PPP1R3A

Summary

PPP1R3A (protein phosphatase 1 regulatory subunit 3A, HGNC:9291) is a protein-coding gene on chromosome 7q31.1, encoding Protein phosphatase 1 regulatory subunit 3A (Q16821). Seems to act as a glycogen-targeting subunit for PP1.

The glycogen-associated form of protein phosphatase-1 (PP1) derived from skeletal muscle is a heterodimer composed of a 37-kD catalytic subunit and a 124-kD targeting and regulatory subunit. This gene encodes the regulatory subunit which binds to muscle glycogen with high affinity, thereby enhancing dephosphorylation of glycogen-bound substrates for PP1 such as glycogen synthase and glycogen phosphorylase kinase.

Source: NCBI Gene 5506 — RefSeq curated summary.

At a glance

• Gene–disease (curated): diabetes mellitus, noninsulin-dependent (Limited, GenCC) — +1 more curated relationship
• GWAS associations: 8
• Clinical variants (ClinVar): 214 total — 1 pathogenic
• Phenotypes (HPO): 5
• MANE Select transcript: NM_002711

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9291
Approved symbol	PPP1R3A
Name	protein phosphatase 1 regulatory subunit 3A
Location	7q31.1
Locus type	gene with protein product
Status	Approved
Aliases	GM
Ensembl gene	ENSG00000154415
Ensembl biotype	protein_coding
OMIM	600917
Entrez	5506

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 2 protein_coding, 1 nonsense_mediated_decay

ENST00000284601, ENST00000284602, ENST00000449795

RefSeq mRNA: 1 — MANE Select: NM_002711 NM_002711

CCDS: CCDS5759

Canonical transcript exons

ENST00000284601 — 4 exons

Exon	Start	End
ENSE00001015769	113918215	113919009
ENSE00001347897	113876777	113880125
ENSE00003509691	113882262	113882320
ENSE00003660664	113882039	113882163

Expression profiles

Bgee: expression breadth broad, 79 present calls, max score 97.93.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 1.0812 / max 216.0315, expressed in 45 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
85788	0.9019	43
85786	0.0807	16
85787	0.0597	19
85789	0.0390	19

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	97.93	gold quality
hindlimb stylopod muscle	UBERON:0004252	95.70	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	93.93	gold quality
biceps brachii	UBERON:0001507	92.39	gold quality
body of tongue	UBERON:0011876	92.16	gold quality
gastrocnemius	UBERON:0001388	90.80	gold quality
muscle of leg	UBERON:0001383	89.37	gold quality
skeletal muscle organ	UBERON:0014892	88.85	gold quality
muscle organ	UBERON:0001630	88.84	gold quality
vastus lateralis	UBERON:0001379	88.67	gold quality
heart left ventricle	UBERON:0002084	87.58	gold quality
skeletal muscle tissue	UBERON:0001134	87.43	gold quality
cardiac ventricle	UBERON:0002082	87.22	gold quality
quadriceps femoris	UBERON:0001377	86.60	gold quality
apex of heart	UBERON:0002098	86.41	gold quality
right atrium auricular region	UBERON:0006631	86.36	gold quality
cardiac atrium	UBERON:0002081	84.34	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	82.69	gold quality
tongue	UBERON:0001723	80.13	gold quality
heart	UBERON:0000948	80.06	gold quality
muscle tissue	UBERON:0002385	79.60	gold quality
triceps brachii	UBERON:0001509	76.75	gold quality
heart right ventricle	UBERON:0002080	75.20	gold quality
diaphragm	UBERON:0001103	72.94	gold quality
gluteal muscle	UBERON:0002000	72.27	gold quality
deltoid	UBERON:0001476	71.02	silver quality
superior surface of tongue	UBERON:0007371	69.34	gold quality
vena cava	UBERON:0004087	65.47	silver quality
pharyngeal mucosa	UBERON:0000355	61.86	silver quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	60.68	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	3.74

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): NCOR1, RELA, ZHX2

miRNA regulators (miRDB)

