MCMBP

Summary

MCMBP (minichromosome maintenance complex binding protein, HGNC:25782) is a protein-coding gene on chromosome 10q26.11, encoding Mini-chromosome maintenance complex-binding protein (Q9BTE3). Associated component of the MCM complex that acts as a regulator of DNA replication. It is a selective cancer dependency (DepMap: 65.1% of cell lines).

This gene encodes a protein which is a component of the hexameric minichromosome maintenance (MCM) complex which regulates initiation and elongation of DNA. Multiple transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 79892 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 96 total
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 65.1% of screened cell lines
• MANE Select transcript: NM_001256378

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25782
Approved symbol	MCMBP
Name	minichromosome maintenance complex binding protein
Location	10q26.11
Locus type	gene with protein product
Status	Approved
Aliases	FLJ13081, MCM-BP
Ensembl gene	ENSG00000197771
Ensembl biotype	protein_coding
OMIM	610909
Entrez	79892

Gene structure

Transcript identifiers

Ensembl transcripts: 16 — 13 protein_coding, 3 protein_coding_CDS_not_defined

ENST00000360003, ENST00000369077, ENST00000466047, ENST00000495407, ENST00000569515, ENST00000895498, ENST00000895499, ENST00000895500, ENST00000895501, ENST00000895502, ENST00000895503, ENST00000895504, ENST00000895505, ENST00000937934, ENST00000966479, ENST00000966480

RefSeq mRNA: 3 — MANE Select: NM_001256378 NM_001256378, NM_001256379, NM_024834

CCDS: CCDS58099, CCDS7617

Canonical transcript exons

ENST00000369077 — 16 exons

Exon	Start	End
ENSE00000933377	119857338	119857439
ENSE00001379582	119872527	119872843
ENSE00001947599	119829440	119831600
ENSE00003464570	119843254	119843426
ENSE00003476303	119836896	119837029
ENSE00003489123	119838535	119838700
ENSE00003510958	119832012	119832100
ENSE00003515729	119858884	119858925
ENSE00003539143	119859041	119859181
ENSE00003561611	119840843	119840960
ENSE00003574583	119859799	119859884
ENSE00003577729	119847613	119847713
ENSE00003593136	119842472	119842595
ENSE00003593734	119853050	119853194
ENSE00003614571	119849425	119849576
ENSE00003632756	119835540	119835704

Expression profiles

Bgee: expression breadth ubiquitous, 272 present calls, max score 96.43.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 45.4270 / max 411.1196, expressed in 1825 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
111708	44.0506	1824
111709	0.7095	179
111707	0.6669	409

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
oocyte	CL:0000023	96.43	gold quality
secondary oocyte	CL:0000655	96.18	gold quality
ventricular zone	UBERON:0003053	95.17	gold quality
ganglionic eminence	UBERON:0004023	94.34	gold quality
monocyte	CL:0000576	93.92	gold quality
mononuclear cell	CL:0000842	93.82	gold quality
leukocyte	CL:0000738	93.81	gold quality
cortical plate	UBERON:0005343	92.68	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	92.13	gold quality
islet of Langerhans	UBERON:0000006	92.06	gold quality
rectum	UBERON:0001052	91.62	gold quality
cartilage tissue	UBERON:0002418	91.58	gold quality
placenta	UBERON:0001987	91.02	gold quality
oral cavity	UBERON:0000167	90.91	gold quality
right lung	UBERON:0002167	90.91	gold quality
popliteal artery	UBERON:0002250	90.87	gold quality
tibial artery	UBERON:0007610	90.87	gold quality
granulocyte	CL:0000094	90.81	gold quality
stromal cell of endometrium	CL:0002255	90.75	gold quality
blood	UBERON:0000178	90.54	gold quality
calcaneal tendon	UBERON:0003701	90.51	gold quality
left uterine tube	UBERON:0001303	90.48	gold quality
lower lobe of lung	UBERON:0008949	90.37	gold quality
omental fat pad	UBERON:0010414	90.34	gold quality
peritoneum	UBERON:0002358	90.33	gold quality
subcutaneous adipose tissue	UBERON:0002190	90.13	gold quality
lower esophagus muscularis layer	UBERON:0035833	90.11	gold quality
lower esophagus	UBERON:0013473	90.09	gold quality
adipose tissue of abdominal region	UBERON:0007808	90.06	gold quality
aorta	UBERON:0000947	90.03	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): GLI1

miRNA regulators (miRDB)

