MT3

Summary

MT3 (metallothionein 3, HGNC:7408) is a protein-coding gene on chromosome 16q13, encoding Metallothionein-3 (P25713). Binds heavy metals.

This gene is a member of the metallothionein family of genes. Proteins encoded by this gene family are low in molecular weight, are cysteine-rich, lack aromatic residues, and bind divalent heavy metal ions. This gene family member displays tissue-specific expression, and contains a threonine insert near its N-terminus and a glutamate-rich hexapeptide insert near its C-terminus relative to the proteins encoded by other gene family members. It plays an important role in zinc and copper homeostasis, and is induced under hypoxic conditions. The encoded protein is a growth inhibitory factor, and reduced levels of the protein are observed in the brains of individuals with some metal-linked neurodegenerative disorders such as Alzheimer’s disease.

Source: NCBI Gene 4504 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 11 total
• MANE Select transcript: NM_005954

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:7408
Approved symbol	MT3
Name	metallothionein 3
Location	16q13
Locus type	gene with protein product
Status	Approved
Aliases	GIF
Ensembl gene	ENSG00000087250
Ensembl biotype	protein_coding
OMIM	139255
Entrez	4504

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 5 protein_coding, 1 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000200691, ENST00000561640, ENST00000565838, ENST00000566451, ENST00000566576, ENST00000570176, ENST00000956704

RefSeq mRNA: 1 — MANE Select: NM_005954 NM_005954

CCDS: CCDS10762

Canonical transcript exons

ENST00000200691 — 3 exons

Exon	Start	End
ENSE00001168816	56589528	56589621
ENSE00001666774	56589870	56589935
ENSE00003485101	56590840	56591085

Expression profiles

Bgee: expression breadth ubiquitous, 149 present calls, max score 99.95.

FANTOM5 (CAGE): breadth broad, TPM avg 38.3884 / max 4450.8451, expressed in 309 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
154228	38.3384	309
154229	0.0500	20

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
putamen	UBERON:0001874	99.95	gold quality
nucleus accumbens	UBERON:0001882	99.95	gold quality
prefrontal cortex	UBERON:0000451	99.94	gold quality
temporal lobe	UBERON:0001871	99.94	gold quality
caudate nucleus	UBERON:0001873	99.94	gold quality
amygdala	UBERON:0001876	99.94	gold quality
substantia nigra	UBERON:0002038	99.94	gold quality
right frontal lobe	UBERON:0002810	99.94	gold quality
Brodmann (1909) area 9	UBERON:0013540	99.94	gold quality
frontal cortex	UBERON:0001870	99.93	gold quality
Ammon’s horn	UBERON:0001954	99.93	gold quality
middle frontal gyrus	UBERON:0002702	99.93	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	99.93	gold quality
hypothalamus	UBERON:0001898	99.92	gold quality
right hemisphere of cerebellum	UBERON:0014890	99.90	gold quality
cerebellar cortex	UBERON:0002129	99.88	gold quality
cerebellar hemisphere	UBERON:0002245	99.88	gold quality
cerebellum	UBERON:0002037	99.86	gold quality
spinal cord	UBERON:0002240	99.85	gold quality
primary visual cortex	UBERON:0002436	99.85	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	99.85	gold quality
superior frontal gyrus	UBERON:0002661	99.83	gold quality
anterior cingulate cortex	UBERON:0009835	99.80	gold quality
telencephalon	UBERON:0001893	99.79	gold quality
Brodmann (1909) area 10	UBERON:0013541	99.78	gold quality
frontal pole	UBERON:0002795	99.76	gold quality
paraflocculus	UBERON:0005351	99.72	gold quality
cerebral cortex	UBERON:0000956	99.71	gold quality
dorsal plus ventral thalamus	UBERON:0001897	99.61	gold quality
cerebellar vermis	UBERON:0004720	99.32	gold quality

Single-cell (SCXA)

Detected in 6 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-MTAB-9435	yes	4311.83
E-GEOD-84465	yes	2206.13
E-GEOD-135922	yes	2104.36
E-MTAB-7316	yes	1163.48
E-HCAD-30	no	1245.15
E-ANND-3	no	0.99

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

6 targets.

