XCL1

Summary

XCL1 (X-C motif chemokine ligand 1, HGNC:10645) is a protein-coding gene on chromosome 1q24.2, encoding Lymphotactin (P47992). Chemotactic activity for lymphocytes but not for monocytes or neutrophils.

This antimicrobial gene encodes a member of the chemokine superfamily. Chemokines function in inflammatory and immunological responses, inducing leukocyte migration and activation. The encoded protein is a member of the C-chemokine subfamily, retaining only two of four cysteines conserved in other chemokines, and is thought to be specifically chemotactic for T cells. This gene and a closely related family member are located on the long arm of chromosome 1.

Source: NCBI Gene 6375 — RefSeq curated summary.

At a glance

• GWAS associations: 17
• Clinical variants (ClinVar): 18 total
• MANE Select transcript: NM_002995

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10645
Approved symbol	XCL1
Name	X-C motif chemokine ligand 1
Location	1q24.2
Locus type	gene with protein product
Status	Approved
Aliases	LPTN, ATAC, SCM-1a, SCM-1
Ensembl gene	ENSG00000143184
Ensembl biotype	protein_coding
OMIM	600250
Entrez	6375

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000367818

RefSeq mRNA: 1 — MANE Select: NM_002995 NM_002995

CCDS: CCDS1274

Canonical transcript exons

ENST00000367818 — 3 exons

Exon	Start	End
ENSE00000958543	168581052	168582069
ENSE00001445684	168576605	168576698
ENSE00002370884	168580063	168580177

Expression profiles

Bgee: expression breadth ubiquitous, 131 present calls, max score 74.72.

FANTOM5 (CAGE): breadth broad, TPM avg 5.9714 / max 1448.5929, expressed in 192 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
6495	5.9651	192
201807	0.0063	5

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
granulocyte	CL:0000094	74.72	gold quality
spleen	UBERON:0002106	69.08	gold quality
lymph node	UBERON:0000029	64.20	gold quality
gall bladder	UBERON:0002110	62.69	gold quality
rectum	UBERON:0001052	61.68	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	59.82	gold quality
mucosa of transverse colon	UBERON:0004991	59.73	gold quality
right lobe of liver	UBERON:0001114	59.58	gold quality
vermiform appendix	UBERON:0001154	59.27	gold quality
right uterine tube	UBERON:0001302	58.81	gold quality
blood	UBERON:0000178	57.73	gold quality
caecum	UBERON:0001153	56.44	gold quality
small intestine Peyer’s patch	UBERON:0003454	54.98	gold quality
left uterine tube	UBERON:0001303	54.89	gold quality
smooth muscle tissue	UBERON:0001135	54.88	gold quality
upper lobe of left lung	UBERON:0008952	54.83	gold quality
colonic epithelium	UBERON:0000397	54.52	silver quality
omental fat pad	UBERON:0010414	54.41	gold quality
peritoneum	UBERON:0002358	54.37	gold quality
small intestine	UBERON:0002108	54.14	gold quality
ascending aorta	UBERON:0001496	53.73	gold quality
adipose tissue of abdominal region	UBERON:0007808	53.66	gold quality
upper lobe of lung	UBERON:0008948	53.63	gold quality
thoracic aorta	UBERON:0001515	53.56	gold quality
apex of heart	UBERON:0002098	52.52	gold quality
endometrium	UBERON:0001295	52.49	gold quality
right lung	UBERON:0002167	51.98	gold quality
liver	UBERON:0002107	51.78	gold quality
right coronary artery	UBERON:0001625	51.46	gold quality
frontal pole	UBERON:0002795	50.41	gold quality

Single-cell (SCXA)

Detected in 22 experiment(s), a significant marker in 21.

