gold quality
zone of skin	UBERON:0000014	99.43	gold quality
skin of leg	UBERON:0001511	99.37	gold quality
pericardium	UBERON:0002407	99.37	gold quality
mammary duct	UBERON:0001765	99.30	gold quality
jejunal mucosa	UBERON:0000399	99.24	gold quality
gingiva	UBERON:0001828	99.23	gold quality
kidney epithelium	UBERON:0004819	99.23	gold quality
penis	UBERON:0000989	99.11	gold quality
mucosa of sigmoid colon	UBERON:0004993	99.11	gold quality
gingival epithelium	UBERON:0001949	99.10	gold quality
renal medulla	UBERON:0000362	99.04	gold quality
duodenum	UBERON:0002114	99.02	gold quality
cervix squamous epithelium	UBERON:0006922	99.00	gold quality
pharyngeal mucosa	UBERON:0000355	98.94	gold quality
adult mammalian kidney	UBERON:0000082	98.92	gold quality
ileal mucosa	UBERON:0000331	98.90	gold quality
renal glomerulus	UBERON:0000074	98.70	gold quality
colonic mucosa	UBERON:0000317	98.64	gold quality
rectum	UBERON:0001052	98.61	gold quality
adult organism	UBERON:0007023	98.59	gold quality
trachea	UBERON:0003126	98.51	gold quality

Single-cell (SCXA)

Detected in 27 experiment(s), a significant marker in 25.

Experiment	Marker?	Max mean expression
E-MTAB-9906	yes	20846.53
E-HCAD-11	yes	13694.06
E-MTAB-8410	yes	13270.66
E-MTAB-8142	yes	9417.31
E-MTAB-6701	yes	9114.36
E-CURD-46	yes	8755.66
E-HCAD-24	yes	6173.12
E-HCAD-25	yes	5240.25
E-MTAB-6678	yes	4883.38
E-MTAB-7407	yes	3440.29
E-HCAD-38	yes	2339.29
E-CURD-126	yes	2009.00
E-MTAB-9154	yes	1860.98
E-HCAD-1	yes	1850.71
E-HCAD-56	yes	1772.77

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AP1, BCL6, CREB3, CUX1, GLI1, HAND2, HIC1, HMGA1, IRF1, IRF3, IRF6, IRF8, NFKB1, NFKB, PAX3, RELA, SP1, TP53, ZNF382

miRNA regulators (miRDB)

116 targeting CXCL14, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-4455	100.00	65.48	1587
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-9-3P	99.96	70.88	2068
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-2110	99.96	66.68	1930
HSA-MIR-3910	99.95	71.13	2227
HSA-MIR-9718	99.94	68.91	918
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-539-5P	99.93	70.30	2855
HSA-MIR-3143	99.93	71.96	3104
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-338-5P	99.92	72.34	2951
HSA-MIR-3119	99.92	71.34	2390
HSA-MIR-3671	99.90	73.04	3897
HSA-MIR-106A-5P	99.90	73.94	2683

Literature-anchored findings (GeneRIF, showing 40)

