MIA

Summary

MIA (MIA SH3 domain containing, HGNC:7076) is a protein-coding gene on chromosome 19q13.2, encoding Melanoma-derived growth regulatory protein (Q16674). Elicits growth inhibition on melanoma cells in vitro as well as some other neuroectodermal tumors, including gliomas.

Predicted to enable growth factor activity. Predicted to be involved in extracellular matrix organization. Predicted to act upstream of or within cell-matrix adhesion. Predicted to be located in extracellular space.

Source: NCBI Gene 8190 — RefSeq curated summary.

At a glance

• GWAS associations: 26
• Clinical variants (ClinVar): 18 total
• MANE Select transcript: NM_006533

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:7076
Approved symbol	MIA
Name	MIA SH3 domain containing
Location	19q13.2
Locus type	gene with protein product
Status	Approved
Aliases	CD-RAP, MIA1
Ensembl gene	ENSG00000261857
Ensembl biotype	protein_coding
OMIM	601340
Entrez	8190

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 7 protein_coding, 1 retained_intron, 1 nonsense_mediated_decay

ENST00000263369, ENST00000593317, ENST00000594436, ENST00000597140, ENST00000597600, ENST00000597784, ENST00000601159, ENST00000928258, ENST00000960537

RefSeq mRNA: 2 — MANE Select: NM_006533 NM_001202553, NM_006533

CCDS: CCDS12566

Canonical transcript exons

ENST00000263369 — 4 exons

Exon	Start	End
ENSE00001137729	40775521	40775669
ENSE00003607775	40775752	40775885
ENSE00003619498	40777397	40777490
ENSE00003638078	40776969	40777079

Expression profiles

Bgee: expression breadth ubiquitous, 137 present calls, max score 98.45.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.4965 / max 32.1226, expressed in 93 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
175900	1.6605	208
175899	0.4048	81
175898	0.0917	51

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
tibial nerve	UBERON:0001323	98.45	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	96.29	gold quality
pituitary gland	UBERON:0000007	93.65	gold quality
adenohypophysis	UBERON:0002196	92.86	gold quality
sural nerve	UBERON:0015488	89.81	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	88.62	gold quality
saliva-secreting gland	UBERON:0001044	87.62	gold quality
minor salivary gland	UBERON:0001830	87.13	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	83.37	gold quality
muscle layer of sigmoid colon	UBERON:0035805	81.79	gold quality
mammary gland	UBERON:0001911	79.69	gold quality
thoracic mammary gland	UBERON:0005200	79.69	gold quality
lower esophagus mucosa	UBERON:0035834	79.12	gold quality
skin of leg	UBERON:0001511	78.95	gold quality
zone of skin	UBERON:0000014	78.34	gold quality
skin of abdomen	UBERON:0001416	77.63	gold quality
left coronary artery	UBERON:0001626	77.52	gold quality
vermiform appendix	UBERON:0001154	76.79	gold quality
mucosa of transverse colon	UBERON:0004991	76.38	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	76.16	gold quality
lower esophagus	UBERON:0013473	75.98	gold quality
lower esophagus muscularis layer	UBERON:0035833	75.97	gold quality
colon	UBERON:0001155	75.67	gold quality
endocervix	UBERON:0000458	75.59	gold quality
fundus of stomach	UBERON:0001160	74.22	gold quality
granulocyte	CL:0000094	74.19	gold quality
intestine	UBERON:0000160	73.86	gold quality
smooth muscle tissue	UBERON:0001135	73.50	gold quality
right ovary	UBERON:0002118	72.98	gold quality
rectum	UBERON:0001052	72.67	gold quality

Single-cell (SCXA)

Detected in 7 experiment(s), a significant marker in 7.

