RGN

Summary

RGN (regucalcin, HGNC:9989) is a protein-coding gene on chromosome Xp11.3, encoding Regucalcin (Q15493). Gluconolactonase with low activity towards other sugar lactones, including gulonolactone and galactonolactone.

The protein encoded by this gene is a highly conserved, calcium-binding protein, that is preferentially expressed in the liver and kidney. It may have an important role in calcium homeostasis. Studies in rat indicate that this protein may also play a role in aging, as it shows age-associated down-regulation. This gene is part of a gene cluster on chromosome Xp11.3-Xp11.23. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 9104 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 86 total
• MANE Select transcript: NM_152869

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9989
Approved symbol	RGN
Name	regucalcin
Location	Xp11.3
Locus type	gene with protein product
Status	Approved
Aliases	SMP30, RC
Ensembl gene	ENSG00000130988
Ensembl biotype	protein_coding
OMIM	300212
Entrez	9104

Gene structure

Transcript identifiers

Ensembl transcripts: 24 — 22 protein_coding, 2 protein_coding_CDS_not_defined

ENST00000336169, ENST00000352078, ENST00000397180, ENST00000457380, ENST00000469346, ENST00000475448, ENST00000899538, ENST00000899539, ENST00000899540, ENST00000899541, ENST00000899542, ENST00000899543, ENST00000899544, ENST00000899545, ENST00000899546, ENST00000899547, ENST00000899548, ENST00000899549, ENST00000899550, ENST00000899551, ENST00000899552, ENST00000925468, ENST00000955704, ENST00000955705

RefSeq mRNA: 4 — MANE Select: NM_152869 NM_001282848, NM_001282849, NM_004683, NM_152869

CCDS: CCDS14272, CCDS75968

Canonical transcript exons

ENST00000397180 — 8 exons

Exon	Start	End
ENSE00001527616	47080317	47080936
ENSE00003499321	47092061	47092215
ENSE00003848714	47078443	47078709
ENSE00003890537	47089776	47089991
ENSE00003892129	47084418	47084600
ENSE00003893148	47092897	47093313
ENSE00003894943	47081130	47081307
ENSE00003895425	47091678	47091809

Expression profiles

Bgee: expression breadth ubiquitous, 240 present calls, max score 99.15.

FANTOM5 (CAGE): breadth broad, TPM avg 2.9557 / max 272.8251, expressed in 519 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
196150	0.9987	250
196149	0.8896	329
196151	0.3646	154
196152	0.3505	40
196148	0.2724	162
196153	0.0554	17
196154	0.0245	6

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right adrenal gland cortex	UBERON:0035827	99.15	gold quality
right adrenal gland	UBERON:0001233	99.04	gold quality
adrenal cortex	UBERON:0001235	98.88	gold quality
left adrenal gland	UBERON:0001234	98.78	gold quality
left adrenal gland cortex	UBERON:0035825	98.77	gold quality
right lobe of liver	UBERON:0001114	98.68	gold quality
adrenal gland	UBERON:0002369	97.80	gold quality
liver	UBERON:0002107	97.57	gold quality
adrenal tissue	UBERON:0018303	95.16	gold quality
nephron tubule	UBERON:0001231	93.78	gold quality
adult mammalian kidney	UBERON:0000082	93.64	gold quality
body of pancreas	UBERON:0001150	93.42	gold quality
jejunal mucosa	UBERON:0000399	92.06	gold quality
kidney	UBERON:0002113	91.36	gold quality
right lung	UBERON:0002167	91.28	gold quality
cerebellar hemisphere	UBERON:0002245	91.18	gold quality
right hemisphere of cerebellum	UBERON:0014890	91.17	gold quality
kidney epithelium	UBERON:0004819	91.12	gold quality
cerebellar cortex	UBERON:0002129	91.10	gold quality
renal medulla	UBERON:0000362	90.18	gold quality
descending thoracic aorta	UBERON:0002345	90.11	gold quality
amygdala	UBERON:0001876	90.05	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	89.76	gold quality
cortex of kidney	UBERON:0001225	89.65	gold quality
lower lobe of lung	UBERON:0008949	89.57	gold quality
renal glomerulus	UBERON:0000074	89.55	gold quality
cerebellum	UBERON:0002037	89.55	gold quality
putamen	UBERON:0001874	89.38	gold quality
caudate nucleus	UBERON:0001873	89.29	gold quality
substantia nigra	UBERON:0002038	89.22	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-MTAB-10553	yes	30.36
E-ANND-3	yes	9.60
E-GEOD-75140	no	16.83