Experiment	Marker?	Max mean expression
E-MTAB-8142	yes	6124.27
E-HCAD-36	yes	5736.34
E-MTAB-6701	yes	4119.10
E-HCAD-24	yes	3168.67
E-CURD-120	yes	1984.26
E-MTAB-10553	yes	1500.67
E-CURD-84	yes	1051.65
E-GEOD-70580	yes	503.62
E-HCAD-32	yes	480.80
E-CURD-122	yes	62.60
E-MTAB-10287	yes	33.32
E-HCAD-10	yes	30.45
E-MTAB-6678	yes	27.51
E-CURD-46	yes	27.46
E-CURD-88	yes	24.61

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): HAND1, NFATC2

miRNA regulators (miRDB)

75 targeting XCL1, 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-5692A	100.00	74.40	6850
HSA-MIR-196A-5P	100.00	68.16	684
HSA-MIR-196B-5P	100.00	68.16	681
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-1236-3P	99.94	68.04	1695
HSA-MIR-548A-5P	99.94	71.27	3482
HSA-MIR-548AD-5P	99.94	71.23	3502
HSA-MIR-548AE-5P	99.94	71.23	3502
HSA-MIR-548AK	99.94	71.24	3488
HSA-MIR-548AM-5P	99.94	71.24	3488
HSA-MIR-548AP-5P	99.94	71.14	3489
HSA-MIR-548AQ-5P	99.94	71.34	3426
HSA-MIR-548AR-5P	99.94	71.28	3515
HSA-MIR-548AS-5P	99.94	71.22	3482
HSA-MIR-548AU-5P	99.94	71.24	3488
HSA-MIR-548AY-5P	99.94	71.23	3502
HSA-MIR-548B-5P	99.94	71.23	3502
HSA-MIR-548BB-5P	99.94	71.27	3509
HSA-MIR-548C-5P	99.94	71.24	3488
HSA-MIR-548D-5P	99.94	71.23	3502
HSA-MIR-548H-5P	99.94	71.24	3488
HSA-MIR-548I	99.94	71.25	3481
HSA-MIR-548J-5P	99.94	71.14	3489
HSA-MIR-548O-5P	99.94	71.24	3488

Literature-anchored findings (GeneRIF, showing 36)

