MCM7

Summary

MCM7 (minichromosome maintenance complex component 7, HGNC:6950) is a protein-coding gene on chromosome 7q22.1, encoding DNA replication licensing factor MCM7 (P33993). Acts as a component of the MCM2-7 complex (MCM complex) which is the replicative helicase essential for ‘once per cell cycle’ DNA replication initiation and elongation in eukaryotic cells. It is a common-essential gene (DepMap: required in 99.7% of cancer cell lines).

The protein encoded by this gene is one of the highly conserved mini-chromosome maintenance proteins (MCM) that are essential for the initiation of eukaryotic genome replication. The hexameric protein complex formed by the MCM proteins is a key component of the pre-replication complex (pre_RC) and may be involved in the formation of replication forks and in the recruitment of other DNA replication related proteins. The MCM complex consisting of this protein and MCM2, 4 and 6 proteins possesses DNA helicase activity, and may act as a DNA unwinding enzyme. Cyclin D1-dependent kinase, CDK4, is found to associate with this protein, and may regulate the binding of this protein with the tumorsuppressor protein RB1/RB. Alternatively spliced transcript variants encoding distinct isoforms have been reported.

Source: NCBI Gene 4176 — RefSeq curated summary.

At a glance

• Gene–disease (curated): syndromic disease (Moderate, GenCC)
• GWAS associations: 3
• Clinical variants (ClinVar): 188 total — 5 pathogenic
• Phenotypes (HPO): 23
• Druggable target: yes
• Cancer driver (intOGen): loss-of-function (tumor-suppressor-like) across 1 cancer types
• Cancer dependency (DepMap): dependent in 99.7% of screened cell lines (common-essential)
• MANE Select transcript: NM_005916

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6950
Approved symbol	MCM7
Name	minichromosome maintenance complex component 7
Location	7q22.1
Locus type	gene with protein product
Status	Approved
Aliases	CDC47, PPP1R104
Ensembl gene	ENSG00000166508
Ensembl biotype	protein_coding
OMIM	600592
Entrez	4176

Gene structure

Transcript identifiers

Ensembl transcripts: 20 — 12 protein_coding, 7 retained_intron, 1 nonsense_mediated_decay

ENST00000303887, ENST00000343023, ENST00000425308, ENST00000463722, ENST00000465688, ENST00000465738, ENST00000467516, ENST00000485286, ENST00000489841, ENST00000493352, ENST00000710813, ENST00000710814, ENST00000710815, ENST00000907652, ENST00000919119, ENST00000919120, ENST00000919121, ENST00000919122, ENST00000919123, ENST00000919124

RefSeq mRNA: 3 — MANE Select: NM_005916 NM_001278595, NM_005916, NM_182776

CCDS: CCDS5683

Canonical transcript exons

ENST00000303887 — 15 exons

Exon	Start	End
ENSE00001694563	100099023	100099203
ENSE00001705403	100098141	100098290
ENSE00003466005	100098578	100098715
ENSE00003468703	100100014	100100093
ENSE00003616290	100099589	100099753
ENSE00003683184	100099279	100099403
ENSE00003896590	100101264	100101397
ENSE00004013664	100097834	100097948
ENSE00004013665	100095774	100096167
ENSE00004013666	100097614	100097745
ENSE00004013667	100092728	100093133
ENSE00004013671	100095387	100095470
ENSE00004013672	100097301	100097384
ENSE00004013674	100094173	100094341
ENSE00004013675	100093292	100093401

Expression profiles

Bgee: expression breadth ubiquitous, 143 present calls, max score 98.87.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 43.3283 / max 357.8567, expressed in 1733 samples.

FANTOM5 promoters (9 alternative TSS)

Promoter ID	TPM avg	Samples expressed
85147	59.5221	1732
38384	43.3283	1733
85149	2.3065	893
85145	2.2383	1039
85143	1.9475	727
85146	1.6399	740
85144	1.0439	500
85150	0.6595	365
85148	0.1408	44

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
embryo	UBERON:0000922	98.87	gold quality
ganglionic eminence	UBERON:0004023	98.87	gold quality
ventricular zone	UBERON:0003053	98.84	gold quality
mucosa of transverse colon	UBERON:0004991	97.07	gold quality
lymph node	UBERON:0000029	96.80	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	96.66	gold quality
right testis	UBERON:0004534	96.63	gold quality
vermiform appendix	UBERON:0001154	96.57	gold quality
left testis	UBERON:0004533	96.50	gold quality
granulocyte	CL:0000094	96.47	gold quality
cortical plate	UBERON:0005343	96.41	gold quality
bone marrow	UBERON:0002371	96.35	gold quality
rectum	UBERON:0001052	96.29	gold quality
testis	UBERON:0000473	96.12	gold quality
spleen	UBERON:0002106	96.11	gold quality
substantia nigra	UBERON:0002038	96.02	gold quality
skin of abdomen	UBERON:0001416	95.55	gold quality
small intestine Peyer’s patch	UBERON:0003454	95.55	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	95.43	gold quality
zone of skin	UBERON:0000014	95.36	gold quality
skin of leg	UBERON:0001511	95.29	gold quality
placenta	UBERON:0001987	95.14	gold quality
fundus of stomach	UBERON:0001160	95.10	gold quality
transverse colon	UBERON:0001157	95.04	gold quality
duodenum	UBERON:0002114	95.00	gold quality
small intestine	UBERON:0002108	94.88	gold quality
left ovary	UBERON:0002119	94.87	gold quality
amygdala	UBERON:0001876	94.79	gold quality
Ammon’s horn	UBERON:0001954	94.79	gold quality
body of stomach	UBERON:0001161	94.77	gold quality

Single-cell (SCXA)

Detected in 22 experiment(s), a significant marker in 19.

