CCL28

Summary

CCL28 (C-C motif chemokine ligand 28, HGNC:17700) is a protein-coding gene on chromosome 5p12, encoding C-C motif chemokine 28 (Q9NRJ3). Chemotactic activity for resting CD4, CD8 T-cells and eosinophils.

This antimicrobial gene belongs to the subfamily of small cytokine CC genes. 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 resting CD4 or CD8 T cells and eosinophils. The product of this gene binds to chemokine receptors CCR3 and CCR10. This chemokine may play a role in the physiology of extracutaneous epithelial tissues, including diverse mucosal organs. Multiple transcript variants encoding two different isoforms have been found for this gene.

Source: NCBI Gene 56477 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 22 total
• MANE Select transcript: NM_148672

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17700
Approved symbol	CCL28
Name	C-C motif chemokine ligand 28
Location	5p12
Locus type	gene with protein product
Status	Approved
Aliases	SCYA28, MEC, CCK1
Ensembl gene	ENSG00000151882
Ensembl biotype	protein_coding
OMIM	605240
Entrez	56477

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 2 protein_coding, 1 nonsense_mediated_decay, 1 retained_intron

ENST00000361115, ENST00000489442, ENST00000513525, ENST00000514421

RefSeq mRNA: 4 — MANE Select: NM_148672 NM_001301873, NM_001301874, NM_001301875, NM_148672

CCDS: CCDS3944, CCDS78006

Canonical transcript exons

ENST00000361115 — 3 exons

Exon	Start	End
ENSE00001489205	43412253	43412391
ENSE00001888938	43379193	43382052
ENSE00003589646	43388350	43388476

Expression profiles

Bgee: expression breadth ubiquitous, 202 present calls, max score 99.54.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 11.5480 / max 1657.5176, expressed in 1084 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
61561	8.3365	1071
61562	3.1512	77
61563	0.0604	19

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
parotid gland	UBERON:0001831	99.54	gold quality
pancreatic ductal cell	CL:0002079	97.45	gold quality
saliva-secreting gland	UBERON:0001044	96.23	gold quality
minor salivary gland	UBERON:0001830	95.39	gold quality
rectum	UBERON:0001052	92.83	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	92.55	gold quality
epithelial cell of pancreas	CL:0000083	92.01	silver quality
colonic mucosa	UBERON:0000317	91.91	gold quality
nasal cavity mucosa	UBERON:0001826	91.37	gold quality
epithelium of mammary gland	UBERON:0003244	91.31	gold quality
mucosa of sigmoid colon	UBERON:0004993	91.26	gold quality
mammary duct	UBERON:0001765	91.25	gold quality
mucosa of transverse colon	UBERON:0004991	91.15	gold quality
mouth mucosa	UBERON:0003729	90.47	gold quality
duodenum	UBERON:0002114	89.25	gold quality
trachea	UBERON:0003126	88.58	gold quality
mammary gland	UBERON:0001911	88.32	gold quality
thoracic mammary gland	UBERON:0005200	88.27	gold quality
gall bladder	UBERON:0002110	87.62	gold quality
thyroid gland	UBERON:0002046	86.25	gold quality
left lobe of thyroid gland	UBERON:0001120	86.12	gold quality
right lobe of thyroid gland	UBERON:0001119	85.65	gold quality
transverse colon	UBERON:0001157	85.55	gold quality
islet of Langerhans	UBERON:0000006	85.37	gold quality
ileal mucosa	UBERON:0000331	84.70	gold quality
palpebral conjunctiva	UBERON:0001812	84.53	gold quality
bronchial epithelial cell	CL:0002328	84.26	gold quality
bronchus	UBERON:0002185	84.12	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	82.98	gold quality
pancreas	UBERON:0001264	81.97	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-HCAD-1	yes	18.55
E-ENAD-27	yes	6.15
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

159 targeting CCL28, 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-4795-3P	100.00	74.62	4024
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-4425	100.00	67.59	1049
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-6758-5P	100.00	66.21	1470
HSA-MIR-6856-5P	100.00	65.47	1298
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-6891-5P	99.98	66.53	1372
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-548AA	99.96	70.64	3753

Literature-anchored findings (GeneRIF, showing 30)