• NMR spectra of human lymphotactin (hLtn), obtained under various solution conditions, have revealed that the protein undergoes a major conformational rearrangement dependent on temperature and salt concentration. (PMID:11889129)
• lymphotactin, as well as MCP-1, may contribute to leukocyte infiltration and disease progression in IgA nephropathy. (PMID:12053063)
• Lymphotactin, (MIP)-1alpha, and MIP-1beta chemokines were all rapidly induced by engagement of CD28 and were calcineurin sensitive. (PMID:12393716)
• Lptn might be a key modulator for T cell trafficking in the pathogenesis of rheumatoid arthritis (PMID:12847680)
• XCL1 displays antimicrobial activity against E. coli and S. aureus. (PMID:12949249)
• In humans XCL1 expression is mainly a property of CD8+ T cells; the contribution to its synthesis by different T cell receptor alpha beta-expressing T cell subsets, namely CD4+ lymphocytes, is negligible. (PMID:14568926)
• lymphotactin utilizes highly specific glycosaminoglycan-binding sites (PMID:14707146)
• XCL1 activation is positively correlated with HIV-1 Tat expression in human U87.MG astrocytes in vitro. (PMID:14734774)
• description of a lymphotactin-producing monoclonal T-cell lymphoproliferative disorder with extreme lymphocytopenia and progressive leukoencephalopathy [case report] (PMID:16923584)
• The monocyte-derived dendritic cells can express Lptn mRNA in a maturation-dependent manner. (PMID:17077010)
• Elevated serum lymphotactin levels correlate with relatively milder manifestations in diffuse cutaneous systemic sclerosis (dSSc), especially lower severity of lung involvement, suggesting that lymphotactin may play a role in the development of dSSc. (PMID:18322986)
• functional repertoire and regulation of a single naturally occurring amino acid sequence can be expanded by access to a set of highly dissimilar native-state structures (PMID:18364395)
• XCL1 enhances regulatory activities of CD4+ CD25(high) CD127(low/-) T cells in human allergic asthma (PMID:18832695)
• ATAC Is a GCN5/PCAF-containing acetylase complex with a novel NC2-like histone fold module that interacts with the TATA-binding protein (PMID:18838386)
• Data indicated increased expression of XCL1 in CD4+ and CD8+ T cells in Wegener’s granulomatosis (WG), and suggest that XCL1 might be a key modulator of T cell recruitment in WG. (PMID:19797511)
• The expression patterns of XCR1 and XCL1 were conserved in human and mice blood cells, including certain dendritic cell subsets. (PMID:20541533)
• In native annulus fibrosus tissue homeostasis and repair, CXCR3 is evident, whereas XCL1 could not be detected. (PMID:21270681)
• XCL1-mediated inhibition is associated with direct interaction of the chemokine with the HIV-1 envelope. (PMID:24385911)
• identified 13 ADCC-activated genes. Six gene expression assays including 8 of the 13 genes (CCL3, CCL4/CCL4L1/CCL4L2, CD160, IFNG, NR4A3 and XCL1/XCL2) were analyzed in 127 kidney biopsies (PMID:25449536)
• analysis of XCL1 and XCL2, members of the C-chemokine subfamily, in the immune system (PMID:25497737)
• XCL1 acts via direct interaction with the external viral envelope glycoprotein, gp120, to block HIV-1 infection (PMID:26085164)
• Electrostatics and Hydrophobic Effects in the Metamorphic Protein Human Lymphotactin (PMID:26134347)
• This study defines a Glycosaminoglycan binding surface on XCL1 dimer that includes residues that are important for HIV-1 inhibition. (PMID:26836755)
• higher serum XCL1 levels at diagnosis and their progressive decline throughout chemotherapy could be correlated with higher survival. (PMID:29027574)
• XCL1-XCR1 chemokine pathway promotes trophoblast invasion by increasing matrix metalloproteinase activity in human first-trimester placenta (PMID:29856101)
• The systemic exercise-released chemokine lymphotactin/XCL1 modulates in vitro adult hippocampal precursor cell proliferation and neuronal differentiation. (PMID:31413355)
• Structure-function guided modeling of chemokine-GPCR specificity for the chemokine XCL1 and its receptor XCR1. (PMID:31481523)
• Study supports the genetic effect on preventing breast cancer survival through XCL1-induced DC1 recruitment in tumor microenvironment. (PMID:31904872)
• Diepoxybutane induces the expression of a novel p53-target gene XCL1 that mediates apoptosis in exposed human lymphoblasts. (PMID:31953984)
• XCL1 expression correlates with CD8-positive T cells infiltration and PD-L1 expression in squamous cell carcinoma arising from mature cystic teratoma of the ovary. (PMID:32115573)
• Specific binding-induced modulation of the XCL1 metamorphic equilibrium. (PMID:32986858)
• Involvement of the ERK/HIF-1alpha/EMT Pathway in XCL1-Induced Migration of MDA-MB-231 and SK-BR-3 Breast Cancer Cells. (PMID:33374849)
• Evolution of fold switching in a metamorphic protein. (PMID:33384377)
• XCL1 Aggravates Diabetic Nephropathy-Mediated Renal Glomerular Endothelial Cell Apoptosis and Inflammatory Response via Regulating p53/Nuclear Factor-Kappa B Pathway. (PMID:34518457)
• XCL1, a serum biomarker in neurological diseases; HTLV-1-associated myelopathy and multiple sclerosis. (PMID:36572194)
• Thermodynamic Evolution of a Metamorphic Protein: A Theoretical-Computational Study of Human Lymphotactin. (PMID:37233895)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	cxcl32b.1	ENSDARG00000071499
mus_musculus	Xcl1	ENSMUSG00000026573
rattus_norvegicus	Xcl1	ENSRNOG00000002964

Paralogs (26): CX3CL1 (ENSG00000006210), CCL26 (ENSG00000006606), CCL22 (ENSG00000102962), CCL17 (ENSG00000102970), CCL24 (ENSG00000106178), CCL7 (ENSG00000108688), CCL2 (ENSG00000108691), CCL8 (ENSG00000108700), CCL1 (ENSG00000108702), CCL20 (ENSG00000115009), CCL25 (ENSG00000131142), CCL21 (ENSG00000137077), XCL2 (ENSG00000143185), CCL11 (ENSG00000172156), CCL19 (ENSG00000172724), CCL13 (ENSG00000181374), CCL5 (ENSG00000271503), CCL23 (ENSG00000274736), CCL16 (ENSG00000275152), CCL4 (ENSG00000275302), CCL18 (ENSG00000275385), CCL15 (ENSG00000275718), CCL4L2 (ENSG00000276070), CCL3L3 (ENSG00000276085), CCL14 (ENSG00000276409), CCL3 (ENSG00000277632)