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AP1, CDX1, CEBPB, ESR1, INSM1, IRF6, NFIA, NFIC, SP1, SRY, THRB

miRNA regulators (miRDB)

24 targeting RGN, 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-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-5582-3P	99.86	72.48	4221
HSA-MIR-1323	99.83	69.89	2471
HSA-MIR-203A-3P	99.49	70.56	2806
HSA-MIR-6780B-3P	99.13	67.18	622
HSA-MIR-485-5P	99.10	64.78	1889
HSA-MIR-6884-5P	99.10	64.50	1987
HSA-MIR-6868-5P	99.06	65.69	1284
HSA-MIR-3194-3P	98.83	66.22	1167
HSA-MIR-5197-3P	98.71	67.05	1905
HSA-MIR-3928-5P	98.50	67.48	980
HSA-MIR-6806-3P	98.50	67.31	980
HSA-MIR-5088-3P	98.29	66.63	1310
HSA-MIR-595	98.25	67.44	699
HSA-MIR-127-5P	97.78	67.64	869
HSA-MIR-708-3P	97.50	68.67	1082
HSA-MIR-6802-3P	97.29	65.42	613
HSA-MIR-3152-5P	96.98	66.88	819
HSA-MIR-382-5P	96.71	65.90	762
HSA-MIR-2276-5P	96.27	65.85	937
HSA-MIR-6879-3P	93.93	64.00	759
HSA-MIR-1249-3P	90.34	67.26	42

Literature-anchored findings (GeneRIF, showing 40)