• CCL28 may play dual roles in mucosal immunity as a chemoattractant for cells expressing CCR10 and/or CCR3 such as plasma cells and also as a broad-spectrum antimicrobial protein secreted into low-salt body fluids. (PMID:12538707)
• CCR10 and its mucosal epithelial ligand CCL28 have roles in the migration of circulating IgA plasmablasts (PMID:12671049)
• CCL28 produced by keratinocytes is mediated by different signal pathways from CCL27, and both CCL27 and CCL28 are involved in the pathogenesis of inflammatory skin diseases. (PMID:16433680)
• CCL28 is one link between microbial insult and the exacerbation of pathologies such as asthma, through an NFkappaB-dependent mechanism (PMID:16581045)
• Expression of CCL28 by epithelial cells from chronically inflamed liver in response to microbial products or interleukin-1 provides a signal to localize CCR10-expressing regulatory T cells at mucosal surfaces. (PMID:16785557)
• CCL28 mediates mucosal immunity in HIV exposure and infection (PMID:17912348)
• These studies are the first to show increased CCL28 production during gastrointestinal infection in humans and provide an explanation for the large influx of IgA-secreting cells to the gastric mucosa in H. pylori-infected individuals. (PMID:18426876)
• There was a robust migration of specific IgA- and IgM-antibody-secreting cells induced by Salmonella vaccination toward the mucosal chemokines CCL25 and CCL28 (PMID:19003934)
• data reinforce concept that CCL28 may contribute to the pathogenesis of atopic dermatitis probably through selective migration & infiltration of effector/memory T-helper-2 cells in the skin; CCL28 may represent a prognostic marker for disease severity (PMID:19659860)
• These results indicate a role for IL-17A in the human lung by enhancing the expression of CCL28 and hence driving the recruitment of IgE-secreting B cells. (PMID:21447959)
• tumour hypoxia promotes the recruitment of regulatory T (T(reg)) cells through induction of expression of the chemokine CC-chemokine ligand 28 (CCL28), which, in turn, promotes tumour tolerance and angiogenesis (PMID:21753853)
• CCL28 is a potent growth-promoting factor with the ability to support the in vitro and in vivo functional properties of cultured human hematopoietic cells. (PMID:23509159)
• CCL28-CCR3 interactions are involved in the homeostatic trafficking of CD4(+) T cells to the upper airways. (PMID:24917456)
• CCL28 was absent in saliva of primary Sjogren’s syndrome patients. This finding did not correlate with salivary IgA levels. (PMID:25567740)
• High CCL28 gene methylation is associated with gastric tumor aggressiveness. (PMID:25740824)
• disease severity of atopic dermatitis in children is not correlated to the level of CCL28, but rather related to that of total IgE (PMID:26642722)
• Results show that CCL28 expression was up-regulated under hypoxic condition in lung adenocarcinoma cells. Besides other effects on tumor biology such as immunosuppression, CCL28 could promote angiogenesis in lung adenocarcinoma by directly activating its receptor, CCR3, on microvascular endothelial cells. (PMID:27250766)
• HCC recruits Tregs to promote angiogenesis under hypoxic condition by upregulating CCL28 expression. These findings establish a link between Tregs and hypoxia in HCC growth and may provide a new potential therapeutic target for treating HCC. (PMID:27716621)
• our results show for the first time that CCL28 contributes to breast cancer progression through the ERK/MAPKmediated anti-apoptotic and metastatic signaling pathway. Antagonists of CCL28 and the MAPK signaling pathway may be used synergistically to treat breast cancer patients. (PMID:28713975)
• this review discusses the role of CCL28 in innate and adaptive immunity (PMID:28843907)
• Expression of Chemokine CCL28 in Ulcerative Colitis Patients. (PMID:32102131)
• Hypoxia Induces Overexpression of CCL28 to Recruit Treg Cells to Enhance Angiogenesis in Lung Adenocarcinoma. (PMID:33639074)
• Knockdown of CCL28 inhibits endometriosis stromal cell proliferation and invasion via ERK signaling pathway inactivation. (PMID:34913072)
• CCL28 Downregulation Attenuates Pancreatic Cancer Progression Through Tumor Cell-Intrinsic and -Extrinsic Mechanisms. (PMID:34939465)
• Serum CCL28 as a biomarker for diagnosis and evaluation of Sjogren’s syndrome. (PMID:35048789)
• Inhibition of CCL28/CCR10-Mediated eNOS Downregulation Improves Skin Wound Healing in the Obesity-Induced Mouse Model of Type 2 Diabetes. (PMID:35899992)
• Mucosal CCL28 Chemokine Improves Protection against Genital Herpes through Mobilization of Antiviral Effector Memory CCR10+CD44+ CD62L-CD8+ T Cells and Memory CCR10+B220+CD27+ B Cells into the Infected Vaginal Mucosa. (PMID:37222480)
• LncRNA H19 aggravates primary graft dysfunction after lung transplantation via KLF5-mediated activation of CCL28. (PMID:37394140)
• Analysis of the mucosal chemokines CCL28, CXCL14, and CXCL17 in dry eye disease: An in vitro and clinical investigation. (PMID:38453037)
• Pericytes recruited by CCL28 promote vascular normalization after anti-angiogenesis therapy through RA/RXRA/ANGPT1 pathway in lung adenocarcinoma. (PMID:39075504)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	ccl27a	ENSDARG00000058570
danio_rerio	ccl27b	ENSDARG00000079713
mus_musculus	Ccl28	ENSMUSG00000074715
rattus_norvegicus	Ccl28	ENSRNOG00000059640

