MCRS1

Summary

MCRS1 (microspherule protein 1, HGNC:6960) is a protein-coding gene on chromosome 12q13.12, encoding Microspherule protein 1 (Q96EZ8). Modulates the transcription repressor activity of DAXX by recruiting it to the nucleolus. It is a selective cancer dependency (DepMap: 75.2% of cell lines).

Enables RNA binding activity and telomerase inhibitor activity. Involved in several processes, including chromatin remodeling; positive regulation of protein localization to nucleolus; and regulation of nucleobase-containing compound metabolic process. Located in cytoplasm; nuclear body; and nucleolus. Part of Ino80 complex; MLL1 complex; and NSL complex.

Source: NCBI Gene 10445 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 56 total
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 75.2% of screened cell lines
• MANE Select transcript: NM_006337

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6960
Approved symbol	MCRS1
Name	microspherule protein 1
Location	12q13.12
Locus type	gene with protein product
Status	Approved
Aliases	ICP22BP, MSP58, P78, MCRS2, INO80Q
Ensembl gene	ENSG00000187778
Ensembl biotype	protein_coding
OMIM	609504
Entrez	10445

Gene structure

Transcript identifiers

Ensembl transcripts: 25 — 18 protein_coding, 4 retained_intron, 2 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000343810, ENST00000357123, ENST00000546244, ENST00000547182, ENST00000548334, ENST00000548596, ENST00000548602, ENST00000548646, ENST00000549000, ENST00000549528, ENST00000550165, ENST00000551598, ENST00000551625, ENST00000552206, ENST00000552596, ENST00000553173, ENST00000879001, ENST00000879002, ENST00000879003, ENST00000879004, ENST00000879005, ENST00000930410, ENST00000930411, ENST00000930412, ENST00000972173

RefSeq mRNA: 3 — MANE Select: NM_006337 NM_001012300, NM_001278341, NM_006337

CCDS: CCDS31795, CCDS61118, CCDS8787

Canonical transcript exons

ENST00000343810 — 15 exons

Exon	Start	End
ENSE00001430306	49566722	49566841
ENSE00002325343	49568048	49568142
ENSE00002415984	49558299	49558729
ENSE00003472018	49559214	49559301
ENSE00003483977	49559939	49559967
ENSE00003484242	49565529	49565667
ENSE00003499842	49566077	49566215
ENSE00003505022	49564737	49564895
ENSE00003513668	49559729	49559821
ENSE00003540624	49563001	49563139
ENSE00003572371	49559453	49559535
ENSE00003606087	49558843	49558970
ENSE00003664882	49563438	49563546
ENSE00003672493	49560295	49560370
ENSE00003785410	49564481	49564590

Expression profiles

Bgee: expression breadth ubiquitous, 278 present calls, max score 97.64.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 36.2747 / max 211.4608, expressed in 1815 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
130840	36.0664	1815
130839	0.2084	90

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
apex of heart	UBERON:0002098	97.64	gold quality
granulocyte	CL:0000094	95.92	gold quality
heart left ventricle	UBERON:0002084	95.61	gold quality
right atrium auricular region	UBERON:0006631	95.58	gold quality
cardiac ventricle	UBERON:0002082	95.30	gold quality
right lobe of thyroid gland	UBERON:0001119	95.28	gold quality
left lobe of thyroid gland	UBERON:0001120	95.12	gold quality
metanephros cortex	UBERON:0010533	94.86	gold quality
cardiac atrium	UBERON:0002081	94.66	gold quality
mucosa of transverse colon	UBERON:0004991	94.65	gold quality
right frontal lobe	UBERON:0002810	94.46	gold quality
heart	UBERON:0000948	94.30	gold quality
thyroid gland	UBERON:0002046	94.06	gold quality
body of stomach	UBERON:0001161	94.01	gold quality
small intestine Peyer’s patch	UBERON:0003454	93.94	gold quality
lower esophagus mucosa	UBERON:0035834	93.80	gold quality
lower esophagus	UBERON:0013473	93.78	gold quality
lower esophagus muscularis layer	UBERON:0035833	93.78	gold quality
left testis	UBERON:0004533	93.70	gold quality
right testis	UBERON:0004534	93.63	gold quality
transverse colon	UBERON:0001157	93.60	gold quality
body of uterus	UBERON:0009853	93.57	gold quality
gastrocnemius	UBERON:0001388	93.55	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	93.51	gold quality
muscle layer of sigmoid colon	UBERON:0035805	93.38	gold quality
prefrontal cortex	UBERON:0000451	93.30	gold quality
hindlimb stylopod muscle	UBERON:0004252	93.29	gold quality
muscle of leg	UBERON:0001383	93.27	gold quality
mucosa of stomach	UBERON:0001199	93.21	gold quality
minor salivary gland	UBERON:0001830	93.18	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	8.89
E-MTAB-7606	no	246.03