80 targeting MCMBP, 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-340-5P	100.00	72.50	4437
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-146A-5P	99.96	68.93	988
HSA-MIR-146B-5P	99.96	69.13	977
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-96-5P	99.95	72.80	2140
HSA-MIR-7153-5P	99.94	68.89	1006
HSA-MIR-12133	99.92	71.82	2006
HSA-MIR-6508-5P	99.92	70.67	2465
HSA-MIR-205-3P	99.92	69.92	3165
HSA-MIR-1271-5P	99.91	71.99	1972
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-605-3P	99.88	69.22	1833
HSA-MIR-3919	99.87	69.45	2489
HSA-MIR-8067	99.86	69.59	2260
HSA-MIR-544A	99.84	68.66	1965
HSA-MIR-944	99.82	70.85	3042
HSA-MIR-6515-3P	99.82	68.19	1933

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 65.1% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 8)

• MCM-BP is conserved in multicellular eukaryotes and shares limited homology with MCM proteins. MCM-BP formed a complex with MCM3 to MCM7, which excluded MCM2. (PMID:17296731)
• Knockdown of the human ETG1 results in defective chromatid cohesion. (PMID:20090939)
• MCM-BP silencing in human cells also delays MCM dissociation in late S phase (PMID:21196493)
• results suggest that MCM-BP makes multiple contributions to human cells that are not limited to unloading of the MCM complex (PMID:22250201)
• MCM-BP can decrease phosphorylation by DDK but is not a substrate. (PMID:22540012)
• Data indicate that MCM-BP binds USP7 on chromatin and can mediate an interaction between the USP7 and MCM proteins. (PMID:24190967)
• the MCMBP protein accumulates to high levels in cancer cells, whereas in normal proliferating tissue its abundance is low, indicating that MCMBP could be exploited as a novel diagnostic marker for this type of carcinoma. (PMID:25246271)
• MCMBP promotes the assembly of the MCM2-7 hetero-hexamer to ensure robust DNA replication in human cells. (PMID:35438632)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	mcmbp	ENSDARG00000055314
mus_musculus	Mcmbp	ENSMUSG00000048170
rattus_norvegicus	Mcmbp	ENSRNOG00000020394
drosophila_melanogaster	CG3430	FBGN0031875

Protein

Protein identifiers

Mini-chromosome maintenance complex-binding protein — Q9BTE3 (reviewed: Q9BTE3)

All UniProt accessions (2): A0A0S2Z5P5, Q9BTE3

UniProt curated annotations — full annotation on UniProt →

Function. Associated component of the MCM complex that acts as a regulator of DNA replication. Binds to the MCM complex during late S phase and promotes the disassembly of the MCM complex from chromatin, thereby acting as a key regulator of pre-replication complex (pre-RC) unloading from replicated DNA. Can dissociate the MCM complex without addition of ATP; probably acts by destabilizing interactions of each individual subunits of the MCM complex. Required for sister chromatid cohesion.

Subunit / interactions. Interacts with the MCM complex: associates with the MCM3-7 complex which lacks MCM2, while it does not interact with the MCM complex when MCM2 is present (MCM2-7 complex). Interacts with the RPA complex, when composed of all RPA1, RPA2 and RPA3 components, but not with RPA1 or RPA2 alone.

Subcellular location. Nucleus.

