ORC2

Summary

ORC2 (origin recognition complex subunit 2, HGNC:8488) is a protein-coding gene on chromosome 2q33.1, encoding Origin recognition complex subunit 2 (Q13416). Component of the origin recognition complex (ORC) that binds origins of replication.

The origin recognition complex (ORC) is a highly conserved six subunits protein complex essential for the initiation of the DNA replication in eukaryotic cells. Studies in yeast demonstrated that ORC binds specifically to origins of replication and serves as a platform for the assembly of additional initiation factors such as Cdc6 and Mcm proteins. The protein encoded by this gene is a subunit of the ORC complex. This protein forms a core complex with ORC3, -4, and -5. It also interacts with CDC45 and MCM10, which are proteins known to be important for the initiation of DNA replication. This protein has been demonstrated to specifically associate with the origin of replication of Epstein-Barr virus in human cells, and is thought to be required for DNA replication from viral origin of replication. Alternatively spliced transcript variants have been found, one of which is a nonsense-mediated mRNA decay candidate.

Source: NCBI Gene 4999 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 91 total
• MANE Select transcript: NM_006190

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:8488
Approved symbol	ORC2
Name	origin recognition complex subunit 2
Location	2q33.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000115942
Ensembl biotype	protein_coding
OMIM	601182
Entrez	4999

Gene structure

Transcript identifiers

Ensembl transcripts: 24 — 20 protein_coding, 2 retained_intron, 2 protein_coding_CDS_not_defined

ENST00000234296, ENST00000410039, ENST00000457595, ENST00000464147, ENST00000467605, ENST00000474877, ENST00000487853, ENST00000879134, ENST00000879135, ENST00000879136, ENST00000879137, ENST00000879138, ENST00000879139, ENST00000938730, ENST00000938731, ENST00000938732, ENST00000938733, ENST00000938734, ENST00000938735, ENST00000938736, ENST00000938737, ENST00000938738, ENST00000938739, ENST00000938740

RefSeq mRNA: 1 — MANE Select: NM_006190 NM_006190

CCDS: CCDS2334

Canonical transcript exons

ENST00000234296 — 18 exons

Exon	Start	End
ENSE00000784501	200913295	200913413
ENSE00000784509	200913931	200913992
ENSE00000784524	200926768	200926900
ENSE00000784526	200931339	200931448
ENSE00000803327	200958030	200958133
ENSE00001022502	200959392	200959440
ENSE00001927137	200908977	200911387
ENSE00003499344	200942685	200942777
ENSE00003521244	200941248	200941279
ENSE00003533745	200925836	200925932
ENSE00003554444	200937906	200937966
ENSE00003559774	200920222	200920393
ENSE00003566824	200935699	200935892
ENSE00003592057	200920993	200921139
ENSE00003616077	200957401	200957544
ENSE00003688608	200933876	200933974
ENSE00003788110	200949554	200949643
ENSE00003848748	200963490	200963660

Expression profiles

Bgee: expression breadth ubiquitous, 267 present calls, max score 94.14.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 22.1372 / max 240.7400, expressed in 1807 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
33195	21.7176	1806
33196	0.4196	225

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
calcaneal tendon	UBERON:0003701	94.14	gold quality
sural nerve	UBERON:0015488	92.56	gold quality
colonic epithelium	UBERON:0000397	92.49	gold quality
buccal mucosa cell	CL:0002336	90.65	gold quality
mucosa of stomach	UBERON:0001199	88.13	gold quality
tendon	UBERON:0000043	88.07	gold quality
body of pancreas	UBERON:0001150	87.79	gold quality
secondary oocyte	CL:0000655	87.54	gold quality
skin of leg	UBERON:0001511	87.38	gold quality
adrenal tissue	UBERON:0018303	87.36	gold quality
right testis	UBERON:0004534	87.27	gold quality
left testis	UBERON:0004533	87.25	gold quality
testis	UBERON:0000473	86.89	gold quality
skin of abdomen	UBERON:0001416	86.89	gold quality
tonsil	UBERON:0002372	86.41	gold quality
rectum	UBERON:0001052	86.25	gold quality
oocyte	CL:0000023	86.20	gold quality
left lobe of thyroid gland	UBERON:0001120	86.07	gold quality
nerve	UBERON:0001021	85.70	gold quality
tibial nerve	UBERON:0001323	85.70	gold quality
metanephros cortex	UBERON:0010533	85.68	gold quality
small intestine Peyer’s patch	UBERON:0003454	85.56	gold quality
thyroid gland	UBERON:0002046	85.55	gold quality
right lobe of thyroid gland	UBERON:0001119	85.54	gold quality
descending thoracic aorta	UBERON:0002345	85.39	gold quality
left ovary	UBERON:0002119	85.38	gold quality
right ovary	UBERON:0002118	85.35	gold quality
subcutaneous adipose tissue	UBERON:0002190	85.33	gold quality
pancreas	UBERON:0001264	85.18	gold quality
zone of skin	UBERON:0000014	85.16	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.75