Experiment	Marker?	Max mean expression
E-ENAD-20	yes	1077.39
E-GEOD-93593	yes	842.83
E-GEOD-99795	yes	774.63
E-MTAB-7037	yes	569.41
E-MTAB-9435	yes	554.76
E-HCAD-5	yes	485.54
E-MTAB-8530	yes	383.83
E-HCAD-10	yes	381.53
E-CURD-114	yes	256.14
E-MTAB-10290	yes	158.45
E-HCAD-4	yes	140.29
E-CURD-112	yes	39.46
E-CURD-122	yes	27.69
E-MTAB-9067	yes	22.21
E-HCAD-13	yes	21.65

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AR, E2F1, E2F2, E2F3, E2F4, MSC, MYC, MYCN, PPARG, PPP3CA, SMARCA1, TP53, VDR

miRNA regulators (miRDB)

24 targeting MCM7, 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-548P	99.98	72.25	3784
HSA-MIR-103A-3P	99.98	69.14	1595
HSA-MIR-107	99.98	69.14	1595
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-548AJ-5P	99.78	71.12	3085
HSA-MIR-548F-5P	99.78	71.02	3093
HSA-MIR-548G-5P	99.78	71.12	3085
HSA-MIR-548X-5P	99.78	71.12	3085
HSA-MIR-1283	99.69	72.42	3009
HSA-MIR-519A-3P	99.67	71.67	1868
HSA-MIR-519B-3P	99.67	71.67	1868
HSA-MIR-519C-3P	99.67	71.67	1870
HSA-MIR-6734-3P	99.15	66.27	1627
HSA-MIR-10A-5P	98.89	69.85	712
HSA-MIR-10B-5P	98.89	69.86	711
HSA-MIR-3944-5P	98.50	67.55	997
HSA-MIR-6878-5P	98.49	67.91	2142
HSA-MIR-4766-3P	98.48	67.94	1347
HSA-MIR-6826-3P	98.19	66.32	1153
HSA-MIR-6732-3P	98.17	67.52	802
HSA-MIR-30C-1-3P	97.80	66.36	1499
HSA-MIR-30C-2-3P	97.80	66.45	1499
HSA-MIR-6788-5P	97.80	66.41	1532
HSA-MIR-1972	97.67	67.38	1172

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 99.7% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 40)

• Minichromosome maintenance protein MCM7 is a direct target of the MYCN transcription factor in neuroblastoma. (PMID:11861392)
• Overexpressed MCM7 protein supports efficient DNA replication of Epstein-Barr virus oriP and rapid formation of tumors in nude mice without altering the activity of cellular DNA replication. (PMID:14550576)
• MCM7 may be a highly informative biomarker for cervical cancer. (PMID:14678972)
• ATM/ATR-dependent (ataxia-telangiectasia-mutated/ATM- and Rad3-related) checkpoint pathways are directly linked to three members of the MCM complex(MCM2,MCM3,MCM7). (PMID:15210935)
• hMCM7 plays a direct role in the transmission of DNA damage signals from active replication forks to the S-phase checkpoint machinery in human cells. (PMID:15538388)
• interaction between endogenous Plk1 and Mcm7 was detected in a soluble chromatin fraction. These findings suggest a new function for Plk1 in coordination of DNA replication and mitotic events. (PMID:15654075)
• MCM7 was found to be a more reliable and useful marker than Ki67 in assessing tumour proliferation and in the prognosis of patients. (PMID:15720416)
• MCM7 amplification is responsible for markedly increased DNA synthesis, cell proliferation and an increased cell invasion in prostate cancer. (PMID:16247466)
• p27Kip1 binds the conserved minichromosome maintenance domain of MCM7 proteins in a growth factor-dependent manner, such that the carboxyl terminal domain of p27Kip1 inhibits DNA replication independent of its function as a cyclin-dependent kinase (PMID:16289477)
• MCM7, the c-myc-regulated gene is involved in genotype-C-HBV-related HCC, suggesting that c-myc is related to the hepatocarcinogenic activity of genotype-C HBV. (PMID:16703398)
• Increase of the MCM7 is associated with tumor aggressiveness in astrocytoma (PMID:17094475)
• INT6 stabilizes chromatin-bound MCM7 and alteration of this effect is associated with replication deficiency. (PMID:17310990)
• MCM7 is part of the GINS complex. (PMID:17557111)
• We find that MCM8, like MCM7, colocalizes on a specific DNA segment of the c-MYC replication initiation zone (c-MYC replicator) of DNA replications together with Cdc6 and cdk2, but differs with MCM7 in spatial relation to RPA70 during S phase. (PMID:18072282)
• MCM7 expression is an independent prognostic factor for human colorectal cancer (PMID:18636144)
• MCM7 is an independent prognostic marker in lung adenocarcinomas (PMID:19144445)
• RT-PCR and immunohistochemistry indicated positive expressions of Mcm7 mRNA and protein in normal oral mucosa, precancerous lesions and oral squamous cell carcinoma. (PMID:19189662)
• the MCM2-7 proteins are co-localized with RNA Pol II on chromatins of constitutively transcribing genes, and MCM5 is required for transcription elongation of RNA Pol II. (PMID:19318354)
• Replisome factors MCM10, MCM2and MCM7 helicase, are the primary interaction partner proteins of human RECQ4. (PMID:19696745)
• interactions between Cdc45, Mcm2-7, and the GINS complex (collectively called the CMG complex), which seem to play a key role in the formation and progression of replication forks (PMID:19805216)
• MCM7 , critical for cell proliferation and maintenance of genome stability, are markedly down-regulated, Data hypothesized that their DNA-related functions could be partially limited in TRAIL-resistant HL-60 cells. (PMID:19834905)
• distribution pattern is similar to Ki-67;can be used as proliferation marker in experimental neoplasms (PMID:20048674)
• Transcriptional activation of Mcm7 is mediated by HAT recruitment to the promoter region upon C. sinensis excretory-secretory products treatment. (PMID:20236609)
• uncovered a proto-oncogenic miRNA-dependent network for PTEN regulation and defined the MCM7 locus as a critical factor in initiating prostate tumorigenesis (PMID:20388916)
• deregulation of MCM2, MCM3 and MCM7 expression might be involved in medulloblastoma tumorigenesis (PMID:20661220)
• MCM7 expression was significantly higher in high-grade serous carcinomas than in serous borderline tumors or other histological subtypes of ovarian cancer. (PMID:21076460)
• Results demonstrate that interaction with Mcm7 is essential for the function of cyclin A in promoting S-phase entry. (PMID:21078875)
• low level of MCM7 of proteins expression which may explain commonly known low mitotic activity of desmoid tumour cells (PMID:21478101)
• elevated expression of MCM7 to be associated with poor prognosis for patients with non-small cell lung cancer (PMID:21619671)
• Lymph node sections from 138 HL patients were immunohistochemically stained for cyclin D3 (CCND3), MCM2 and MCM7 aiming to investigate clinical outcome. (PMID:21965782)
• MCM7 and Ki67 in tumor tissues may be potential markers of a poor prognosis for non-small cell lung cancer patients (PMID:22456526)
• MCM7 expression may be a useful predictor of prognosis in patients with hepatocellular carcinoma after resection. (PMID:22784096)
• Mcm2-7 loads onto origins during initiation as a double hexamer, yet does not act as a double-stranded DNA pump during elongation. (PMID:22918583)
• the expression of cyclin D1, MCM7, TRIM29, and UBE2C was found to be significantly associated with progression to muscle-invasive bladder cancer. (PMID:23201130)
• MCM7 interacts with the receptor for activated protein kinase C 1 (RACK1), a protein kinase C (PKC) adaptor, in vivo and in vitro. (PMID:23313748)
• Protein levels of MCM7 and p63 were associated significantly with high-grade cervical lesion, and aberrant p63 protein level may distinguish different histopathologic types of cervical carcinoma. (PMID:23318911)
• MCM7 is a substrate of cyclin E/Cdk2 and can be phosphorylated on Ser-121. (PMID:23720738)
• EGFR enhances MCM7 phosphorylation and DNA replication through Lyn phosphorylation in human cancer cells. (PMID:23764002)
• ORC/Cdc6/MCM2-7 complex is a new regulatory mechanism for the helicase. (PMID:23803736)
• MCM 7, geminin and topo IIalpha can be reliable tools for the differential diagnosis of reactive mesothelial cells and malignant mesothelioma cells. (PMID:23860238)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	mcm7	ENSDARG00000101180
mus_musculus	Mcm7	ENSMUSG00000029730
rattus_norvegicus	Mcm7	ENSRNOG00000001349
drosophila_melanogaster	Mcm7	FBGN0020633
caenorhabditis_elegans		WBGENE00003159

