CCL26

Summary

CCL26 (C-C motif chemokine ligand 26, HGNC:10625) is a protein-coding gene on chromosome 7q11.23, encoding C-C motif chemokine 26 (Q9Y258). Chemoattractant for eosinophils and basophils.

This gene is one of two Cys-Cys (CC) cytokine genes clustered on the q arm of chromosome 7. Cytokines are a family of secreted proteins involved in immunoregulatory and inflammatory processes. The CC cytokines are proteins characterized by two adjacent cysteines. The cytokine encoded by this gene displays chemotactic activity for normal peripheral blood eosinophils and basophils. This protein also has antimicrobial activity, displaying an antibacterial effect on S. pneumoniae, S. aureus, Non-typeable H. influenzae, and P. aeruginosa. The product of this gene is one of three related chemokines that specifically activate chemokine receptor CCR3. This chemokine may contribute to the eosinophil accumulation in atopic diseases.

Source: NCBI Gene 10344 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 15 total
• MANE Select transcript: NM_001371938

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10625
Approved symbol	CCL26
Name	C-C motif chemokine ligand 26
Location	7q11.23
Locus type	gene with protein product
Status	Approved
Aliases	MIP-4alpha, eotaxin-3, IMAC, MIP-4a, TSC-1
Ensembl gene	ENSG00000006606
Ensembl biotype	protein_coding
OMIM	604697
Entrez	10344

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000005180, ENST00000394905

RefSeq mRNA: 3 — MANE Select: NM_001371938 NM_001371936, NM_001371938, NM_006072

CCDS: CCDS5578

Canonical transcript exons

ENST00000005180 — 3 exons

Exon	Start	End
ENSE00000370452	75771889	75772003
ENSE00001519960	75772104	75772211
ENSE00003907883	75769538	75769789

Expression profiles

Bgee: expression breadth ubiquitous, 149 present calls, max score 86.64.

FANTOM5 (CAGE): breadth broad, TPM avg 0.5191 / max 52.9799, expressed in 190 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
84382	0.5191	190

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	86.64	gold quality
right ovary	UBERON:0002118	84.11	gold quality
left ovary	UBERON:0002119	83.64	gold quality
tibial nerve	UBERON:0001323	78.61	gold quality
adenohypophysis	UBERON:0002196	78.50	gold quality
ovary	UBERON:0000992	76.99	gold quality
pituitary gland	UBERON:0000007	76.61	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	76.16	gold quality
left uterine tube	UBERON:0001303	71.55	gold quality
right adrenal gland	UBERON:0001233	71.08	gold quality
lower esophagus mucosa	UBERON:0035834	70.81	gold quality
ectocervix	UBERON:0012249	70.44	gold quality
left adrenal gland	UBERON:0001234	70.38	gold quality
islet of Langerhans	UBERON:0000006	70.36	gold quality
left adrenal gland cortex	UBERON:0035825	70.13	gold quality
right adrenal gland cortex	UBERON:0035827	70.09	gold quality
rectum	UBERON:0001052	69.86	gold quality
right coronary artery	UBERON:0001625	69.02	gold quality
mucosa of paranasal sinus	UBERON:0005030	68.83	gold quality
apex of heart	UBERON:0002098	68.46	gold quality
metanephros cortex	UBERON:0010533	68.44	gold quality
vagina	UBERON:0000996	68.15	gold quality
adrenal cortex	UBERON:0001235	68.05	gold quality
pigmented layer of retina	UBERON:0001782	67.54	gold quality
omental fat pad	UBERON:0010414	67.23	gold quality
peritoneum	UBERON:0002358	67.15	gold quality
left coronary artery	UBERON:0001626	66.27	gold quality
adipose tissue of abdominal region	UBERON:0007808	65.81	gold quality
adrenal gland	UBERON:0002369	65.63	gold quality
coronary artery	UBERON:0001621	65.62	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.70

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CREB1, HAND2, STAT6

miRNA regulators (miRDB)