Experiment	Marker?	Max mean expression
E-MTAB-10885	yes	1364.14
E-GEOD-75688	yes	528.07
E-CURD-114	yes	483.47
E-HCAD-11	yes	26.36
E-HCAD-1	yes	20.14
E-CURD-112	yes	7.95
E-ANND-3	yes	5.99

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CEBPA, DLX4, HMGA2, NONO, RELA, SOX10, SOX9, SP1, TFAP2A, YBX1, ZBTB7A

Literature-anchored findings (GeneRIF, showing 39)

• The assignments, solution structure, & dynamics of human MIA were determined by heteronuclear NMR methods. The structure consists of an SH3-like subdomain with N- and C-terminal extensions of about 20 amino acids each that form a novel fold. (PMID:11991352)
• Melanoma-inhibiting activity (MIA/CD-RAP) is expressed in a variety of malignant tumors of mainly neuroectodermal origin. (PMID:12014625)
• expression pattern of a novel splice product MIA (splice) of malignant melanoma-derived growth-inhibiting activity (MIAY CD-RAP). (PMID:12230496)
• Stable antisense-HMG1 expression in melanoma cells led to the reduction of melanoma inhibitory activity (MIA) promoter activity and protein expression. (PMID:12665595)
• increased MIA production may, in turn, increase the invasive properties of the cells by modulating the attachment of human uveal melanoma cells to the extracellular matrix (PMID:15057037)
• MIA may promote the detachment of radial and vertical growth phase melanomas. (PMID:15201995)
• The MIA protein enhances the migration of melanocytes and promotes melanoma progression. (PMID:15208686)
• MIA may contribute to immunosuppression frequently seen in malignant melanomas by inhibiting cellular antitumor immune reactions. (PMID:15386421)
• MIA in homogenates of surgical specimen directly relate to a more benign clinical prognosis in patients with high-grade glioma (PMID:15547763)
• There is a correlation between MIA expression and pigmentation and morphology of melanocytic cells. (PMID:15760338)
• Increased levels of MIA is associated with gastric cancer (PMID:16331256)
• When patients progressed, level of MIA increased significantly. (PMID:17348447)
• A candidate autoantigen in rheumatoid arthritis found in synovial fluid cells. (PMID:17599744)
• An antigen in melanoma, elevated in 22 per cent of patients, predicting recurrence. (PMID:17661202)
• Measurement of Melan-A, gp100, MAGE-3, MIA and tyrosinase represents a prognostic factor and a method for early detection of metastasis and treatment response of melanoma patients. (PMID:18181974)
• MIA serum level is the ideal test for screening the skin melanoma spread to sentinel lymph nodes. (PMID:18477894)
• MIA expression is enhanced by the interaction of intracellular HMGB1 and NFkBp65 and MIA is closely involved in tumor progression and nodal metastasis by the increments of VEGF-C and VEGF-D in oral squamous cell carcinomas. (PMID:18616526)
• MIA protein, binding to integrins and thus promoting detachment of cells from extracellular matrix structures, is internalized into the cell together with these cell adhesion receptors at the cell rear. (PMID:19521988)
• A fluorescence polarization biological assay was developed using MIA protein-binding compounds for studies of the binding properties of this protein. (PMID:19852767)
• MIA/CD-RAP stabilizes cartilage differentiation and inhibits differentiation into bone potentially by regulating signaling processes during differentiation. (PMID:20164682)
• pancreatic cancer patients with high intratumoral expression are antibody-negative and have shorter survival (PMID:20514540)
• The cell-specific production rate of MIA was quantitatively proportional to the aggrecan gene expression level in the early and middle phase of cartilage chondrocyte differentiation. (PMID:21277254)
• Data suggest that plasma markers: CEACAM, ICAM-1, osteopontin, MIA, TIMP-1 and S100B particularly when assessed in combination, can be used to monitor patients for disease recurrenc. (PMID:21487066)
• Further diagnostics should be initiated in uveal melanoma patients with serum MIA above 8.3ng/ml. (PMID:21540751)
• assessed the utility of melanoma inhibitory activity (MIA) serum marker in the follow up and primary diagnosis of stage III melanoma patients (PMID:21658116)
• Results show that S-100B, MIA and LDH levels were significantly higher in patients with advanced melanoma than in disease-free patients or healthy controls. (PMID:21858537)
• MIA protein is present in non-segmental vitiligo skin and may cause the detachment of melanocytes; its target is integrin alpha5beta1, which determines the breaking and/or weakening of connections among melanocytes and basal membrane (PMID:23664187)
• Functional promoter analysis identified the transcription factor YBX1 as the mediator of MIA activation of p54(nrb) transcription. (PMID:23672612)
• The effects of MIA/CD-RAP on transcriptional regulation in chondrocytes, through the regulation of p54(nrb) via YBX1 contributes to the understanding of chondrogenesis. (PMID:24349210)
• Focus on the quantitative analysis of the MIA protein as a prognostic tool because it has proven to be a useful serum marker for documenting disease progression of malignant melanoma. Review. (PMID:24372647)
• data provide evidence for a critical role of SOX10 in melanoma cell invasion through the regulation of MIA and highlight its role as a therapeutic target in melanoma (PMID:24608986)
• Our results suggest that MIA-STOX2 signaling may be a useful diagnostic and therapeutic target in oral squamous cell carcinoma (PMID:27050375)
• The frequency of MIA gene family expression was higher among squamous cell carcinomas than among other tumor types subjected to screening. MIA gene family staining was observed frequently in esophageal and lung cancers associated with nodal and/or distant metastasis. In cervical cancers, MIA and TANGO immunostaining also correlated with tumor progression and metastasis. (PMID:27145272)
• real-time RT-PCR assays showed that expressions of MIA and MIA-RAB4B located 35 kb upstream of the deletion, were up-regulated in the polyps compared to the matched mucosa of the proband. MIA-RAB4B, the read-through long non-coding RNA (lncRNA), RAB4B, PIM2 and TAOK1 share common binding site of a microRNA, miR-24, in their 3’UTRs (PMID:28306719)
• the molecular basis of the interaction of MIA with the Hep II domain of fibronectin based on nuclear magnetic resonance spectroscopic binding assays. (PMID:28565914)
• MIA had a slightly superior sensitivity to detect progressive disease compared to S100 and seems to be more useful in monitoring of patients with metastatic melanoma receiving immunotherapy (PMID:28870930)
• MIA is a regulator of cellular senescence in human and murine melanocytes. (PMID:31172672)
• The clinical significance of MIA gene in tumorigenesis of lung cancer. (PMID:31986890)
• The value of melanoma inhibitory activity and LDH with melanoma patients in a Chinese population. (PMID:33663104)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	mia	ENSDARG00000052437
mus_musculus	Mia	ENSMUSG00000089661
rattus_norvegicus	Mia	ENSRNOG00000001499
drosophila_melanogaster	Tango1	FBGN0286898