Paralogs (8): MCM2 (ENSG00000073111), MCM6 (ENSG00000076003), MCM5 (ENSG00000100297), MCM4 (ENSG00000104738), MCM9 (ENSG00000111877), MCM3 (ENSG00000112118), MCM8 (ENSG00000125885), MCMDC2 (ENSG00000178460)

Protein

Protein identifiers

DNA replication licensing factor MCM7 — P33993 (reviewed: P33993)

Alternative names: CDC47 homolog, P1.1-MCM3

All UniProt accessions (4): A0A0S2Z4A5, A0AA34QVT8, C9J8M6, P33993

UniProt curated annotations — full annotation on UniProt →

Function. Acts as a component of the MCM2-7 complex (MCM complex) which is the replicative helicase essential for ‘once per cell cycle’ DNA replication initiation and elongation in eukaryotic cells. Core component of CDC45-MCM-GINS (CMG) helicase, the molecular machine that unwinds template DNA during replication, and around which the replisome is built. The active ATPase sites in the MCM2-7 ring are formed through the interaction surfaces of two neighboring subunits such that a critical structure of a conserved arginine finger motif is provided in trans relative to the ATP-binding site of the Walker A box of the adjacent subunit. The six ATPase active sites, however, are likely to contribute differentially to the complex helicase activity. Required for S-phase checkpoint activation upon UV-induced damage.

Subunit / interactions. Component of the MCM2-7 complex. The complex forms a toroidal hexameric ring with the proposed subunit order MCM2-MCM6-MCM4-MCM7-MCM3-MCM5. Component of the CMG helicase complex, a hexameric ring of related MCM2-7 subunits stabilized by CDC45 and the tetrameric GINS complex. Interacts with the ATR-ATRIP complex and with RAD17. Interacts with TIPIN. Interacts with MCMBP. Interacts with ANKRD17. Component of the replisome complex composed of at least DONSON, MCM2, MCM7, PCNA and TICRR.

Subcellular location. Nucleus. Chromosome.

Post-translational modifications. O-glycosylated (O-GlcNAcylated), in a cell cycle-dependent manner. Ubiquitinated by ECS(LRR1) E3 ubiquitin-protein ligase complex when forks converge following formation of DNA interstrand cross-links. During mitosis, ubiquitinated by TRAIP when forks converge following formation of DNA interstrand cross-links. Short ubiquitin chains on MCM7 promote recruitment of DNA glycosylase NEIL3. If the interstrand cross-link cannot be cleaved by NEIL3, the ubiquitin chains continue to grow on MCM7, promoting the unloading of the CMG helicase complex by the VCP/p97 ATPase.

