MARCO

Summary

MARCO (macrophage receptor with collagenous structure, HGNC:6895) is a protein-coding gene on chromosome 2q14.2, encoding Macrophage receptor MARCO (Q9UEW3). Pattern recognition receptor (PRR) which binds Gram-positive and Gram-negative bacteria.

The protein encoded by this gene is a member of the class A scavenger receptor family and is part of the innate antimicrobial immune system. The protein may bind both Gram-negative and Gram-positive bacteria via an extracellular, C-terminal, scavenger receptor cysteine-rich (SRCR) domain. In addition to short cytoplasmic and transmembrane domains, there is an extracellular spacer domain and a long, extracellular collagenous domain. The protein may form a trimeric molecule by the association of the collagenous domains of three identical polypeptide chains.

Source: NCBI Gene 8685 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 85 total — 1 pathogenic
• MANE Select transcript: NM_006770

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6895
Approved symbol	MARCO
Name	macrophage receptor with collagenous structure
Location	2q14.2
Locus type	gene with protein product
Status	Approved
Aliases	SCARA2, SR-A6
Ensembl gene	ENSG00000019169
Ensembl biotype	protein_coding
OMIM	604870
Entrez	8685

Gene structure

Transcript identifiers

Ensembl transcripts: 26 — 25 protein_coding, 1 retained_intron

ENST00000327097, ENST00000412481, ENST00000494979, ENST00000874349, ENST00000874350, ENST00000874351, ENST00000874352, ENST00000874353, ENST00000874354, ENST00000874355, ENST00000874356, ENST00000874357, ENST00000874358, ENST00000874359, ENST00000958823, ENST00000958824, ENST00000958825, ENST00000958826, ENST00000958827, ENST00000958828, ENST00000958829, ENST00000958830, ENST00000958831, ENST00000958832, ENST00000958833, ENST00000958834

RefSeq mRNA: 1 — MANE Select: NM_006770 NM_006770

CCDS: CCDS2124

Canonical transcript exons

ENST00000327097 — 17 exons

Exon	Start	End
ENSE00000559968	118981409	118981507
ENSE00000774693	118974521	118974565
ENSE00000774694	118977471	118977515
ENSE00000774701	118981621	118981656
ENSE00000774707	118990589	118990633
ENSE00000774709	118992432	118992476
ENSE00000774710	118993124	118993300
ENSE00000857064	118994387	118994660
ENSE00000963699	118977828	118977935
ENSE00000963700	118982156	118982254
ENSE00000963701	118982348	118982410
ENSE00000963702	118991777	118991875
ENSE00000963703	118974333	118974440
ENSE00001020593	118942194	118942397
ENSE00001406468	118971499	118971534
ENSE00003651151	118969160	118969261
ENSE00003680366	118970114	118970338

Expression profiles

Bgee: expression breadth ubiquitous, 186 present calls, max score 95.64.

FANTOM5 (CAGE): breadth broad, TPM avg 5.3156 / max 1197.6881, expressed in 320 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
22249	3.7206	252
22245	0.8043	181
22247	0.5151	136
22248	0.1939	63
22246	0.0816	37

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right lung	UBERON:0002167	95.64	gold quality
upper lobe of left lung	UBERON:0008952	95.63	gold quality
upper lobe of lung	UBERON:0008948	94.48	gold quality
visceral pleura	UBERON:0002401	93.26	gold quality
layer of synovial tissue	UBERON:0007616	92.20	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	90.32	gold quality
synovial joint	UBERON:0002217	90.32	gold quality
monocyte	CL:0000576	90.26	gold quality
lung	UBERON:0002048	89.64	gold quality
pleura	UBERON:0000977	89.59	gold quality
mononuclear cell	CL:0000842	89.24	gold quality
parietal pleura	UBERON:0002400	89.05	gold quality
leukocyte	CL:0000738	88.86	gold quality
lower lobe of lung	UBERON:0008949	88.33	gold quality
liver	UBERON:0002107	87.14	gold quality
right atrium auricular region	UBERON:0006631	87.00	gold quality
omental fat pad	UBERON:0010414	86.19	gold quality
peritoneum	UBERON:0002358	86.11	gold quality
cardiac atrium	UBERON:0002081	85.55	gold quality
spleen	UBERON:0002106	85.50	gold quality
adipose tissue of abdominal region	UBERON:0007808	85.37	gold quality
granulocyte	CL:0000094	85.29	gold quality
right adrenal gland	UBERON:0001233	85.25	gold quality
germinal epithelium of ovary	UBERON:0001304	84.71	gold quality
right lobe of liver	UBERON:0001114	84.67	gold quality
amniotic fluid	UBERON:0000173	84.52	gold quality
tendon of biceps brachii	UBERON:0008188	84.51	gold quality
lymph node	UBERON:0000029	83.66	gold quality
right adrenal gland cortex	UBERON:0035827	83.58	gold quality
pericardium	UBERON:0002407	83.07	gold quality

Single-cell (SCXA)

Detected in 15 experiment(s), a significant marker in 14.