Protein

Protein identifiers

Lymphotactin — P47992 (reviewed: P47992)

Alternative names: ATAC, C motif chemokine 1, Cytokine SCM-1, Lymphotaxin, SCM-1-alpha, Small-inducible cytokine C1, XC chemokine ligand 1

All UniProt accessions (1): P47992

UniProt curated annotations — full annotation on UniProt →

Function. Chemotactic activity for lymphocytes but not for monocytes or neutrophils. In thymus, mediates medullary accumulation of thymic dendritic cells and contributes to regulatoy T cell development, playing a role in self-tolerance establishment.

Subcellular location. Secreted.

Tissue specificity. Highest level in spleen, lower in peripheral leukocytes and very low levels in lung, colon and small intestine.

Similarity. Belongs to the intercrine gamma family.

RefSeq proteins (1): NP_002986* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001811	Chemokine_IL8-like_dom	Domain
IPR008105	Chemokine_XCL1/XCL2	Family
IPR036048	Interleukin_8-like_sf	Homologous_superfamily
IPR039809	Chemokine_b/g/d	Family

Pfam: PF00048

UniProt features (14 total): strand 6, helix 3, signal peptide 1, chain 1, turn 1, region of interest 1, disulfide bond 1

Structure

Experimental structures (PDB)

7 structures.

PDB	Method	Resolution (Å)
2NYZ	X-RAY DIFFRACTION	2.6
9AST	ELECTRON MICROSCOPY	3.07
1J8I	SOLUTION NMR
1J9O	SOLUTION NMR
2HDM	SOLUTION NMR
2JP1	SOLUTION NMR
2N54	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P47992-F1	79.51	0.47

Antibody-complex structures (SAbDab): 1 — 9AST

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 (1): 32–69

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-380108	Chemokine receptors bind chemokines
R-HSA-416476	G alpha (q) signalling events

MSigDB gene sets: 453 (showing top): GOBP_POSITIVE_REGULATION_OF_CALCIUM_ION_TRANSPORT, GOBP_REGULATION_OF_CELL_ACTIVATION, MODULE_92, GOBP_REGULATION_OF_LEUKOCYTE_PROLIFERATION, GOBP_POSITIVE_REGULATION_OF_ADAPTIVE_IMMUNE_RESPONSE, GOBP_ANTIMICROBIAL_HUMORAL_RESPONSE, GOBP_NEGATIVE_REGULATION_OF_ADAPTIVE_IMMUNE_RESPONSE, GOBP_REGULATION_OF_ALPHA_BETA_T_CELL_ACTIVATION, GOBP_REGULATION_OF_T_CELL_CHEMOTAXIS, GOBP_MYELOID_LEUKOCYTE_MIGRATION, MODULE_169, GOBP_CELL_CHEMOTAXIS, GOBP_INFLAMMATORY_RESPONSE, GOBP_RESPONSE_TO_INTERLEUKIN_4, GOBP_RESPONSE_TO_PEPTIDE