Miscellaneous. Early fractionation of eukaryotic MCM proteins yielded a variety of dimeric, trimeric and tetrameric complexes with unclear biological significance. Specifically a MCM467 subcomplex is shown to have in vitro helicase activity which is inhibited by the MCM2 subunit. The MCM2-7 hexamer is the proposed physiological active complex.

Similarity. Belongs to the MCM family.

Isoforms (3)

UniProt ID	Names	Canonical?
P33993-1	1	yes
P33993-2	2
P33993-3	3

RefSeq proteins (3): NP_001265524, NP_005907, NP_877577 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001208	MCM_dom	Domain
IPR003593	AAA+_ATPase	Domain
IPR008050	MCM7	Family
IPR012340	NA-bd_OB-fold	Homologous_superfamily
IPR018525	MCM_CS	Conserved_site
IPR027417	P-loop_NTPase	Homologous_superfamily
IPR027925	MCM_N	Domain
IPR031327	MCM	Family
IPR033762	MCM_OB	Domain
IPR041562	MCM_lid	Domain

Pfam: PF00493, PF14551, PF17207, PF17855, PF24901

Catalyzed reactions (Rhea), 1 shown:

• ATP + H2O = ADP + phosphate + H(+) (RHEA:13065)

UniProt features (81 total): helix 24, strand 22, binding site 8, modified residue 6, turn 5, sequence variant 3, cross-link 2, splice variant 2, region of interest 2, short sequence motif 2, initiator methionine 1, chain 1, site 1, domain 1, sequence conflict 1

Structure

Experimental structures (PDB)

28 structures.

PDB	Method	Resolution (Å)
7W1Y	ELECTRON MICROSCOPY	2.59
9E2Z	ELECTRON MICROSCOPY	2.6
7PLO	ELECTRON MICROSCOPY	2.8
8W0F	ELECTRON MICROSCOPY	2.8
8S09	ELECTRON MICROSCOPY	3.1
7PFO	ELECTRON MICROSCOPY	3.2
8S0A	ELECTRON MICROSCOPY	3.2
9CAQ	ELECTRON MICROSCOPY	3.2
9LXD	ELECTRON MICROSCOPY	3.27
6XTX	ELECTRON MICROSCOPY	3.29
22VT	ELECTRON MICROSCOPY	3.3
8B9D	ELECTRON MICROSCOPY	3.4
8W0E	ELECTRON MICROSCOPY	3.4
9VLN	ELECTRON MICROSCOPY	3.42
9UQ0	ELECTRON MICROSCOPY	3.47
8W0I	ELECTRON MICROSCOPY	3.5
8S0B	ELECTRON MICROSCOPY	3.6
8S0D	ELECTRON MICROSCOPY	3.6
8S0E	ELECTRON MICROSCOPY	3.8
8W0G	ELECTRON MICROSCOPY	3.8
9LXF	ELECTRON MICROSCOPY	3.86
9LXE	ELECTRON MICROSCOPY	3.96
9VLW	ELECTRON MICROSCOPY	4.06
8S0F	ELECTRON MICROSCOPY	4.1
9C6G	ELECTRON MICROSCOPY	4.26
7W68	ELECTRON MICROSCOPY	4.4
8RWV	ELECTRON MICROSCOPY	6.68
6XTY	ELECTRON MICROSCOPY	6.77

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P33993-F1	80.63	0.11

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): 514 (arginine finger)

Ligand- & substrate-binding residues (8): 387; 388; 489; 514; 604; 345; 384; 386

Post-translational modifications (8): 2, 121, 314, 365, 500, 678, 15, 28

Function

Pathways and Gene Ontology

Reactome pathways

17 pathways

ID	Pathway
R-HSA-176187	Activation of ATR in response to replication stress
R-HSA-176974	Unwinding of DNA
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
R-HSA-69052	Switching of origins to a post-replicative state
R-HSA-1640170	Cell Cycle
R-HSA-453279	Mitotic G1 phase and G1/S transition
R-HSA-69002	DNA Replication Pre-Initiation
R-HSA-69190	DNA strand elongation
R-HSA-69206	G1/S Transition
R-HSA-69239	Synthesis of DNA
R-HSA-69242	S Phase
R-HSA-69278	Cell Cycle, Mitotic
R-HSA-69306	DNA Replication
R-HSA-69481	G2/M Checkpoints
R-HSA-69620	Cell Cycle Checkpoints

MSigDB gene sets: 798 (showing top): E2F_Q4, KALMA_E2F1_TARGETS, MORF_DNMT1, WU_APOPTOSIS_BY_CDKN1A_VIA_TP53, REACTOME_DNA_REPLICATION, MODULE_52, E2F_Q4_01, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, GNF2_MSH2, HORIUCHI_WTAP_TARGETS_DN, FREAC2_01, SHIPP_DLBCL_VS_FOLLICULAR_LYMPHOMA_UP, MORF_ESPL1, GNF2_CENPF, MORF_SMC1L1

GO Biological Process (11): double-strand break repair via break-induced replication (GO:0000727), DNA replication (GO:0006260), DNA replication initiation (GO:0006270), DNA strand elongation involved in DNA replication (GO:0006271), DNA damage response (GO:0006974), cell population proliferation (GO:0008283), regulation of DNA-templated DNA replication initiation (GO:0030174), regulation of phosphorylation (GO:0042325), cellular response to epidermal growth factor stimulus (GO:0071364), cellular response to xenobiotic stimulus (GO:0071466), response to xenobiotic stimulus (GO:0009410)

