OBI1

Summary

OBI1 (ORC ubiquitin ligase 1, HGNC:20308) is a protein-coding gene on chromosome 13q31.1, encoding ORC ubiquitin ligase 1 (Q5W0B1). E3 ubiquitin ligase essential for DNA replication origin activation during S phase.

Enables chromatin binding activity and ubiquitin-protein transferase activity. Involved in protein autoubiquitination; protein monoubiquitination; and regulation of DNA replication. Located in chromatin.

Source: NCBI Gene 79596 — RefSeq curated summary.

At a glance

• GWAS associations: 5
• Clinical variants (ClinVar): 115 total
• MANE Select transcript: NM_024546

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:20308
Approved symbol	OBI1
Name	ORC ubiquitin ligase 1
Location	13q31.1
Locus type	gene with protein product
Status	Approved
Aliases	FLJ13449
Ensembl gene	ENSG00000152193
Ensembl biotype	protein_coding
OMIM	615906
Entrez	79596

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 3 protein_coding

ENST00000282003, ENST00000880927, ENST00000916103

RefSeq mRNA: 1 — MANE Select: NM_024546 NM_024546

CCDS: CCDS31997

Canonical transcript exons

ENST00000282003 — 6 exons

Exon	Start	End
ENSE00001003871	78659049	78659155
ENSE00001003874	78614289	78617122
ENSE00001003875	78638823	78639071
ENSE00001231589	78635110	78635198
ENSE00001473081	78642122	78642213
ENSE00001473085	78644862	78644997

Expression profiles

Bgee: expression breadth ubiquitous, 274 present calls, max score 96.93.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 15.1587 / max 315.7795, expressed in 1750 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
137713	14.0457	1738
137714	1.1131	650

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	96.93	gold quality
oocyte	CL:0000023	95.60	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	94.51	gold quality
cortical plate	UBERON:0005343	92.77	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	90.57	gold quality
germinal epithelium of ovary	UBERON:0001304	86.93	gold quality
Brodmann (1909) area 23	UBERON:0013554	86.11	gold quality
calcaneal tendon	UBERON:0003701	85.39	gold quality
ganglionic eminence	UBERON:0004023	85.10	gold quality
embryo	UBERON:0000922	85.00	gold quality
esophagus squamous epithelium	UBERON:0006920	84.26	gold quality
palpebral conjunctiva	UBERON:0001812	83.86	gold quality
amniotic fluid	UBERON:0000173	83.74	gold quality
tendon	UBERON:0000043	83.43	gold quality
parietal pleura	UBERON:0002400	83.34	gold quality
epithelium of nasopharynx	UBERON:0001951	83.01	gold quality
nasopharynx	UBERON:0001728	82.99	gold quality
middle temporal gyrus	UBERON:0002771	82.60	gold quality
sperm	CL:0000019	82.53	gold quality
pleura	UBERON:0000977	82.29	gold quality
ventricular zone	UBERON:0003053	82.28	gold quality
eye	UBERON:0000970	81.88	gold quality
tibia	UBERON:0000979	81.73	gold quality
primary visual cortex	UBERON:0002436	81.52	gold quality
visceral pleura	UBERON:0002401	81.09	gold quality
adrenal tissue	UBERON:0018303	80.76	gold quality
endometrium	UBERON:0001295	80.57	gold quality
islet of Langerhans	UBERON:0000006	80.54	gold quality
male germ cell	CL:0000015	80.47	gold quality
cerebellar cortex	UBERON:0002129	79.61	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.55

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

66 targeting OBI1, 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-8485	100.00	77.57	4731
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-101-3P	99.94	75.03	2230
HSA-MIR-218-5P	99.93	72.22	2103
HSA-MIR-338-5P	99.92	72.34	2951
HSA-MIR-6499-3P	99.90	66.38	1212
HSA-MIR-627-3P	99.90	71.42	3316
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-6124	99.87	69.78	3551
HSA-MIR-3941	99.86	70.54	2735
HSA-MIR-4698	99.84	71.41	4303
HSA-MIR-4495	99.82	72.08	3080
HSA-MIR-3681-5P	99.82	66.88	387
HSA-MIR-3133	99.81	70.92	3506
HSA-MIR-148A-3P	99.74	73.77	1700
HSA-MIR-148B-3P	99.74	73.75	1700