Paralogs (1): CCL27 (ENSG00000213927)

Protein

Protein identifiers

C-C motif chemokine 28 — Q9NRJ3 (reviewed: Q9NRJ3)

Alternative names: Mucosae-associated epithelial chemokine, Protein CCK1, Small-inducible cytokine A28

All UniProt accessions (3): A0N0Q3, D6RC73, Q9NRJ3

UniProt curated annotations — full annotation on UniProt →

Function. Chemotactic activity for resting CD4, CD8 T-cells and eosinophils. Binds to CCR3 and CCR10 and induces calcium mobilization in a dose-dependent manner.

Subcellular location. Secreted.

Tissue specificity. Preferentially expressed by epithelial cells of diverse tissues including normal and pathological colon, salivary gland, mammary gland, trachea and rectum. Also found in prostate, spleen, thyroid, psoriasis skin and in lower levels in peripheral blood leukocytes, small intestine, Peyer patches, stomach and normal skin.

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

Isoforms (2)

UniProt ID	Names	Canonical?
Q9NRJ3-1	1	yes
Q9NRJ3-2	2, CCL28chi

RefSeq proteins (4): NP_001288802, NP_001288803, NP_001288804, NP_683513* (*=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 (18 total): strand 5, helix 2, turn 2, compositionally biased region 2, disulfide bond 2, signal peptide 1, chain 1, region of interest 1, glycosylation site 1, splice variant 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
6CWS	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NRJ3-F1	72.76	0.23

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): 30–58, 31–73

Glycosylation sites (1): 78

Function

Pathways and Gene Ontology

Reactome pathways

8 pathways

ID	Pathway
R-HSA-380108	Chemokine receptors bind chemokines
R-HSA-418594	G alpha (i) signalling events
R-HSA-162582	Signal Transduction
R-HSA-372790	Signaling by GPCR
R-HSA-373076	Class A/1 (Rhodopsin-like receptors)
R-HSA-375276	Peptide ligand-binding receptors
R-HSA-388396	GPCR downstream signalling
R-HSA-500792	GPCR ligand binding

MSigDB gene sets: 194 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_DN, GOBP_ANTIMICROBIAL_HUMORAL_RESPONSE, GOBP_MYELOID_LEUKOCYTE_MIGRATION, GOBP_CELL_CHEMOTAXIS, GOBP_INFLAMMATORY_RESPONSE, GOBP_CELLULAR_RESPONSE_TO_LIPID, GOCC_SECRETORY_GRANULE, GOBP_CELLULAR_RESPONSE_TO_BIOTIC_STIMULUS, GOZGIT_ESR1_TARGETS_DN, GOBP_NEGATIVE_REGULATION_OF_CELL_CELL_ADHESION, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, GOBP_REGULATION_OF_LEUKOCYTE_MIGRATION, GOBP_LEUKOCYTE_CHEMOTAXIS, GOBP_POSITIVE_REGULATION_OF_CELL_ADHESION, GOBP_CELL_CELL_ADHESION