Experiment	Marker?	Max mean expression
E-GEOD-130148	yes	4190.77
E-MTAB-8322	yes	3640.56
E-MTAB-6308	yes	3240.39
E-MTAB-8495	yes	2696.79
E-HCAD-9	yes	2220.15
E-HCAD-15	yes	2138.44
E-CURD-126	yes	1836.07
E-MTAB-6653	yes	1806.14
E-MTAB-7407	yes	1797.87
E-HCAD-1	yes	84.16
E-CURD-122	yes	77.79
E-MTAB-8142	yes	47.83
E-MTAB-10553	yes	31.72
E-ANND-3	yes	23.64
E-HCAD-30	no	34.63

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

5 targeting MARCO, 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-188-3P	100.00	68.76	1240
HSA-MIR-3919	99.87	69.45	2489
HSA-MIR-6081	99.48	66.07	1446
HSA-MIR-767-3P	98.61	67.69	1192
HSA-MIR-27B-5P	97.34	66.55	549

Literature-anchored findings (GeneRIF, showing 40)

• An arginine-rich segment in domain V of MARCO and particularly its RXR motifs play a critical role in high-affinity bacterial binding. (PMID:11820786)
• characterization of a MARCO protein domain involved in binding to bacteria (PMID:12097327)
• Northern blot and in situ hybridization experiments indicate that MARCO is expressed by alveolar macrophages in the lung; retroviral vector-mediated expression cloning determines that MARCO is a receptor for UGRP1. (PMID:12847263)
• a dominant role for MARCO in the human AM defense against inhaled particles and pathogens. (PMID:16237101)
• Expansion of small sputum macrophages in cystic fibrosis shows a failure to express MARCO and CD206. (PMID:19403625)
• MARCO is an important phagocytic receptor used by human and mouse macrophages to clear C. sordellii from the infected uterus (PMID:20810988)
• Data suggest that bacteria induce glial cell activation and rCRAMP expression via FPRL1 and MARCO, and these receptors contribute to the host defence against infection. (PMID:21299846)
• genetic variants in MARCO gene were associated with pulmonary tuberculosis susceptibility in Chinese Han population (PMID:21886847)
• These results demonstrate that the S. mutans lipoprotein PpiA contributes to suppression of MARCO-mediated phagocytosis of this bacterium by macrophages. (PMID:21986627)
• In this review, we showed that SR-A and MARCO trigger intracellular signaling, modulating pro-inflammatory and microbicidal activities of macrophages. (PMID:22470185)
• This review demonstrated that class A SR and MARCO are major pattern recognition receptors mediating opsonin-independent phagocytosis. (PMID:22470186)
• We identified 9 non-synonymous variants in the MARCO gene and showed that these variants are not major risk factors for COPD or lung infection. H101Q heterozygotes had increased sepsis risk. (PMID:23154236)
• Significant associations of four SNPs and haplotypes with antibody response to cholera vaccine in three genes, MARCO, TNFAIP3 and CXCL12. (PMID:23249958)
• Polymorphisms within the human class A scavenger receptor MARCO correlate with susceptibility/resistance to tuberculosis in a Gambian population. (PMID:23617307)
• herpes simplex virus type 1 binds to MARCO to enhance its capacity for disease. (PMID:23739639)
• Vaccinia virus bound directly to MARCO, and overexpression of MARCO increased susceptibility to vaccinia infection. (PMID:25089661)
• None of the nonsynonymous variants discovered by resequencing of the structurally similar MARCO were associated with lung function or risk of COPD. (PMID:25186548)
• identified as a disease-associated molecule in IgG4-related disease by DNA microarray (PMID:26886650)
• These data suggest the SRCR domain of MARCO is the key domain in modulating ligand binding, enhancing downstream pro-inflammatory signaling and MARCO-mediated cellular adhesion. (PMID:26888252)
• Identifying N-linked glycan moiety and motifs in the cysteine-rich domain critical for N-glycosylation and intracellular trafficking of SR-AI and MARCO. (PMID:26892079)
• this translational investigation identified gene candidates, including Marco, for host susceptibility to multiple phenotypes of RSV disease in mice that closely mimic human disease, and a polymorphism in human MARCO associated with increased risk of RSV disease severity in infants. (PMID:27554839)