Literature-anchored findings (GeneRIF, showing 4)

• RNF219 silencing result in defective replication origin firing, as shown by reduced CDC45/MCM2-7/GINS complex formation, without affecting pre-replicative complex establishment. RNF219 catalyses the multi-mono-ubiquitylation of a subset of chromatin-bound ORC3 and ORC5 during S-phase. (PMID:31160578)
• A potential association of RNF219-AS1 with ADHD: Evidence from categorical analysis of clinical phenotypes and from quantitative exploration of executive function and white matter microstructure endophenotypes. (PMID:33644999)
• RNF219 attenuates global mRNA decay through inhibition of CCR4-NOT complex-mediated deadenylation. (PMID:34887419)
• RNF219 Promotes Nasopharyngeal Carcinoma Progression by Activating the NF-kappaB Pathway. (PMID:36512252)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio		ENSDARG00000090904
mus_musculus	Obi1	ENSMUSG00000022120
rattus_norvegicus	Obi1	ENSRNOG00000009690

Protein

Protein identifiers

ORC ubiquitin ligase 1 — Q5W0B1 (reviewed: Q5W0B1)

Alternative names: RING finger protein 219

All UniProt accessions (1): Q5W0B1

UniProt curated annotations — full annotation on UniProt →

Function. E3 ubiquitin ligase essential for DNA replication origin activation during S phase. Acts as a replication origin selector which selects the origins to be fired and catalyzes the multi-mono-ubiquitination of a subset of chromatin-bound ORC3 and ORC5 during S-phase.

Subunit / interactions. Associates with ORC complex. Binds to chromatin; association is cell cycle-regulated, absent from mitotic chromosomes, is associated with chromatin from G1 and partially released from chromatin from mid S-phase.

Subcellular location. Chromosome.

Post-translational modifications. Auto-ubiquitinated.

RefSeq proteins (1): NP_078822* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001841	Znf_RING	Domain
IPR013083	Znf_RING/FYVE/PHD	Homologous_superfamily
IPR035691	OBI1_RING-HC	Domain
IPR039209	OBI1	Family

Pfam: PF13923

UniProt features (27 total): modified residue 8, compositionally biased region 7, region of interest 4, sequence conflict 3, coiled-coil region 2, chain 1, zinc finger region 1, mutagenesis site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q5W0B1-F1	57.65	0.21

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 (8): 210, 526, 553, 561, 568, 570, 719, 721

Mutagenesis-validated functional residues (1):

Position	Phenotype
38	loss of e3 ubiquitin transferase activity. no effect on association with orc complex.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-69273	Cyclin A/B1/B2 associated events during G2/M transition

MSigDB gene sets: 136 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_UP, WEI_MYCN_TARGETS_WITH_E_BOX, GATA1_01, GOBP_PROTEIN_AUTOUBIQUITINATION, GOBP_PROTEIN_MONOUBIQUITINATION, GOBP_POST_TRANSLATIONAL_PROTEIN_MODIFICATION, BENPORATH_NOS_TARGETS, FISCHER_DREAM_TARGETS, IVANOVA_HEMATOPOIESIS_EARLY_PROGENITOR, GOBP_DNA_REPLICATION, MODULE_332, SUZUKI_RESPONSE_TO_TSA, GOMF_CHROMATIN_BINDING, CAIRO_LIVER_DEVELOPMENT_UP, BENPORATH_OCT4_TARGETS

GO Biological Process (3): regulation of DNA replication (GO:0006275), protein monoubiquitination (GO:0006513), protein autoubiquitination (GO:0051865)

GO Molecular Function (7): chromatin binding (GO:0003682), ubiquitin-protein transferase activity (GO:0004842), zinc ion binding (GO:0008270), ubiquitin protein ligase activity (GO:0061630), protein binding (GO:0005515), transferase activity (GO:0016740), metal ion binding (GO:0046872)