Paralogs (10): OTOR (ENSG00000125879), MIA2 (ENSG00000150527), MIA3 (ENSG00000154305), SPZ1 (ENSG00000164299), CTAGE1 (ENSG00000212710), CTAGE9 (ENSG00000236761), CTAGE15 (ENSG00000271079), CTAGE6 (ENSG00000271321), CTAGE4 (ENSG00000288784), CTAGE8 (ENSG00000289604)

Protein

Protein identifiers

Melanoma-derived growth regulatory protein — Q16674 (reviewed: Q16674)

Alternative names: Melanoma inhibitory activity protein

All UniProt accessions (4): M0QZM4, M0R0T9, M0R343, Q16674

UniProt curated annotations — full annotation on UniProt →

Function. Elicits growth inhibition on melanoma cells in vitro as well as some other neuroectodermal tumors, including gliomas.

Subunit / interactions. Interacts with FASLG. Interacts with TMIGD2.

Subcellular location. Secreted.

Tissue specificity. All malignant melanoma cell lines tested and infrequently in glioma cell lines.

Post-translational modifications. May possess two intramolecular disulfide bonds.

Similarity. Belongs to the MIA/OTOR family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q16674-1	1	yes
Q16674-2	2, MIA-splice

RefSeq proteins (2): NP_001189482, NP_006524* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001452	SH3_domain	Domain
IPR036028	SH3-like_dom_sf	Homologous_superfamily
IPR043369	MIA	Family

Pfam: PF07653

UniProt features (17 total): strand 8, helix 3, disulfide bond 2, signal peptide 1, chain 1, domain 1, splice variant 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
1I1J	X-RAY DIFFRACTION	1.39
5IXB	X-RAY DIFFRACTION	1.39
1HJD	SOLUTION NMR
1K0X	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q16674-F1	87.06	0.72