GO Molecular Function (10): DNA helicase activity (GO:0003678), single-stranded DNA binding (GO:0003697), ATP binding (GO:0005524), ATP hydrolysis activity (GO:0016887), nucleotide binding (GO:0000166), DNA binding (GO:0003677), helicase activity (GO:0004386), protein binding (GO:0005515), hydrolase activity (GO:0016787), single-stranded DNA helicase activity (GO:0017116)

GO Cellular Component (8): chromosome, telomeric region (GO:0000781), chromatin (GO:0000785), nucleus (GO:0005634), nucleoplasm (GO:0005654), membrane (GO:0016020), MCM complex (GO:0042555), CMG complex (GO:0071162), chromosome (GO:0005694)

Reactome top-level categories

Rollup of top-12 pathways:

Category	Pathways
DNA Replication Pre-Initiation	2
Synthesis of DNA	2
Cell Cycle, Mitotic	2
DNA Replication	2
Cell Cycle	2
G2/M Checkpoints	1
DNA strand elongation	1
Switching of origins to a post-replicative state	1
G1/S Transition	1
Mitotic G1 phase and G1/S transition	1
S Phase	1
Cell Cycle Checkpoints	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
DNA metabolic process	2
DNA-templated DNA replication	2
ATP-dependent activity	2
double-strand break repair via homologous recombination	1
DNA biosynthetic process	1
DNA replication	1
DNA strand elongation	1
DNA synthesis involved in DNA replication	1
cellular response to stress	1
cellular process	1
DNA replication initiation	1
regulation of DNA-templated DNA replication	1
phosphorylation	1
regulation of metabolic process	1
response to epidermal growth factor	1
cellular response to growth factor stimulus	1
response to xenobiotic stimulus	1
cellular response to chemical stimulus	1
response to chemical	1
helicase activity	1
ATP-dependent activity, acting on DNA	1
DNA binding	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
ribonucleoside triphosphate phosphatase activity	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
nucleic acid binding	1
nucleic acid conformation isomerase activity	1
catalytic activity, acting on a nucleic acid	1
binding	1
catalytic activity	1
DNA helicase activity	1
chromosomal region	1
chromosome	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
protein-containing complex	1
MCM core complex	1

Protein interactions and networks

STRING

4171 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MCM7	MCM5	P33992	991
MCM7	MCM4	P33991	991
MCM7	MCM6	Q14566	990
MCM7	MCM3	P25205	990
MCM7	CDC6	Q99741	981
MCM7	CDT1	Q9H211	981
MCM7	CDC45	O75419	962
MCM7	ATRIP	Q8WXE1	916
MCM7	MCM10	Q7L590	873
MCM7	TIPIN	Q9BVW5	870
MCM7	MCMBP	Q9BTE3	867
MCM7	ORC5	O43913	824
MCM7	CDC7	O00311	821
MCM7	ORC4	O43929	804
MCM7	CDK4	P11802	790

IntAct

503 interactions, top by confidence:

A	B	Type	Score
MCM7	MCM4	psi-mi:“MI:0914”(association)	0.930
MCM2	MCM3	psi-mi:“MI:0915”(physical association)	0.920
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
MCM6	MCM7	psi-mi:“MI:0915”(physical association)	0.860
MCM6	MCM3	psi-mi:“MI:0914”(association)	0.810
MCM7	MCM3	psi-mi:“MI:0914”(association)	0.810
CCAR2	MYC	psi-mi:“MI:0915”(physical association)	0.750
MYC	MCM7	psi-mi:“MI:0915”(physical association)	0.730
MCM7	MYC	psi-mi:“MI:0915”(physical association)	0.730
MCM7	MCMBP	psi-mi:“MI:0915”(physical association)	0.720
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
H4C16	HAT1	psi-mi:“MI:0914”(association)	0.700
AK8	MCM7	psi-mi:“MI:0915”(physical association)	0.670
MCM7	AK8	psi-mi:“MI:0915”(physical association)	0.670

BioGRID (739): MCM7 (Two-hybrid), MCM7 (Two-hybrid), NAB2 (Two-hybrid), TRIM27 (Two-hybrid), SP2 (Two-hybrid), PNMA1 (Two-hybrid), UBQLN1 (Two-hybrid), MBIP (Two-hybrid), TRIM54 (Two-hybrid), CCDC102B (Two-hybrid), MCMBP (Two-hybrid), USHBP1 (Two-hybrid), C8orf34 (Two-hybrid), MIPOL1 (Two-hybrid), AK8 (Two-hybrid)

ESM2 similar proteins: A0A1L4BKS3, A5I9P3, A7XXB7, A9IR19, B8BMI1, B8DJT9, B8G8R1, P03708, P17312, P25479, P26745, P27753, P33993, P36693, P39786, P44184, P45916, P51718, P54308, P56981, P59217, P75978, Q2L244, Q2QNM1, Q32I48, Q3A8D0, Q3SIK7, Q3ZBH9, Q3ZZK7, Q473K3, Q48KA6, Q4ZV05, Q5KVB5, Q5X0E6, Q5X906, Q5XLR0, Q5ZZD9, Q605S7, Q61881, Q62CK6

Diamond homologs: A4FUD9, B8AEH3, B8AZ14, B8AZ99, B8AZX3, B8B406, B8BKI8, B8BMI1, B9FKM7, D3ZVK1, E1BPX4, F1M5F3, F1N2W9, F1QDI9, F4KAB8, I0IUP3, I0IUP4, O75001, O80786, P24279, P25205, P25206, P29458, P29469, P29496, P30664, P30665, P30666, P33991, P33992, P33993, P34647, P38132, P40377, P41389, P43299, P49717, P49718, P49731, P49735

SIGNOR signaling

5 interactions.