GO Cellular Component (3): chromatin (GO:0000785), nucleoplasm (GO:0005654), chromosome (GO:0005694)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
G2/M Transition	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein ubiquitination	2
binding	2
cellular anatomical structure	2
DNA replication	1
regulation of DNA metabolic process	1
ubiquitin-like protein transferase activity	1
transition metal ion binding	1
ubiquitin-protein transferase activity	1
ubiquitin-like protein ligase activity	1
catalytic activity	1
cation binding	1
chromosome	1
nuclear lumen	1
intracellular membraneless organelle	1

Protein interactions and networks

STRING

460 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
OBI1	LRWD1	Q9UFC0	518
OBI1	ORC3	Q9UBD5	502
OBI1	SV2A	Q7L0J3	499
OBI1	SCEL	O95171	483
OBI1	FKBP4	Q02790	482
OBI1	F8	P00451	479
OBI1	ORC5	O43913	470
OBI1	FKBP5	Q13451	467
OBI1	MYCBP2	O75592	443
OBI1	APBA2	Q99767	426
OBI1	TOGARAM2	Q6ZUX3	400
OBI1	DNAJC5B	Q9UF47	381
OBI1	ZNF184	Q99676	370
OBI1	POU4F1	Q01851	365
OBI1	ATOSB	Q7L5A3	351

IntAct

153 interactions, top by confidence:

A	B	Type	Score
CNOT6L	CNOT1	psi-mi:“MI:0914”(association)	0.810
CNOT11	CNOT1	psi-mi:“MI:0914”(association)	0.770
MLF1	DNAJB6	psi-mi:“MI:0914”(association)	0.750
TOB1	CNOT1	psi-mi:“MI:0914”(association)	0.710
RAB15	RAP1GDS1	psi-mi:“MI:0914”(association)	0.640
OBI1	TCEANC	psi-mi:“MI:0915”(physical association)	0.560
TCEANC	OBI1	psi-mi:“MI:0915”(physical association)	0.560
OBI1	SPRED1	psi-mi:“MI:0915”(physical association)	0.560
EBNA-LP	HAX1	psi-mi:“MI:0914”(association)	0.530
FANCD2OS	CNOT1	psi-mi:“MI:0914”(association)	0.530
RIBC1	CNOT1	psi-mi:“MI:0914”(association)	0.530
CNOT10	CNOT1	psi-mi:“MI:0914”(association)	0.530
DNAJB8	DNAJB6	psi-mi:“MI:0914”(association)	0.530
RPP21	POP7	psi-mi:“MI:0914”(association)	0.530
LRRK2	OBI1	psi-mi:“MI:0407”(direct interaction)	0.440
Cnot3	CNOT1	psi-mi:“MI:0915”(physical association)	0.400
OBI1	FKBP5	psi-mi:“MI:0915”(physical association)	0.400
Pcna	SIVA1	psi-mi:“MI:0914”(association)	0.350
CNOT1	IBTK	psi-mi:“MI:0914”(association)	0.350

BioGRID (219): TCEANC (Two-hybrid), RNF219 (Affinity Capture-RNA), RNF219 (Affinity Capture-MS), RNF219 (Biochemical Activity), RNF219 (Proximity Label-MS), RNF219 (Two-hybrid), RNF219 (Affinity Capture-MS), RNF219 (Affinity Capture-MS), RNF219 (Affinity Capture-MS), RNF219 (Affinity Capture-MS), RNF219 (Affinity Capture-MS), RNF219 (Affinity Capture-MS), RNF219 (Affinity Capture-MS), RNF219 (Affinity Capture-MS), RNF219 (Affinity Capture-MS)