Target	Regulation
HIF1A	Activation
HMOX1	Activation
LAMP1	Repression
LEPR	Activation
MAPK3	Activation
NFE2L2	Activation

Upstream regulators (CollecTRI, top): MTF1

miRNA regulators (miRDB)

9 targeting MT3, 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-6722-3P	99.45	67.62	1919
HSA-MIR-1206	99.30	69.32	1016
HSA-MIR-1909-3P	99.03	66.56	1662
HSA-MIR-5701	98.97	69.54	1502
HSA-MIR-4691-5P	98.41	66.77	1343
HSA-MIR-6792-3P	98.41	66.86	1359
HSA-MIR-197-3P	98.09	69.23	1004
HSA-MIR-6815-5P	96.05	65.55	662
HSA-MIR-6865-5P	96.05	65.58	675

Literature-anchored findings (GeneRIF, showing 40)

• MT-3 expression is involved in the transport function of a human renal cell line that retains properties of the proximal tubule. (PMID:11849386)
• Overexpression of human metallothionein-III prevents hydrogen peroxide-induced oxidative stress in human fibroblasts. “metallothionein-III " (PMID:12067712)
• overexpression can influence the growth and chemotherapeutic drug resistance of the PC-3 prostate cancer cell line (PMID:12111700)
• Hypermethylation of metallothionein-3 CpG island in gastric carcinoma (PMID:12538345)
• Metallothionein-III has anticarcinogenic and neuroprotective roles in cells exposed to gamma rays (PMID:15190073)
• The affect the role of MT3 on cell viability, which may explain in part why the comprehensive effect of MT3 on the cells was elusive. (PMID:16087360)
• analysis of the epitope of neuronal growth inhibitory factor (GIF) (PMID:16336778)
• MT3 expression is frequently down-regulated in oesophageal squamous cell carcinoma , by DNA methylation, but that this is not a prognostic indicator (PMID:16351731)
• mutation of MT3 at Glu23 may alter the NO metabolism and/or affect zinc homeostasis in brain, thus altering the neuronal growth inhibitory activity (PMID:16945328)
• The alpha-domain is indispensable and plays an important role in modulating the stability of the metal cluster in the beta-domain by domain-domain interactions, thus influencing the bioactivity of hMT3. (PMID:17712581)
• The level of MT-3 expression in human proximal tubular cells influences transepithelial resistance and cadherin expression but does not the Cd(+2)-induced loss of vectorial active transport. (PMID:18182399)
• MT-3 is a highly hypoxia-inducible gene in human adipocytes; the protein may protect adipocytes from hypoxic damage (PMID:18206644)
• The goals of this study were to define the expression of the isoforms of MT 1, 2, 3 at both mRNA and protein levels, in normal prostate, benign prostatic hyperplasia (BPH) and malignant PC-3 cells. (PMID:18208603)
• These results suggest that MT-III upregulates VEGF production in brain endothelial cells by a HIF-1alpha-dependent mechanism. (PMID:18295594)
• The structure adopted by the (6)CPCP(9) motif is the determinant factor of the inhibitory bioactivity of hGIF; but residues within the N-terminal fragment may also influence the peptide conformation and contribute to the protein’s bioactivity. (PMID:18533104)
• Metallothionein-III-induced activation of phosphatidylinositol 3-kinase/Akt and extracellular signal-regulated kinase1/2 up-regulates expression and activity of heme oxygenase-1, which provides protection against oxidative damage in dopaminergic cells. (PMID:18554677)
• the bioactivity of hGIF is mainly related to the essential metal release and its characteristic conformation. (PMID:18757100)
• metallothionein in decidual cells seems to be responsible for the proper coexistence between decidual cells and activated immune cells that infiltrate both eutopic and ectopic decidua during cesarean section and placental abruption (PMID:18782281)