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

29 targeting MCRS1, 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-6758-5P	100.00	66.21	1470
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-6856-5P	100.00	65.47	1298
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-6768-5P	99.92	67.36	1942
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-12119	99.87	68.35	1653
HSA-MIR-12130	99.75	65.47	452
HSA-MIR-4699-3P	99.71	70.15	3142
HSA-MIR-1303	99.65	69.77	1662
HSA-MIR-3975	99.62	65.97	697
HSA-MIR-4649-3P	99.56	66.90	1783
HSA-MIR-4293	99.22	65.46	1263
HSA-MIR-296-3P	99.21	66.56	474
HSA-MIR-7109-5P	99.18	66.13	1057
HSA-MIR-1207-3P	98.99	66.22	1532
HSA-MIR-760	98.81	66.65	1392
HSA-MIR-7977	98.65	66.18	2590
HSA-MIR-3135B	98.61	65.33	1470
HSA-MIR-518C-5P	98.53	69.20	1640
HSA-MIR-4433A-3P	97.75	62.82	1435
HSA-MIR-665	97.60	65.64	1781
HSA-MIR-4433B-3P	97.22	63.62	663
HSA-MIR-6815-5P	96.05	65.55	662
HSA-MIR-6865-5P	96.05	65.58	675
HSA-MIR-139-3P	95.24	63.10	316

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 75.2% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 36)