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): E2F2, KAT7, SP1

miRNA regulators (miRDB)

81 targeting ORC2, 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-3163	100.00	77.23	8605
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-6798-5P	100.00	65.77	699
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-6758-5P	100.00	66.21	1470
HSA-MIR-6856-5P	100.00	65.47	1298
HSA-MIR-3925-3P	100.00	69.95	1237
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-381-3P	99.93	71.87	2854
HSA-MIR-300	99.92	71.76	2856
HSA-MIR-515-5P	99.92	69.82	2343
HSA-MIR-519E-5P	99.92	69.62	2358
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-548AR-3P	99.85	71.26	3889
HSA-MIR-548AZ-3P	99.82	70.56	3549
HSA-MIR-548BC	99.82	70.61	3524
HSA-MIR-548E-3P	99.82	70.59	3514
HSA-MIR-548F-3P	99.82	70.59	3540

Literature-anchored findings (GeneRIF, showing 17)

• ORC2 physically interacts with ORC1 on non-chromatin nuclear structures (PMID:11779870)
• the human origin recognition complex has a role in sequence-independent DNA binding and replication initiation (PMID:12897055)
• The precise nucleotide of binding for ORC2 was identified near the stgart site for leading-strand synthesis; the transition to the post-replicative complex is accompanied by a 17 bp displacement of ORC2 towards the start site. (PMID:12912926)
• Study using HCT116 haplo-insufficient cells and Orc2 hypomorphic cells demonstrates that human Ku80 and Orc2 bind to replication origins independently of each other. (PMID:15910003)
• The low level of Orc2 in Orc2 hypomorphic cells hinders normal cell cycle progression by delaying the activation of G1 cyclin-dependent kinases. (PMID:16407251)
• human Orc2 has specific domains that are required in vivo for assembly and nuclear localization of the origin recognition complex (PMID:16762929)
• Plk1 phosphorylation of Orc2 promotes DNA replication under conditions of stress (PMID:21947279)
• The phosphorylation of ORC2 dissociates origin recognition complex (ORC) from chromatin and replication origins and inhibits binding of ORC to newly replicated DNA. (PMID:22334659)
• Orc2 protects ORCA from ubiquitin-mediated degradation in vivo. (PMID:22935713)
• Gemcitabine resistance is dependent on Plk1-mediated phosphorylation of Orc2 and Hbo1. (PMID:23188630)
• These results suggest that PP1 dephosphorylates Orc2 to promote the binding of ORC to chromatin. (PMID:24732362)
• Protein phosphatase 1 dephosphorylates Orc2 to promote the binding of ORC to chromatin and replication origins for the subsequent round of the cell cycle. (PMID:24792176)
• ORC2 SUMOylation promotes recruitment of KDM5A to centromeres. (PMID:27052177)
• the ORC2 complex with E2 restricts viral replication in the maintenance phase of the viral replication program (PMID:27701460)
• The authors have discovered that human cell lines in culture proliferate with intact chromosomal origins of replication after disruption of both alleles of ORC2 or of the ATPase subunit, ORC1. (PMID:27906128)
• The circ_ORC2 binds with miR-19a and enhances its expression, thereby inhibiting downstream PTEN expression and activating Akt pathway to promote osteosarcoma cell growth and invasion. (PMID:31103262)
• A human cancer cell line initiates DNA replication normally in the absence of ORC5 and ORC2 proteins. (PMID:32989049)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	orc2	ENSDARG00000101465
mus_musculus	Orc2	ENSMUSG00000026037
rattus_norvegicus	Orc2	ENSRNOG00000012558
drosophila_melanogaster	Orc2	FBGN0015270
caenorhabditis_elegans		WBGENE00003882