GO Biological Process (12): positive regulation of cell-matrix adhesion (GO:0001954), chemotaxis (GO:0006935), inflammatory response (GO:0006954), positive regulation of cytosolic calcium ion concentration (GO:0007204), response to nutrient (GO:0007584), neutrophil chemotaxis (GO:0030593), cell chemotaxis (GO:0060326), antimicrobial humoral immune response mediated by antimicrobial peptide (GO:0061844), cellular response to lipopolysaccharide (GO:0071222), negative regulation of leukocyte tethering or rolling (GO:1903237), immune response (GO:0006955), signal transduction (GO:0007165)

GO Molecular Function (5): chemokine activity (GO:0008009), CXCR chemokine receptor binding (GO:0045236), cytokine activity (GO:0005125), protein binding (GO:0005515), chemokine receptor binding (GO:0042379)

GO Cellular Component (3): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), extracellular exosome (GO:0070062)

Reactome top-level categories

Rollup of top-6 pathways:

Category	Pathways
Signaling by GPCR	2
Peptide ligand-binding receptors	1
GPCR downstream signalling	1
Signal Transduction	1
GPCR ligand binding	1
Class A/1 (Rhodopsin-like receptors)	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
response to chemical	2
chemokine receptor binding	2
regulation of cell-matrix adhesion	1
cell-matrix adhesion	1
positive regulation of cell-substrate adhesion	1
taxis	1
defense response	1
regulation of biological quality	1
response to nutrient levels	1
granulocyte chemotaxis	1
neutrophil migration	1
chemotaxis	1
cell migration	1
cellular response to chemical stimulus	1
antimicrobial humoral response	1
response to lipopolysaccharide	1
cellular response to molecule of bacterial origin	1
cellular response to lipid	1
cellular response to oxygen-containing compound	1
negative regulation of cellular extravasation	1
leukocyte tethering or rolling	1
regulation of leukocyte tethering or rolling	1
negative regulation of leukocyte adhesion to vascular endothelial cell	1
immune system process	1
response to stimulus	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
cytokine activity	1
cell chemotaxis	1
receptor ligand activity	1
binding	1
G protein-coupled receptor binding	1
cytokine receptor binding	1
cellular anatomical structure	1
extracellular vesicle	1

Protein interactions and networks

STRING

506 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CCL28	CCK	P06307	995
CCL28	CCKAR	P32238	950
CCL28	GAST	P01350	923
CCL28	CCR10	P46092	882
CCL28	ACKR2	O00590	863
CCL28	PYY	P10082	737
CCL28	CRYGC	P07315	725
CCL28	CCR9	P51686	702
CCL28	CCKBR	P32239	697
CCL28	GCG	P01275	629
CCL28	ACKR4	Q9NPB9	601
CCL28	CXCR5	P32302	572
CCL28	GHRL	Q9UBU3	521
CCL28	NPY	P01303	480
CCL28	LEP	P41159	447

IntAct

54 interactions, top by confidence:

A	B	Type	Score
DDI1	CCL28	psi-mi:“MI:0915”(physical association)	0.830
CCL28	DDI1	psi-mi:“MI:0915”(physical association)	0.830
PSMA3	CCL28	psi-mi:“MI:0915”(physical association)	0.560
STUB1	CCL28	psi-mi:“MI:0915”(physical association)	0.560
CCL28	PSMA3	psi-mi:“MI:0915”(physical association)	0.560
CCL28	CCL5	psi-mi:“MI:0407”(direct interaction)	0.560
CCL28	PF4	psi-mi:“MI:0407”(direct interaction)	0.560
CCL28	CXCL12	psi-mi:“MI:0407”(direct interaction)	0.560
CCL28	CCL17	psi-mi:“MI:0407”(direct interaction)	0.560
CCL17	CCL28	psi-mi:“MI:0407”(direct interaction)	0.560
PF4	CCL28	psi-mi:“MI:0407”(direct interaction)	0.560
DYNLT3	CCL28	psi-mi:“MI:0915”(physical association)	0.560
TSC1	CCL28	psi-mi:“MI:0915”(physical association)	0.560
crmD	CCL28	psi-mi:“MI:0407”(direct interaction)	0.440
OPG002	CCL28	psi-mi:“MI:0407”(direct interaction)	0.440
CCL28	CCL11	psi-mi:“MI:0407”(direct interaction)	0.440
CCL28	CCL13	psi-mi:“MI:0407”(direct interaction)	0.440
CCL28	CCL21	psi-mi:“MI:0407”(direct interaction)	0.440
CCL28	CCL26	psi-mi:“MI:0407”(direct interaction)	0.440