• this paper shows that key gene of intermediate proinflammatory monocytes, such as MARCO, is expressed three- to fourfold more in juvenile idiopathic arthritis-enthesitis-related arthritis (PMID:27706807)
• Expression of MARCO declined progressively as hepatocellular carcinoma condition is aggravated. (PMID:27806438)
• results suggest that MARCO polymorphisms may regulate phagocytosis of M. tuberculosis and susceptibility and severity of pulmonary tuberculosis (PMID:27853145)
• this study shows that MARCO modulates inflammatory responses against Cryptococcus neoformans infection (PMID:28298522)
• Increasing MARCO expression by targeting Nrf2 signaling or the Akt-TFEB-MARCO pathway are promising strategies to improve bacterial clearance and survival in postinfluenza bacterial pneumonia. (PMID:28408365)
• MARCO single nucleotide polymorphisms rs12998782 increases risk to pulmonary tuberculosis in a Chinese Han population. (PMID:28693442)
• CD36 and MARCO are associated with the susceptibility of Chinese Han females to carotid atherosclerosis. Menopausal status may affect the association between gene polymorphisms and carotid atherosclerosis in the female Chinese Han population. (PMID:28866086)
• Q452 and F282 are important for ligand association and phagocytosis of bacteria. Q452 and F282 are examples of positively selected mutations in MARCO, and both enhance the intrinsic function of the receptor. (PMID:29165618)
• High surface expression of SR-A6 facilitates HAdV-C5 infection. (PMID:29522575)
• the absence of MARCO does not interfere with the efficiency of HSV-1 entry and that the inhibitory effect on viral adsorption by poly(I), a ligand of MARCO, is independent of MARCO. (PMID:29769337)
• MARCO is involved in hepatocellular carcinoma (HCC)progression and it can be defined as a novel probable biomarker as well as treatment target for HCC. (PMID:31381879)
• Genetic Susceptibility to Life-threatening Respiratory Syncytial Virus Infection in Previously Healthy Infants. (PMID:32740454)
• Targeting MARCO and IL37R on Immunosuppressive Macrophages in Lung Cancer Blocks Regulatory T Cells and Supports Cytotoxic Lymphocyte Function. (PMID:33293426)
• Scavenger receptor MARCO contributes to cellular internalization of exosomes by dynamin-dependent endocytosis and macropinocytosis. (PMID:33311558)
• Binding of Macrophage Receptor MARCO, LDL, and LDLR to Disease-Associated Crystalline Structures. (PMID:33363539)
• Single-cell characterization of macrophages in glioblastoma reveals MARCO as a mesenchymal pro-tumor marker. (PMID:34011400)
• TLR2 Potentiates SR-Marco-Mediated Neuroinflammation by Interacting with the SRCR Domain. (PMID:34398403)
• Scavenger receptor MARCO contributes to macrophage phagocytosis and clearance of tumor cells. (PMID:34626585)
• Association of the MARCO polymorphism rs6761637 with hepatocellular carcinoma susceptibility and clinical characteristics. (PMID:35364781)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Marco	ENSMUSG00000026390
rattus_norvegicus	Marco	ENSRNOG00000049303

Paralogs (3): MSR1 (ENSG00000038945), COLEC12 (ENSG00000158270), SCARA5 (ENSG00000168079)

Protein

Protein identifiers

Macrophage receptor MARCO — Q9UEW3 (reviewed: Q9UEW3)

Alternative names: Macrophage receptor with collagenous structure, Scavenger receptor class A member 2

All UniProt accessions (3): C9JKT8, Q9UEW3, Q4ZG40

UniProt curated annotations — full annotation on UniProt →

Function. Pattern recognition receptor (PRR) which binds Gram-positive and Gram-negative bacteria. Also plays a role in binding of unopsonized particles by alveolar macrophages. Binds to the secretoglobin SCGB3A2.

Subunit / interactions. Homotrimer; disulfide-linked. Trimers may assemble in larger oligomers thus resulting in the creation of a large surface capable of interacting with very large ligands.