• a domain of the SMP30 sequence 51 amino acid residues long was 60-66% similar to bacterial and yeast RNA polymerases (PMID:12619687)
• SMP30 acts as a survival factor in hepatocytes (PMID:15358188)
• crystal structure of regucalcin (PMID:15502314)
• SMP30 induces formation of microvilli and bile canaliculi in HepG2 cells. (PMID:15714273)
• regucalcin plays an important role as a suppressor in the enhancement of cell proliferation (PMID:15962315)
• SMP30 also plays a very important role in a self-protective mechanism in survival and participates in the pathophysiological processes of acute liver failure. (PMID:18507831)
• effect of sex steroid hormones on regucalcin expression in breast and prostate cancer cells suggest that it may be associated with development and progression of these human tumors (PMID:19347872)
• Data suggest that through regucalcin and L-gulonolactone oxidase expression, beta-catenin regulates vitamin C biosynthesis in liver. (PMID:19690176)
• over-expression of SMP30/GNL in Hep G2 cells contributed to a decrease of reactive oxygen species formation accompanied by decreases of lipid peroxidation, superoxide dismutase activity and glutathione levels (PMID:19801822)
• These results suggest that hepatic SMP30 is closely associated with the pathogenesis of nonalcoholic fatty liver disease, although it is not known whether decreased hepatic SMP30 is a result or a cause of cirrhosis (PMID:19946731)
• SMP30 may be useful for hepatocellular carcinoma serologic screening, especially for the patients that are alpha-fetaprotein negative. (PMID:21047503)
• existence of multiple forms of SMP30 (PMID:21347421)
• Studies indicate that regucalcin plays an important role as a regulatory protein in cell signaling system, and it is proposed to play a pivotal role in keep of cell homeostasis and function. (PMID:21431902)
• Rgn is a novel androgen-target gene in testis and may have a role in male reproductive function, particularly in the control of spermatogenesis. (PMID:21680783)
• Data show that regucalcin (RGN) reduces agonist (histamine)-induced Ca(2+) transients in RGN(+) transfected COS-7 cells (RGN(+)) and also increases their Ca(2+) storage capacity. (PMID:21684279)
• RGN has a role in spermatogenesis, directly or as a mediator of androgen action. [review] (PMID:22121208)
• Regucalcin may play a pivotal role in the regulation of Ca(2+) signaling which is stimulated through a neurotransmitter in the brain neurons with aging (PMID:22652898)
• structural feature of mouse SMP30/GNL seems to facilitate the gamma-lactone-ring formation (PMID:23349732)
• Regucalcin may be a key molecule in lipid metabolic disorder and diabetes–{review} (PMID:23453039)
• SMP30 can inhibit the proliferation and invasion of human hepatoma cells and thus can be regarded as a cancer suppressive factor. (PMID:24606440)
• Overexpression of prostate RGN transgene in the prostate inhibits cell proliferation and apoptotic pathways. (PMID:24975685)
• The alternatively spliced variants of the regucalcin gene were found to be expressed in various human normal and tumor tissues. (PMID:25050833)
• RGN overexpression protected from carcinogen-induced mammary gland tumor development and was linked with reduced proliferation and increased apoptosis. These findings indicated the protective role of RGN in the carcinogenesis of mammary gland. (PMID:25128811)
• This review will discuss regarding to an involvement of regucalcin as a suppressor protein in human carcinogenesis in insight into the gene therapy. [review] (PMID:25230901)
• data suggest that exogenous regucalcin exerts suppressive effects on the proliferation of human pancreatic cancer cells. (PMID:25847529)
• immunohistochemistry revealed a significant decrease of regucalcin in human kidney disease tissue vs control kidney tissue, and regucalcin was detected in exosomes isolated from healthy donors’ urine but not from kidney disease patients (PMID:26072307)
• results highlighted the importance of RGN as a regulatory protein in Ca2+-dependent signaling pathways and its deregulation of RGN expression by Ca2+o may contribute for onset and progression of PCa. (PMID:26171977)
• Study results suggest that senescence marker protein-30 and senescence-associated beta-galactosidase expressions in both nuclear cataract and cortical cataract patients were associated with lens epithelial cells apoptosis. (PMID:26619319)
• Study demonstrates that increased regucalcin gene expression greatly contributes to prolonged survival in human pancreatic cancer patients. Morover, overexpression of regucalcin was found to suppress the proliferation, which is enhanced through various signaling pathways. (PMID:26935290)
• the present study suggests that regucalcin may have important anticancer properties in human breast cancer patients. Mechanistically, these effects are likely mediated through suppression of multiple signaling pathways, upregulation of p53 and downregulation of oncogenes leading to anti-proliferative effects and reduced metastases to bone, a phenotype associated with poor clinical outcome. (PMID:27221776)
• The role of RGN suppressing cell proliferation is associated with the regulation of expression of oncogenes and tumor suppressor genes. [review] (PMID:27411833)
• High RGN expression is associated with hepatocellular carcinoma. (PMID:27633001)
• The SMP30 may serve as a candidate of HCC clinical prognostic marker. (PMID:27991558)
• Dat show that regucalcin (RGN) is lowly expressed in hepatocellular carcinoma (HCC) tissues and down-regulates the proliferation ability of HepG2 cells. (PMID:28028056)
• These findings suggest that regucalcin may play a potential role as a suppressor of human lung cancer, and that downregulation of regucalcin expression may predispose patients to development of lung cancer. (PMID:28181135)
• SMP-30 overexpression plays a protective role in UVB-induced apoptosis via regulating the expression of apoptosis-related proteins and inhibiting the production of ROS in HLE-B3 cells (PMID:29141388)
• Study suggests that regucalcin plays a crucial role as a suppressor in human colorectal cancer, and that the suppressed expression of the regucalcin gene may predispose patients to the promotion of colorectal cancer. (PMID:29956741)
• In vitro experiments on colonic epithelial cells showed that stable SMP30 expression inhibited but that SMP30 siRNA expression increased TNF-alpha-induced apoptosis. SMP30 inhibition decreased Nrf2 mRNA expression levels (p<0.0001), but SMP30 overexpression increased Nrf2 mRNA expression levels (p=0.0495). (PMID:30266650)
• Data obtained demonstrated that the prolonged survival of patients with renal cell carcinoma (RCC) was associated with a higher regucalcin gene expression, and that the diminished regucalcin gene expression was accompanied by the poor prognosis of patients with RCC. Further findings suggest that regucalcin plays a suppressive role in the promotion of human RCC. (PMID:30387835)
• Results demonstrate that RGN is epigenetically modified in non-small cell lung cancer (NSCLC) tissues. A high expression of RGN on the RNA level was positively correlated with patients’ survival in adenocarcinomas. Also, high expression of Regucalcin seems to be protective in never smokers. (PMID:31718698)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	rgn	ENSDARG00000098645
mus_musculus	Rgn	ENSMUSG00000023070
rattus_norvegicus	Rgn	ENSRNOG00000007949
drosophila_melanogaster	regucalcin	FBGN0030362
drosophila_melanogaster	smp-30	FBGN0038257