83 targeting PPP1R3A, 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-6867-5P	100.00	82.21	3464
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-6740-5P	100.00	65.64	932
HSA-MIR-12118	100.00	65.88	1270
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-6891-5P	99.98	66.53	1372
HSA-MIR-3173-3P	99.98	66.49	1217
HSA-MIR-32-5P	99.98	75.21	1964
HSA-MIR-92A-3P	99.98	75.21	1960
HSA-MIR-92B-3P	99.98	75.25	1955
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-3912-5P	99.95	66.11	925
HSA-MIR-4760-3P	99.93	70.50	2385
HSA-MIR-10523-5P	99.91	69.22	2038
HSA-MIR-5680	99.91	69.83	3421
HSA-MIR-1305	99.91	71.43	3443
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-30A-3P	99.87	69.74	2928
HSA-MIR-30D-3P	99.87	69.92	2917
HSA-MIR-30E-3P	99.87	69.68	2942
HSA-MIR-609	99.82	64.26	505
HSA-MIR-3121-3P	99.82	71.96	3630
HSA-MIR-205-5P	99.81	70.05	1557
HSA-MIR-4668-5P	99.79	70.58	3782
HSA-MIR-4713-5P	99.78	67.80	1794

Literature-anchored findings (GeneRIF, showing 11)

• A joint effect between the Asp905 and BMI increases the risk of type 2 diabetes, and Asp905Tyr and ARE polymorphism of PPP1R3 gene are not the major diabetogenic gene variants in Chinese population. (PMID:11793847)
• We describe a family in which five individuals with severe insulin resistance, but no unaffected family members, were compound heterozygous with respect to frameshift/premature stop mutations in two unlinked genes, PPARG and PPP1R3A (PMID:12118251)
• G(M) promotes glycogen storage and inversely regulates glycogen synthase and glycogen phosphorylase activities, while, specifically, synthase phosphatase activity of G(M)-PP1 is inhibited by glycogen. (PMID:12941760)
• Among the largest cohort of nondiabetic subjects (Caucasian, n = 112), the presence of the deletion allele (ARE-2) was associated with insulin resistance and hyperandrogenemia. (PMID:15181086)
• Inactivation of PPP1R3 gene is associated with tumor progression and metastasis of colorectal cancers (PMID:15870946)
• PPP1R3A C1984DeltaAG (stop codon 668) isthe 1st prevalent mutation that directly impairs glycogen synthesis & decreases glycogen levels in human skeletal muscle. It is present in approximately 1 in 70 UK whites. (PMID:18232732)
• results demonstrate that hScrib acts as a scaffold to integrate the control of the PP1gamma and ERK signaling pathways and explains how disruption of hScrib localisation can contribute towards the development of human malignancy (PMID:23359326)
• In the univariate analyses, TP53, PPP1R3A, and KMT2B were significantly more frequently mutated in interval cancers than in screen-detected cancers. (PMID:27587435)
• Variant in PPP1R3A is associated with type 2 diabetes. (PMID:29948331)
• Genome-wide genotyping study and gene expression measurements of healthy and failing human hearts revealed important regulators and cardiac expression quantitative trait loci. PPP1R3A emerges as a regulator whose network connectivity changes significantly between health and disease. RNA sequencing after PPP1R3A knockdown validates network-based predictions and establish PPP1R3A as a central regulator in heart failure. (PMID:31235787)
• Decreased PPP1R3G in pre-eclampsia impairs human trophoblast invasion and migration via Akt/MMP-9 signaling pathway. (PMID:37642261)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	ppp1r3ab	ENSDARG00000088813
danio_rerio	ppp1r3aa	ENSDARG00000090468
mus_musculus	Ppp1r3a	ENSMUSG00000042717
rattus_norvegicus	Ppp1r3a	ENSRNOG00000059350
drosophila_melanogaster	Gbs-70E	FBGN0036428
caenorhabditis_elegans		WBGENE00019211

Paralogs (6): PPP1R3F (ENSG00000049769), PPP1R3C (ENSG00000119938), PPP1R3D (ENSG00000132825), PPP1R3B (ENSG00000173281), PPP1R3G (ENSG00000219607), PPP1R3E (ENSG00000235194)