6 targeting CCL26, 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-6829-5P	98.86	65.12	1480
HSA-MIR-330-5P	98.73	67.63	1788
HSA-MIR-224-5P	98.33	70.12	1256
HSA-MIR-326	98.25	66.44	1565
HSA-MIR-3614-3P	97.81	67.15	582
HSA-MIR-514A-5P	96.94	65.49	801

Literature-anchored findings (GeneRIF, showing 40)

• Expression is modulated by cytokines and glucocorticoids. (PMID:12061839)
• Pretreatment or co-treatment with each of the eotaxins augmented PMAtate-induced superoxide generation, concentration-dependent degranulation of eosinophil peroxidase, & potentiation of A23187-induced degranulation. (PMID:12192108)
• eotaxin-3 inhibits MCP-1-mediated responses, thus acting as a natural antagonist for CCR2, and promotes active movement of monocytes away from a gradient of eotaxin-3 (PMID:12689946)
• eotaxin-3 is the first human chemokine that features broadband antagonistic activities; may have a modulatory rather than an inflammatory function;may play an unrecognized role in the polarization of cellular recruitment by attracting Th2 lymphocytes (PMID:15039444)
• results suggest that types 1 and 2 IL-4 receptors and nuclear factor-kappaB may have a role in eotaxin-3 production in bronchial epithelial cells (PMID:15521376)
• CCL26 is major eotaxin synthesized and released by alveolar epithelial cells and is involved in autoregulation of CCR3 receptors and other eotaxins. This CCL26-CCR3 ligand-receptor system may be an attractive target in therapy of airway inflammation. (PMID:15863444)
• results demonstrate that epithelial eotaxin-3 is up-regulated in the context of a T helper 2 mediated inflammatory bowel disease via the signal transducer and activator of transcription 6 (PMID:16084752)
• In conclusion, these results suggest that viral airway infection may enhance interleukin-4-induced eotaxin-3 production through upregulation of the interleukin-4 receptor in airway epithelial cells. (PMID:16264039)
• association of eotaxin-3 polymorphisms in ulcerative colitis in Korean patients (PMID:16391516)
• results implicate eotaxin-3 as a critical effector molecule for eosinophilic esophagitis and provide insight into disease pathogenesis (PMID:16453027)
• Contributes to dermal and epidermal eosinophil infiltration in Th2-polarized skin inflammation in which interleukin-4 is produced. (PMID:17073866)
• Data suggest atherosclerotic inflammation may be a trigger for sclerosis in calcified stenotic aortic valves through upregulation TGF-beta, VAP-1, MIG and Eotaxin3, which is only partially inhibited by previous statin therapy. (PMID:17490641)
• The Th2 cytokine IL-4 preferentially stimulated eotaxin-3 expression. (PMID:17541284)
• Determination of eotaxin-3 levels by real-time polymerase chain reaction on paraffinized, formalin-fixed tissue may be a useful test in the differentiation of eosinophilic esophagitis from gastroesophageal reflux disease (PMID:17900656)
• Developing lung expresses the eotaxins and functional CCR3 receptor. (PMID:18055844)
• This study demonstrated upregulation of type 1 IL-4R by IFN-gamma, which resulted in enhanced IL-4-induced production of CCL26 from keratinocytes. (PMID:18774776)
• Eotaxin-3/CCL26 gene expression levels were significantly increased in EE. Although they were significantly downregulated upon steroid treatment, control expression levels were not reached in any of the cases analyzed. (PMID:18844613)
• increased levels in patients with eosinophilic esophagitis (PMID:19141347)
• is the most strongly up-regulated gene of the transcriptom in eosinophilic esophagitis patients (PMID:19141349)
• CCL26-directed small-interfering RNA (siRNA) treatments significantly decreased release of CCL5 (RANTES), CCL15 (MIP-1delta), CCL8 (MCP-2), and CCL13 (MCP-4). (PMID:19203252)