Subcellular location. Cell membrane.

Tissue specificity. Expressed in alveolar macrophages (at protein level). Detected in macrophages from various tissues including thymus, kidney, Kupffer cells of liver, and spleen.

Post-translational modifications. N-glycosylated.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9UEW3-1	1	yes
Q9UEW3-2	2

RefSeq proteins (1): NP_006761* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001190	SRCR	Domain
IPR008160	Collagen	Repeat
IPR036772	SRCR-like_dom_sf	Homologous_superfamily
IPR050149	Collagen_superfamily	Family

Pfam: PF00530, PF01391

UniProt features (19 total): compositionally biased region 4, disulfide bond 3, topological domain 2, glycosylation site 2, domain 2, chain 1, splice variant 1, sequence variant 1, sequence conflict 1, transmembrane region 1, region of interest 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UEW3-F1	59.73	0.24

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 (3): 447–508, 460–518, 488–498

Glycosylation sites (2): 83, 136

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-3000480	Scavenging by Class A Receptors
R-HSA-2173782	Binding and Uptake of Ligands by Scavenger Receptors
R-HSA-5653656	Vesicle-mediated transport

MSigDB gene sets: 203 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_MCMV_INFECTION_UP, GOCC_COLLAGEN_TRIMER, GOBP_POSITIVE_REGULATION_OF_MAPK_CASCADE, GOBP_APOPTOTIC_CELL_CLEARANCE, GOBP_VESICLE_MEDIATED_TRANSPORT, ACEVEDO_LIVER_CANCER_WITH_H3K27ME3_UP, GOBP_ADENYLATE_CYCLASE_MODULATING_G_PROTEIN_COUPLED_RECEPTOR_SIGNALING_PATHWAY, GOBP_DEFENSE_RESPONSE_TO_OTHER_ORGANISM, FOSTER_TOLERANT_MACROPHAGE_DN, HOWLIN_PUBERTAL_MAMMARY_GLAND, CAIRO_HEPATOBLASTOMA_DN, MODULE_99, COATES_MACROPHAGE_M1_VS_M2_UP, GOBP_POSITIVE_REGULATION_OF_INTRACELLULAR_SIGNAL_TRANSDUCTION, RYTTCCTG_ETS2_B

GO Biological Process (10): receptor-mediated endocytosis (GO:0006898), phagocytosis, engulfment (GO:0006911), cell surface receptor signaling pathway (GO:0007166), adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway (GO:0007193), apoptotic cell clearance (GO:0043277), innate immune response (GO:0045087), positive regulation of ERK1 and ERK2 cascade (GO:0070374), amyloid-beta clearance (GO:0097242), immune system process (GO:0002376), endocytosis (GO:0006897)

GO Molecular Function (5): amyloid-beta binding (GO:0001540), G protein-coupled receptor binding (GO:0001664), transmembrane signaling receptor activity (GO:0004888), cargo receptor activity (GO:0038024), pattern recognition receptor activity (GO:0038187)

GO Cellular Component (5): collagen trimer (GO:0005581), cytoplasm (GO:0005737), plasma membrane (GO:0005886), endocytic vesicle membrane (GO:0030666), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Binding and Uptake of Ligands by Scavenger Receptors	1
Vesicle-mediated transport	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
phagocytosis	2
vesicle-mediated transport	2
signaling receptor activity	2
cellular anatomical structure	2
endocytosis	1
plasma membrane invagination	1
signal transduction	1
adenylate cyclase-modulating G protein-coupled receptor signaling pathway	1
adenylate cyclase inhibitor activity	1
immune response	1
defense response to symbiont	1
positive regulation of MAPK cascade	1
ERK1 and ERK2 cascade	1
regulation of ERK1 and ERK2 cascade	1
multicellular organismal process	1
biological_process	1
vesicle budding from membrane	1
membrane invagination	1
import into cell	1
peptide binding	1
signaling receptor binding	1
molecular_function	1
molecular adaptor activity	1
protein-containing complex	1
intracellular anatomical structure	1
membrane	1
cell periphery	1
endocytic vesicle	1
cytoplasmic vesicle membrane	1
bounding membrane of organelle	1