ESM2 similar proteins: A0JM80, A0JNH1, A0JNH9, A3KMW7, A6NMK8, A6QNQ6, B0BM16, B1H1S4, B1WC58, B2GUZ2, D3Z987, D3ZF42, E7FAP1, F6SNN2, P23497, P70347, Q0P5X5, Q14B71, Q283Q6, Q29RT4, Q2M2Z5, Q3U0P1, Q3ULM6, Q3UXL4, Q3V089, Q571C7, Q5HZI1, Q5R9I1, Q5RD97, Q5W0B1, Q6GNV6, Q6KAQ7, Q6P1D7, Q6PDM4, Q7TSY8, Q7ZZH7, Q80WQ8, Q80YR6, Q86YC2, Q8BUH8

Diamond homologs: A8Y4B2, O49691, O55176, O60683, Q20798, Q28GL3, Q3UF64, Q4KLN8, Q5FWL3, Q5M7Z0, Q5R7T5, Q5RAG4, Q5RD97, Q5W0B1, Q5XHH7, Q5ZM74, Q6NKR1, Q6NPT7, Q6NRL6, Q6NTV1, Q6NZ21, Q803C1, Q803I8, Q84TF5, Q86TM6, Q8BH75, Q8HXW8, Q8L9T5, Q8NG27, Q96EX2, Q9DBY1, Q9DCN7, Q9FIR0, Q9H4P4, Q9LW77, Q9VE61, Q9XF63, B6VQ60, O64762, O64763

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
Ub:E2	“up-regulates activity”	OBI1	ubiquitination

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 184 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
TP53 regulates transcription of additional cell cycle genes whose exact role in the p53 pathway remain uncertain	6	26.9×	2e-05
Deadenylation of mRNA	5	18.9×	6e-04
M-decay: degradation of maternal mRNAs by maternally stored factors	5	14.1×	2e-03
SARS-CoV-1-host interactions	6	9.1×	3e-03
mRNA Polyadenylation	10	7.6×	1e-04
mRNA Splicing	7	6.6×	5e-03
mRNA Splicing - Major Pathway	14	6.6×	1e-05
Processing of Capped Intron-Containing Pre-mRNA	8	5.7×	5e-03

GO biological processes:

GO term	Partners	Fold	FDR
nuclear-transcribed mRNA poly(A) tail shortening	5	24.9×	5e-04
negative regulation of translation	8	9.7×	5e-04
mRNA splicing, via spliceosome	12	6.8×	2e-04
mRNA processing	10	4.9×	1e-02

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	102
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1095 predictions. Top by Δscore:

Variant	Effect	Δscore
13:78617120:AAC:A	acceptor_gain	1.0000
13:78617123:C:CC	acceptor_gain	1.0000
13:78617123:CT:C	acceptor_loss	1.0000
13:78633485:ATT:A	donor_gain	1.0000
13:78635106:ATAC:A	donor_loss	1.0000
13:78635107:TA:T	donor_loss	1.0000
13:78635108:A:AC	donor_gain	1.0000
13:78635109:C:CC	donor_gain	1.0000
13:78635109:CTT:C	donor_gain	1.0000
13:78635194:TTTGC:T	acceptor_gain	1.0000
13:78635195:TTGC:T	acceptor_gain	1.0000
13:78635195:TTGCC:T	acceptor_loss	1.0000
13:78635199:C:CC	acceptor_gain	1.0000
13:78635199:CT:C	acceptor_loss	1.0000
13:78635200:T:G	acceptor_loss	1.0000
13:78638818:CTTA:C	donor_loss	1.0000
13:78638819:TTAC:T	donor_loss	1.0000
13:78638820:TACCT:T	donor_loss	1.0000
13:78638821:ACCT:A	donor_gain	1.0000
13:78638822:C:G	donor_loss	1.0000
13:78638822:CCT:C	donor_gain	1.0000
13:78638822:CCTC:C	donor_gain	1.0000
13:78642118:TTAC:T	donor_loss	1.0000
13:78642119:TAC:T	donor_loss	1.0000
13:78642120:AC:A	donor_loss	1.0000
13:78642121:C:CT	donor_loss	1.0000
13:78642169:T:TA	donor_gain	1.0000
13:78642211:CTC:C	acceptor_gain	1.0000
13:78642213:CCTG:C	acceptor_loss	1.0000
13:78642214:C:CC	acceptor_gain	1.0000