• role in the modulation of Daxx-dependent transcriptional repression (PMID:11948183)
• Mi-2beta and RFP, known to be involved in transcriptional repression in the nucleus, co-localize with MCRS1 in the nucleolus and appear to activate the rRNA transcription. (PMID:16186106)
• A subset of the p78 proteins comprises a component of the centrosome; p78 is essential for cell viability. (PMID:16547491)
• Escorts fragile X mental retardation protein-containing silent ribonucleoparticles (mRNP)from the nucleus and nucleolus to the somato-dendritic compartment where it might participate in neuronal translation regulation. (PMID:16571602)
• DIPA can act as a repressor of gene transcription, an activity that appears to be enhanced by p78. (PMID:17014843)
• modulation of Ndrg2 level influences the cell cycle process together with MSP58 (PMID:17109818)
• These data highlight the importance of MSP58 in glioma progression. (PMID:18798870)
• MCRS2, a new Nrf1-interacting protein, has a repression effect on Nrf1-mediated transcriptional activation (PMID:19187526)
• Overexpression of MSP58 is associated with colorectal cancer. (PMID:19549253)
• the sequence of MCRS2 and determines that the nuclear localization signal, which has the sequence KRKK, is situated between amino acids 66 and 69 (PMID:21533551)
• MCRS1 is a RanGTP-regulated factor essential for non-centrosomal microtubule assembly. (PMID:22081094)
• Our findings highlight new aspects of MSP58 in modulating cellular senescence and suggest that MSP58 has both oncogenic and tumor-suppressive properties. (PMID:22563078)
• MCRS2 plays a negative role in stress-induced ASK1 activation. (PMID:22609355)
• Our results demonstrated MSP58 might serve as a novel prognostic marker for colorectal cancer (PMID:22773039)
• MSP58 contributes to the tumorigenesis of neuroblastoma by promoting cell proliferation. (PMID:22975844)
• MSP58 depletion induced cell cycle arrest. (PMID:22994740)
• Interaction between microspherule protein Msp58 and ubiquitin E3 ligase EDD regulates cell cycle progression. (PMID:23069210)
• RACGAP1 and MCRS1 overexpression in nonsmall-cell lung cancer.RACGAP1 and MCRS1 may be cancer-related genes in NSCLC. (PMID:23225332)
• MSP58 expression in hepatocellular carcinoma is closely related to the prognosis. (PMID:23519485)
• High expression of MSP58 was also an independent unfavorable prognostic factor. (PMID:23996240)
• MSP58 could suppress the transcription of hTERT promoter. (PMID:24361335)
• MiR-129* down-regulation induced MCRS1 overexpression. (PMID:25373388)
• MSP58 subnuclear localization is regulated by two nuclear import signals, and proper subcellular localization of MSP58 is critical for its role in transcriptional regulation. A molecular mechanism controls nuclear and nucleolar localization of MSP58. (PMID:25981436)
• BAP1 loss and MCRS1 down-regulation in renal cell carcinoma are associated with adverse clinicopathological features. (PMID:26300492)
• MCRS1 overexpression induced non-small cell lung cancer proliferation through the miR-155-Rb1 pathway and DNA copy-number amplification is one of the mechanisms underlying MCRS1 overexpression in non-small cell lung cancer. (PMID:26467212)
• The immunoreactivity score (IRS) of MSP58 increased with tumor grade with grade IV gliomas exhibiting the highest expression and showed a highly significant positive correlation with the Ki-67 index (r = 0.65, P < 0.001). (PMID:26849376)
• MCRS1 is phosphorylated by the Aurora-A kinase in mitosis on Ser35/36. (PMID:27192185)
• Study shows that MCRS1 binds to cytoplasmic dynein and contributes to the establishment of centriolar satellites and ciliogenesis. (PMID:27263857)
• Suggest that MSP58 plays an important role in tumorigenesis and progression and may help predict the prognosis of gastric cancer patients. (PMID:27468560)
• RINT-1 interacts with MSP58 and UBF within nucleoli and plays a role in ribosomal gene transcription. (PMID:27530925)
• MSP58 downregulation suppressed the proliferation and invasion of renal cell carcinoma cells. (PMID:28448870)
• Authors show that Mps1 regulates chromosome alignment through MCRS1, a spindle assembly factor that controls the dynamics of the minus end of kinetochore microtubules. Mps1 binds and phosphorylates MCRS1. (PMID:30785839)
• This study confirmed the specific tumor suppressive activity of MCRS1 in gastric cancer proliferation, invasion and migration and suggested that it might inhibit the progression of gastric cancer through its interaction with Pkmyt1. (PMID:30953699)
• Our data suggest that decreased expression of miR-186 in hepatocellular carcinoma is responsible for the high expression of MCRS1 (PMID:31140612)
• MCRS1 modulates the heterogeneity of microtubule minus-end morphologies in mitotic spindles. (PMID:36350698)
• The molecular characteristics and functional roles of microspherule protein 1 (MCRS1) in gene expression, cell proliferation, and organismic development. (PMID:36384428)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	mcrs1	ENSDARG00000020840
mus_musculus	Mcrs1	ENSMUSG00000037570
rattus_norvegicus	Mcrs1	ENSRNOG00000054838
drosophila_melanogaster	Rcd5	FBGN0263832
caenorhabditis_elegans	mcrs-1	WBGENE00010420

Protein

Protein identifiers

Microspherule protein 1 — Q96EZ8 (reviewed: Q96EZ8)

Alternative names: 58 kDa microspherule protein, Cell cycle-regulated factor p78, INO80 complex subunit J, MCRS2

All UniProt accessions (8): F8VP44, F8VVA6, F8VZC2, F8W0I9, F8W126, Q96EZ8, H0YI67, H0YIA0

UniProt curated annotations — full annotation on UniProt →

Function. Modulates the transcription repressor activity of DAXX by recruiting it to the nucleolus. As part of the NSL complex, may be involved in acetylation of nucleosomal histone H4 on several lysine residues. Putative regulatory component of the chromatin remodeling INO80 complex which is involved in transcriptional regulation, DNA replication and probably DNA repair. May also be an inhibitor of TERT telomerase activity. Binds to G-quadruplex structures in mRNA. Binds to RNA homomer poly(G) and poly(U). Maintains RHEB at the lysosome in its active GTP-bound form and prevents its interaction with the mTORC1 complex inhibitor TSC2, ensuring activation of the mTORC1 complex by RHEB. Stabilizes the minus ends of kinetochore fibers by protecting them from depolymerization, ensuring functional spindle assembly during mitosis. Following phosphorylation by TTK/MPS1, enhances recruitment of KIF2A to the minus ends of mitotic spindle microtubules which promotes chromosome alignment. Regulates the morphology of microtubule minus ends in mitotic spindle by maintaining them in a closed conformation characterized by the presence of an electron-dense cap. Regulates G2/M transition and spindle assembly during oocyte meiosis. Mediates histone modifications and transcriptional regulation in germinal vesicle oocytes which are required for meiotic progression. Also regulates microtubule nucleation and spindle assembly by activating aurora kinases during oocyte meiosis. Contributes to the establishment of centriolar satellites and also plays a role in primary cilium formation by recruiting TTBK2 to the mother centriole which is necessary for removal of the CP110 cap from the mother centriole, an early step in ciliogenesis. Required for epiblast development during early embryogenesis. Essential for cell viability.