• overexpressed in eosinophilic esophagitis, expression level correlates with disease severity (PMID:19331716)
• The abundant biopolymer chitin appears to be recognized by a yet uncharacterized receptor on sinonasal epithelial cells. Chitin stimulates production of AMCase and eotaxin-3, two pro-Th2 effector proteins. (PMID:19379605)
• We did not replicate the association of eotaxin-3 with rheumatoid arthrits described in Koreans, or that of the MHC2T single nucleotide polymorphism in Spanish patients (PMID:19567623)
• data show that IL-4 and pro-inflammatory cytokines such as TNF-alpha, IL-1beta and IFN-gamma regulate CCL26 synthesis in human monocytic cells (PMID:20059579)
• promotes lung fibroblast migration (PMID:20143648)
• The mean gene expression level for CCL11, CCL24, CCL26 was higher in skin changes of atopic dermatitis patients than in uninvolved skin. (PMID:20236835)
• interaction of eotaxins and CCR3 regulates the Th2-dominant tumor environment, which is closely related to the development of cutaneous T-cell lymphoma (PMID:20505746)
• CCL26 is an agonist for CX3CR1 and may play a dual role in allergic diseases by attracting eosinophils via CCR3 and killer lymphocytes and resident monocytes via chemokine receptor CX3CR1. (PMID:20974991)
• Serum CCL11 was increased in ulcerative colitis (UC) and less in Crohn’s disease (CD), whereas CCL24 and CCL26 were increased only in UC. Colon expression of the CCL’s was higher in UC vs. CD, and was induced by Th2 cytokines in colon epithelial cells. (PMID:21077277)
• Serum eotaxin-3 is a sensitive and specific marker for the diagnosis of active Churg-Strauss syndrome suitable for routine clinical practice. (PMID:21266446)
• AMCase and eotaxin-3 may be important mediators in the pathogenesis of nasal polyps. The increased AMCase and eotaxin-3 might lead to nasal polyp formation and growth. (PMID:21303604)
• Epigenetic regulation of the IL-13-induced human eotaxin-3 gene by CREB-binding protein-mediated histone 3 acetylation. (PMID:21325281)
• The expression of AMCase, eotaxin-3, IL-13, and mRNA was significantly higher in patients with CRSwNP than in the control group. (PMID:21493274)
• CCL26 but not CCL24 was elevated in bullous pemphigoid lesions. (PMID:21881593)
• these data link the up-regulation of the eosinophil chemotactic factor CCL26 in bullous pemphigoid to the lesional accumulation of activated eosinophils in the skin. (PMID:21985360)
• Data show that that IL-4 signals through the Jak1, 2/Stat6 pathway in keratinocytes to stimulate CCL26 expression and this may provide an explanation for the pathogenesis of atopic dermatitis (AD). (PMID:22226123)
• Oesophageal squamous cells from gastro-oesophageal reflux disease and Eosinophilic oesophagitis patients express similar levels of eotaxin-3 when stimulated by Th2 cytokines, and omeprazole blocks that eotaxin-3 expression. (PMID:22580413)
• Up-regulation of CCL2, CCL26, IL6 and LOXL2 genes in cancer cells are part of the common effects of cancer-associated fibroblasts on hepatocellular carcinoma cells (PMID:22739041)
• The level of eotaxin expression and inflammatory cell count were measured in the material from nasal brushing in healthy controls and in patients with allergic rhinitis, asthma, and chronic obstructive pulmonary disease. (PMID:22846146)
• Phosphodiesterase 4 inhibitors, rolipram and RO-20-1724 have no effect on CCL26 expression in human primary bronchial epithelial cells. (PMID:22946025)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	ccl35.2	ENSDARG00000070378
danio_rerio	ccl35.1	ENSDARG00000103466
rattus_norvegicus	Ccl24	ENSRNOG00000031162