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): 36–41, 59–130

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 124 (showing top): GSE45365_NK_CELL_VS_CD8_TCELL_DN, CREL_01, GOMF_GROWTH_FACTOR_ACTIVITY, MODULE_75, ROZANOV_MMP14_TARGETS_UP, RYTTCCTG_ETS2_B, MODULE_6, GOMF_SIGNALING_RECEPTOR_BINDING, MODULE_46, PARENT_MTOR_SIGNALING_UP, HARRIS_BRAIN_CANCER_PROGENITORS, SMID_BREAST_CANCER_LUMINAL_B_DN, RAY_TUMORIGENESIS_BY_ERBB2_CDC25A_UP, GOMF_SIGNALING_RECEPTOR_REGULATOR_ACTIVITY, HMGIY_Q6

GO Biological Process (2): extracellular matrix organization (GO:0030198), signal transduction (GO:0007165)

GO Molecular Function (2): growth factor activity (GO:0008083), 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
extracellular structure organization	1
external encapsulating structure organization	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
receptor ligand activity	1
binding	1
cellular anatomical structure	1

Protein interactions and networks

STRING

320 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MIA	S100B	P04271	746
MIA	FN1	P02751	664
MIA	COL11A2	P13942	608
MIA	SOX10	P56693	578
MIA	MATN1	P21941	570
MIA	SOX9	P48436	561
MIA	SPP1	P10451	536
MIA	KCNJ2	P48049	497
MIA	GDF15	P78360	484
MIA	TAC3	Q9UHF0	461
MIA	CDH7	Q9ULB5	457
MIA	SOX5	P35711	444
MIA	SOX6	P35712	430
MIA	MSX1	P28360	407
MIA	ACAN	P16112	405

IntAct

2 interactions, top by confidence:

A	B	Type	Score
FASLG	MIA	psi-mi:“MI:0407”(direct interaction)	0.440

BioGRID (5): MIA (Reconstituted Complex), MIA (Proximity Label-MS), MIA (Affinity Capture-MS), MIA (Protein-peptide), MIA (Affinity Capture-Luminescence)

ESM2 similar proteins: A0A8M9PFP2, A6NFU0, A7UA95, B0S5G3, B5KFD7, D4ACE5, E7F221, E7FCN8, O14525, P59240, P82350, Q0VCN6, Q13145, Q14B46, Q16586, Q16674, Q28038, Q28686, Q5R9Q9, Q5RJL6, Q61137, Q61865, Q62946, Q64255, Q6V7V2, Q7ZV46, Q8C6B2, Q8HYZ0, Q8R553, Q8VDA1, Q8VE43, Q91XN4, Q92918, Q99JH7, Q99KF0, Q99MQ3, Q9BQT9, Q9BST9, Q9BXL6, Q9BXM7

Diamond homologs: Q0VC16, Q16674, Q28038, Q5JRA6, Q61865, Q62946, Q8BI84, Q9I8P5, Q9I8P6, Q9JIE3, Q9NRC9, P52735, Q60992, Q96PC5, Q9R0C8, Q9UKW4, A4D2H0, A4FU28, P0CG41, Q86UF2, Q8IX94, Q8IX95, Q91ZV0, Q96RT6, D3YZU1, E7F1U2, F1LRS8, G5EC32, G5EE56, M0R4F8, O00459, O08908, O35413, O42287, O43125, O43639, O45539, O46404, O55033, O55043

SIGNOR signaling

0 interactions.

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	14
Likely benign	2
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

854 predictions. Top by Δscore:

Variant	Effect	Δscore
19:40775535:A:AG	acceptor_gain	1.0000
19:40775536:G:GG	acceptor_gain	1.0000
19:40775536:GTC:G	acceptor_gain	1.0000
19:40775536:GTCCA:G	acceptor_gain	1.0000
19:40775667:GCC:G	donor_gain	1.0000
19:40775670:G:GG	donor_gain	1.0000
19:40775829:GTGGT:G	donor_gain	1.0000
19:40775881:GCAGC:G	donor_gain	1.0000
19:40775884:GC:G	donor_gain	1.0000
19:40775886:G:GG	donor_gain	1.0000
19:40776964:CCCAG:C	acceptor_loss	1.0000
19:40776966:CA:C	acceptor_loss	1.0000
19:40776967:A:AG	acceptor_gain	1.0000
19:40776967:AG:A	acceptor_gain	1.0000
19:40776968:G:GG	acceptor_gain	1.0000
19:40776968:GG:G	acceptor_gain	1.0000
19:40776968:GGT:G	acceptor_gain	1.0000
19:40776968:GGTT:G	acceptor_gain	1.0000
19:40776968:GGTTC:G	acceptor_gain	1.0000
19:40777075:CAGAC:C	donor_gain	1.0000
19:40777076:AGAC:A	donor_gain	1.0000
19:40777076:AGACG:A	donor_loss	1.0000
19:40777077:GAC:G	donor_gain	1.0000
19:40777077:GACG:G	donor_gain	1.0000
19:40777077:GACGT:G	donor_loss	1.0000
19:40777078:AC:A	donor_gain	1.0000
19:40777078:ACGTG:A	donor_loss	1.0000
19:40777079:CG:C	donor_loss	1.0000
19:40777080:G:GG	donor_gain	1.0000
19:40777080:GTG:G	donor_loss	1.0000