Subunit / interactions. Component of the chromatin remodeling INO80 complex; specifically part of a complex module associated with the N-terminus of INO80. Component of some MLL1/MLL complex, at least composed of the core components KMT2A/MLL1, ASH2L, HCFC1, WDR5 and RBBP5, as well as the facultative components BACC1, CHD8, E2F6, HSP70, INO80C, KANSL1, LAS1L, MAX, MCRS1, MGA, KAT8/MOF, PELP1, PHF20, PRP31, RING2, RUVB1/TIP49A, RUVB2/TIP49B, SENP3, TAF1, TAF4, TAF6, TAF7, TAF9 and TEX10. Component of the NSL complex at least composed of MOF/KAT8, KANSL1, KANSL2, KANSL3, MCRS1, PHF20, OGT1/OGT, WDR5 and HCFC1. Interacts with NOP2. Interacts with PINX1. Interacts with TERT. Interacts with CCDC85B. Interacts with DAXX. Interacts (via N-terminus) with FMR1 (via phosphorylated form). Interacts with FXR1 and FXR2. Interacts (via C-terminus) with NDE1 (via C-terminus); phosphorylation of NDE1 inhibits the interaction. Interacts (via C-terminus) with ZNF375. Interacts (via C-terminus) with active GTP-bound RHEB (via N-terminus) under conditions of high amino acid concentration; the interaction promotes mTORC1 complex activation by RHEB. Interacts (via N-terminus) with the mTORC1 complex; the interaction ensures mTORC1 activation by RHEB. Interacts with DYNC1I1; the interaction is required for the proper distribution of centriolar satellites. Interacts with TTBK2; the interaction is required for recruitment of TTBK2 to the mother centriole. Interacts with KIF2A; the interaction occurs during mitosis and facilitates chromosome alignment. (Microbial infection) Interacts with Herpes simplex virus ICP22.

Subcellular location. Nucleus. Nucleolus. Cytoplasm. Cytoskeleton. Microtubule organizing center. Centrosome. Spindle pole. Chromosome. Centromere. Kinetochore. Lysosome. Centriolar satellite.

Tissue specificity. Detected in testis, and at lower levels in spleen, thymus, prostate, uterus, small intestine, colon and leukocytes.

Post-translational modifications. Ubiquitinated by UBR5 when not assembled in the INO80 complex, leading to its degradation: UBR5 recognizes and binds a degron that is not accessible when MCRS1 is part of the INO80 complex. Phosphorylated by AURKA on Ser-35 and/or Ser-36 during mitosis which is required for kinetochore fiber assembly and mitotic progression but not for spindle localization or for chromosome-induced microtubule aster formation. Also phosphorylated by AURKA on Ser-85 and/or Ser-87. Phosphorylated by TTK/MPS1 which enhances recruitment of KIF2A to the minus end of spindle microtubules and facilitates precise chromosome segregation.

Domain organisation. The N-terminal region is required for nuclear localization while the C-terminal region encompassing the FHA domain is required for centrosomal localization.

Miscellaneous. May be due to intron retention.

Isoforms (4)

UniProt ID	Names	Canonical?
Q96EZ8-1	1	yes
Q96EZ8-2	2, MCRS2
Q96EZ8-3	3
Q96EZ8-4	4

RefSeq proteins (3): NP_001012300, NP_001265270, NP_006328* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000253	FHA_dom	Domain
IPR008984	SMAD_FHA_dom_sf	Homologous_superfamily
IPR025999	MCRS_N	Domain
IPR037912	MCRS1	Family

Pfam: PF00498, PF13325

UniProt features (26 total): modified residue 8, mutagenesis site 5, splice variant 3, short sequence motif 2, compositionally biased region 2, chain 1, domain 1, sequence variant 1, region of interest 1, sequence conflict 1, coiled-coil region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96EZ8-F1	75.90	0.50

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): 102, 103, 108, 123, 130, 282, 1, 22

Mutagenesis-validated functional residues (5):

Position	Phenotype
35–36	reduces phosphorylation by aurka. does not rescue the mitotic defect seen in mcrs1-silenced cells. does not affect local
35–36	phosphomimetic mutant; shows a more severe mitotic defect than mcrs1-silenced cells. does not affect localization to the
64–65	reduces phosphorylation by ttk. cells show a mitotic defect and remain longer in mitosis.
65	exhibits mitotic defect. does not rescue the misaligned chromosome phenotype seen in mcrs1-silenced cells. does not affe
65	exhibits normal mitotic timing. rescues the misaligned chromosome phenotype seen in mcrs1-silenced cells.