Paralogs (26): CX3CL1 (ENSG00000006210), CCL22 (ENSG00000102962), CCL17 (ENSG00000102970), CCL24 (ENSG00000106178), CCL7 (ENSG00000108688), CCL2 (ENSG00000108691), CCL8 (ENSG00000108700), CCL1 (ENSG00000108702), CCL20 (ENSG00000115009), CCL25 (ENSG00000131142), CCL21 (ENSG00000137077), XCL1 (ENSG00000143184), 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

C-C motif chemokine 26 — Q9Y258 (reviewed: Q9Y258)

Alternative names: CC chemokine IMAC, Eotaxin-3, Macrophage inflammatory protein 4-alpha, Small-inducible cytokine A26, Thymic stroma chemokine-1

All UniProt accessions (1): Q9Y258

UniProt curated annotations — full annotation on UniProt →

Function. Chemoattractant for eosinophils and basophils. Acts as a ligand for C-C chemokine receptor CCR3 which triggers Ca(2+) mobilization in eosinophils. Also acts as a ligand for CX3C chemokine receptor CX3CR1, inducing cell chemotaxis.

Subunit / interactions. Monomer.

Subcellular location. Secreted.

Tissue specificity. Ubiquitously expressed at low levels in various tissues including heart and ovary.

Similarity. Belongs to the intercrine beta (chemokine CC) family.

RefSeq proteins (3): NP_001358865, NP_001358867, NP_006063 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000827	Chemokine_CC_CS	Conserved_site
IPR001811	Chemokine_IL8-like_dom	Domain
IPR036048	Interleukin_8-like_sf	Homologous_superfamily
IPR039809	Chemokine_b/g/d	Family

Pfam: PF00048

UniProt features (12 total): strand 5, helix 2, disulfide bond 2, signal peptide 1, chain 1, sequence variant 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
1G2S	SOLUTION NMR
1G2T	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9Y258-F1	85.46	0.66

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): 33–57, 34–73

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 124 (showing top): GOBP_REGULATION_OF_PROTEIN_POLYMERIZATION, GOBP_ANTIMICROBIAL_HUMORAL_RESPONSE, GOBP_MYELOID_LEUKOCYTE_MIGRATION, GOBP_CELL_CHEMOTAXIS, GOBP_INFLAMMATORY_RESPONSE, GOBP_RESPONSE_TO_PEPTIDE, GOBP_POSITIVE_REGULATION_OF_ORGANELLE_ORGANIZATION, GOBP_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, GOBP_CELL_CELL_SIGNALING, GOBP_LEUKOCYTE_CHEMOTAXIS, GOBP_REGULATION_OF_ACTIN_FILAMENT_BASED_PROCESS, SENESE_HDAC1_AND_HDAC2_TARGETS_DN, GOBP_POSITIVE_REGULATION_OF_RESPONSE_TO_EXTERNAL_STIMULUS, GOBP_TAXIS, GOBP_LEUKOCYTE_MIGRATION

GO Biological Process (15): positive regulation of endothelial cell proliferation (GO:0001938), monocyte chemotaxis (GO:0002548), chemotaxis (GO:0006935), inflammatory response (GO:0006954), signal transduction (GO:0007165), cell-cell signaling (GO:0007267), T cell chemotaxis (GO:0010818), positive regulation of cell migration (GO:0030335), positive regulation of actin filament polymerization (GO:0030838), eosinophil chemotaxis (GO:0048245), positive regulation of chemotaxis (GO:0050921), cell chemotaxis (GO:0060326), antimicrobial humoral immune response mediated by antimicrobial peptide (GO:0061844), chemokine-mediated signaling pathway (GO:0070098), immune response (GO:0006955)

GO Molecular Function (7): chemokine activity (GO:0008009), CCR3 chemokine receptor binding (GO:0031728), CX3C chemokine receptor binding (GO:0031737), receptor ligand activity (GO:0048018), CCR chemokine receptor binding (GO:0048020), cytokine activity (GO:0005125), protein binding (GO:0005515)