Protein interactions and networks

STRING

1276 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MARCO	TLR2	O60603	754
MARCO	FPR1	P21462	525
MARCO	SCARB1	Q8WTV0	507
MARCO	COLEC12	Q5KU26	506
MARCO	CD36	P16671	475
MARCO	SCARB2	Q14108	471
MARCO	MRC1	P22897	436
MARCO	DHRS4	Q9BTZ2	429
MARCO	PDIA5	Q14554	411
MARCO	SIGLEC1	Q9BZZ2	400
MARCO	RRAD	P55042	396
MARCO	CD68	P34810	377
MARCO	MED20	Q9H944	370
MARCO	SRA1	Q9HD15	370
MARCO	OLR1	P78380	368
MARCO	IL10	P22301	368

IntAct

6 interactions, top by confidence:

A	B	Type	Score
APP	MARCO	psi-mi:“MI:0407”(direct interaction)	0.440
MARCO	PLOD3	psi-mi:“MI:0915”(physical association)	0.400
MARCO	NEC2	psi-mi:“MI:0915”(physical association)	0.370
MARCO	NEC1	psi-mi:“MI:0915”(physical association)	0.370
M		psi-mi:“MI:0914”(association)	0.350

BioGRID (9): DDX55 (Co-fractionation), SCGB3A2 (FRET), SCGB3A1 (FRET), PLOD3 (Affinity Capture-MS), UBE2I (Cross-Linking-MS (XL-MS)), MARCO (Cross-Linking-MS (XL-MS)), MARCO (Cross-Linking-MS (XL-MS)), LDHA (Cross-Linking-MS (XL-MS)), MARCO (Two-hybrid)

ESM2 similar proteins: A8WR59, C0HJB4, C0HLL1, C0HLN2, C0HLQ6, C0HM51, E2IYB3, O35167, O35348, O76368, P02456, P08125, P12114, P14282, P18856, P20850, P20909, P22800, P23206, P23805, P25067, P25318, P25508, P27658, P30251, P30252, P53420, P55787, P56683, P58522, P81130, P86290, Q00780, Q03637, Q05306, Q07643, Q14031, Q14055, Q28084, Q60754

Diamond homologs: A1L0T3, A1L1V4, A1L4H1, A5PJQ2, A6H737, A7E3W2, B4F6N6, B5DF27, B8A4W9, E1C3U7, F1QQC3, F1RD85, F7J220, G3V801, M9NDE3, O08762, O43866, O70513, P21757, P21758, P30203, P30204, P30205, P56730, P58022, P58215, P70117, P85521, Q05585, Q07797, Q08380, Q08B63, Q14DK5, Q24JV9, Q2VL90, Q2VLG4, Q2VLG6, Q2VLH6, Q4A3R3, Q4G0T1

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
HOOK3	down-regulates	MARCO	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	59
Likely benign	9
Benign	1

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
814297	GRCh37/hg19 2q14.2-14.3(chr2:118872395-128069813)x1	Pathogenic

SpliceAI

2910 predictions. Top by Δscore:

Variant	Effect	Δscore
2:118974328:CTCA:C	acceptor_loss	1.0000
2:118974331:A:AG	acceptor_gain	1.0000
2:118974332:G:GC	acceptor_gain	1.0000
2:118974332:GGT:G	acceptor_gain	1.0000
2:118974332:GGTC:G	acceptor_gain	1.0000
2:118974437:ACAGG:A	donor_loss	1.0000
2:118974438:CAGGT:C	donor_loss	1.0000
2:118974439:AGGT:A	donor_loss	1.0000
2:118974440:GGT:G	donor_loss	1.0000
2:118974441:G:GG	donor_gain	1.0000
2:118974441:GTACG:G	donor_loss	1.0000
2:118981751:T:TA	donor_gain	1.0000
2:118981752:A:AA	donor_gain	1.0000
2:118993120:CCAG:C	acceptor_loss	1.0000
2:118993121:CAG:C	acceptor_loss	1.0000
2:118993123:G:GT	acceptor_loss	1.0000
2:118993274:G:GT	donor_gain	1.0000
2:118993297:GCTG:G	donor_gain	1.0000
2:118993300:GGTA:G	donor_loss	1.0000
2:118993302:T:A	donor_loss	1.0000
2:118993305:G:GG	donor_gain	1.0000
2:118942403:G:GG	donor_gain	0.9900
2:118969158:A:AG	acceptor_gain	0.9900
2:118969159:G:GA	acceptor_gain	0.9900
2:118971498:GGGAT:G	acceptor_gain	0.9900
2:118974327:CCTCA:C	acceptor_gain	0.9900
2:118974328:CTCAG:C	acceptor_gain	0.9900
2:118974329:TCAG:T	acceptor_gain	0.9900
2:118974330:CAGGT:C	acceptor_gain	0.9900
2:118974331:AG:A	acceptor_gain	0.9900