BioGRID (33): CCL28 (Two-hybrid), CCL28 (Two-hybrid), DDI1 (Two-hybrid), CCL28 (Two-hybrid), DYNLT3 (Two-hybrid), TSC1 (Two-hybrid), DDI1 (Two-hybrid), CCL28 (Reconstituted Complex), CCL28 (Reconstituted Complex), CCL28 (Reconstituted Complex), CCL28 (Reconstituted Complex), CCL28 (Reconstituted Complex), CCL11 (Reconstituted Complex), CCL13 (Reconstituted Complex), CCL17 (Reconstituted Complex)

ESM2 similar proteins: A0MTF4, A4FUY1, A8MVS5, M3X9S6, O15444, O18796, O35793, O54693, O60565, O70326, O73754, O73755, P01344, P01346, P07456, P09535, P10764, P12034, P15656, P17085, P19438, P48540, P48807, P50555, P51459, Q02815, Q07731, Q14CZ8, Q20FD0, Q3TMX7, Q4PR21, Q5BJT4, Q640R3, Q68A91, Q6P6J9, Q70EL4, Q7TSQ1, Q7Z692, Q86Y78, Q8R0A6

Diamond homologs: Q68A91, Q9JIL2, Q9NRJ3, Q9Y4X3, Q9Z1X0

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 26 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	14	145.6×	1e-27
Class A/1 (Rhodopsin-like receptors)	6	24.7×	2e-06
Peptide ligand-binding receptors	6	24.7×	2e-06
G alpha (i) signalling events	10	21.6×	2e-10
GPCR ligand binding	6	21.4×	4e-06
Signaling by GPCR	6	13.4×	6e-05

GO biological processes:

GO term	Partners	Fold	FDR
chemokine-mediated signaling pathway	12	169.1×	7e-23
eosinophil chemotaxis	5	159.3×	3e-09
neutrophil chemotaxis	8	99.3×	4e-13
antimicrobial humoral immune response mediated by antimicrobial peptide	12	84.5×	3e-19
chemotaxis	10	59.1×	2e-14
cell chemotaxis	7	56.4×	1e-09
cell-cell signaling	10	30.3×	1e-11
cellular response to lipopolysaccharide	6	25.6×	2e-06

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	17
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

511 predictions. Top by Δscore:

Variant	Effect	Δscore
5:43388348:A:AC	donor_gain	1.0000
5:43388349:C:CC	donor_gain	1.0000
5:43388474:TGG:T	acceptor_gain	1.0000
5:43412248:CTCA:C	donor_loss	1.0000
5:43412249:TCA:T	donor_loss	1.0000
5:43412250:CA:C	donor_loss	1.0000
5:43412252:C:CG	donor_loss	1.0000
5:43382049:AAGG:A	acceptor_gain	0.9900
5:43382051:GG:G	acceptor_gain	0.9900
5:43382052:GC:G	acceptor_loss	0.9900
5:43382053:C:CA	acceptor_loss	0.9900
5:43382053:C:CC	acceptor_gain	0.9900
5:43382056:T:C	acceptor_gain	0.9900
5:43382056:T:TC	acceptor_gain	0.9900
5:43388342:GCAC:G	donor_loss	0.9900
5:43388343:CACTC:C	donor_loss	0.9900
5:43388344:ACTCA:A	donor_loss	0.9900
5:43388345:C:CT	donor_loss	0.9900
5:43388346:T:TA	donor_loss	0.9900
5:43388347:C:CC	donor_loss	0.9900
5:43388348:A:AT	donor_loss	0.9900
5:43388349:C:A	donor_loss	0.9900
5:43388349:CATGA:C	donor_gain	0.9900
5:43388472:TATGG:T	acceptor_gain	0.9900
5:43388473:ATGG:A	acceptor_gain	0.9900
5:43388475:GG:G	acceptor_gain	0.9900
5:43388475:GGCTA:G	acceptor_loss	0.9900
5:43388476:GCTA:G	acceptor_loss	0.9900
5:43388477:C:CC	acceptor_gain	0.9900
5:43388477:CT:C	acceptor_loss	0.9900