GO Biological Process (42): positive regulation of T cell mediated cytotoxicity (GO:0001916), positive regulation of leukocyte chemotaxis (GO:0002690), negative regulation of T cell cytokine production (GO:0002725), positive regulation of T cell cytokine production (GO:0002726), negative regulation of T-helper 1 type immune response (GO:0002826), inflammatory response (GO:0006954), signal transduction (GO:0007165), cell-cell signaling (GO:0007267), response to virus (GO:0009615), positive regulation of T cell chemotaxis (GO:0010820), positive regulation of cell migration (GO:0030335), neutrophil chemotaxis (GO:0030593), negative regulation of type II interferon production (GO:0032689), negative regulation of interleukin-2 production (GO:0032703), positive regulation of interleukin-10 production (GO:0032733), mature natural killer cell chemotaxis (GO:0035782), negative regulation of DNA-templated transcription (GO:0045892), positive regulation of transcription by RNA polymerase II (GO:0045944), regulation of inflammatory response (GO:0050727), release of sequestered calcium ion into cytosol (GO:0051209), positive regulation of release of sequestered calcium ion into cytosol (GO:0051281), cell chemotaxis (GO:0060326), antimicrobial humoral immune response mediated by antimicrobial peptide (GO:0061844), chemokine-mediated signaling pathway (GO:0070098), cellular response to interleukin-4 (GO:0071353), cellular response to transforming growth factor beta stimulus (GO:0071560), positive regulation of transforming growth factor beta production (GO:0071636), positive regulation of granzyme B production (GO:0071663), positive regulation of neutrophil chemotaxis (GO:0090023), positive regulation of thymocyte migration (GO:2000412), positive regulation of natural killer cell chemotaxis (GO:2000503), positive regulation of granzyme A production (GO:2000513), negative regulation of T-helper 1 cell activation (GO:2000518), positive regulation of B cell chemotaxis (GO:2000538), positive regulation of T-helper 2 cell cytokine production (GO:2000553), positive regulation of T-helper 1 cell cytokine production (GO:2000556), positive regulation of immunoglobulin production in mucosal tissue (GO:2000558), negative regulation of CD4-positive, alpha-beta T cell proliferation (GO:2000562), positive regulation of CD4-positive, alpha-beta T cell proliferation (GO:2000563), positive regulation of CD8-positive, alpha-beta T cell proliferation (GO:2000566)

GO Molecular Function (6): chemokine activity (GO:0008009), chemokine receptor binding (GO:0042379), protein homodimerization activity (GO:0042803), CCR chemokine receptor binding (GO:0048020), cytokine activity (GO:0005125), protein binding (GO:0005515)

GO Cellular Component (2): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Peptide ligand-binding receptors	1
GPCR downstream signalling	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
positive regulation of T cell mediated immunity	2
T cell cytokine production	2
regulation of T cell cytokine production	2
cell communication	2
signaling	2
negative regulation of cytokine production	2
chemokine receptor binding	2
positive regulation of leukocyte mediated cytotoxicity	1
T cell mediated cytotoxicity	1
regulation of T cell mediated cytotoxicity	1
positive regulation of leukocyte migration	1
regulation of leukocyte chemotaxis	1
leukocyte chemotaxis	1
positive regulation of chemotaxis	1
negative regulation of T cell mediated immunity	1
negative regulation of cytokine production involved in immune response	1
positive regulation of cytokine production involved in immune response	1
negative regulation of adaptive immune response based on somatic recombination of immune receptors built from immunoglobulin superfamily domains	1
regulation of T-helper 1 type immune response	1
T-helper 1 type immune response	1
defense response	1
cellular process	1
regulation of cellular process	1
cellular response to stimulus	1
response to other organism	1
T cell chemotaxis	1
regulation of T cell chemotaxis	1
positive regulation of lymphocyte chemotaxis	1
positive regulation of T cell migration	1
cell migration	1
regulation of cell migration	1
positive regulation of cell motility	1
granulocyte chemotaxis	1
neutrophil migration	1
type II interferon production	1
regulation of type II interferon production	1
interleukin-2 production	1
regulation of interleukin-2 production	1
positive regulation of cytokine production	1
interleukin-10 production	1

Protein interactions and networks

STRING

1580 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
XCL1	XCR1	P46094	999
XCL1	CCR7	P32248	855
XCL1	CCL3	P10147	842
XCL1	CD8A	P01732	723
XCL1	CCR5	P51681	721
XCL1	CCR1	P32246	716
XCL1	MPPE1	Q53F39	713
XCL1	CCL21	O00585	704
XCL1	CCL4	P13236	684
XCL1	CCR2	P41597	682
XCL1	CCL25	O15444	680
XCL1	CX3CR1	P49238	679
XCL1	CD4	P01730	676
XCL1	GZMA	P12544	667
XCL1	CCRL2	O00421	648