AlphaMissense

4841 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
13:78644916:A:G	C52R	1.000
13:78644949:A:G	C41R	1.000
13:78644958:A:G	C38R	1.000
13:78659067:G:C	C18W	1.000
13:78659068:C:T	C18Y	1.000
13:78659069:A:G	C18R	1.000
13:78616139:A:G	L541S	0.999
13:78644907:A:G	C55R	0.999
13:78644914:A:C	C52W	0.999
13:78644915:C:G	C52S	0.999
13:78644916:A:T	C52S	0.999
13:78644937:A:G	W45R	0.999
13:78644937:A:T	W45R	0.999
13:78644947:A:C	C41W	0.999
13:78644948:C:T	C41Y	0.999
13:78644956:A:C	C38W	0.999
13:78644957:C:T	C38Y	0.999
13:78644959:A:C	F37L	0.999
13:78644959:A:T	F37L	0.999
13:78644960:A:G	F37S	0.999
13:78644961:A:G	F37L	0.999
13:78644977:G:C	C31W	0.999
13:78644978:C:T	C31Y	0.999
13:78644979:A:G	C31R	0.999
13:78659058:G:C	C21W	0.999
13:78659059:C:T	C21Y	0.999
13:78659060:A:G	C21R	0.999
13:78659068:C:A	C18F	0.999
13:78659068:C:G	C18S	0.999
13:78659069:A:T	C18S	0.999

dbSNP variants (sampled 300 via entrez): RS1000018810 (13:78650121 A>C,G), RS1000048383 (13:78660247 G>GT), RS1000071132 (13:78650362 G>T), RS1000105031 (13:78625880 A>T), RS1000247224 (13:78660515 G>A), RS1000311978 (13:78619527 A>G), RS1000319462 (13:78627295 T>G), RS1000356974 (13:78648587 C>G,T), RS1000410580 (13:78648223 G>A,C), RS1000415126 (13:78619260 G>A), RS1000431212 (13:78654936 A>G,T), RS1000488658 (13:78632959 A>C), RS1000541101 (13:78644595 G>A,C), RS1000634674 (13:78654722 T>A), RS1000655133 (13:78628588 A>C)

Disease associations

OMIM: gene MIM:615906 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST000635_35	Response to statin therapy	5.000000e-06
GCST002288_2	Large artery stroke	5.000000e-06
GCST005146_30	Birth weight	2.000000e-09
GCST006629_40	Pulse pressure	3.000000e-11
GCST009391_1670	Metabolite levels	6.000000e-06

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004344	birth weight
EFO:0005763	pulse pressure measurement
EFO:0010470	carnosine measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects cotreatment, decreases methylation, increases expression	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	2
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
FR900359	affects phosphorylation	1
TAK-243	increases sumoylation	1
dicrotophos	decreases expression	1
urushiol	decreases expression	1
pirinixic acid	affects binding, increases activity, increases expression	1
sodium arsenite	decreases expression	1
beta-methylcholine	affects expression	1
jinfukang	affects cotreatment, decreases expression	1
MT19c compound	increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Temozolomide	decreases expression	1
Fulvestrant	affects cotreatment, decreases methylation	1
Arsenic	affects methylation	1
Caffeine	affects phosphorylation	1
Cisplatin	affects cotreatment, decreases expression	1
Dexamethasone	affects cotreatment, increases expression	1
Doxorubicin	decreases expression	1
Formaldehyde	decreases expression	1
Gold	decreases expression	1
Hydrogen Peroxide	affects expression	1
Indomethacin	affects cotreatment, increases expression	1
Plant Extracts	affects cotreatment, increases expression	1
Thimerosal	increases expression	1
Valproic Acid	increases expression	1
1-Methyl-3-isobutylxanthine	affects cotreatment, increases expression	1
Aflatoxin B1	decreases methylation	1
Aflatoxin M1	decreases expression	1

Clinical trials (associated diseases)

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