AlphaMissense

842 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:43388368:C:G	C58S	0.990
5:43388369:A:T	C58S	0.990
5:43381992:C:A	W84C	0.988
5:43381992:C:G	W84C	0.988
5:43382026:C:G	C73S	0.987
5:43382027:A:T	C73S	0.987
5:43388356:G:T	A62D	0.987
5:43382027:A:G	C73R	0.986
5:43388368:C:T	C58Y	0.986
5:43382026:C:T	C73Y	0.985
5:43388368:C:A	C58F	0.984
5:43382025:A:C	C73W	0.981
5:43388369:A:G	C58R	0.981
5:43388449:C:G	C31S	0.981
5:43388449:C:T	C31Y	0.981
5:43388450:A:T	C31S	0.981
5:43388385:C:A	Q52H	0.980
5:43388385:C:G	Q52H	0.980
5:43388367:A:C	C58W	0.978
5:43388353:A:T	V63D	0.976
5:43388448:G:C	C31W	0.975
5:43388453:A:G	C30R	0.975
5:43388450:A:G	C31R	0.974
5:43382050:A:T	L65H	0.973
5:43388452:C:T	C30Y	0.973
5:43382026:C:A	C73F	0.972
5:43382023:A:T	V74D	0.971
5:43388452:C:G	C30S	0.968
5:43388453:A:T	C30S	0.968
5:43381994:A:G	W84R	0.965

dbSNP variants (sampled 300 via entrez): RS1000028138 (5:43360048 C>T), RS1000082254 (5:43399961 T>G), RS1000099907 (5:43403766 A>T), RS1000148948 (5:43412039 T>C), RS1000259522 (5:43405410 A>G), RS1000319609 (5:43365681 T>G), RS1000402664 (5:43378539 A>G), RS1000421964 (5:43405666 T>C,G), RS1000431930 (5:43411811 A>G), RS1000484456 (5:43359829 C>A,T), RS1000502327 (5:43356735 C>G,T), RS1000512176 (5:43380492 C>G), RS1000656491 (5:43373585 C>A), RS1000721901 (5:43387855 G>A), RS1000730923 (5:43384682 A>G)

Disease associations

OMIM: gene MIM:605240 | 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
GCST002119_18	Metabolite levels (X-11787)	4.000000e-07
GCST003265_399	Post bronchodilator FEV1/FVC ratio in COPD	1.000000e-06

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0005276	hydroxy-leucine measurement
EFO:0004713	FEV/FVC ratio

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

25 total (human), top 25 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases expression	2
Ozone	affects expression, increases abundance, increases expression	2
aristolochic acid I	decreases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	affects cotreatment, increases methylation, decreases methylation	1
decabromobiphenyl ether	affects expression	1
nickel sulfate	decreases expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression, affects cotreatment, decreases expression	1
cobalt oxide	increases expression	1
bisphenol S	decreases expression	1
Resveratrol	decreases expression, affects cotreatment	1
Zoledronic Acid	increases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Air Pollutants	affects expression, increases abundance	1
Arsenic	affects expression	1
Cadmium	decreases expression, increases abundance	1
Copper	decreases expression, affects cotreatment	1
Dimethyl Sulfoxide	affects expression	1
Hydralazine	affects cotreatment, increases expression	1
Lipopolysaccharides	decreases expression, affects response to substance, increases expression, affects cotreatment	1
Nickel	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Valproic Acid	affects cotreatment, increases expression	1
Aflatoxin B1	increases methylation	1
Cadmium Chloride	decreases expression, increases abundance	1

Clinical trials (associated diseases)

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