Protein

Protein identifiers

Origin recognition complex subunit 2 — Q13416 (reviewed: Q13416)

All UniProt accessions (3): B8ZZ80, C9JK08, Q13416

UniProt curated annotations — full annotation on UniProt →

Function. Component of the origin recognition complex (ORC) that binds origins of replication. DNA-binding is ATP-dependent. The specific DNA sequences that define origins of replication have not been identified yet. ORC is required to assemble the pre-replication complex necessary to initiate DNA replication. Binds histone H3 and H4 trimethylation marks H3K9me3, H3K20me3 and H4K27me3. Stabilizes LRWD1, by protecting it from ubiquitin-mediated proteasomal degradation. Also stabilizes ORC3.

Subunit / interactions. Component of ORC, a complex composed of at least 6 subunits: ORC1, ORC2, ORC3, ORC4, ORC5 and ORC6. ORC is regulated in a cell-cycle dependent manner. It is sequentially assembled at the exit from anaphase of mitosis and disassembled as cells enter S phase. Interacts with DBF4. Interacts with MCM10. Interacts with LRWD1 throughout the cell cycle; this interaction, which occurs only with non-ubiquitinated form of LRWD1, prevents LRWD1 ubiquitination and hence stabilizes the protein. Interacts with POLQ.

Subcellular location. Nucleus.

Similarity. Belongs to the ORC2 family.

RefSeq proteins (1): NP_006181* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR007220	ORC2	Family
IPR056772	RecA-like_ORC2	Domain
IPR056773	WHD_ORC2	Domain

Pfam: PF04084, PF24882

Enzyme classification (BRENDA):

• EC 3.6.4.B8 — (BRENDA: organisms, substrates, inhibitors, Km, kcat entries)

UniProt features (47 total): helix 14, strand 11, modified residue 6, turn 6, sequence conflict 3, sequence variant 2, compositionally biased region 2, chain 1, repeat 1, region of interest 1

Structure

Experimental structures (PDB)

16 structures.

PDB	Method	Resolution (Å)
5C8H	X-RAY DIFFRACTION	2.01
7JPO	ELECTRON MICROSCOPY	3.2
7JPQ	ELECTRON MICROSCOPY	3.5
8S0D	ELECTRON MICROSCOPY	3.6
7JPP	ELECTRON MICROSCOPY	3.7
7CTE	ELECTRON MICROSCOPY	3.8
8S0E	ELECTRON MICROSCOPY	3.8
7JPR	ELECTRON MICROSCOPY	4
8S0C	ELECTRON MICROSCOPY	4
8S0F	ELECTRON MICROSCOPY	4.1
7JPS	ELECTRON MICROSCOPY	4.4
7CTF	ELECTRON MICROSCOPY	4.8
7CTG	ELECTRON MICROSCOPY	5
5UJ8	X-RAY DIFFRACTION	6
8RWV	ELECTRON MICROSCOPY	6.68
5UJM	ELECTRON MICROSCOPY	18

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q13416-F1	65.09	0.17

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 (6): 280, 116, 122, 138, 226, 248

Function

Pathways and Gene Ontology

Reactome pathways

7 pathways

ID	Pathway
R-HSA-113507	E2F-enabled inhibition of pre-replication complex formation
R-HSA-176187	Activation of ATR in response to replication stress
R-HSA-68616	Assembly of the ORC complex at the origin of replication
R-HSA-68689	CDC6 association with the ORC:origin complex
R-HSA-68867	Assembly of the pre-replicative complex
R-HSA-68949	Orc1 removal from chromatin
R-HSA-68962	Activation of the pre-replicative complex