Protein

Protein identifiers

Protein phosphatase 1 regulatory subunit 3A — Q16821 (reviewed: Q16821)

Alternative names: Protein phosphatase 1 glycogen-associated regulatory subunit, Protein phosphatase type-1 glycogen targeting subunit

All UniProt accessions (2): Q16821, C9JZB3

UniProt curated annotations — full annotation on UniProt →

Function. Seems to act as a glycogen-targeting subunit for PP1. PP1 is essential for cell division, and participates in the regulation of glycogen metabolism, muscle contractility and protein synthesis. Plays an important role in glycogen synthesis but is not essential for insulin activation of glycogen synthase.

Subunit / interactions. Interacts with PPP1CC catalytic subunit of PP1, and associates with glycogen.

Subcellular location. Membrane.

Tissue specificity. Skeletal muscle and heart.

Post-translational modifications. Phosphorylation at Ser-46 by ISPK stimulates the dephosphorylation of glycogen synthase and phosphorylase kinase.

Disease relevance. Type 2 diabetes mellitus (T2D) [MIM:125853] A multifactorial disorder of glucose homeostasis caused by a lack of sensitivity to insulin. Affected individuals usually have an obese body habitus and manifestations of a metabolic syndrome characterized by diabetes, insulin resistance, hypertension and hypertriglyceridemia. The disease results in long-term complications that affect the eyes, kidneys, nerves, and blood vessels. Disease susceptibility is associated with variants affecting the gene represented in this entry.

Domain organisation. The CBM21 domain is known to be involved in the localization to glycogen and is characteristic of some regulatory subunit of phosphatase complexes.

Miscellaneous. May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.

Isoforms (2)

UniProt ID	Names	Canonical?
Q16821-1	1	yes
Q16821-2	2

RefSeq proteins (1): NP_002702* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR005036	CBM21_dom	Domain
IPR038175	CBM21_dom_sf	Homologous_superfamily
IPR050782	PP1_regulatory_subunit_3	Family

Pfam: PF03370

UniProt features (39 total): sequence variant 11, modified residue 7, region of interest 7, compositionally biased region 6, splice variant 2, chain 1, transmembrane region 1, short sequence motif 1, domain 1, turn 1, strand 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
5ZQV	X-RAY DIFFRACTION	2.95

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q16821-F1	45.23	0.09

Functional residue map

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

Post-translational modifications (7): 38, 42, 46, 49, 56, 65, 844

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 115 (showing top): MULLIGHAN_NPM1_SIGNATURE_3_UP, MOOTHA_GLYCOGEN_METABOLISM, GOBP_POLYSACCHARIDE_BIOSYNTHETIC_PROCESS, MEF2_02, HNF1_Q6, GOBP_GENERATION_OF_PRECURSOR_METABOLITES_AND_ENERGY, CEBP_Q2, GOBP_REGULATION_OF_CARBOHYDRATE_METABOLIC_PROCESS, MODULE_99, GOBP_CARBOHYDRATE_METABOLIC_PROCESS, GOBP_REGULATION_OF_GLYCOGEN_METABOLIC_PROCESS, TGACATY_UNKNOWN, GOBP_REGULATION_OF_CARBOHYDRATE_BIOSYNTHETIC_PROCESS, GOBP_REGULATION_OF_POLYSACCHARIDE_METABOLIC_PROCESS, GOBP_REGULATION_OF_GENERATION_OF_PRECURSOR_METABOLITES_AND_ENERGY

GO Biological Process (2): glycogen metabolic process (GO:0005977), regulation of glycogen biosynthetic process (GO:0005979)

GO Molecular Function (3): protein phosphatase 1 binding (GO:0008157), glycogen binding (GO:2001069), protein binding (GO:0005515)