Similarity. Belongs to the MCMBP family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q9BTE3-1	1	yes
Q9BTE3-2	2
Q9BTE3-3	3

RefSeq proteins (3): NP_001243307, NP_001243308, NP_079110 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR019140	MCM_complex-bd	Family

Pfam: PF09739

UniProt features (12 total): modified residue 4, sequence conflict 3, splice variant 2, chain 1, region of interest 1, compositionally biased region 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
4KG9	X-RAY DIFFRACTION	1.7

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BTE3-F1	81.76	0.49

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 (4): 154, 160, 167, 298

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 171 (showing top): GSE45365_NK_CELL_VS_CD8_TCELL_DN, E2F_Q4, GOBP_CHROMOSOME_ORGANIZATION, MYOGENIN_Q6, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, E2F4DP1_01, MODULE_255, SHEPARD_CRASH_AND_BURN_MUTANT_UP, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, MODULE_317, GGGTGGRR_PAX4_03, CEBPB_01, MONNIER_POSTRADIATION_TUMOR_ESCAPE_UP, WEI_MYCN_TARGETS_WITH_E_BOX, E2F1DP1_01

GO Biological Process (4): DNA-templated DNA replication (GO:0006261), sister chromatid cohesion (GO:0007062), cell division (GO:0051301), DNA replication (GO:0006260)

GO Molecular Function (2): chromatin binding (GO:0003682), protein binding (GO:0005515)

GO Cellular Component (5): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytosol (GO:0005829), cell junction (GO:0030054), MCM complex (GO:0042555)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
binding	2
DNA replication	1
cell cycle process	1
chromosome organization	1
cellular process	1
DNA metabolic process	1
DNA biosynthetic process	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
cytoplasm	1
protein-containing complex	1
MCM core complex	1

Protein interactions and networks

STRING

1060 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MCMBP	MCM4	P33991	939
MCMBP	MCM3	P25205	915
MCMBP	MCM7	P33993	867
MCMBP	MCM6	Q14566	859
MCMBP	MCM5	P33992	718
MCMBP	MCM10	Q7L590	698
MCMBP	DBF4	Q9UBU7	652
MCMBP	CDC45	O75419	578
MCMBP	UBE2E1	P51965	566
MCMBP	CDT1	Q9H211	552
MCMBP	GMPS	P49915	525
MCMBP	CDC6	Q99741	519
MCMBP	MCM9	Q9NXL9	511
MCMBP	POLA2	Q14181	506
MCMBP	FAM117B	Q6P1L5	504

IntAct

125 interactions, top by confidence:

A	B	Type	Score
MCM7	MCM4	psi-mi:“MI:0914”(association)	0.930
MCM4	MCM7	psi-mi:“MI:0915”(physical association)	0.930
MCMBP	MCM7	psi-mi:“MI:0915”(physical association)	0.900
MCM7	MCMBP	psi-mi:“MI:0915”(physical association)	0.900
MCMBP	MCM3	psi-mi:“MI:0914”(association)	0.890
MCMBP	MCM3	psi-mi:“MI:0915”(physical association)	0.890
MCM3	MCMBP	psi-mi:“MI:0915”(physical association)	0.890
MCMBP	MCM5	psi-mi:“MI:0915”(physical association)	0.890
MCMBP	MCM5	psi-mi:“MI:0914”(association)	0.890
MCM5	MCMBP	psi-mi:“MI:0915”(physical association)	0.890
MCMBP	MCM4	psi-mi:“MI:0914”(association)	0.850
MCM5	MCM3	psi-mi:“MI:0914”(association)	0.850
MCM4	MCMBP	psi-mi:“MI:0915”(physical association)	0.850
MCM6	MCMBP	psi-mi:“MI:0915”(physical association)	0.850