• CXCL14 displays antimicrobial activity against E. coli and S. aureus. (PMID:12949249)
• loss of BRAK expression from tumors may facilitate neovascularization and possibly contributes to immunologic escape (PMID:15548693)
• The finding that CXCL14 expression inhibits prostate tumor growth suggests this gene has tumor suppressive functions. (PMID:15651028)
• CXCL14 is a potent chemoattractant and activator of dendritic cells (DC) and may be involved in DC homing in vivo. (PMID:15843547)
• results indicate that BRAK/CXCL14 is a chemokine, having suppressive activity toward tumor progression of oral carcinoma in vivo (PMID:16884687)
• This study elucidates a post-translational mechanism for the loss of CXCL14 in cancer and a novel mode of chemokine regulation. (PMID:16987528)
• CXCL14 might play a pivotal role in the pathobiology of pancreatic cancer, probably by regulating cancer invasion. (PMID:18054154)
• CST6, CXCL14, DHRS3, and SPP1 are regulated by BRAF signaling and may play a role in papillary thyroid carcinoma pathogenesis (PMID:18676742)
• CXCL14 is a gene target of RhoBTB2 and supports downregulation of CXCL14 as a functional outcome of RhoBTB2 loss in cancer. (PMID:18762809)
• CXCL14-positive epithelial cells were found in all tissue types. The expression of CXCL14 was not associated with any tumor or patient characteristics analyzed (PMID:18765527)
• Data suggest that despite the structural homology and similarity in tissue distribution of human and murine CXCL14, distinct differences point to diverse, species-specific needs for CXCL14 in epithelial immunity. (PMID:18809336)
• Cell supernatant-derived CXCL14 fights bacteria at the earliest stage of infection, well before the establishment of inflammation, and thus fulfills a unique role in antimicrobial immunity. (PMID:19109182)
• regulates energy metabolism and eating behaviior, induces insulin resistance, suppresses induction of neovascularization. (review) (PMID:19172796)
• identify CXCL14 as a novel autocrine stimulator of fibroblast growth and migration, with multi-modal tumor-stimulatory activities (PMID:19218429)
• CXCL14 expression is upregulated by ROS through the AP-1 signaling pathway and promotes cell motility through elevation of cytosolic Ca(2+) by binding to the inositol 1,4,5-trisphosphate receptor on the endoplasmic reticulum in breast cancer. (PMID:19276362)
• -A-induced migration depends on the selective and polarized release of 2 chemokines, namely CXC chemokine ligands 12 and 14 (PMID:19339694)
• Results suggest that CXCL14 plays an important role in regulating trophoblast invasion through an autocrine/paracrine manner during early pregnancy. (PMID:19833716)
• Data conclude that CXCL14 is likely to be regulated by progesterone in human endometrium and that it may exert a chemoattractive effect on uNK cells and in part be responsible for their clustering around the epithelial glands. (PMID:19903701)
• Data indicate that the expression of BRAK stimulated the formation of elongated focal adhesions of the HSC-3 cells in an autocrine or paracrine fashion, in which stimulation may be responsible for the reduced migration of the cells. (PMID:20067447)
• Increased severity of collagen-induced arthritis in CXCL14-transgenic mice is associated with enhanced T helper (Th) type 1 cytokine production, elevated autoantibody levels and increased inflammatory cell infiltration into the joints. (PMID:20212097)
• CXCL14 removal from conditioned media abolished its chemotactic properties. Findings offer direct evidence for epigenetic regulation of chemokine expression in tumor cells. (PMID:20460540)
• Taken together, the data indicate that the respective stress-dependent action of p38 isoforms is responsible for the up-regulation of the gene expression of the chemokine BRAK/CXCL14. (PMID:20478268)
• CXCL14 methylation in sputum from asymptomatic early-stage lung cancer cases was associated with a 2.9-fold elevated risk for this disease compared with controls, substantiating its potential as a biomarker for early detection of lung cancer (PMID:20562917)
• CEACAM-1 and CXCL-14 are involved in the occurrence and development of infantile hemangioma. (PMID:20737948)
• The results indicate that oxidative stress induced by H(2)O(2) or HO(*) stimulates angiogenesis and tumuor progression by altering the gene expression of CXCL14 via the EGFR/MEK/ERK pathway in human HNSCC cells. (PMID:20815772)
• The rs2237062 polymorphism in the CXCL14 gene might influence Hepatits B Virus-related hepatocellular carcinoma progression in a Chinese population. (PMID:21556757)
• These results indicated that upregulation of BRAK was accompanied by differentiation of epithelial cells induced by calcium/calmodulin signaling, and that SP1 binding to the BRAK promoter region played an important role in this signaling. (PMID:22382027)
• CXCL14 is a negative regulator of growth and metastasis in breast cancer. (PMID:22910931)
• CXCL14 binding to glycoproteins harboring heparan sulfate proteoglycans and sialic acids leads proliferation and migration of some cancer cells. (PMID:23161284)
• CXCL14 might be a potential novel prognostic factor to predict the disease recurrence and overall survival and could be a potential target of postoperative adjuvant therapy in CRC patients (PMID:23294544)
• Smoking-induced CXCL14 expression in the human airway epithelium links chronic obstructive pulmonary disease to lung cancer. (PMID:23597004)
• CXCL14 represents, along with CXCR7, molecules that co-evolved with the CXCL12-CXCR4 axis to modulate important physiological processes in development, stem cell maintenance, and immune responses (PMID:23669361)
• Downregulation of CXCL14 expression is associated with gastric adenocarcinoma. (PMID:23982764)
• CXCL14 plays a pivotal role as a potential tumor suppressor in hepatocellular carcinoma. (PMID:24033560)
• CXCL14 inhibits colorectal cancer migration, invasion, and epithelial-to-mesenchymal transition (EMT) by suppressing NF-kappaB signaling. (PMID:24099668)
• Genetic or pharmacologic inhibition of NOS1 reduced the growth of CXCL14-expressing fibroblasts. (PMID:24710408)
• CXCL14 overexpression influences proliferation and changes in cell cycle distributions of HT29 colorectal carcinoma cells. (PMID:24938992)
• Data indicate that site-specific CpG methylation in the CXC chemokine CXCL14 promoter is associated with altered expression. (PMID:25102097)
• three of these five genes (CXCL14, ITGAX, and LPCAT2) harbored polymorphisms associated with aggressive disease development in a human GWAS cohort consisting of 1,172 prostate cancer patients. (PMID:25411967)
• essential CXCL12-operated functions of CXCR4 are insensitive to CXCL14 (PMID:25451233)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	cxcl14	ENSDARG00000056627
mus_musculus	Cxcl14	ENSMUSG00000021508
rattus_norvegicus	Cxcl14	ENSRNOG00000011984