Protein

Protein identifiers

Regucalcin — Q15493 (reviewed: Q15493)

Alternative names: Gluconolactonase, Senescence marker protein 30

All UniProt accessions (2): Q15493, V9HWF8

UniProt curated annotations — full annotation on UniProt →

Function. Gluconolactonase with low activity towards other sugar lactones, including gulonolactone and galactonolactone. Can also hydrolyze diisopropyl phosphorofluoridate and phenylacetate (in vitro). Calcium-binding protein. Modulates Ca(2+) signaling, and Ca(2+)-dependent cellular processes and enzyme activities.

Subunit / interactions. Monomer.

Subcellular location. Cytoplasm.

Cofactor. Binds 1 divalent metal cation per subunit. Most active with Zn(2+) and Mn(2+) ions. The physiological cofactor is most likely Ca(2+) or Mg(2+).

Similarity. Belongs to the SMP-30/CGR1 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q15493-1	1	yes
Q15493-2	2

RefSeq proteins (4): NP_001269777, NP_001269778, NP_004674, NP_690608* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR005511	SMP-30	Family
IPR008367	Regucalcin	Family
IPR011042	6-blade_b-propeller_TolB-like	Homologous_superfamily
IPR013658	SGL	Domain

Pfam: PF08450

Enzyme classification (BRENDA):

• EC 3.1.1.17 — gluconolactonase (BRENDA: 20 organisms, 69 substrates, 17 inhibitors, 12 Km, 6 kcat entries)

Substrate kinetics (BRENDA)

7 substrates with measured Km, best-characterized 7. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
D-GLUCONO-1,5-LACTONE	0.0162–25	5
D-GULONO-1,5-LACTONE	2.08	1
GLUCONO-1,5-LACTONE	6.2	1
L-GALACTONIC ACID	1.55	1
L-GALACTONO-1,4-LACTONE	1.67	1
L-GULONIC ACID	4.55	1
L-GULONO-1,4-LACTONE	3.05	1

Catalyzed reactions (Rhea), 1 shown:

• D-glucono-1,5-lactone + H2O = D-gluconate + H(+) (RHEA:10440)

UniProt features (54 total): strand 24, turn 8, binding site 6, mutagenesis site 4, helix 4, modified residue 3, splice variant 2, chain 1, active site 1, sequence conflict 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
3G4E	X-RAY DIFFRACTION	1.42
4GNB	X-RAY DIFFRACTION	1.5
4GNC	X-RAY DIFFRACTION	1.75
3G4H	X-RAY DIFFRACTION	1.92

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q15493-F1	97.90	0.99

Functional residue map

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

Catalytic / active sites (1): 204 (proton donor/acceptor)

Ligand- & substrate-binding residues (6): 18; 101; 103; 121; 154; 204

Post-translational modifications (3): 253, 144, 244

Mutagenesis-validated functional residues (4):

Position	Phenotype
18	reduces enzyme activity by about 90%.
103	reduces enzyme activity by about 95%.
154	reduces enzyme activity by about 95%.
204	reduces enzyme activity by over 98%.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 113 (showing top): GRUETZMANN_PANCREATIC_CANCER_DN, GOBP_REGULATION_OF_CALCIUM_MEDIATED_SIGNALING, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, CEBPB_01, CEBP_Q2, GOBP_POSITIVE_REGULATION_OF_MOLECULAR_FUNCTION, HOSHIDA_LIVER_CANCER_SUBCLASS_S3, BLALOCK_ALZHEIMERS_DISEASE_UP, HSIAO_LIVER_SPECIFIC_GENES, LEE_LIVER_CANCER_DENA_DN, MODULE_88, TGGNNNNNNKCCAR_UNKNOWN, GOBP_MONOATOMIC_ION_HOMEOSTASIS, FLECHNER_BIOPSY_KIDNEY_TRANSPLANT_REJECTED_VS_OK_DN, LEE_LIVER_CANCER_ACOX1_DN

GO Biological Process (4): intracellular calcium ion homeostasis (GO:0006874), L-ascorbic acid biosynthetic process (GO:0019853), positive regulation of ATP-dependent activity (GO:0032781), regulation of calcium-mediated signaling (GO:0050848)