BioGRID (268): MCMBP (Two-hybrid), MCMBP (Two-hybrid), MCMBP (Affinity Capture-RNA), MCMBP (Affinity Capture-RNA), MCMBP (Affinity Capture-MS), MCMBP (Affinity Capture-MS), MCMBP (Affinity Capture-MS), MCMBP (Affinity Capture-MS), MCMBP (Affinity Capture-MS), MCMBP (Two-hybrid), MCMBP (Affinity Capture-MS), MCMBP (Affinity Capture-MS), MCMBP (Affinity Capture-RNA), MCMBP (Co-fractionation), MCMBP (Co-fractionation)

ESM2 similar proteins: A0A0R4IC37, A0AUR5, A2RT67, A2RUS2, A5PJM5, A5PKL6, A7E2V1, B1H268, B5DG51, O75694, P48553, P59764, Q0VEJ0, Q14181, Q14997, Q1LX49, Q28DH9, Q28DV7, Q3TLI0, Q4R6Y8, Q5F3K0, Q5JPI3, Q5M8J0, Q5R5S1, Q5RCP7, Q5RL51, Q5XH48, Q5ZJV4, Q6DC53, Q6DDX8, Q6DFF4, Q6DJG6, Q6NX27, Q7ZYP6, Q803A6, Q8C5P5, Q8N1I0, Q8NEC7, Q8R3C0, Q8TAP6

Diamond homologs: A5PJM5, B1H268, B5DG51, O94450, Q28DV7, Q501D5, Q5ZJV4, Q7ZYP6, Q803A6, Q8R3C0, Q9BTE3, Q9VM60, Q55CZ6

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 103 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 ATR in response to replication stress	10	43.5×	2e-12
Activation of the pre-replicative complex	9	42.6×	3e-11
DNA Replication Pre-Initiation	9	41.4×	3e-11
Synthesis of DNA	8	34.8×	2e-09
DNA Replication	10	34.5×	2e-11
Switching of origins to a post-replicative state	7	30.5×	7e-08
G1/S Transition	9	30.4×	5e-10
Mitotic G1 phase and G1/S transition	9	24.0×	4e-09

GO biological processes:

GO term	Partners	Fold	FDR
regulation of DNA-templated DNA replication initiation	6	69.5×	6e-08
DNA replication initiation	6	41.1×	1e-06
DNA replication	9	16.3×	1e-06
DNA damage response	9	5.3×	5e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	68
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2143 predictions. Top by Δscore:

Variant	Effect	Δscore
10:119832008:TTA:T	donor_loss	1.0000
10:119832010:A:AC	donor_gain	1.0000
10:119832010:ACC:A	donor_loss	1.0000
10:119832011:C:CC	donor_gain	1.0000
10:119832097:CTGC:C	acceptor_gain	1.0000
10:119832098:TGC:T	acceptor_gain	1.0000
10:119832100:CCTT:C	acceptor_gain	1.0000
10:119832101:C:CC	acceptor_gain	1.0000
10:119832103:T:C	acceptor_gain	1.0000
10:119832103:T:TC	acceptor_gain	1.0000
10:119832107:C:CT	acceptor_gain	1.0000
10:119832108:A:T	acceptor_gain	1.0000
10:119835535:CATA:C	donor_loss	1.0000
10:119835536:ATAC:A	donor_loss	1.0000
10:119835537:TACC:T	donor_loss	1.0000
10:119835539:C:CA	donor_loss	1.0000
10:119835701:CTGC:C	acceptor_gain	1.0000
10:119835702:TGC:T	acceptor_gain	1.0000
10:119835704:CCT:C	acceptor_loss	1.0000
10:119835705:C:CC	acceptor_gain	1.0000
10:119837027:CAC:C	acceptor_gain	1.0000
10:119837028:ACCT:A	acceptor_loss	1.0000
10:119837030:C:CC	acceptor_gain	1.0000
10:119837031:T:C	acceptor_loss	1.0000
10:119838531:GTA:G	donor_loss	1.0000
10:119838532:TAC:T	donor_loss	1.0000
10:119838533:A:AC	donor_gain	1.0000
10:119838533:A:AT	donor_loss	1.0000
10:119838533:AC:A	donor_gain	1.0000
10:119838534:C:CG	donor_gain	1.0000