• In this study, the binding of Zn(2+), Ca(2+), and Mg(2+) to human Zn(7)MT-3 and its mutant lacking an acidic hexapeptide insert, Zn(7)MT-3(Delta55-60), was investigated and compared with the binding of Zn(7)MT-2. (PMID:19425569)
• Results provide information on the domain-domain interaction at the molecular level, and shed new light on the mechanism of the bioactivity of human neuronal growth inhibitory factor. (PMID:19490120)
• study of reaction/binding of cisplatin and transplatin with MT-3 and MT-2 initially bound with zinc; study includes kinetics and stoichiometry of the reactions (PMID:19536566)
• weak in pancreatic serous cystadenomas; increased expressions in adenomocarcinomas; potential prognostic marker (PMID:19578815)
• It plays a role in the detoxification of heavy metals and reactive oxygen species. (review) (PMID:19881214)
• Metallothionein-III is a specific component of glial cytoplasmic inclusions and is upregulated in multiple system atrophy. (PMID:20039155)
• MT2 diminishes Transthyretin-Abeta binding, whereas MT3 has the opposite effect (PMID:20646067)
• The roles of zinc and metallothionein-3 in autophagy and/or lysosomal function are reviewed. (PMID:20974010)
• Esophageal adenocarcinomas are characterized by frequent epigenetic silencing of MT3. (PMID:21818286)
• MT-3 modulates the catalytic redox properties of PrP-Cu(II) (PMID:22615124)
• the molecular mechanism for protection against the neuronal cytotoxicity of Abeta(1-42) with copper ions (PMID:23086305)
• MT-III expression may have an impact on the pathogenesis of non-small cell lung cancer. (PMID:23482768)
• The experiments indicate that MT3 is an androgen-upregulated gene, and promotes tumorigenesis of prostate carcinoma cells. (PMID:23794209)
• Upregulation of MT-3 gene expression can inhibit esophageal cancer cell proliferation and induce apoptosis. (PMID:24222235)
• The presence of MT-3 in the zona glomerulosa of pathological adrenal cortex may imply a role in the pathophysiology of aldosterone-producing tissues. (PMID:24242700)
• MT-capital I, Ukrainiancapital I, Ukrainiancapital I, Ukrainian increases the amount of active ADAM10 in association with furin, PC7 and PKCalpha. (PMID:24859040)
• The epidermis of human skin and resulting malignancies express high level of MT-3. (PMID:25290577)
• The study implicates the unique C-terminal sequence of MT-3 in the conversion of HK-2 cells to display an enhanced epithelial phenotype. (PMID:25803827)
• MT3 may regulate breast cancer cell invasiveness by modulating the expression of MMP3. (PMID:25933064)
• The present study was undertaken to explore further the interrelationship between p53 and metallothioneins. (PMID:27049123)
• The expression of MT-3 mRNA in breast cancer cell lines was significantly lower than in the normal human breast epithelial cell line. The results suggest that MT-3 may play a role in the malignant transformation of breast epithelial cells and in tumor progression. (PMID:27840910)
• In recent years, the roles of zinc dynamics and MT3 function in neurodegeneration are slowly emerging. This short review focuses on the recent developments regarding the chemistry and biology of MT3. [review] (PMID:28538697)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	mt2	ENSDARG00000041623
mus_musculus	Mt3	ENSMUSG00000031760
rattus_norvegicus	Mt3	ENSRNOG00000018958

Paralogs (11): MT4 (ENSG00000102891), MT1G (ENSG00000125144), MT2A (ENSG00000125148), MT1B (ENSG00000169688), MT1E (ENSG00000169715), MT1X (ENSG00000187193), MT1F (ENSG00000198417), MT1H (ENSG00000205358), MT1A (ENSG00000205362), MT1M (ENSG00000205364), MT1HL1 (ENSG00000244020)