A	Effect	B	Mechanism
CDC7	up-regulates	MCM7	phosphorylation
EIF3E	“up-regulates quantity by stabilization”	MCM7	binding
MCM7	“form complex”	MCM	binding
UBE3A	“down-regulates quantity by destabilization”	MCM7	polyubiquitination
LYN	“up-regulates activity”	MCM7	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 145 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
DNA Replication Pre-Initiation	8	28.8×	4e-08
Activation of the pre-replicative complex	7	25.9×	7e-07
Activation of ATR in response to replication stress	7	23.9×	1e-06
Synthesis of DNA	7	23.9×	1e-06
G1/S Transition	9	23.8×	3e-08
DNA Replication	8	21.6×	3e-07
Switching of origins to a post-replicative state	6	20.5×	2e-05
Mitotic G1 phase and G1/S transition	9	18.8×	1e-07

GO biological processes:

GO term	Partners	Fold	FDR
regulation of DNA-templated DNA replication initiation	5	47.4×	2e-05
DNA replication initiation	6	33.7×	9e-06
DNA replication	8	11.9×	7e-05
nucleosome assembly	9	11.4×	2e-05
DNA damage response	10	4.8×	5e-03

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: loss-of-function (tumor-suppressor-like) across 1 cancer types — CESC.

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	5
Likely pathogenic	0
Uncertain significance	143
Likely benign	6
Benign	5

Top pathogenic / likely-pathogenic (5)

Variant ID	HGVS	Classification
1173057	NM_005916.5(MCM7):c.415C>T (p.Gln139Ter)	Pathogenic
1173058	NM_005916.5(MCM7):c.1616A>G (p.Tyr539Cys)	Pathogenic
1173069	NM_005916.5(MCM7):c.776G>C (p.Gly259Ala)	Pathogenic
1173070	NM_005916.5(MCM7):c.1579C>T (p.Arg527Ter)	Pathogenic
1804007	NM_005916.5(MCM7):c.133C>T (p.Gln45Ter)	Pathogenic

SpliceAI

2397 predictions. Top by Δscore:

Variant	Effect	Δscore
7:100093133:CCT:C	acceptor_loss	1.0000
7:100093134:C:CC	acceptor_gain	1.0000
7:100093287:CTCA:C	donor_loss	1.0000
7:100093288:TCA:T	donor_loss	1.0000
7:100093289:CACC:C	donor_loss	1.0000
7:100093290:A:C	donor_loss	1.0000
7:100093291:CCTAG:C	donor_gain	1.0000
7:100093295:G:C	donor_gain	1.0000
7:100093397:CGTGC:C	acceptor_gain	1.0000
7:100093398:GTGC:G	acceptor_gain	1.0000
7:100093399:TGC:T	acceptor_gain	1.0000
7:100093399:TGCC:T	acceptor_loss	1.0000
7:100093400:GC:G	acceptor_gain	1.0000
7:100093401:CC:C	acceptor_gain	1.0000
7:100093401:CCTAA:C	acceptor_loss	1.0000
7:100093402:C:CC	acceptor_gain	1.0000
7:100093403:T:G	acceptor_loss	1.0000
7:100093413:G:C	acceptor_gain	1.0000
7:100094168:CTTA:C	donor_loss	1.0000
7:100094169:TTAC:T	donor_loss	1.0000
7:100094170:TACCA:T	donor_loss	1.0000
7:100094171:A:AC	donor_gain	1.0000
7:100094171:AC:A	donor_gain	1.0000
7:100094172:C:CC	donor_gain	1.0000
7:100094172:CC:C	donor_gain	1.0000
7:100094172:CCA:C	donor_gain	1.0000
7:100094172:CCAG:C	donor_gain	1.0000
7:100094172:CCAGA:C	donor_gain	1.0000
7:100094337:AACGC:A	acceptor_gain	1.0000
7:100094338:ACGC:A	acceptor_gain	1.0000

AlphaMissense

4671 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:100095465:G:T	A534D	1.000
7:100095902:G:C	N489K	1.000
7:100095902:G:T	N489K	1.000
7:100095909:G:T	A487D	1.000
7:100095912:G:T	A486D	1.000
7:100096031:C:A	E446D	1.000
7:100096031:C:G	E446D	1.000
7:100096032:T:A	E446V	1.000
7:100096033:C:T	E446K	1.000
7:100096035:T:A	D445V	1.000
7:100096035:T:C	D445G	1.000
7:100096035:T:G	D445A	1.000
7:100096036:C:G	D445H	1.000
7:100096038:A:T	I444N	1.000
7:100096040:G:C	C443W	1.000
7:100096043:G:C	C442W	1.000
7:100096120:C:G	A417P	1.000
7:100096128:A:G	L414P	1.000
7:100096128:A:T	L414H	1.000
7:100096131:C:T	G413E	1.000
7:100096132:C:G	G413R	1.000
7:100096132:C:T	G413R	1.000
7:100096152:C:T	G406D	1.000
7:100097330:A:G	L391P	1.000
7:100097333:A:G	L390P	1.000
7:100097339:G:A	S388F	1.000
7:100097340:A:G	S388P	1.000
7:100097341:C:A	K387N	1.000
7:100097341:C:G	K387N	1.000
7:100097342:T:A	K387M	1.000

dbSNP variants (sampled 300 via entrez): RS1000164199 (7:100098100 A>G), RS1000404937 (7:100093901 G>A,C,T), RS1000501282 (7:100097079 C>A,T), RS1000637019 (7:100097223 A>G), RS1001010924 (7:100100965 C>G,T), RS1001391263 (7:100103153 C>A,G), RS1001397202 (7:100100638 G>A,C,T), RS1001565564 (7:100095549 T>A), RS1001912842 (7:100095716 C>T), RS1001999947 (7:100100068 C>A,G,T), RS1002114496 (7:100100321 G>A,C,T), RS1002309378 (7:100096455 C>T), RS1002360932 (7:100099279 A>G), RS1002520750 (7:100096649 C>T), RS1002645151 (7:100095414 A>T)