AlphaMissense

841 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:40775805:T:C	F61L	0.997
19:40775807:C:A	F61L	0.997
19:40775807:C:G	F61L	0.997
19:40777015:T:G	F103C	0.996
19:40777406:T:C	F128L	0.995
19:40777408:C:A	F128L	0.995
19:40777408:C:G	F128L	0.995
19:40777015:T:C	F103S	0.994
19:40777030:T:A	V108D	0.994
19:40775806:T:G	F61C	0.993
19:40775876:G:C	W84C	0.993
19:40775876:G:T	W84C	0.993
19:40775839:T:A	V72D	0.992
19:40775806:T:C	F61S	0.991
19:40775849:G:C	K75N	0.991
19:40775849:G:T	K75N	0.991
19:40775663:T:A	C41S	0.990
19:40775664:G:C	C41S	0.990
19:40777407:T:G	F128C	0.990
19:40777014:T:C	F103L	0.989
19:40777016:C:A	F103L	0.989
19:40777016:C:G	F103L	0.989
19:40775841:T:C	F73L	0.988
19:40775843:C:A	F73L	0.988
19:40775843:C:G	F73L	0.988
19:40775644:G:C	K34N	0.987
19:40775644:G:T	K34N	0.987
19:40775648:T:A	C36S	0.987
19:40775649:G:C	C36S	0.987
19:40775773:C:A	A50D	0.986

dbSNP variants (sampled 300 via entrez): RS1000827255 (19:40776547 C>A), RS1000931237 (19:40776738 T>C), RS1001399212 (19:40775098 T>C), RS1001783863 (19:40773318 C>A,T), RS1003025395 (19:40774457 C>A), RS1003715791 (19:40774826 G>A,C), RS1004356798 (19:40774435 G>A), RS1004785150 (19:40773238 A>G), RS1006183518 (19:40774099 G>A), RS1006580559 (19:40773425 C>A,G,T), RS1007837441 (19:40777402 G>A), RS1008152926 (19:40773811 G>A), RS1008183945 (19:40773612 C>G,T), RS1008486179 (19:40776397 C>A,T), RS1009358657 (19:40773693 T>C,G)

Disease associations

OMIM: gene MIM:601340 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

26 associations (top):