AlphaMissense

3325 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:118993200:G:C	W443C	0.999
2:118993200:G:T	W443C	0.999
2:118993224:G:C	W451C	0.999
2:118993224:G:T	W451C	0.999
2:118994419:T:A	C488S	0.999
2:118994420:G:C	C488S	0.999
2:118993211:G:A	C447Y	0.998
2:118994419:T:C	C488R	0.998
2:118994509:T:A	C518S	0.998
2:118994510:G:C	C518S	0.998
2:118993210:T:A	C447S	0.997
2:118993211:G:C	C447S	0.997
2:118993212:C:G	C447W	0.997
2:118993249:T:A	C460S	0.997
2:118993250:G:C	C460S	0.997
2:118993251:C:G	C460W	0.997
2:118994449:T:A	C498S	0.997
2:118994450:G:C	C498S	0.997
2:118994509:T:C	C518R	0.997
2:118993250:G:A	C460Y	0.996
2:118994408:A:T	D484V	0.996
2:118994421:T:G	C488W	0.996
2:118994466:G:C	W503C	0.996
2:118994466:G:T	W503C	0.996
2:118994479:T:A	C508S	0.996
2:118994480:G:C	C508S	0.996
2:118993210:T:C	C447R	0.995
2:118993211:G:T	C447F	0.995
2:118993249:T:C	C460R	0.995
2:118994420:G:A	C488Y	0.995

dbSNP variants (sampled 300 via entrez): RS1000014732 (2:118956381 G>A,T), RS1000076074 (2:118962262 G>A,T), RS1000128176 (2:118962032 C>T), RS1000152272 (2:118951189 C>T), RS1000153657 (2:118990139 C>A,T), RS1000197324 (2:118986897 G>A), RS1000200198 (2:118992956 A>G), RS1000380601 (2:118945574 G>A), RS1000435332 (2:118951487 T>C), RS1000445214 (2:118949074 T>C), RS1000501381 (2:118989114 A>C), RS1000542587 (2:118994137 T>A,G), RS1000599091 (2:118958085 G>A,T), RS1000618457 (2:118973158 T>C), RS1000649474 (2:118978888 T>C)

Disease associations

OMIM: gene MIM:604870 | 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
GCST006483_12	Lung function (FVC)	4.000000e-08
GCST007941_41	Medication use (adrenergics, inhalants)	7.000000e-09
GCST010244_374	Triglyceride levels	7.000000e-11

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004312	vital capacity
EFO:0009941	Inhalant adrenergic use measurement
EFO:0004530	triglyceride measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases expression	2
Allergens	increases expression, decreases expression, affects cotreatment	2
Benzo(a)pyrene	affects methylation, increases expression, increases methylation	2
Silicon Dioxide	increases expression, affects binding	2
titanium dioxide	affects binding, increases reaction	1
butyraldehyde	increases expression	1
3,4,5,3’,4’-pentachlorobiphenyl	decreases expression	1
benzo(e)pyrene	increases methylation	1
S-(1,2-dichlorovinyl)cysteine	decreases reaction, increases expression	1
CGP 52608	affects binding, increases reaction	1
2,2’,4,4’-tetrabromodiphenyl ether	increases expression	1
jinfukang	affects cotreatment, increases expression	1
gardiquimod	decreases reaction, increases expression	1
(+)-JQ1 compound	decreases expression	1
Air Pollutants	increases abundance, increases expression	1
Vehicle Emissions	affects cotreatment, increases expression	1
Calcium	affects binding, increases reaction	1
Carcinogens	decreases expression	1
Cisplatin	affects cotreatment, increases expression	1
Drugs, Chinese Herbal	increases expression	1
Lipopolysaccharides	increases expression, decreases reaction	1
Magnesium	affects binding, increases reaction	1
Methapyrilene	increases methylation	1
Mutagens	decreases expression	1
Naphthoquinones	increases expression	1
Smoke	decreases expression	1
Valproic Acid	decreases methylation	1
Aflatoxin B1	decreases methylation	1
Medroxyprogesterone Acetate	increases expression	1
Antirheumatic Agents	decreases expression	1

Clinical trials (associated diseases)

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