Protein

Protein identifiers

Metallothionein-3 — P25713 (reviewed: P25713)

Alternative names: GIFB, Growth inhibitory factor, Metallothionein-III

All UniProt accessions (4): P25713, H3BPK2, H3BQX6, H3BTG5

UniProt curated annotations — full annotation on UniProt →

Function. Binds heavy metals. Contains three zinc and three copper atoms per polypeptide chain and only a negligible amount of cadmium. Inhibits survival and neurite formation of cortical neurons in vitro.

Tissue specificity. Abundant in a subset of astrocytes in the normal human brain, but greatly reduced in the Alzheimer disease (AD) brain.

Similarity. Belongs to the metallothionein superfamily. Type 1 family.

RefSeq proteins (1): NP_005945* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000006	Metalthion_vert	Family
IPR017854	Metalthion_dom_sf	Homologous_superfamily
IPR018064	Metalthion_vert_metal_BS	Binding_site
IPR023587	Metalthion_dom_sf_vert	Homologous_superfamily

Pfam: PF00131

UniProt features (39 total): binding site 28, region of interest 2, modified residue 2, strand 2, helix 2, turn 2, chain 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
2F5H	SOLUTION NMR
2FJ4	SOLUTION NMR
2FJ5	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P25713-F1	69.01	0.00

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (28): 22; 25; 25; 27; 30; 34; 35; 35; 37; 38; 38; 42 …

Post-translational modifications (2): 1, 33

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-5661231	Metallothioneins bind metals
R-HSA-5660526	Response to metal ions
R-HSA-8953897	Cellular responses to stimuli

MSigDB gene sets: 296 (showing top): GOBP_NEGATIVE_REGULATION_OF_NEURON_APOPTOTIC_PROCESS, GOBP_REGULATION_OF_CELLULAR_RESPONSE_TO_GROWTH_FACTOR_STIMULUS, GOBP_NEGATIVE_REGULATION_OF_CELL_DEVELOPMENT, BENPORATH_ES_WITH_H3K27ME3, GOBP_RESPONSE_TO_ZINC_ION, GOBP_NEURON_PROJECTION_EXTENSION, GOBP_REGULATION_OF_PHOSPHORYLATION, GOBP_NEGATIVE_REGULATION_OF_AXON_EXTENSION, GOBP_RESPONSE_TO_PEPTIDE, GOBP_REGULATION_OF_DEVELOPMENTAL_GROWTH, GOBP_TRANSITION_METAL_ION_TRANSPORT, GOBP_HYDROGEN_PEROXIDE_CATABOLIC_PROCESS, GOBP_NEGATIVE_REGULATION_OF_CELL_GROWTH, GOBP_NEGATIVE_REGULATION_OF_REACTIVE_OXYGEN_SPECIES_METABOLIC_PROCESS, GOBP_CELLULAR_RESPONSE_TO_CADMIUM_ION

GO Biological Process (34): response to hypoxia (GO:0001666), positive regulation of protein phosphorylation (GO:0001934), energy reserve metabolic process (GO:0006112), zinc ion transport (GO:0006829), intracellular zinc ion homeostasis (GO:0006882), detoxification of copper ion (GO:0010273), positive regulation of gene expression (GO:0010628), negative regulation of neuron projection development (GO:0010977), removal of superoxide radicals (GO:0019430), intracellular monoatomic cation homeostasis (GO:0030003), negative regulation of cell growth (GO:0030308), negative regulation of axon extension (GO:0030517), positive regulation of vascular endothelial growth factor receptor signaling pathway (GO:0030949), regulation of response to food (GO:0032095), activation of protein kinase B activity (GO:0032148), leptin-mediated signaling pathway (GO:0033210), cellular response to oxidative stress (GO:0034599), cellular response to reactive oxygen species (GO:0034614), negative regulation of neuron apoptotic process (GO:0043524), positive regulation of DNA-templated transcription (GO:0045893), protein stabilization (GO:0050821), negative regulation of oxidoreductase activity (GO:0051354), positive regulation of ERK1 and ERK2 cascade (GO:0070374), cellular response to cadmium ion (GO:0071276), cellular response to copper ion (GO:0071280), cellular response to zinc ion (GO:0071294), cellular response to hypoxia (GO:0071456), detoxification of cadmium ion (GO:0071585), cellular detoxification (GO:1990748), negative regulation of hydrogen peroxide catabolic process (GO:2000296), obsolete positive regulation of oxygen metabolic process (GO:2000376), response to oxidative stress (GO:0006979), negative regulation of apoptotic process (GO:0043066), negative regulation of neurogenesis (GO:0050768)