AlphaMissense

4233 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:119838624:C:G	R442P	1.000
10:119838641:T:A	K436N	1.000
10:119838641:T:G	K436N	1.000
10:119853129:C:A	K165N	1.000
10:119853129:C:G	K165N	1.000
10:119831554:A:G	W617R	0.999
10:119831554:A:T	W617R	0.999
10:119832072:C:G	R581P	0.999
10:119832096:A:T	V573D	0.999
10:119836968:G:C	F492L	0.999
10:119836968:G:T	F492L	0.999
10:119836970:A:G	F492L	0.999
10:119838621:A:G	L443S	0.999
10:119838642:T:A	K436I	0.999
10:119842550:A:G	L351P	0.999
10:119847661:C:T	G260D	0.999
10:119853126:C:A	R166S	0.999
10:119853126:C:G	R166S	0.999
10:119853127:C:A	R166M	0.999
10:119853127:C:G	R166T	0.999
10:119853131:T:C	K165E	0.999
10:119857372:A:T	V132D	0.999
10:119857374:A:C	C131W	0.999
10:119857376:A:G	C131R	0.999
10:119857389:T:A	R126S	0.999
10:119857389:T:G	R126S	0.999
10:119859105:T:A	D74V	0.999
10:119859106:C:G	D74H	0.999
10:119859116:G:C	C70W	0.999
10:119859118:A:G	C70R	0.999

dbSNP variants (sampled 300 via entrez): RS1000007053 (10:119866734 T>A), RS1000099148 (10:119866347 C>T), RS1000161336 (10:119872208 C>G), RS1000227831 (10:119866433 C>G), RS1000238337 (10:119840581 G>C), RS1000260113 (10:119830784 A>C), RS1000325596 (10:119846817 A>T), RS1000376674 (10:119830640 G>A), RS1000482115 (10:119853833 G>A,C), RS1000491936 (10:119837085 A>G), RS1000555812 (10:119866133 G>A,C), RS1000591169 (10:119829840 C>G), RS1000596381 (10:119870174 T>C), RS1000643669 (10:119830077 G>A), RS1000725075 (10:119834234 C>T)

Disease associations

OMIM: gene MIM:610909 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST008163_189	Height	2.000000e-07
GCST010989_91	Body size at age 10	2.000000e-08

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0009819	comparative body size at age 10, self-reported

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5724633 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases abundance, increases expression	3
bisphenol A	decreases expression	2
Nickel	decreases expression, increases expression	2
Valproic Acid	decreases expression	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	2
Cadmium Chloride	decreases expression	2
FR900359	affects phosphorylation	1
methylparaben	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
cobaltous chloride	decreases expression	1
ICG 001	decreases expression	1
bisphenol S	affects cotreatment, increases expression	1
NSC 689534	affects binding, decreases expression	1
Resveratrol	affects cotreatment, increases expression	1
Sunitinib	increases expression	1
Air Pollutants	increases abundance, decreases expression	1
Air Pollutants, Occupational	decreases expression	1
Arsenic	increases abundance, decreases expression	1
Caffeine	affects phosphorylation	1
Calcitriol	decreases expression, affects cotreatment	1
Cisplatin	increases expression	1
Copper	affects binding, decreases expression	1
Dichlorodiphenyl Dichloroethylene	increases expression	1
Dexamethasone	increases expression, affects cotreatment	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Fluorouracil	increases expression	1
Hydrogen Peroxide	affects expression	1
Indomethacin	affects cotreatment, increases expression	1
Ivermectin	decreases expression	1
Plant Extracts	affects cotreatment, increases expression	1

ChEMBL screening assays

6 unique, capped per target: 6 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5697764	Binding	Inhibition of C10ORF119 (unknown origin) assessed as fold change at 10 uM incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	Inhibition of BET recruitment to chromatin as an effective treatment for MLL-fusion leukaemia. — Nature

Clinical trials (associated diseases)

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