Disease associations

OMIM: gene MIM:600592 | disease phenotypes: MIM:224690, MIM:603047

GenCC curated gene-disease

Disease	Classification	Inheritance
syndromic disease	Moderate	Autosomal recessive

Mondo (8): Meier-Gorlin syndrome (MONDO:0016817), microcephaly (MONDO:0001149), enophthalmos (MONDO:0001210), anisometropia (MONDO:0001478), hyperopia (MONDO:0004891), astigmatism (MONDO:0011284), microphthalmia (MONDO:0021129), syndromic disease (MONDO:0002254)

Orphanet (1): Ear-patella-short stature syndrome (Orphanet:2554)

HPO phenotypes

23 total (27 of 23 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000076	Vesicoureteral reflux
HP:0000122	Unilateral renal agenesis
HP:0000219	Thin upper lip vermilion
HP:0000252	Microcephaly
HP:0000340	Sloping forehead
HP:0000408	Progressive sensorineural hearing impairment
HP:0000582	Upslanted palpebral fissure
HP:0001263	Global developmental delay
HP:0001274	Agenesis of corpus callosum
HP:0001302	Pachygyria
HP:0001347	Hyperreflexia
HP:0001510	Growth delay
HP:0001751	Abnormal vestibular function
HP:0002119	Ventriculomegaly
HP:0002282	Gray matter heterotopia
HP:0003103	Abnormal cortical bone morphology
HP:0003581	Adult onset
HP:0003621	Juvenile onset
HP:0003677	Slowly progressive
HP:0004322	Short stature
HP:0007333	Hypoplasia of the frontal lobes
HP:0010864	Severe intellectual disability
HP:0000490	Deeply set eye
HP:0012803	Anisometropia
HP:0000483	Astigmatism
HP:0000568	Microphthalmia

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST010002_259	Refractive error	3.000000e-16
GCST010702_48	Subcortical volume (MOSTest)	6.000000e-10
GCST010703_289	Brain morphology (MOSTest)	6.000000e-15

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004346	neuroimaging measurement

MeSH disease descriptors (8)

Descriptor	Name	Tree numbers
D015858	Anisometropia	C11.744.126
D001251	Astigmatism	C11.744.212
D015841	Enophthalmos	C11.675.319
D006956	Hyperopia	C11.744.479
D008831	Microcephaly	C05.660.207.620; C10.500.507.400.500; C16.131.621.207.620; C16.131.666.507.400.500
D008850	Microphthalmos	C11.250.566; C16.131.384.666
D013577	Syndrome	C23.550.288.500
C538012	Meier-Gorlin syndrome (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4630816 (SINGLE PROTEIN)

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

ChEMBL bioactivities

2 potent at pChembl≥5 of 4 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
5.27	Kd	5392	nM	CHEMBL3752910
5.27	ED50	5392	nM	CHEMBL3752910

PubChem BioAssay actives

1 with measured affinity, of 12 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148735: Binding affinity to human MCM7 incubated for 45 mins by Kinobead based pull down assay	kd	5.3925	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects expression, decreases expression, decreases methylation, increases expression	5
sodium arsenite	decreases expression, affects cotreatment, increases abundance, increases expression	5
Benzo(a)pyrene	increases expression, decreases expression	5
Valproic Acid	decreases expression, affects expression	5
Arsenic Trioxide	increases expression, affects binding, decreases reaction, decreases expression	4
Particulate Matter	increases abundance, increases expression, affects cotreatment, decreases expression	4
Estradiol	decreases reaction, affects cotreatment, increases expression	3
Cyclosporine	decreases expression	3
Cadmium Chloride	decreases expression	3
trichostatin A	affects expression, decreases reaction	2
mercuric bromide	decreases expression, affects cotreatment	2
palbociclib	decreases expression, affects reaction	2
Resveratrol	affects cotreatment, increases expression	2
Copper	decreases expression, affects binding	2
Fluorouracil	affects response to substance, affects reaction, decreases expression	2
Phenylmercuric Acetate	decreases expression, affects cotreatment	2
Tamoxifen	affects cotreatment, decreases reaction, increases expression, decreases expression	2
Tetrachlorodibenzodioxin	affects expression, decreases expression	2
Tretinoin	decreases expression	2
Aflatoxin B1	increases methylation, increases expression	2
p-Chloromercuribenzoic Acid	affects cotreatment, decreases expression	2
TAK-243	increases sumoylation	1
methylmercuric chloride	decreases expression	1
propionaldehyde	decreases expression	1
2,2’-methylenebis(4-methyl-6-tert-butylphenol)	affects response to substance, affects expression	1
methylselenic acid	decreases expression	1
sodium arsenate	decreases expression	1
beta-lapachone	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
cobaltous chloride	decreases expression	1

ChEMBL screening assays

9 unique, capped per target: 9 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4605074	Binding	Induction of ubiquitination of MCM7 in human NCI-H1975 cells incubated for 24 hrs by immunoblot analysis	Suppression of Drug-Resistant Non-Small-Cell Lung Cancer with Inhibitors Targeting Minichromosomal Maintenance Protein. — J Med Chem