GO Molecular Function (7): copper ion binding (GO:0005507), zinc ion binding (GO:0008270), antioxidant activity (GO:0016209), protein kinase activator activity (GO:0030295), cadmium ion binding (GO:0046870), metal ion binding (GO:0046872), protein binding (GO:0005515)

GO Cellular Component (14): obsolete extracellular space (GO:0005615), nucleus (GO:0005634), cytoplasm (GO:0005737), mitochondrial outer membrane (GO:0005741), cytosol (GO:0005829), ribosome (GO:0005840), microtubule (GO:0005874), synaptic vesicle (GO:0008021), inclusion body (GO:0016234), axon (GO:0030424), dendritic spine (GO:0043197), perinuclear region of cytoplasm (GO:0048471), astrocyte end-foot (GO:0097450), astrocyte projection (GO:0097449)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Response to metal ions	1
Cellular responses to stimuli	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
transition metal ion binding	3
cellular anatomical structure	3
cellular oxidant detoxification	2
intracellular anatomical structure	2
cytoplasm	2
response to stress	1
response to decreased oxygen levels	1
regulation of protein phosphorylation	1
protein phosphorylation	1
positive regulation of protein modification process	1
positive regulation of phosphorylation	1
energy derivation by oxidation of organic compounds	1
transition metal ion transport	1
intracellular monoatomic cation homeostasis	1
inorganic ion homeostasis	1
detoxification of inorganic compound	1
stress response to copper ion	1
gene expression	1
regulation of gene expression	1
positive regulation of macromolecule biosynthetic process	1
regulation of neuron projection development	1
neuron projection development	1
negative regulation of cell projection organization	1
superoxide metabolic process	1
cellular response to superoxide	1
intracellular monoatomic ion homeostasis	1
monoatomic cation homeostasis	1
regulation of cell growth	1
cell growth	1
negative regulation of growth	1
negative regulation of cellular process	1
negative regulation of cell growth	1
regulation of axon extension	1
negative regulation of developmental growth	1
axon extension	1
negative regulation of axonogenesis	1
positive regulation of signal transduction	1
regulation of vascular endothelial growth factor receptor signaling pathway	1
vascular endothelial growth factor receptor signaling pathway	1
response to food	1

Protein interactions and networks

STRING

1370 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MT3	H3BSS0	H3BSS0	889
MT3	SLC30A3	Q99726	645
MT3	SLC30A1	Q9Y6M5	551
MT3	EREG	O14944	545
MT3	SLC30A4	O14863	450
MT3	VRK3	Q8IV63	445
MT3	CCS	O14618	433
MT3	ANGPTL4	Q9BY76	427
MT3	ATP7B	P35670	423
MT3	CD7	P09564	422
MT3	PLA2G2A	P14555	419
MT3	MT2A	P02795	407
MT3	MT4	P47944	403
MT3	PLA2G2D	Q9UNK4	401
MT3	ATOX1	O00244	384

IntAct

6 interactions, top by confidence:

A	B	Type	Score
TTR	MT3	psi-mi:“MI:0915”(physical association)	0.590
MT3	TTR	psi-mi:“MI:0407”(direct interaction)	0.590
MT3	TTR	psi-mi:“MI:0915”(physical association)	0.590
TERF2IP	MT3	psi-mi:“MI:0915”(physical association)	0.510
TERF2IP	MT3	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (14): ENO1 (Affinity Capture-MS), TPM3 (Affinity Capture-MS), ALDOA (Affinity Capture-MS), MYH9 (Affinity Capture-MS), ACTB (Affinity Capture-MS), TPM1 (Affinity Capture-MS), MYH9 (Affinity Capture-Western), ENO1 (Affinity Capture-Western), ACTB (Affinity Capture-Western), MT3 (Two-hybrid), MT3 (Two-hybrid), MT3 (Protein-peptide), MT3 (Affinity Capture-Western), MT3 (Reconstituted Complex)

ESM2 similar proteins: A1L3X4, O18842, O42152, P02797, P02798, P02800, P02801, P02802, P02803, P02804, P04355, P04731, P04733, P07438, P09577, P09578, P0DM35, P11957, P13640, P14425, P15786, P17808, P18055, P25713, P27087, P37360, P55942, P55943, P55944, P58280, P67981, P67982, P67983, P68041, P68301, P68302, P68303, P68304, P79376, P79377

Diamond homologs: O42152, P0DM35, P13640, P15786, P25713, P27087, P37359, P37360, P37361, P47944, P47945, P55944, P68494, P68495, P68497, P68498, P68499, Q2MJS5, Q2PFZ0, Q2PS21, Q6J1T3, Q6XUW5, Q8MKE4, P25127, P25128, P28184, P52720, P52721, P52728, P68503, P68504, P68505, P80593, Q7ZSY6, Q8AWG2, Q9I9I0, Q9TUI5, O19000, P02800, P58280

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	8
Likely benign	1
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

290 predictions. Top by Δscore:

Variant	Effect	Δscore
16:56589931:GAAGA:G	donor_gain	1.0000
16:56589934:GA:G	donor_gain	1.0000
16:56589936:G:GG	donor_gain	1.0000
16:56589618:TCTGG:T	donor_loss	0.9900
16:56589619:CTGG:C	donor_loss	0.9900
16:56589620:TGGTG:T	donor_loss	0.9900
16:56589621:GGT:G	donor_loss	0.9900
16:56589622:G:C	donor_loss	0.9900
16:56589623:TGAGC:T	donor_loss	0.9900
16:56589933:AGA:A	donor_gain	0.9900
16:56589934:GAG:G	donor_gain	0.9900
16:56590835:TGCA:T	acceptor_loss	0.9900
16:56590836:GCAGG:G	acceptor_loss	0.9900
16:56590837:CAG:C	acceptor_loss	0.9900
16:56590838:A:AT	acceptor_loss	0.9900
16:56590839:GGCT:G	acceptor_gain	0.9900
16:56589594:GACCC:G	donor_gain	0.9800
16:56589622:G:GG	donor_gain	0.9800
16:56589624:GAGC:G	donor_loss	0.9800
16:56589932:AAGA:A	donor_gain	0.9800
16:56589932:AAGAG:A	donor_loss	0.9800
16:56589933:AGAG:A	donor_loss	0.9800
16:56589935:AG:A	donor_loss	0.9800
16:56589936:GTGA:G	donor_loss	0.9800
16:56589937:T:A	donor_loss	0.9800
16:56589938:GAGT:G	donor_loss	0.9800
16:56589939:AGTG:A	donor_loss	0.9800
16:56590006:G:GT	donor_gain	0.9800
16:56590834:CTGCA:C	acceptor_loss	0.9800
16:56590838:A:AG	acceptor_gain	0.9800