IntAct

32 interactions, top by confidence:

A	B	Type	Score
XCL1		psi-mi:“MI:0915”(physical association)	0.560
	XCL1	psi-mi:“MI:0915”(physical association)	0.560
XCL1	CCL5	psi-mi:“MI:0407”(direct interaction)	0.560
XCL1	PF4	psi-mi:“MI:0407”(direct interaction)	0.560
XCL1	CXCL12	psi-mi:“MI:0407”(direct interaction)	0.560
CCL5	XCL1	psi-mi:“MI:0407”(direct interaction)	0.560
CXCL12	XCL1	psi-mi:“MI:0407”(direct interaction)	0.560
OPG002	XCL1	psi-mi:“MI:0407”(direct interaction)	0.440
XCL1	XCL1	psi-mi:“MI:0407”(direct interaction)	0.440
	XCL1	psi-mi:“MI:0407”(direct interaction)	0.440
XCL1	CCL11	psi-mi:“MI:0407”(direct interaction)	0.440
XCL1	CCL13	psi-mi:“MI:0407”(direct interaction)	0.440
XCL1	CCL21	psi-mi:“MI:0407”(direct interaction)	0.440
XCL1	CCL24	psi-mi:“MI:0407”(direct interaction)	0.440
XCL1	CCL26	psi-mi:“MI:0407”(direct interaction)	0.440
XCL1	CCL28	psi-mi:“MI:0407”(direct interaction)	0.440
CCL13	XCL1	psi-mi:“MI:0407”(direct interaction)	0.440
CCL26	XCL1	psi-mi:“MI:0407”(direct interaction)	0.440
PF4V1	XCL1	psi-mi:“MI:0407”(direct interaction)	0.440
CXCL9	XCL1	psi-mi:“MI:0407”(direct interaction)	0.440
CXCL11	XCL1	psi-mi:“MI:0407”(direct interaction)	0.440
XCL1	CXCL14	psi-mi:“MI:0407”(direct interaction)	0.440
XCL1	CXCL2	psi-mi:“MI:0407”(direct interaction)	0.440
XCL1	PF4V1	psi-mi:“MI:0407”(direct interaction)	0.440
XCL1	CXCL10	psi-mi:“MI:0407”(direct interaction)	0.440
XCL1	CXCL17	psi-mi:“MI:0407”(direct interaction)	0.440
XCL1	COL6A2	psi-mi:“MI:0914”(association)	0.350

BioGRID (33): KRTAP10-3 (Two-hybrid), FAT4 (Affinity Capture-MS), TUBB8 (Affinity Capture-MS), TUBB3 (Affinity Capture-MS), FAT3 (Affinity Capture-MS), COL6A2 (Affinity Capture-MS), GPR98 (Affinity Capture-MS), FSTL1 (Affinity Capture-MS), XCL1 (Reconstituted Complex), XCL1 (Reconstituted Complex), XCL1 (Reconstituted Complex), XCL1 (Reconstituted Complex), XCL1 (Reconstituted Complex), XCL1 (Reconstituted Complex), XCL1 (Reconstituted Complex)

ESM2 similar proteins: A0A0R4INB9, A9QWP9, B0R191, K7XWG4, O00175, O35903, O43927, O55038, O62812, O70460, P02775, P02778, P10146, P10720, P17515, P18340, P22362, P26894, P27784, P28292, P41324, P43030, P47992, P47993, P48298, P48973, P49113, P50228, P51672, P79255, P84444, P86792, P86793, P97545, P97885, Q07325, Q08782, Q2KIQ8, Q5KSV9, Q62401

Diamond homologs: K7XWG4, P16619, P42831, P47992, P47993, P49873, P51671, P51672, P52203, P80075, P80343, P82943, P97545, Q03366, Q09141, Q62401, Q68AY9, Q68Y88, Q8MIT7, Q99616, Q9JKC0, Q9QXY8, Q9TTQ4, Q9TTS6, Q9UBD3, F5HET8, O00626, O15467, O55145, O70460, O88430, O89093, O97919, P10147, P10148, P10855, P13236, P13500, P13501, P14097