MSigDB gene sets: 181 (showing top): REACTOME_DNA_REPLICATION, BROWNE_HCMV_INFECTION_6HR_DN, REACTOME_ACTIVATION_OF_ATR_IN_RESPONSE_TO_REPLICATION_STRESS, CTATGCA_MIR153, BILD_SRC_ONCOGENIC_SIGNATURE, GOCC_MICROTUBULE_ORGANIZING_CENTER, GTGCCTT_MIR506, MUELLER_PLURINET, MILI_PSEUDOPODIA_HAPTOTAXIS_UP, SHETH_LIVER_CANCER_VS_TXNIP_LOSS_PAM5, GOCC_CENTROSOME, DACOSTA_UV_RESPONSE_VIA_ERCC3_COMMON_DN, DODD_NASOPHARYNGEAL_CARCINOMA_UP, FISCHER_DREAM_TARGETS, GOBP_DNA_REPLICATION

GO Biological Process (3): negative regulation of transcription by RNA polymerase II (GO:0000122), DNA replication initiation (GO:0006270), DNA replication (GO:0006260)

GO Molecular Function (2): DNA replication origin binding (GO:0003688), protein binding (GO:0005515)

GO Cellular Component (10): chromosome, telomeric region (GO:0000781), heterochromatin (GO:0000792), origin recognition complex (GO:0000808), inner kinetochore (GO:0000939), nucleus (GO:0005634), nucleoplasm (GO:0005654), nuclear origin of replication recognition complex (GO:0005664), centrosome (GO:0005813), membrane (GO:0016020), chromatin (GO:0000785)

Reactome top-level categories

Rollup of top-6 pathways:

Category	Pathways
Assembly of the pre-replicative complex	2
DNA Replication Pre-Initiation	2
E2F mediated regulation of DNA replication	1
G2/M Checkpoints	1
Switching of origins to a post-replicative state	1
G1/S Transition	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
DNA metabolic process	2
chromosome	2
protein-containing complex	2
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
negative regulation of DNA-templated transcription	1
DNA-templated DNA replication	1
DNA biosynthetic process	1
sequence-specific double-stranded DNA binding	1
binding	1
chromosomal region	1
chromatin	1
kinetochore	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
nuclear chromosome	1
origin recognition complex	1
nuclear protein-containing complex	1
centriole	1
microtubule organizing center	1

Protein interactions and networks

STRING

2072 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ORC2	ORC1	Q13415	972
ORC2	ORC4	O43929	960
ORC2	ORC6	Q9Y5N6	957
ORC2	ORC3	Q9UBD5	953
ORC2	ORC5	O43913	937
ORC2	MCM10	Q7L590	908
ORC2	CDC45	O75419	852
ORC2	MCM5	P33992	759
ORC2	MCM6	Q14566	719
ORC2	CDC7	O00311	674
ORC2	CDC6	Q99741	646
ORC2	CINP	Q9BW66	587
ORC2	CDT1	Q9H211	527
ORC2	LRWD1	Q9UFC0	525
ORC2	MCM4	P33991	504

IntAct

126 interactions, top by confidence:

A	B	Type	Score
MCM4	MCM7	psi-mi:“MI:0914”(association)	0.930
RBM8A	CASC3	psi-mi:“MI:0914”(association)	0.900
ORC1	ORC2	psi-mi:“MI:0407”(direct interaction)	0.890
ORC1	ORC5	psi-mi:“MI:0915”(physical association)	0.870
ORC1	ORC5	psi-mi:“MI:0914”(association)	0.870
MCM3	MCM5	psi-mi:“MI:0914”(association)	0.850
ORC2	ORC5	psi-mi:“MI:0914”(association)	0.810
ORC2	ORC5	psi-mi:“MI:0915”(physical association)	0.810
ORC2	ORC4	psi-mi:“MI:0915”(physical association)	0.810
ORC2	ORC5	psi-mi:“MI:0407”(direct interaction)	0.810
ORC2	ORC4	psi-mi:“MI:0407”(direct interaction)	0.810
ORC2	ORC4	psi-mi:“MI:0914”(association)	0.810
ORC4	ORC2	psi-mi:“MI:0914”(association)	0.810
ORC1	CCNA2	psi-mi:“MI:0914”(association)	0.730
MCM10	ORC2	psi-mi:“MI:0915”(physical association)	0.710