Protein

Protein identifiers

C-X-C motif chemokine 14 — O95715 (reviewed: O95715)

Alternative names: Chemokine BRAK, MIP-2G, Small-inducible cytokine B14

All UniProt accessions (2): A0A0C4DGC1, O95715

UniProt curated annotations — full annotation on UniProt →

Function. Potent chemoattractant for neutrophils, and weaker for dendritic cells. Not chemotactic for T-cells, B-cells, monocytes, natural killer cells or granulocytes. Does not inhibit proliferation of myeloid progenitors in colony formation assays.

Subcellular location. Secreted.

Tissue specificity. Expressed in heart, brain, placenta, lung, liver, skeletal muscle, kidney and pancreas. Highly expressed in normal tissue without inflammatory stimuli and infrequently expressed in cancer cell lines. Weakly expressed in monocyte-derived dendritic cells. Not detected in lung or unstimulated peripheral blood lymphocytes.

Post-translational modifications. Ubiquitinated, followed by degradation by the proteasome.

Domain organisation. The destruction box (D-box) acts as a recognition signal for degradation via the ubiquitin-proteasome pathway.

Induction. Up-regulated in peripheral blood lymphocytes in response to bacterial lipopolysaccharides (LPS).

Similarity. Belongs to the intercrine alpha (chemokine CxC) family.

RefSeq proteins (1): NP_004878* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001811	Chemokine_IL8-like_dom	Domain
IPR036048	Interleukin_8-like_sf	Homologous_superfamily

Pfam: PF00048

UniProt features (15 total): strand 6, helix 2, disulfide bond 2, signal peptide 1, chain 1, turn 1, short sequence motif 1, sequence conflict 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
2HDL	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O95715-F1	85.54	0.53

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Disulfide bonds (2): 37–63, 39–84

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 261 (showing top): GSE45365_NK_CELL_VS_CD11B_DC_DN, MYAATNNNNNNNGGC_UNKNOWN, MODULE_92, BENPORATH_ES_WITH_H3K27ME3, GOBP_ANTIMICROBIAL_HUMORAL_RESPONSE, GOBP_CELL_CHEMOTAXIS, JAEGER_METASTASIS_DN, NKX25_02, PEREZ_TP63_TARGETS, GCANCTGNY_MYOD_Q6, MODULE_64, SMID_BREAST_CANCER_RELAPSE_IN_LUNG_DN, YAO_TEMPORAL_RESPONSE_TO_PROGESTERONE_CLUSTER_1, HUMMERICH_SKIN_CANCER_PROGRESSION_DN, GOBP_CELL_CELL_SIGNALING

GO Biological Process (9): chemotaxis (GO:0006935), signal transduction (GO:0007165), cell-cell signaling (GO:0007267), antimicrobial humoral immune response mediated by antimicrobial peptide (GO:0061844), immune response (GO:0006955), negative regulation of myoblast differentiation (GO:0045662), inner ear development (GO:0048839), cell chemotaxis (GO:0060326), positive regulation of natural killer cell chemotaxis (GO:2000503)