GO Cellular Component (2): protein phosphatase type 1 complex (GO:0000164), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
energy reserve metabolic process	1
glucan metabolic process	1
glycogen biosynthetic process	1
regulation of glucan biosynthetic process	1
regulation of glycogen metabolic process	1
protein phosphatase binding	1
polysaccharide binding	1
binding	1
cytoplasm	1
protein serine/threonine phosphatase complex	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1276 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PPP1R3A	RBL2	Q08999	981
PPP1R3A	RHAG	Q02094	916
PPP1R3A	RHCE	P18577	849
PPP1R3A	H3BT10	H3BT10	802
PPP1R3A	PPP1R8	Q12972	774
PPP1R3A	PPP1CC	P36873	760
PPP1R3A	PPP1CB	P37140	742
PPP1R3A	PPP1R1A	Q13522	669
PPP1R3A	NR3C1	P04150	651
PPP1R3A	UNC119	Q13432	629
PPP1R3A	BCL2	P10415	613
PPP1R3A	PPP1R2	P41236	608
PPP1R3A	PIK3R1	P27986	589
PPP1R3A	PPP1CA	P08129	575
PPP1R3A	PPARG	P37231	571

IntAct

3 interactions, top by confidence:

A	B	Type	Score
CBX6	IGF2BP3	psi-mi:“MI:0914”(association)	0.530
FAM20C	PPP1R3A	psi-mi:“MI:0217”(phosphorylation reaction)	0.440

BioGRID (67): PPP1R13B (Affinity Capture-MS), TP53BP2 (Affinity Capture-MS), CCDC85B (Affinity Capture-MS), CCDC85C (Affinity Capture-MS), CDCA2 (Affinity Capture-MS), CNST (Affinity Capture-MS), C20orf27 (Affinity Capture-MS), PPP1R13L (Affinity Capture-MS), PPP1R2 (Affinity Capture-MS), KIF18A (Affinity Capture-MS), MKI67 (Affinity Capture-MS), ERBB2IP (Affinity Capture-MS), LMTK2 (Affinity Capture-MS), PPP1R9A (Affinity Capture-MS), PPP1R9B (Affinity Capture-MS)

ESM2 similar proteins: A0JNH1, E9Q394, E9Q3S4, F1M3G7, M0RD54, O02665, O94854, P0C6C0, P48754, Q00756, Q0VGT4, Q12802, Q16821, Q283Q6, Q29106, Q2M3C7, Q3KR64, Q3U0P1, Q3ULM6, Q3URK3, Q3UXL4, Q3V089, Q49AJ0, Q5DTT3, Q5HZI1, Q5R5G4, Q5ZK13, Q69ZZ9, Q6DIA7, Q6NSW3, Q6RJR6, Q6ZVF9, Q711Q0, Q7T005, Q7Z434, Q80U44, Q86TB3, Q86YC2, Q8BJM3, Q8BWS5

Diamond homologs: A6QNP3, O95685, P40036, P40187, Q00756, Q0VCR4, Q16821, Q28E28, Q5BL87, Q5U2R5, Q6DDQ5, Q6GL23, Q6GQ68, Q6IN01, Q6P950, Q7TMB3, Q803M0, Q86XI6, Q8C767, Q99MR9, Q9UQK1, Q9VVY3, T1SFR8, Q6ZSY5, Q9H7J1, Q9JIG4, P28006, B7ZBB8, Q06216, Q9CW07, P0C7L8, Q8BRJ4, P07683

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
PPP1R3A	up-regulates	GYS1	dephosphorylation
RPS6KA1	“up-regulates activity”	PPP1R3A	phosphorylation
RPS6K	“up-regulates activity”	PPP1R3A	phosphorylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	170
Likely benign	20
Benign	16

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
1706493	GRCh37/hg19 7q31.1(chr7:112520887-113741230)x3	Pathogenic

SpliceAI

745 predictions. Top by Δscore:

Variant	Effect	Δscore
7:113882032:CACTT:C	donor_loss	1.0000
7:113882033:ACTTA:A	donor_loss	1.0000
7:113882034:CTTA:C	donor_loss	1.0000
7:113882035:TTA:T	donor_loss	1.0000
7:113882036:T:TG	donor_loss	1.0000
7:113882038:C:T	donor_loss	1.0000
7:113882038:CCAT:C	donor_gain	1.0000
7:113882164:C:CC	acceptor_gain	1.0000
7:113882256:TATTA:T	donor_loss	1.0000
7:113882257:ATTAC:A	donor_loss	1.0000
7:113882258:TTACC:T	donor_loss	1.0000
7:113882259:TA:T	donor_loss	1.0000
7:113882260:A:AT	donor_loss	1.0000
7:113882261:CCTG:C	donor_loss	1.0000
7:113882319:TA:T	acceptor_gain	1.0000
7:113885596:C:T	acceptor_gain	1.0000
7:113880127:T:C	acceptor_gain	0.9900
7:113880127:T:TC	acceptor_gain	0.9900
7:113882031:ACACT:A	donor_loss	0.9900
7:113882037:A:AC	donor_gain	0.9900
7:113882038:C:CC	donor_gain	0.9900
7:113882161:TAT:T	acceptor_gain	0.9900
7:113882163:TC:T	acceptor_loss	0.9900
7:113882164:C:A	acceptor_loss	0.9900
7:113882165:T:G	acceptor_loss	0.9900
7:113882260:A:AC	donor_gain	0.9900
7:113882261:C:CC	donor_gain	0.9900
7:113882316:CTTTA:C	acceptor_gain	0.9900
7:113882321:C:CC	acceptor_gain	0.9900
7:113882324:T:TC	acceptor_gain	0.9900

AlphaMissense

7411 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:113918433:G:C	F188L	0.998
7:113918433:G:T	F188L	0.998
7:113918435:A:G	F188L	0.998
7:113918434:A:G	F188S	0.997
7:113918557:C:G	R147P	0.997
7:113918368:C:G	R210P	0.996
7:113918342:A:G	W219R	0.994
7:113918342:A:T	W219R	0.994
7:113918377:A:G	F207S	0.994
7:113918427:A:C	F190L	0.994
7:113918427:A:T	F190L	0.994
7:113918429:A:G	F190L	0.994
7:113918428:A:G	F190S	0.993
7:113918373:A:C	C208W	0.992
7:113918340:C:A	W219C	0.991
7:113918340:C:G	W219C	0.991
7:113918371:A:T	I209K	0.991
7:113918476:G:T	A174E	0.991
7:113918501:A:G	W166R	0.991
7:113918501:A:T	W166R	0.991
7:113918343:A:C	F218L	0.990
7:113918343:A:T	F218L	0.990
7:113918345:A:G	F218L	0.990
7:113918799:A:C	F66L	0.990
7:113918799:A:T	F66L	0.990
7:113918801:A:G	F66L	0.990
7:113918499:C:A	W166C	0.989
7:113918499:C:G	W166C	0.989
7:113918513:A:G	S162P	0.989
7:113918521:A:T	V159E	0.989

dbSNP variants (sampled 300 via entrez): RS1000057055 (7:113893307 T>C), RS1000232345 (7:113876302 C>A), RS1000242898 (7:113919383 A>T), RS1000414919 (7:113899870 A>T), RS1000423249 (7:113894683 T>A), RS1000474052 (7:113913771 T>G), RS1000506528 (7:113885943 T>C), RS1000537980 (7:113912290 C>T), RS1000538926 (7:113877756 C>T), RS1000597065 (7:113899562 T>G), RS1000601063 (7:113877443 A>G), RS1000653130 (7:113892819 G>A), RS1000673104 (7:113877189 T>A), RS1000785012 (7:113883340 C>A,T), RS1000798811 (7:113907075 G>T)

Disease associations

OMIM: gene MIM:600917 | disease phenotypes: MIM:125853, MIM:609040

GenCC curated gene-disease

Disease	Classification	Inheritance
diabetes mellitus, noninsulin-dependent	Limited	Unknown
type 2 diabetes mellitus	Limited	Autosomal dominant

Mondo (4): type 2 diabetes mellitus (MONDO:0005148), monogenic diabetes (MONDO:0015967), arrhythmogenic right ventricular dysplasia 9 (MONDO:0012180), (MONDO:0007455)

Orphanet (1): Rare genetic diabetes mellitus (Orphanet:183625)

HPO phenotypes

5 total (5 of 5 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000855	Insulin resistance
HP:0003584	Late onset
HP:0005978	Type II diabetes mellitus
HP:0031819	Increased waist to hip ratio