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

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
chemokine receptor binding	3
cell communication	2
signaling	2
cell migration	2
chemotaxis	2
endothelial cell proliferation	1
regulation of endothelial cell proliferation	1
positive regulation of epithelial cell proliferation	1
leukocyte chemotaxis	1
mononuclear cell migration	1
myeloid leukocyte migration	1
response to chemical	1
taxis	1
defense response	1
cellular process	1
regulation of cellular process	1
cellular response to stimulus	1
lymphocyte chemotaxis	1
T cell migration	1
regulation of cell migration	1
positive regulation of cell motility	1
actin filament polymerization	1
regulation of actin filament polymerization	1
positive regulation of protein polymerization	1
positive regulation of cytoskeleton organization	1
positive regulation of supramolecular fiber organization	1
granulocyte chemotaxis	1
eosinophil migration	1
positive regulation of response to external stimulus	1
positive regulation of locomotion	1
regulation of chemotaxis	1
cellular response to chemical stimulus	1
antimicrobial humoral response	1
G protein-coupled receptor signaling pathway	1
cytokine-mediated signaling pathway	1
cellular response to chemokine	1
immune system process	1
response to stimulus	1
cytokine activity	1
cell chemotaxis	1

Protein interactions and networks

STRING

948 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CCL26	CCR3	P51677	999
CCL26	CX3CR1	P49238	968
CCL26	CCR1	P32246	893
CCL26	CCR2	P41597	830
CCL26	IL13	P35225	797
CCL26	IL4	P05112	783
CCL26	CCL22	O00626	776
CCL26	CCL27	Q9Y4X3	754
CCL26	CXCL10	P02778	747
CCL26	CCL2	P13500	745
CCL26	CXCR3	P49682	740
CCL26	CXCL8	P10145	739
CCL26	CCL20	P78556	729
CCL26	CX3CL1	P78423	727
CCL26	CCR5	P51681	724

IntAct

42 interactions, top by confidence:

A	B	Type	Score
CCL26	CCL5	psi-mi:“MI:0407”(direct interaction)	0.560
CCL26	PF4	psi-mi:“MI:0407”(direct interaction)	0.560
CCL26	CXCL12	psi-mi:“MI:0407”(direct interaction)	0.560
CCL26	CCL17	psi-mi:“MI:0407”(direct interaction)	0.560
CCL5	CCL26	psi-mi:“MI:0407”(direct interaction)	0.560
CCL17	CCL26	psi-mi:“MI:0407”(direct interaction)	0.560
PF4	CCL26	psi-mi:“MI:0407”(direct interaction)	0.560
PAX6	CCL26	psi-mi:“MI:0915”(physical association)	0.560
TTMP	CCL26	psi-mi:“MI:0915”(physical association)	0.560
CCL26	CCL8	psi-mi:“MI:0407”(direct interaction)	0.440
CCL26	CCL13	psi-mi:“MI:0407”(direct interaction)	0.440
CCL26	CCL21	psi-mi:“MI:0407”(direct interaction)	0.440
CCL11	CCL26	psi-mi:“MI:0407”(direct interaction)	0.440
CCL13	CCL26	psi-mi:“MI:0407”(direct interaction)	0.440
CCL21	CCL26	psi-mi:“MI:0407”(direct interaction)	0.440
CCL28	CCL26	psi-mi:“MI:0407”(direct interaction)	0.440
XCL1	CCL26	psi-mi:“MI:0407”(direct interaction)	0.440
PF4V1	CCL26	psi-mi:“MI:0407”(direct interaction)	0.440
PPBP	CCL26	psi-mi:“MI:0407”(direct interaction)	0.440
CXCL9	CCL26	psi-mi:“MI:0407”(direct interaction)	0.440
CXCL10	CCL26	psi-mi:“MI:0407”(direct interaction)	0.440
CXCL11	CCL26	psi-mi:“MI:0407”(direct interaction)	0.440
CXCL14	CCL26	psi-mi:“MI:0407”(direct interaction)	0.440
CCL26	CCL28	psi-mi:“MI:0407”(direct interaction)	0.440
CCL26	XCL1	psi-mi:“MI:0407”(direct interaction)	0.440
CCL26	XCL2	psi-mi:“MI:0407”(direct interaction)	0.440