GO Molecular Function (6): gluconolactonase activity (GO:0004341), calcium ion binding (GO:0005509), zinc ion binding (GO:0008270), enzyme regulator activity (GO:0030234), hydrolase activity (GO:0016787), metal ion binding (GO:0046872)

GO Cellular Component (2): nucleus (GO:0005634), cytoplasm (GO:0005737)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
catalytic activity	2
intracellular monoatomic cation homeostasis	1
calcium ion homeostasis	1
L-ascorbic acid metabolic process	1
water-soluble vitamin biosynthetic process	1
monosaccharide biosynthetic process	1
carboxylic acid biosynthetic process	1
lactone biosynthetic process	1
regulation of ATP-dependent activity	1
positive regulation of molecular function	1
ATP-dependent activity	1
calcium-mediated signaling	1
regulation of intracellular signal transduction	1
carboxylic ester hydrolase activity	1
metal ion binding	1
transition metal ion binding	1
molecular function regulator activity	1
cation binding	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1747 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RGN	SEC16B	Q96JE7	946
RGN	SEC16A	O15027	881
RGN	CALML4	Q96GE6	782
RGN	CALM1	P02593	729
RGN	CALML3	P27482	729
RGN	CALML5	Q9NZT1	729
RGN	CALML6	Q8TD86	710
RGN	H6PD	O95479	576
RGN	PGD	P52209	523
RGN	GPI	P06744	502
RGN	G6PD	P11413	494
RGN	GNMT	Q14749	468
RGN	TALDO1	P37837	454
RGN	RPIA	P49247	443
RGN	IDNK	Q5T6J7	442

IntAct

4 interactions, top by confidence:

A	B	Type	Score
OAZ3	AZIN1	psi-mi:“MI:0914”(association)	0.800
SGO2	DUSP14	psi-mi:“MI:0914”(association)	0.350

BioGRID (9): HINT1 (Co-fractionation), RGN (Co-fractionation), RGN (Co-fractionation), WDR1 (Co-fractionation), RGN (Affinity Capture-MS), RGN (Affinity Capture-MS), RGN (Affinity Capture-MS), RGN (Affinity Capture-Western), RGN (Two-hybrid)

ESM2 similar proteins: A0A0F5HSE8, A0A8F4N283, A7GKX6, A8FEH6, B0UWY1, B9DNI9, C0Z8L5, O07012, O07016, O34614, O34748, O34940, O86271, O86281, P12045, P39839, P42437, P46218, P59745, Q03336, Q06AA3, Q0I195, Q15493, Q2FFH4, Q2FWX8, Q2PFX5, Q2YU76, Q4L7N4, Q59536, Q5HEJ8, Q5HN15, Q5R837, Q64374, Q65CX4, Q65K51, Q6DF62, Q6G811, Q6GFD5, Q6TLF6, Q7A4P4

Diamond homologs: D4GP31, O34940, P0DOV6, P46218, Q03336, Q06AA3, Q15493, Q2PFX5, Q5R837, Q64374, Q6DF62, Q6TLF6, Q9A9Z1, Q9I922, Q9TTJ5, Q9TTJ6, Q1JUP5, Q9I923, Q2TXF4

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	42
Likely benign	1
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

1139 predictions. Top by Δscore:

Variant	Effect	Δscore
X:47084414:ACAG:A	acceptor_loss	1.0000
X:47084415:CAGAT:C	acceptor_loss	1.0000
X:47084416:A:AG	acceptor_gain	1.0000
X:47084416:A:C	acceptor_loss	1.0000
X:47084416:AGAT:A	acceptor_gain	1.0000
X:47084417:G:GT	acceptor_gain	1.0000
X:47084417:GA:G	acceptor_gain	1.0000
X:47084417:GAT:G	acceptor_gain	1.0000
X:47084417:GATG:G	acceptor_gain	1.0000
X:47084417:GATGC:G	acceptor_gain	1.0000
X:47084597:GCTG:G	donor_gain	1.0000
X:47084601:G:A	donor_loss	1.0000
X:47084601:G:GG	donor_gain	1.0000
X:47084602:T:A	donor_loss	1.0000
X:47089987:GATCT:G	donor_gain	1.0000
X:47089992:G:GG	donor_gain	1.0000
X:47091670:A:AG	acceptor_gain	1.0000
X:47091676:A:AG	acceptor_gain	1.0000
X:47091677:G:GG	acceptor_gain	1.0000
X:47091780:G:GT	donor_gain	1.0000
X:47081306:GG:G	donor_gain	0.9900
X:47081307:GG:G	donor_gain	0.9900
X:47084408:A:AG	acceptor_gain	0.9900
X:47084409:C:G	acceptor_gain	0.9900
X:47084413:TACAG:T	acceptor_gain	0.9900
X:47084414:ACAGA:A	acceptor_gain	0.9900
X:47084415:C:G	acceptor_gain	0.9900
X:47084415:CAGA:C	acceptor_gain	0.9900
X:47084416:AGATG:A	acceptor_gain	0.9900
X:47084570:A:T	donor_gain	0.9900