GWAS associations

8 associations (top):

Study	Trait	p-value
GCST002587_11	Blood pressure (smoking interaction)	3.000000e-07
GCST002587_12	Blood pressure (smoking interaction)	3.000000e-06
GCST004946_203	Schizophrenia	2.000000e-08
GCST005830_37	Hand grip strength	3.000000e-08
GCST007201_12	Schizophrenia	5.000000e-07
GCST007576_345	Chronotype	1.000000e-12
GCST010988_168	Adult body size	2.000000e-08
GCST011122_64	Walking pace	2.000000e-12

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0006335	systolic blood pressure
EFO:0006525	cigarettes per day measurement
EFO:0006526	pack-years measurement
EFO:0006941	grip strength measurement
EFO:0008328	chronotype measurement

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D003924	Diabetes Mellitus, Type 2	C18.452.394.750.149; C19.246.300
C563808	Arrhythmogenic Right Ventricular Dysplasia, Familial, 9 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

12 total (human), top 12 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Doxorubicin	decreases expression	3
Daunorubicin	decreases expression	2
Mitoxantrone	decreases expression	2
testosterone enanthate	affects expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression	1
Sunitinib	decreases expression	1
Acetaminophen	decreases expression	1
Benzo(a)pyrene	increases methylation	1
Lipopolysaccharides	affects response to substance, increases expression	1
Triclosan	decreases expression	1
Valproic Acid	decreases methylation	1
Aflatoxin B1	decreases methylation	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00006163	PHASE4	COMPLETED	Computer-assisted Diabetes Self-management Interventions
NCT00036504	PHASE4	COMPLETED	Efficacy and Safety of Twice-Daily Insulin Lispro Low Mixture Compared to a Once-Daily Long Acting Insulin Comparator in Patients Who Have Been Using One or More Oral Antihyperglycemic Agents Without Insulin
NCT00044460	PHASE4	COMPLETED	Efficacy and Safety In Poorly Controlled Type 2 Diabetics
NCT00095446	PHASE4	COMPLETED	NovoLog Observation Trial in Subjects With Type 1 and Type 2 Diabetes
NCT00101751	PHASE4	COMPLETED	INITIATE Plus (INITiation of Insulin to Reach A1c TargEt) Study
NCT00110370	PHASE4	COMPLETED	Comparing Pre-Mixed Insulin With Insulin Glargine Combined With Rapid-Acting Insulin in Patients With Type 2 Diabetes
NCT00110448	PHASE4	COMPLETED	Japanese Primary Prevention of Atherosclerosis With Aspirin for Diabetes (JPAD) Trial
NCT00118950	PHASE4	COMPLETED	Effect of Metformin Versus Repaglinide Treatment in Non-Obese Type 2 Diabetic Patients Uncontrolled by Diet
NCT00118963	PHASE4	COMPLETED	Effect of Repaglinide Versus Metformin Treatment in Non-Obese Patients With Type-2-Diabetes
NCT00121966	PHASE4	COMPLETED	South Danish Diabetes Study: Evaluation of the Antidiabetic Treatment of Type 2 Diabetes Mellitus
NCT00123604	PHASE4	COMPLETED	Vascular Effects of Carvedilol Versus Metoprolol in Hypertensive Patients With Type 2 Diabetes
NCT00123643	PHASE4	COMPLETED	Vascular Effects of Rosiglitazone Versus Glyburide in Type 2 Diabetic Patients
NCT00124397	PHASE4	COMPLETED	Atorvastatin and Endothelial Function in Type 2 Diabetes Mellitus (ATTEND-Study)
NCT00129233	PHASE4	COMPLETED	Comparison of Valsartan With Amlodipine in Hypertensive Patients With Glucose Intolerance