Study	Trait	p-value
GCST001322_2	Kawasaki disease	2.000000e-12
GCST001455_1	Kawasaki disease	4.000000e-10
GCST002945_35	Emphysema imaging phenotypes	2.000000e-06
GCST003847_2	Caffeine metabolism (plasma 1,7-dimethylxanthine (paraxanthine) level)	6.000000e-08
GCST003849_1	Caffeine metabolism (plasma 3,7-dimethylxanthine (theobromine) level)	4.000000e-06
GCST003851_10	Caffeine metabolism (plasma 1,7-dimethylxanthine (paraxanthine) to 1,3,7-trimethylxanthine (caffeine) ratio)	5.000000e-12
GCST003851_11	Caffeine metabolism (plasma 1,7-dimethylxanthine (paraxanthine) to 1,3,7-trimethylxanthine (caffeine) ratio)	8.000000e-09
GCST003851_12	Caffeine metabolism (plasma 1,7-dimethylxanthine (paraxanthine) to 1,3,7-trimethylxanthine (caffeine) ratio)	2.000000e-10
GCST003851_13	Caffeine metabolism (plasma 1,7-dimethylxanthine (paraxanthine) to 1,3,7-trimethylxanthine (caffeine) ratio)	9.000000e-22
GCST003851_14	Caffeine metabolism (plasma 1,7-dimethylxanthine (paraxanthine) to 1,3,7-trimethylxanthine (caffeine) ratio)	9.000000e-10
GCST003851_15	Caffeine metabolism (plasma 1,7-dimethylxanthine (paraxanthine) to 1,3,7-trimethylxanthine (caffeine) ratio)	9.000000e-11
GCST003851_16	Caffeine metabolism (plasma 1,7-dimethylxanthine (paraxanthine) to 1,3,7-trimethylxanthine (caffeine) ratio)	3.000000e-09
GCST003851_17	Caffeine metabolism (plasma 1,7-dimethylxanthine (paraxanthine) to 1,3,7-trimethylxanthine (caffeine) ratio)	2.000000e-11
GCST003851_18	Caffeine metabolism (plasma 1,7-dimethylxanthine (paraxanthine) to 1,3,7-trimethylxanthine (caffeine) ratio)	1.000000e-08
GCST003851_19	Caffeine metabolism (plasma 1,7-dimethylxanthine (paraxanthine) to 1,3,7-trimethylxanthine (caffeine) ratio)	3.000000e-11
GCST003851_20	Caffeine metabolism (plasma 1,7-dimethylxanthine (paraxanthine) to 1,3,7-trimethylxanthine (caffeine) ratio)	3.000000e-09
GCST003851_21	Caffeine metabolism (plasma 1,7-dimethylxanthine (paraxanthine) to 1,3,7-trimethylxanthine (caffeine) ratio)	1.000000e-09
GCST003851_22	Caffeine metabolism (plasma 1,7-dimethylxanthine (paraxanthine) to 1,3,7-trimethylxanthine (caffeine) ratio)	2.000000e-08
GCST003851_23	Caffeine metabolism (plasma 1,7-dimethylxanthine (paraxanthine) to 1,3,7-trimethylxanthine (caffeine) ratio)	3.000000e-08
GCST003851_26	Caffeine metabolism (plasma 1,7-dimethylxanthine (paraxanthine) to 1,3,7-trimethylxanthine (caffeine) ratio)	5.000000e-12
GCST003851_27	Caffeine metabolism (plasma 1,7-dimethylxanthine (paraxanthine) to 1,3,7-trimethylxanthine (caffeine) ratio)	1.000000e-08
GCST003851_9	Caffeine metabolism (plasma 1,7-dimethylxanthine (paraxanthine) to 1,3,7-trimethylxanthine (caffeine) ratio)	6.000000e-09
GCST006585_1104	Blood protein levels	1.000000e-164
GCST009573_1	melanoma-derived growth regulatory protein levels	1.000000e-16
GCST009921_7	Carotid intima media thickness (mean)	1.000000e-10
GCST90013406_284	Liver enzyme levels (alkaline phosphatase)	1.000000e-22

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0007626	emphysema imaging measurement
EFO:0007872	caffeine metabolite measurement
EFO:0004533	alkaline phosphatase measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

27 total (human), top 27 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
trichostatin A	affects cotreatment, increases expression	3
Valproic Acid	affects cotreatment, increases expression	3
Resveratrol	affects cotreatment, decreases expression	2
Vorinostat	affects cotreatment, increases expression	2
Panobinostat	affects cotreatment, increases expression	2
aristolochic acid I	increases expression	1
propionaldehyde	increases expression	1
bisphenol A	decreases methylation	1
butyraldehyde	increases expression	1
manganese chloride	increases expression	1
versicolorin A	increases expression	1
entinostat	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
2,2’,4,4’,5-brominated diphenyl ether	decreases expression	1
abrine	increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
theaflavin-3,3’-digallate	affects expression	1
Decitabine	increases expression	1
Air Pollutants	decreases expression, increases abundance	1
Arsenic	affects methylation	1
Benzo(a)pyrene	affects expression	1
Cisplatin	decreases expression	1
Manganese	increases expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Smoke	decreases expression, increases abundance	1
Tobacco Smoke Pollution	increases expression	1
Vitamin E	increases expression	1

Clinical trials (associated diseases)

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