AlphaMissense

1952 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:47089891:T:A	N154K	0.998
X:47089891:T:G	N154K	0.998
X:47091758:T:A	W215R	0.998
X:47091758:T:C	W215R	0.998
X:47089901:T:A	W158R	0.997
X:47089901:T:C	W158R	0.997
X:47091726:A:T	D204V	0.997
X:47091727:T:A	D204E	0.997
X:47091727:T:G	D204E	0.997
X:47084563:T:A	N103K	0.996
X:47084563:T:G	N103K	0.996
X:47089890:A:T	N154I	0.996
X:47089937:A:C	S170R	0.996
X:47089939:C:A	S170R	0.996
X:47089939:C:G	S170R	0.996
X:47089823:G:T	G132W	0.995
X:47089893:G:A	G155D	0.995
X:47089893:G:T	G155V	0.995
X:47091729:G:A	G205E	0.995
X:47091729:G:T	G205V	0.995
X:47089887:C:A	S153Y	0.994
X:47089889:A:T	N154Y	0.994
X:47091725:G:C	D204H	0.994
X:47091760:G:C	W215C	0.994
X:47091760:G:T	W215C	0.994
X:47092105:T:C	S247P	0.994
X:47084556:G:C	R101P	0.993
X:47084568:G:A	G105E	0.993
X:47084591:T:G	Y113D	0.993
X:47089887:C:T	S153F	0.993

dbSNP variants (sampled 300 via entrez): RS1000470853 (X:47077694 G>A), RS1000606111 (X:47078119 G>A), RS1000794627 (X:47085523 A>T), RS1001101222 (X:47085285 C>T), RS1001529586 (X:47079923 G>A), RS1002200820 (X:47087545 T>C), RS1002780424 (X:47090060 G>A,C,T), RS1003624889 (X:47091309 G>A), RS1004037421 (X:47083454 A>C), RS1004638585 (X:47085200 T>C), RS1004947661 (X:47084685 G>A,C), RS1005372160 (X:47078883 A>G,T), RS1005544277 (X:47086593 G>T), RS1005612580 (X:47078547 C>G,T), RS1006620174 (X:47080803 G>A)

Disease associations

OMIM: gene MIM:300212 | 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

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	decreases expression, decreases methylation, increases mutagenesis	7
Aflatoxin B1	affects expression, decreases expression, increases methylation	4
Acetaminophen	decreases expression	3
Valproic Acid	decreases expression, increases methylation	3
entinostat	increases expression, affects cotreatment	2
Nickel	decreases expression	2
Quercetin	decreases expression	2
Tetrachlorodibenzodioxin	decreases expression	2
Cyclosporine	decreases expression	2
dicrotophos	decreases expression	1
testosterone enanthate	affects expression	1
methylmercuric chloride	decreases expression	1
methyleugenol	decreases expression	1
bisphenol A	decreases expression	1
decabromobiphenyl ether	decreases expression	1
sodium arsenite	decreases expression	1
9,10-dihydro-9,10-dihydroxybenzo(a)pyrene	decreases expression	1
tetrabromobisphenol A	decreases expression	1
tobacco tar	decreases reaction, increases expression	1
periodate-oxidized adenosine	affects expression	1
diallyl disulfide	decreases reaction, increases expression	1
aflatoxin B2	increases methylation	1
K 7174	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression, decreases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
dorsomorphin	affects cotreatment, increases expression, decreases expression	1
pentabrominated diphenyl ether 100	decreases expression	1
hexabrominated diphenyl ether 153	decreases expression	1
5-hydroxythalidomide	affects binding	1
Pioglitazone	decreases expression, decreases reaction, increases reaction	1

Clinical trials (associated diseases)

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