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00800774	PHASE4	COMPLETED	Ten-year Follow-up of Laser in Situ Keratomileusis in Patients 8 to 15 Years Old
NCT00347204	PHASE4	COMPLETED	Comparison of Acular LS Versus Nevanac for Pain Control in Eyes Undergoing PRK
NCT00455455	PHASE4	COMPLETED	Corneal and Conjunctival Sensitivity and Staining Study
NCT00937105	PHASE4	COMPLETED	Daily Wear Corneal Infiltrative Event Study
NCT01387360	PHASE4	COMPLETED	Presbyopic Supracor Treatment for Near Myopic/Hyperopic Pseudophakic Eyes
NCT01977807	PHASE4	UNKNOWN	A Prospective Safety and Effectiveness Study of the 500 Hz Technolas Perfect Vision Excimer Laser in Asian Eyes Using LASIK
NCT02071576	PHASE4	UNKNOWN	A Prospective Safety and Effectiveness Study of the 500 Hz Technolas Perfect Vision Excimer Laser Using LASIK
NCT02112968	PHASE4	UNKNOWN	A Prospective Safety and Effectiveness Study of a New High Repetition Rate Excimer Laser Using LASIK for the Correction of Ammetropia and Presbyopia
NCT03881670	PHASE4	COMPLETED	On-Eye Optical Quality of Lotrafilcon B Lenses Over 12 Hours
NCT04208750	PHASE4	COMPLETED	Clinical Investigation of the Vision-R800 Device.
NCT04283331	PHASE4	UNKNOWN	Anesthetic Impregnated Bandage Soft Contact Lens (BSCL) in Pain Management After Photorefractive Keratectomy (PRK)
NCT00770094	PHASE4	UNKNOWN	Multi Laser Platform Comparison Study for LASIK
NCT00821236	PHASE4	COMPLETED	Contralateral Comparison of Three Excimer Laser Systems in Performing LASIK
NCT00825513	PHASE4	COMPLETED	Safety and Effectiveness of the Akreos Toric Intraocular Lens.
NCT01018797	PHASE4	COMPLETED	Intrastromal Corneal Ring for High Astigmatism on Postkeratoplasty
NCT01279031	PHASE4	COMPLETED	Randomized Comparison of the Abbott WHITESTAR Signature System With Ellips Tranversal Ultrasound vs. the Alcon Infiniti With the Ozil Torsional Handpiece in Phacoemulsification: A Contralaterally-Controlled Trial
NCT01396616	PHASE4	UNKNOWN	Clinical Evaluation of Toric Intraocular Lens Made by Aurolab
NCT01454843	PHASE4	COMPLETED	LASIK Using the Alcon Allegretto Wavefront-Guided Excimer Laser vs AMO Visx Wavefront-Guided Excimer Laser
NCT01554761	PHASE4	UNKNOWN	Effect of Posterior Corneal Toricity on Refractive Outcome of Pseudophakia
NCT01885780	PHASE4	COMPLETED	Prospective Evaluation of the Effectiveness of the Femtosecond Laser-assisted Refractive Astigmatic Keratotomy.
NCT04321226	PHASE4	UNKNOWN	Femtosecond Laser-assisted Astigmatism Treatment
NCT04418986	PHASE4	COMPLETED	Incisional Correction of Corneal Astigmatism During Phacoemulsification
NCT07140653	PHASE4	RECRUITING	Arcuate Incisions With Light Adjustable Lens for Astigmatism Correction in Lens Surgery
NCT00001864	PHASE3	COMPLETED	Amblyopia (Lazy Eye) Treatment Study
NCT00520689	PHASE3	COMPLETED	Multipurpose Disinfecting Solution Compatibility With a Silicone Hydrogel Contact Lens
NCT00910403	PHASE3	COMPLETED	Multicenter Evaluation of Safety and Effectiveness of Presbyopic LASIK for Hyperopes
NCT00928122	PHASE3	UNKNOWN	Intrastromal Correction of Ametropia by a Femtosecond Laser
NCT01028378	PHASE3	COMPLETED	Safety and Efficacy Study of Topography-Guided LASIK to Treat Myopia and Hyperopia
NCT01322919	PHASE3	COMPLETED	Safety and Efficacy Study to Evaluate the Treatment of Both Near and Distance Vision in a Simultaneous Laser Procedure
NCT05247658	PHASE3	TERMINATED	Use of a Disk of Amniotic Membrane (Visio-AMTRIX) in Postoperative Care After PKR
NCT00000123	PHASE3	COMPLETED	The Berkeley Orthokeratology Study
NCT00663923	PHASE3	COMPLETED	Comparison of Cross-cylinder and Conventional Photorefractive Keratectomy(PRK) in Correcting Medium-high Astigmatism
NCT01673503	PHASE3	COMPLETED	A Prospective Study of Femtosecond Laser Intracorneal Lensectomi
NCT00027456	PHASE2	COMPLETED	Leptin to Treat Severe Insulin Resistance - Pilot Study
NCT01119144	PHASE2	UNKNOWN	Polycaprolactone / Tricalcium Phosphate (PCL/TCP) v Titanium Orbital Implant : Randomised Trial
NCT05477875	PHASE2	COMPLETED	Cannabinoid vs Opioid for Photorefractive Keratectomy Pain Control
NCT02246556	PHASE1	TERMINATED	Dichoptic Virtual Reality Therapy for Amblyopia in Adults
NCT01556893	PHASE1	COMPLETED	Creating LASIK Flaps With the LenSx Femtosecond Laser
NCT06896357	PHASE1	NOT_YET_RECRUITING	Effectiveness and Safety of Limbal Relaxing Incisions for Correcting Post Phacoemulsification High Astigmatism
NCT00213447	Not specified	COMPLETED	T Cell Response in Hypersensitivity Syndrome