AlphaMissense

447 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:56590854:T:A	C38S	0.877
16:56590855:G:C	C38S	0.877
16:56590875:T:A	C45S	0.872
16:56590876:G:C	C45S	0.872
16:56589878:T:C	C14R	0.869
16:56590856:C:G	C38W	0.868
16:56589614:C:G	C8W	0.866
16:56590854:T:C	C38R	0.863
16:56590889:T:G	C49W	0.850
16:56589917:T:C	C27R	0.846
16:56590851:T:C	C37R	0.844
16:56589884:T:C	C16R	0.843
16:56589896:T:A	C20S	0.839
16:56589897:G:C	C20S	0.839
16:56589612:T:C	C8R	0.837
16:56589902:T:A	C22S	0.837
16:56589903:G:C	C22S	0.837
16:56589608:C:G	C6W	0.835
16:56590887:T:A	C49S	0.835
16:56590888:G:C	C49S	0.835
16:56590932:T:A	C64S	0.835
16:56590933:G:C	C64S	0.835
16:56589878:T:A	C14S	0.834
16:56589879:G:C	C14S	0.834
16:56589880:C:G	C14W	0.833
16:56589917:T:A	C27S	0.828
16:56589918:G:C	C27S	0.828
16:56590893:T:A	C51S	0.828
16:56590894:G:C	C51S	0.828
16:56590932:T:C	C64R	0.828

dbSNP variants (sampled 300 via entrez): RS1000291533 (16:56588808 A>C,G), RS1003581270 (16:56591207 A>C), RS1003612417 (16:56591474 A>G), RS1005205896 (16:56588083 C>A,T), RS1009204096 (16:56590317 T>C), RS1009917407 (16:56590078 A>G), RS1010618936 (16:56588829 C>T), RS1011158766 (16:56591514 G>A), RS1012455468 (16:56588429 T>C), RS1014356786 (16:56588179 C>T), RS1015086689 (16:56589350 C>A,G,T), RS1016266211 (16:56590476 T>C), RS1018940011 (16:56588841 C>G), RS1021034884 (16:56590392 T>G), RS1023002744 (16:56587865 A>G)

Disease associations

OMIM: gene MIM:139255 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Cadmium	affects binding, increases expression, decreases response to substance, increases response to substance, decreases reaction	15
Zinc	affects abundance, affects transport, increases reaction, increases activity, increases expression (+5 more)	15
Copper	affects binding, decreases expression, affects cotreatment, decreases reaction, increases chemical synthesis (+2 more)	8
Cisplatin	increases expression, affects expression, affects reaction, decreases response to substance	3
Hydrogen Peroxide	decreases response to substance, increases reaction, decreases reaction	3
cadmium sulfate	increases expression	2
entinostat	increases expression, increases reaction	2
Arsenic Trioxide	affects binding, decreases reaction, decreases expression	2
Arsenic	increases expression	2
Edetic Acid	increases alkylation, affects metabolic processing	2
Oxygen	affects response to substance, decreases response to substance, increases expression	2
Tobacco Smoke Pollution	decreases expression, increases expression	2
Cadmium Chloride	increases expression, decreases reaction, affects cotreatment	2
tungsten carbide	affects cotreatment, increases expression	1
naringin	decreases reaction, increases expression	1
bisphenol A	decreases methylation	1
lead acetate	affects cotreatment, increases expression	1
terbufos	increases methylation	1
zinc chloride	increases expression	1
chromous chloride	affects cotreatment, increases expression	1
sodium arsenite	affects cotreatment, increases expression	1
W 7	affects cotreatment, increases expression	1
ferric nitrilotriacetate	decreases response to substance	1
chromic oxide	affects cotreatment, increases expression	1
8-hydroxyguanine	decreases abundance	1
benzo(e)pyrene	decreases methylation	1
gallium nitrate	increases expression	1
4-aminophenylarsenoxide	affects binding, decreases reaction	1
staurosporine aglycone	decreases reaction, decreases response to substance	1
tamibarotene	affects expression	1

Clinical trials (associated diseases)

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