BioGRID (45): PAX6 (Two-hybrid), C3orf52 (Two-hybrid), CCL26 (Reconstituted Complex), CCL26 (Reconstituted Complex), CCL26 (Reconstituted Complex), CCL26 (Reconstituted Complex), CCL13 (Reconstituted Complex), CCL2 (Reconstituted Complex), CCL21 (Reconstituted Complex), CCL28 (Reconstituted Complex), CCL5 (Reconstituted Complex), CCL8 (Reconstituted Complex), CXCL10 (Reconstituted Complex), CXCL11 (Reconstituted Complex), CXCL12 (Reconstituted Complex)

ESM2 similar proteins: F5HET8, O00175, O43927, O55038, O62812, O70460, P02776, P02778, P06765, P10146, P10720, P17515, P22362, P27784, P43030, P47992, P47993, P48298, P48973, P49113, P50228, P51670, P80325, P82943, P97545, P97884, P97885, Q03366, Q08782, Q09141, Q102R3, Q62401, Q64H35, Q68FP3, Q68Y86, Q865F5, Q8HYP8, Q8I021, Q8MIZ1, Q95N01

Diamond homologs: F5HET8, O00175, O00585, O15467, O35188, O55145, P10147, P10148, P13236, P13500, P14097, P14844, P16619, P27784, P28291, P28292, P42831, P46632, P48298, P50229, P50230, P51670, P52203, P55773, P55774, P61274, P61275, P78423, P80075, P80098, P80343, P97545, Q09141, Q16627, Q16663, Q17QA1, Q5I1Z0, Q5RA36, Q64H35, Q68A92

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 23 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	15	156.0×	1e-30
Class A/1 (Rhodopsin-like receptors)	8	33.0×	9e-10
Peptide ligand-binding receptors	8	33.0×	9e-10
GPCR ligand binding	8	28.5×	2e-09
G alpha (i) signalling events	10	21.6×	2e-10
Signaling by GPCR	8	17.8×	8e-08
GPCR downstream signalling	5	12.1×	5e-04

GO biological processes:

GO term	Partners	Fold	FDR
eosinophil chemotaxis	6	209.3×	7e-12
chemokine-mediated signaling pathway	13	200.6×	3e-26
neutrophil chemotaxis	8	108.8×	2e-13
antimicrobial humoral immune response mediated by antimicrobial peptide	13	100.3×	2e-22
chemotaxis	12	77.7×	3e-19
cell chemotaxis	7	61.7×	4e-10
intracellular calcium ion homeostasis	5	34.6×	4e-06
response to virus	5	34.3×	4e-06

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	10
Likely benign	4
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

115 predictions. Top by Δscore:

Variant	Effect	Δscore
7:75769790:C:CC	acceptor_gain	1.0000
7:75771885:TCA:T	donor_loss	1.0000
7:75771886:CACA:C	donor_loss	1.0000
7:75771887:A:AC	donor_gain	1.0000
7:75771888:C:CC	donor_gain	1.0000
7:75771888:C:CT	donor_loss	1.0000
7:75771888:CAT:C	donor_gain	1.0000
7:75771888:CATCA:C	donor_gain	1.0000
7:75772102:A:AC	donor_gain	1.0000
7:75772103:C:CC	donor_gain	1.0000
7:75769785:TGAAT:T	acceptor_gain	0.9900
7:75769786:GAAT:G	acceptor_gain	0.9900
7:75769790:CT:C	acceptor_loss	0.9900
7:75769791:T:A	acceptor_loss	0.9900
7:75769792:G:C	acceptor_gain	0.9900
7:75771881:ATACT:A	donor_loss	0.9900
7:75771883:ACTC:A	donor_loss	0.9900
7:75772099:CGT:C	donor_loss	0.9900
7:75772100:GTACG:G	donor_loss	0.9900
7:75772101:TAC:T	donor_loss	0.9900
7:75772103:CGT:C	donor_gain	0.9900
7:75772103:CGTGT:C	donor_gain	0.9900
7:75769787:AAT:A	acceptor_gain	0.9800
7:75769788:AT:A	acceptor_gain	0.9800
7:75769792:G:GC	acceptor_gain	0.9800
7:75771887:ACAT:A	donor_gain	0.9800
7:75771888:CA:C	donor_gain	0.9800
7:75771888:CATC:C	donor_gain	0.9800
7:75771999:CCCAC:C	acceptor_gain	0.9800
7:75772000:CCACC:C	acceptor_gain	0.9800