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
XCL1	up-regulates	XCR1	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 19 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	11	147.1×	8e-22
Class A/1 (Rhodopsin-like receptors)	6	31.8×	2e-07
Peptide ligand-binding receptors	6	31.8×	2e-07
G alpha (i) signalling events	10	27.8×	3e-12
GPCR ligand binding	6	27.5×	4e-07
Signaling by GPCR	6	17.2×	5e-06
GPCR downstream signalling	5	15.5×	8e-05

GO biological processes:

GO term	Partners	Fold	FDR
eosinophil chemotaxis	6	244.2×	2e-12
chemokine-mediated signaling pathway	11	198.1×	5e-22
neutrophil chemotaxis	6	95.2×	8e-10
chemotaxis	12	90.6×	3e-20
antimicrobial humoral immune response mediated by antimicrobial peptide	10	90.0×	2e-16
cell chemotaxis	6	61.7×	9e-09
cell-cell signaling	9	34.8×	3e-11
positive regulation of cell migration	8	27.4×	4e-09

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	13
Likely benign	1
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

220 predictions. Top by Δscore:

Variant	Effect	Δscore
1:168576694:GGAAG:G	donor_gain	1.0000
1:168576695:GAAGG:G	donor_gain	1.0000
1:168576696:AAGG:A	donor_loss	1.0000
1:168576697:AGGT:A	donor_loss	1.0000
1:168576700:T:G	donor_loss	1.0000
1:168580058:A:AG	acceptor_gain	1.0000
1:168580058:ACCAG:A	acceptor_gain	1.0000
1:168580059:CCA:C	acceptor_loss	1.0000
1:168580061:A:AG	acceptor_gain	1.0000
1:168580061:AG:A	acceptor_gain	1.0000
1:168580061:AGGT:A	acceptor_gain	1.0000
1:168580062:G:GA	acceptor_gain	1.0000
1:168580062:GG:G	acceptor_gain	1.0000
1:168580062:GGT:G	acceptor_gain	1.0000
1:168580062:GGTG:G	acceptor_gain	1.0000
1:168580062:GGTGT:G	acceptor_gain	1.0000
1:168580155:G:GT	donor_gain	1.0000
1:168580168:GAGCA:G	donor_gain	1.0000
1:168580170:GCA:G	donor_gain	1.0000
1:168580173:G:GG	donor_gain	1.0000
1:168580173:GTAAT:G	donor_loss	1.0000
1:168580174:TAAT:T	donor_gain	1.0000
1:168580174:TAATG:T	donor_loss	1.0000
1:168580178:G:GG	donor_gain	1.0000
1:168580180:G:GG	donor_loss	1.0000
1:168581050:A:AG	acceptor_gain	1.0000
1:168581051:G:GG	acceptor_gain	1.0000
1:168581051:GTTTT:G	acceptor_gain	1.0000
1:168576695:GAAG:G	donor_gain	0.9900
1:168576699:G:GG	donor_gain	0.9900

AlphaMissense

729 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:168581103:G:C	W76C	0.997
1:168581103:G:T	W76C	0.997
1:168581054:T:C	F60S	0.993
1:168581101:T:A	W76R	0.992
1:168581101:T:C	W76R	0.992
1:168581054:T:G	F60C	0.967
1:168581060:C:T	T62I	0.966
1:168580135:T:G	I45S	0.965
1:168580143:T:G	Y48D	0.965
1:168581080:T:A	C69S	0.965
1:168581081:G:C	C69S	0.965
1:168581084:C:A	A70D	0.964
1:168580135:T:C	I45T	0.958
1:168581083:G:C	A70P	0.956
1:168581080:T:C	C69R	0.952
1:168581081:G:A	C69Y	0.944
1:168580095:T:A	C32S	0.938
1:168580096:G:C	C32S	0.938
1:168581066:G:C	R64P	0.938
1:168581102:G:T	W76L	0.936
1:168580135:T:A	I45N	0.934
1:168580095:T:C	C32R	0.932
1:168581102:G:C	W76S	0.932
1:168581101:T:G	W76G	0.928
1:168581104:G:C	V77L	0.928
1:168581104:G:T	V77L	0.928
1:168581082:T:G	C69W	0.925
1:168580174:T:A	V58E	0.921
1:168581069:G:T	G65V	0.921
1:168581068:G:T	G65C	0.910