NCT00133718	PHASE4	COMPLETED	A 2 Year Trial of Patients With Type 2 Diabetes Focusing on Cardiovascular Diagnostics and Metabolic Control
NCT00135070	PHASE4	TERMINATED	Hospital In-Patient Insulin Study
NCT00141232	PHASE4	COMPLETED	Evaluating Atorvastatin With Omega-3 Fatty Acids in Cardiovascular Risk Reduction in Patients With Type 2 Diabetes
NCT00144144	PHASE4	UNKNOWN	A Study on Ca Blocker Versus AII Antagonists in Hypertension With Type 2 Diabetes
NCT00149331	PHASE4	COMPLETED	The Effects of Two Education Strategies About Insulin on Patient Preferences and Perceptions About Insulin Therapy
NCT00162357	PHASE4	COMPLETED	Post-PCI:Cardiac Imaging in Patients With Diabetes to Detect Coronary Artery Blockages Previously Opened by Angioplasty
NCT00174681	PHASE4	COMPLETED	Tulip Study: Testing the Usefulness of Lantus When Initiated Prematurely In Patients With Type 2 Diabetes
NCT00174824	PHASE4	COMPLETED	Comparison of Insulin Glargine and NPH Human Insulin in Progression of Diabetic Retinopathy in Type 2 Diabetic Patients
NCT00177398	PHASE4	COMPLETED	Effect of Glargine Insulin on Glucose Control in Hospitalized Patients Who Receive Tube Feedings
NCT00179400	PHASE4	COMPLETED	The Role of Acute Combined PPAR Alpha and Gamma Stimulation on Insulin Action in Humans
NCT00184561	PHASE4	COMPLETED	Effectiveness and Safety of Biphasic Insulin Aspart 70/30 in Subjects With Type 2 Diabetes
NCT00184626	PHASE4	COMPLETED	Comparison of Insulin Glargine Versus Biphasic Insulin Aspart 30/70 or Biphasic Insulin Aspart 30/70 in Combination With Metformin in Subjects With Type 2 Diabetes.
NCT00191178	PHASE4	COMPLETED	Effects of Insulin in Perceived Mood Symptoms in Patients With Type 2 Diabetes
NCT00191282	PHASE4	COMPLETED	Hyperglycemia and Cardiovascular Outcomes With Type 2 Diabetes
NCT00191464	PHASE4	COMPLETED	Long-Term Effects of Insulin Plus Metformin Regimens on the Overall and Postprandial Glycemic Control of Patients With Type 2 Diabetes
NCT00192803	PHASE4	UNKNOWN	Non-Insulin Dependent Diabetes Mellitus (NIDDM) and Angiotensin Converting Enzyme 2 (ACE2): Diabetic Patients Treated With Antihypertensive Drugs
NCT00202033	PHASE4	COMPLETED	Impact of Self-Monitoring Blood Glucose Frequency on Glycemic Control in Patients With Type 2 Diabetes
NCT00205660	PHASE4	COMPLETED	Changes in Adiposity, Metabolic Measures From Atypicals to Aripiprazole
NCT00212290	PHASE4	COMPLETED	Insulin Resistance and Central Nervous System (CNS) Function in Type 2 Diabetes
NCT00212303	PHASE4	COMPLETED	Exercise Training in Type 2 Diabetes and Hypertension
NCT00225342	PHASE4	WITHDRAWN	Study Protocol for Rosiglitazone Versus Gliclazide in Diabetics With Angina
NCT00238472	PHASE4	COMPLETED	A Pilot Study to Evaluate the Effects of Nateglinide vs. Glibenclamide on Renal Hemodynamics and Albumin Excretion
NCT00239538	PHASE4	COMPLETED	SMOOTH - Blood Pressure Control in Diabetic/Obese Patients
NCT00240253	PHASE4	COMPLETED	A Study Evaluating the Efficacy and Safety of Adding Symlin® to Lantus® (Insulin Glargine) in Subjects With Type 2 Diabetes
NCT00240422	PHASE4	COMPLETED	Trial to Compare the Effects of Either Telmisartan (40-80 mg PO Once Daily) or Ramipril (5-10 mg PO Once Daily) on Renal Endothelial Dysfunction in Hypertensive Patients With Type 2 Diabetes
NCT00241085	PHASE4	COMPLETED	Effect of Valsartan on Proteinuria in Patients With Hypertension and Diabetes Mellitus