AlphaMissense

607 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:75769738:C:A	W80C	0.992
7:75769738:C:G	W80C	0.992
7:75769787:A:G	F64S	0.981
7:75769740:A:G	W80R	0.971
7:75769740:A:T	W80R	0.971
7:75769760:C:G	C73S	0.970
7:75769761:A:T	C73S	0.970
7:75769787:A:C	F64C	0.967
7:75769761:A:G	C73R	0.946
7:75769786:G:C	F64L	0.939
7:75769786:G:T	F64L	0.939
7:75769788:A:G	F64L	0.939
7:75771907:C:G	C57S	0.936
7:75771908:A:T	C57S	0.936
7:75771929:A:C	Y50D	0.931
7:75771892:A:T	V62E	0.930
7:75771976:C:G	C34S	0.930
7:75771977:A:T	C34S	0.930
7:75769760:C:T	C73Y	0.917
7:75771907:C:T	C57Y	0.913
7:75771977:A:G	C34R	0.907
7:75771952:A:T	L42H	0.906
7:75771908:A:G	C57R	0.905
7:75771906:G:C	C57W	0.902
7:75769759:A:C	C73W	0.898
7:75769781:G:A	T66I	0.897
7:75771937:A:T	V47E	0.897
7:75769761:A:C	C73G	0.889
7:75771945:C:A	W44C	0.886
7:75771945:C:G	W44C	0.886

dbSNP variants (sampled 300 via entrez): RS1000016318 (7:75776145 C>G), RS1000069524 (7:75781705 C>G), RS1000389392 (7:75791713 G>C,T), RS1000671810 (7:75790760 G>A), RS1000815763 (7:75770312 C>T), RS1001395722 (7:75793031 G>A,T), RS1001477290 (7:75773128 C>T), RS1001758906 (7:75773428 G>A), RS1001811147 (7:75771636 A>G), RS1002410914 (7:75782807 A>C), RS1002463081 (7:75782611 C>T), RS1002891021 (7:75790445 C>T), RS1003171818 (7:75783584 G>C), RS1003276207 (7:75788554 C>G,T), RS1003424390 (7:75779889 C>T)

Disease associations

OMIM: gene MIM:604697 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST004162_11	Carotid plaque burden	9.000000e-06
GCST008361_9	Response to cognitive-behavioural therapy in major depressive disorder	6.000000e-06

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0006501	carotid plaque build
EFO:0007820	cognitive behavioural therapy

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Tobacco Smoke Pollution	affects expression, increases expression	5
sodium arsenite	increases expression, decreases expression	3
Valproic Acid	increases expression	3
Cadmium Chloride	decreases expression, increases expression	3
chloropicrin	increases expression	2
entinostat	increases expression, affects cotreatment	2
belinostat	increases expression, affects cotreatment	2
Resveratrol	increases expression, affects cotreatment, decreases expression	2
Panobinostat	affects cotreatment, increases expression	2
Cadmium	increases expression	2
Copper	affects binding, decreases expression, increases expression	2
Lipopolysaccharides	decreases expression, affects cotreatment, increases expression	2
Nickel	increases expression	2
Plant Extracts	increases abundance, affects cotreatment, decreases expression, decreases reaction	2
propionaldehyde	increases expression	1
lead acetate	increases expression	1
2-methyl-4-isothiazolin-3-one	increases expression	1
trichostatin A	increases expression	1
2-butenal	increases expression	1
arsenite	affects binding, increases reaction	1
trimellitic anhydride	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
zinc chloride	increases expression	1
butyraldehyde	increases expression	1
ceric oxide	affects cotreatment, increases expression	1
1-nitropyrene	decreases expression	1
S-(1,2-dichlorovinyl)cysteine	affects cotreatment, increases expression	1
gallium arsenide	increases expression	1
pentanal	increases expression	1
1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione	affects binding, decreases reaction, increases activity	1

Clinical trials (associated diseases)

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