BioGRID (242): ORC2 (Affinity Capture-MS), ORC2 (Protein-peptide), ORC2 (Protein-peptide), LRWD1 (Affinity Capture-MS), ORC3 (Affinity Capture-MS), ORC4 (Affinity Capture-MS), ORC5 (Affinity Capture-MS), ORC1 (Affinity Capture-MS), ORC2 (Affinity Capture-MS), ORC2 (Affinity Capture-MS), ORC2 (Affinity Capture-MS), ORC2 (Affinity Capture-MS), ORC2 (Reconstituted Complex), CDC42BPB (Co-fractionation), LRWD1 (Co-fractionation)

ESM2 similar proteins: A0JMA8, A1A5P5, A2A6Q5, A6QNM3, A7Z061, E7F187, E9Q6P5, F7BJB9, O13046, O76094, P09798, P10505, P17885, P30260, P33731, P38042, P41889, Q05B30, Q06AN9, Q07617, Q13099, Q13416, Q32NR4, Q32NU8, Q3UMY5, Q4R6M4, Q4V8A2, Q5R629, Q5RE52, Q5TYV4, Q5U245, Q5ZKQ3, Q61371, Q6NU95, Q6PA97, Q6XV80, Q7Z3E5, Q7ZUV2, Q86TV6, Q8BGB2

Diamond homologs: A6QNM3, B8APQ0, Q09142, Q10QS7, Q13416, Q24168, Q38899, Q60862, Q75PQ8, Q91628, Q55CU7

SIGNOR signaling

6 interactions.

A	Effect	B	Mechanism
CDK2	up-regulates	ORC2	phosphorylation
CyclinA2/CDK2	up-regulates	ORC2	phosphorylation
ORC2	“form complex”	ORC	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 85 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Activation of the pre-replicative complex	14	76.1×	2e-21
Activation of ATR in response to replication stress	13	65.1×	5e-19
Extension of Telomeres	6	60.1×	1e-08
DNA Replication Pre-Initiation	9	47.6×	8e-12
Switching of origins to a post-replicative state	9	45.1×	1e-11
Synthesis of DNA	9	45.1×	1e-11
Orc1 removal from chromatin	14	41.6×	1e-17
DNA Replication	10	39.6×	3e-12

GO biological processes:

GO term	Partners	Fold	FDR
DNA replication initiation	12	96.0×	4e-19
regulation of DNA-templated DNA replication initiation	6	81.0×	2e-08
telomere maintenance	5	17.1×	7e-04
DNA replication	8	16.9×	3e-06
nucleosome assembly	5	9.0×	7e-03
mRNA splicing, via spliceosome	6	7.0×	7e-03
DNA repair	7	5.7×	7e-03
DNA damage response	8	5.5×	4e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	60
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2671 predictions. Top by Δscore:

Variant	Effect	Δscore
2:200913289:TCTTA:T	donor_loss	1.0000
2:200913290:CTTA:C	donor_loss	1.0000
2:200913291:TTA:T	donor_loss	1.0000
2:200913292:TA:T	donor_loss	1.0000
2:200913293:ACC:A	donor_loss	1.0000
2:200913294:C:A	donor_loss	1.0000
2:200913294:CCTT:C	donor_gain	1.0000
2:200913424:C:CT	acceptor_gain	1.0000
2:200920390:CACA:C	acceptor_gain	1.0000
2:200920392:CA:C	acceptor_gain	1.0000
2:200920394:C:CC	acceptor_gain	1.0000
2:200920398:CACA:C	acceptor_gain	1.0000
2:200920400:C:CT	acceptor_gain	1.0000
2:200920401:A:AC	acceptor_gain	1.0000
2:200920401:A:C	acceptor_gain	1.0000
2:200920406:C:CT	acceptor_gain	1.0000
2:200920407:A:T	acceptor_gain	1.0000
2:200920991:A:AC	donor_gain	1.0000
2:200920992:C:CC	donor_gain	1.0000
2:200921135:AGAAT:A	acceptor_gain	1.0000
2:200921136:GAAT:G	acceptor_gain	1.0000
2:200921137:AAT:A	acceptor_gain	1.0000
2:200921137:AATCT:A	acceptor_gain	1.0000
2:200921138:AT:A	acceptor_gain	1.0000
2:200921138:ATCTA:A	acceptor_gain	1.0000
2:200921140:C:CC	acceptor_gain	1.0000
2:200926766:A:AC	donor_gain	1.0000
2:200926767:C:CC	donor_gain	1.0000
2:200931331:ATACT:A	donor_loss	1.0000
2:200931332:TACTT:T	donor_loss	1.0000