dbSNP variants (sampled 300 via entrez): RS1000396385 (1:168581510 A>G), RS1000515705 (1:168577053 T>G), RS1000994101 (1:168576815 A>C), RS1001868019 (1:168581415 C>T), RS1002054994 (1:168576248 C>A), RS1002900709 (1:168580261 G>A), RS1003317539 (1:168582010 T>A), RS1004394144 (1:168579967 T>A,C), RS1004425187 (1:168579719 G>A,T), RS1005427302 (1:168578592 T>C), RS1006397393 (1:168577721 G>A), RS1006429904 (1:168577473 G>A), RS1006727086 (1:168578011 A>G), RS1006804444 (1:168582407 T>C,G), RS1006949380 (1:168578433 A>C)

Disease associations

OMIM: gene MIM:600250 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

17 associations (top):

Study	Trait	p-value
GCST006585_2688	Blood protein levels	2.000000e-06
GCST009391_2075	Metabolite levels	1.000000e-06
GCST010796_3930	Electrocardiogram morphology (amplitude at temporal datapoints)	4.000000e-09
GCST010796_3931	Electrocardiogram morphology (amplitude at temporal datapoints)	8.000000e-09
GCST010796_3932	Electrocardiogram morphology (amplitude at temporal datapoints)	2.000000e-08
GCST010796_3933	Electrocardiogram morphology (amplitude at temporal datapoints)	4.000000e-08
GCST010796_3934	Electrocardiogram morphology (amplitude at temporal datapoints)	3.000000e-08
GCST010796_3935	Electrocardiogram morphology (amplitude at temporal datapoints)	2.000000e-08
GCST010796_3936	Electrocardiogram morphology (amplitude at temporal datapoints)	3.000000e-08
GCST010796_3937	Electrocardiogram morphology (amplitude at temporal datapoints)	4.000000e-08
GCST010796_3938	Electrocardiogram morphology (amplitude at temporal datapoints)	8.000000e-09
GCST010796_3939	Electrocardiogram morphology (amplitude at temporal datapoints)	6.000000e-09
GCST010796_3942	Electrocardiogram morphology (amplitude at temporal datapoints)	4.000000e-08
GCST010796_3943	Electrocardiogram morphology (amplitude at temporal datapoints)	2.000000e-09
GCST010796_4014	Electrocardiogram morphology (amplitude at temporal datapoints)	1.000000e-08
GCST90019016_2	Psoriasis	6.000000e-07
GCST90019017_2	Psoriasis	2.000000e-09

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0010347	cholesteryl ester 20:3 measurement
EFO:0004327	electrocardiography

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

28 total (human), top 28 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Progesterone	affects cotreatment, decreases expression, increases expression	2
Valproic Acid	increases expression	2
Asian ginseng	decreases expression, decreases reaction	1
diepoxybutane	increases expression, affects reaction	1
decabromobiphenyl ether	affects expression	1
trichostatin A	increases expression	1
arsenite	affects expression	1
cyanoginosin LR	increases expression	1
entinostat	increases expression	1
abrine	increases expression	1
Bortezomib	decreases expression	1
Vorinostat	increases expression	1
Panobinostat	affects cotreatment, affects expression	1
Air Pollutants	increases expression	1
Benzo(a)pyrene	increases methylation	1
Cadmium	decreases expression	1
Calcitriol	increases expression	1
Cisplatin	affects cotreatment, affects expression	1
Diethylhexyl Phthalate	decreases reaction, decreases expression	1
Diuron	decreases expression	1
Estradiol	affects cotreatment, decreases expression	1
Flavonoids	decreases expression	1
Nickel	increases expression	1
Plant Extracts	decreases expression	1
Silicon Dioxide	increases expression	1
Antirheumatic Agents	decreases expression	1
Cadmium Chloride	decreases expression	1
Polyphenols	decreases expression	1

Clinical trials (associated diseases)

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