GO Molecular Function (3): chemokine activity (GO:0008009), cytokine activity (GO:0005125), protein binding (GO:0005515)

GO Cellular Component (3): obsolete extracellular space (GO:0005615), Golgi apparatus (GO:0005794), extracellular region (GO:0005576)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cell communication	2
signaling	2
response to chemical	1
taxis	1
cellular process	1
regulation of cellular process	1
cellular response to stimulus	1
antimicrobial humoral response	1
immune system process	1
response to stimulus	1
myoblast differentiation	1
negative regulation of cell differentiation	1
regulation of myoblast differentiation	1
ear development	1
anatomical structure development	1
chemotaxis	1
cell migration	1
cellular response to chemical stimulus	1
natural killer cell chemotaxis	1
positive regulation of lymphocyte chemotaxis	1
regulation of natural killer cell chemotaxis	1
cytokine activity	1
chemokine receptor binding	1
cell chemotaxis	1
receptor ligand activity	1
binding	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1648 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CXCL14	CXCR4	P30991	941
CXCL14	GPR85	P60893	778
CXCL14	CXCL3	P19876	768
CXCL14	CXCL12	P48061	692
CXCL14	CXCR5	P32302	659
CXCL14	CCL21	O00585	656
CXCL14	CCL3	P10147	650
CXCL14	CXCR3	P49682	633
CXCL14	IL6	P05231	629
CXCL14	CCL22	O00626	621
CXCL14	CCL24	O00175	604
CXCL14	CCRL2	O00421	589
CXCL14	PTGER2	P43116	588
CXCL14	CXCL13	O43927	588
CXCL14	CXCL16	Q9H2A7	584

IntAct

42 interactions, top by confidence:

A	B	Type	Score
CXCL14	TRIM23	psi-mi:“MI:0915”(physical association)	0.560
TEX11	CXCL14	psi-mi:“MI:0915”(physical association)	0.560
TRIM23	CXCL14	psi-mi:“MI:0915”(physical association)	0.560
CXCL14	TEX11	psi-mi:“MI:0915”(physical association)	0.560
CXCL14	CCL5	psi-mi:“MI:0407”(direct interaction)	0.560
CXCL14	PF4	psi-mi:“MI:0407”(direct interaction)	0.560
CXCL14	CXCL12	psi-mi:“MI:0407”(direct interaction)	0.560
PF4	CXCL14	psi-mi:“MI:0407”(direct interaction)	0.560
OPG002	CXCL14	psi-mi:“MI:0407”(direct interaction)	0.440
crmD	CXCL14	psi-mi:“MI:0407”(direct interaction)	0.440
CXCL14	CCL17	psi-mi:“MI:0407”(direct interaction)	0.440
CXCL14	CCL11	psi-mi:“MI:0407”(direct interaction)	0.440
CXCL14	CCL13	psi-mi:“MI:0407”(direct interaction)	0.440
CXCL14	CCL21	psi-mi:“MI:0407”(direct interaction)	0.440
CXCL14	CCL26	psi-mi:“MI:0407”(direct interaction)	0.440
CXCL14	CCL28	psi-mi:“MI:0407”(direct interaction)	0.440
XCL1	CXCL14	psi-mi:“MI:0407”(direct interaction)	0.440
CXCL14	CXCL5	psi-mi:“MI:0407”(direct interaction)	0.440
CXCL14	CXCL9	psi-mi:“MI:0407”(direct interaction)	0.440
CXCL14	CXCL10	psi-mi:“MI:0407”(direct interaction)	0.440
CXCL14	CXCL11	psi-mi:“MI:0407”(direct interaction)	0.440
CCL21	CXCL14	psi-mi:“MI:0407”(direct interaction)	0.440
CCL26	CXCL14	psi-mi:“MI:0407”(direct interaction)	0.440
CXCL2	CXCL14	psi-mi:“MI:0407”(direct interaction)	0.440
PPBP	CXCL14	psi-mi:“MI:0407”(direct interaction)	0.440