AlphaMissense

3831 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:200913347:A:G	L532P	0.999
2:200913380:C:G	R521P	0.999
2:200913311:A:G	L544P	0.998
2:200913316:G:C	H542Q	0.998
2:200913316:G:T	H542Q	0.998
2:200913318:G:C	H542D	0.998
2:200913382:A:C	C520W	0.998
2:200920391:A:G	W433R	0.998
2:200920391:A:T	W433R	0.998
2:200913326:A:G	F539S	0.997
2:200913358:A:C	S528R	0.997
2:200913358:A:T	S528R	0.997
2:200913360:T:G	S528R	0.997
2:200913365:A:T	V526D	0.997
2:200913383:C:T	C520Y	0.997
2:200913384:A:G	C520R	0.997
2:200920237:A:G	L484P	0.997
2:200920239:G:C	S483R	0.997
2:200920239:G:T	S483R	0.997
2:200920241:T:G	S483R	0.997
2:200931355:A:G	W301R	0.997
2:200931355:A:T	W301R	0.997
2:200913317:T:G	H542P	0.996
2:200913344:C:G	R533P	0.996
2:200913368:A:G	L525P	0.996
2:200913335:A:G	L536S	0.995
2:200913347:A:T	L532H	0.995
2:200913413:C:T	G510D	0.995
2:200920249:A:T	V480D	0.995
2:200913308:A:T	I545K	0.994

dbSNP variants (sampled 300 via entrez): RS1000098761 (2:200926998 A>G), RS1000140267 (2:200943740 A>G), RS1000171788 (2:200962257 A>G,T), RS1000175294 (2:200914500 T>C), RS1000205288 (2:200934526 A>T), RS1000234520 (2:200922432 G>A), RS1000245893 (2:200922728 A>C), RS1000334593 (2:200954864 G>A), RS1000355414 (2:200952657 G>A), RS1000370041 (2:200912587 CTTT>C,CT,CTT,CTTTT), RS1000418012 (2:200960246 G>A), RS1000424978 (2:200941767 G>A), RS1000488073 (2:200963010 C>T), RS1000548142 (2:200913200 G>A), RS1000550697 (2:200920635 T>A)

Disease associations

OMIM: gene MIM:601182 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST003008_16	Triptolide cytotoxicity	3.000000e-06
GCST003008_2	Triptolide cytotoxicity	6.000000e-07
GCST006431_21	Plasma parathyroid hormone levels	5.000000e-06

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0006952	cytotoxicity measurement
EFO:0007664	outer ear morphology trait

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression, increases expression	3
Quercetin	decreases expression	2
Cadmium Chloride	decreases expression, increases expression, increases methylation	2
aristolochic acid I	decreases expression	1
FR900359	decreases phosphorylation	1
bisphenol A	affects cotreatment, decreases expression	1
sodium arsenite	decreases expression	1
coumarin	affects phosphorylation	1
beta-methylcholine	affects expression	1
tamibarotene	decreases expression	1
CGP 52608	increases reaction, affects binding	1
bisphenol S	affects cotreatment, decreases expression	1
Resveratrol	affects cotreatment, increases expression	1
Sunitinib	decreases expression	1
Zoledronic Acid	decreases expression	1
Atrazine	increases expression	1
Dexamethasone	affects cotreatment, decreases expression	1
Dimethyl Sulfoxide	increases expression	1
Doxorubicin	decreases expression	1
Ethyl Methanesulfonate	decreases expression	1
Formaldehyde	decreases expression	1
Indomethacin	affects cotreatment, decreases expression	1
Methyl Methanesulfonate	decreases expression	1
Nicotine	increases expression	1
Plant Extracts	affects cotreatment, increases expression	1
Progesterone	increases expression	1
Thiram	decreases expression	1
Tretinoin	decreases expression	1
1-Methyl-3-isobutylxanthine	affects cotreatment, decreases expression	1
Aflatoxin B1	decreases methylation	1

Clinical trials (associated diseases)

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