BioGRID (46): CXCL14 (Two-hybrid), TEX11 (Two-hybrid), CXCL14 (Affinity Capture-MS), CXCL14 (Two-hybrid), CXCL14 (Reconstituted Complex), CXCL14 (Reconstituted Complex), CXCL14 (Reconstituted Complex), CXCL14 (Reconstituted Complex), CXCL14 (Reconstituted Complex), CXCL14 (Reconstituted Complex), CXCL14 (Reconstituted Complex), GPR85 (Affinity Capture-Western), CXCL14 (Reconstituted Complex), CXCL14 (Reconstituted Complex), CXCL14 (Reconstituted Complex)

ESM2 similar proteins: A8WCC4, O19011, O35757, O88273, O95715, P01137, P03970, P04202, P07200, P07995, P08476, P09533, P17246, P18331, P18341, P27092, P43032, P49767, P50414, P50555, P54831, P55102, P58658, P58659, P97953, Q04998, Q29108, Q29RS5, Q38HS2, Q5R551, Q60GF7, Q62522, Q68US5, Q6WN34, Q6X2S4, Q8CI19, Q8HDG8, Q8TBF5, Q99969, Q99LV7

Diamond homologs: O95715, P10889, Q6W5C0, Q9WUQ5, A9QWP9, O46675, O46676, O46677, O46678, O55038, O55235, P02775, P02776, P02777, P06765, P08317, P09340, P09341, P10145, P10720, P12850, P14095, P18340, P19874, P19875, P19876, P22952, P30034, P30035, P30348, P30782, P36925, P41324, P42830, P43030, P46653, P47854, P50228, P67813, P67814

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 28 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Chemokine receptors bind chemokines	16	142.6×	5e-32
Class A/1 (Rhodopsin-like receptors)	7	24.7×	9e-08
Peptide ligand-binding receptors	7	24.7×	9e-08
G alpha (i) signalling events	13	24.1×	7e-15
GPCR ligand binding	7	21.4×	2e-07
Signaling by GPCR	7	13.4×	4e-06
GPCR downstream signalling	5	10.3×	6e-04

GO biological processes:

GO term	Partners	Fold	FDR
eosinophil chemotaxis	5	152.6×	4e-09
chemokine-mediated signaling pathway	11	148.5×	4e-20
neutrophil chemotaxis	8	95.2×	5e-13
chemotaxis	12	68.0×	3e-18
antimicrobial humoral immune response mediated by antimicrobial peptide	10	67.5×	6e-15
cell chemotaxis	8	61.7×	2e-11
response to virus	5	30.0×	9e-06
cell-cell signaling	10	29.0×	2e-11

Disease & clinical

Clinical variants and AI predictions

ClinVar

29 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	19
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

432 predictions. Top by Δscore:

Variant	Effect	Δscore
5:135574566:GCGTA:G	donor_loss	1.0000
5:135574567:CGTA:C	donor_loss	1.0000
5:135574568:GTAC:G	donor_loss	1.0000
5:135574569:TACC:T	donor_loss	1.0000
5:135574570:A:C	donor_loss	1.0000
5:135574571:CCTGC:C	donor_loss	1.0000
5:135578428:ACTC:A	donor_loss	1.0000
5:135578430:TCA:T	donor_loss	1.0000
5:135578432:A:AC	donor_gain	1.0000
5:135578433:C:CC	donor_gain	1.0000
5:135578433:CATAA:C	donor_gain	1.0000
5:135578437:A:C	donor_gain	1.0000
5:135578536:GACCC:G	acceptor_loss	1.0000
5:135578540:C:CC	acceptor_gain	1.0000
5:135578540:CTGC:C	acceptor_loss	1.0000
5:135578541:T:A	acceptor_loss	1.0000
5:135574684:TG:T	acceptor_gain	0.9900
5:135574686:C:CC	acceptor_gain	0.9900
5:135578435:TA:T	donor_gain	0.9900
5:135578436:AA:A	donor_gain	0.9900
5:135578535:GGACC:G	acceptor_gain	0.9900
5:135578536:GACC:G	acceptor_gain	0.9900
5:135578538:CC:C	acceptor_gain	0.9900
5:135578539:CC:C	acceptor_gain	0.9900
5:135578548:G:T	acceptor_gain	0.9900
5:135578551:C:CT	acceptor_gain	0.9900
5:135578708:CACT:C	donor_loss	0.9900
5:135578711:TCAC:T	donor_loss	0.9900
5:135578712:CA:C	donor_loss	0.9900
5:135578713:A:AC	donor_gain	0.9900

AlphaMissense

638 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:135574641:C:G	C84S	1.000
5:135574642:A:G	C84R	1.000
5:135574642:A:T	C84S	1.000
5:135578452:C:G	C63S	1.000
5:135578452:C:T	C63Y	1.000
5:135578453:A:T	C63S	1.000
5:135574597:A:C	Y99D	0.999
5:135574598:C:A	W98C	0.999
5:135574598:C:G	W98C	0.999
5:135574608:A:G	F95S	0.999
5:135574626:A:G	L89P	0.999
5:135574638:A:G	L85P	0.999
5:135574640:G:C	C84W	0.999
5:135574641:C:T	C84Y	0.999
5:135578437:A:T	V68D	0.999
5:135578451:G:C	C63W	0.999
5:135578452:C:A	C63F	0.999
5:135578453:A:G	C63R	0.999
5:135578488:A:T	V51E	0.999
5:135578503:A:G	I46T	0.999
5:135578524:C:G	C39S	0.999
5:135578525:A:G	C39R	0.999
5:135578525:A:T	C39S	0.999
5:135574608:A:C	F95C	0.998
5:135574617:G:A	T92I	0.998
5:135574619:G:C	S91R	0.998
5:135574619:G:T	S91R	0.998
5:135574621:T:G	S91R	0.998
5:135574632:G:T	P87H	0.998
5:135574633:G:A	P87S	0.998

dbSNP variants (sampled 300 via entrez): RS1000341601 (5:135579223 T>G), RS1000883172 (5:135572860 A>C), RS1001006665 (5:135579128 G>A,T), RS1001383465 (5:135572465 G>A), RS1001770811 (5:135572141 G>A), RS1002279773 (5:135580761 G>A,C,T), RS1002440538 (5:135574790 T>C), RS1002460597 (5:135570919 G>A), RS1002752480 (5:135574502 G>C,T), RS1002888701 (5:135576292 C>G), RS1003112729 (5:135577755 T>G), RS1003823420 (5:135577941 G>C), RS1003854091 (5:135576251 A>T), RS1004025232 (5:135578853 C>A,G,T), RS10042445 (5:135571198 C>T)

Disease associations

OMIM: gene MIM:604186 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST001113_20	Age at smoking initiation in chronic obstructive pulmonary disease	7.000000e-06
GCST006992_1	Cerebrospinal fluid p-tau levels in Alzheimer’s disease dementia	8.000000e-07
GCST007007_2	Cerebrospinal fluid t-tau levels	2.000000e-07

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0005670	smoking initiation
EFO:0004763	p-tau measurement
EFO:0004760	t-tau measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs7716492	CXCL14, SLC25A48		0.00	0

CTD chemical–gene interactions

72 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Tobacco Smoke Pollution	increases expression, affects expression, decreases expression	7
trichostatin A	affects cotreatment, increases expression, decreases acetylation, decreases expression	5
Valproic Acid	affects cotreatment, increases expression, decreases expression, decreases methylation	5
sodium arsenite	increases expression, decreases expression	4
Estradiol	affects cotreatment, decreases expression, increases expression	4
2-methyl-4-isothiazolin-3-one	increases expression, affects cotreatment, decreases expression	3
Progesterone	affects cotreatment, decreases expression, increases expression, increases reaction	3
mercuric bromide	increases expression, affects cotreatment	2
Vorinostat	affects cotreatment, increases expression	2
Panobinostat	affects cotreatment, increases expression	2
Aerosols	decreases expression, increases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Tetrachlorodibenzodioxin	affects expression, decreases expression	2
Particulate Matter	increases abundance, decreases expression	2
urushiol	decreases expression	1
ethylene dimethacrylate	decreases expression	1
propionaldehyde	increases expression	1
captax	decreases expression	1
5-chloro-2-methyl-4-isothiazolin-3-one	affects cotreatment, decreases expression	1
terbufos	increases methylation	1
cinnamaldehyde	increases expression	1
arsenite	decreases methylation	1
zinc chloride	increases expression	1
cobaltous chloride	decreases expression	1
butyraldehyde	increases expression	1
ferrous sulfate	decreases expression	1
nickel chloride	decreases expression	1
tobacco tar	decreases expression, decreases reaction	1
manganese chloride	increases expression	1
diallyl disulfide	decreases reaction, decreases expression	1

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.