Function

Pathways and Gene Ontology

Reactome pathways

15 pathways

ID	Pathway
R-HSA-3214847	HATs acetylate histones
R-HSA-5689603	UCH proteinases
R-HSA-5696394	DNA Damage Recognition in GG-NER
R-HSA-9772755	Formation of WDR5-containing histone-modifying complexes
R-HSA-212165	Epigenetic regulation of gene expression
R-HSA-3247509	Chromatin modifying enzymes
R-HSA-392499	Metabolism of proteins
R-HSA-4839726	Chromatin organization
R-HSA-5688426	Deubiquitination
R-HSA-5696398	Nucleotide Excision Repair
R-HSA-5696399	Global Genome Nucleotide Excision Repair (GG-NER)
R-HSA-597592	Post-translational protein modification
R-HSA-73894	DNA Repair
R-HSA-74160	Gene expression (Transcription)
R-HSA-9917777	Epigenetic regulation by WDR5-containing histone modifying complexes

MSigDB gene sets: 197 (showing top): GOBP_CHROMOSOME_ORGANIZATION, MODULE_52, TGCGCANK_UNKNOWN, LFA1_Q6, MODULE_45, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GOBP_POSITIVE_REGULATION_OF_PROTEIN_LOCALIZATION, GOBP_TELOMERE_MAINTENANCE_VIA_TELOMERE_LENGTHENING, GOBP_TELOMERE_ORGANIZATION, GOBP_POSITIVE_REGULATION_OF_ORGANELLE_ORGANIZATION, GOBP_REGULATION_OF_DNA_REPAIR, GOCC_MICROTUBULE_ORGANIZING_CENTER, PATIL_LIVER_CANCER, GOBP_NEGATIVE_REGULATION_OF_CELLULAR_COMPONENT_ORGANIZATION, MODULE_118

GO Biological Process (22): telomere maintenance (GO:0000723), regulation of DNA replication (GO:0006275), DNA repair (GO:0006281), regulation of DNA repair (GO:0006282), DNA recombination (GO:0006310), chromatin remodeling (GO:0006338), regulation of chromosome organization (GO:0033044), protein modification process (GO:0036211), positive regulation of DNA repair (GO:0045739), positive regulation of DNA-templated transcription (GO:0045893), positive regulation of transcription by RNA polymerase II (GO:0045944), regulation of embryonic development (GO:0045995), regulation of cell cycle (GO:0051726), regulation of DNA strand elongation (GO:0060382), negative regulation of telomere maintenance via telomere lengthening (GO:1904357), positive regulation of telomere maintenance in response to DNA damage (GO:1904507), positive regulation of protein localization to nucleolus (GO:1904751), chromatin organization (GO:0006325), DNA damage response (GO:0006974), positive regulation of macromolecule metabolic process (GO:0010604), regulation of telomere maintenance (GO:0032204), obsolete positive regulation of nucleobase-containing compound metabolic process (GO:0045935)

GO Molecular Function (5): G-quadruplex RNA binding (GO:0002151), poly(U) RNA binding (GO:0008266), telomerase inhibitor activity (GO:0010521), poly(G) binding (GO:0034046), protein binding (GO:0005515)

GO Cellular Component (19): histone acetyltransferase complex (GO:0000123), kinetochore (GO:0000776), spindle pole (GO:0000922), nucleus (GO:0005634), nucleoplasm (GO:0005654), nucleolus (GO:0005730), cytoplasm (GO:0005737), lysosome (GO:0005764), nuclear body (GO:0016604), dendrite (GO:0030425), Ino80 complex (GO:0031011), centriolar satellite (GO:0034451), perikaryon (GO:0043204), NSL complex (GO:0044545), MLL1 complex (GO:0071339), chromosome, centromeric region (GO:0000775), chromosome (GO:0005694), centrosome (GO:0005813), cytoskeleton (GO:0005856)

Reactome top-level categories

Rollup of top-11 pathways:

Category	Pathways
Chromatin modifying enzymes	1
Deubiquitination	1
Global Genome Nucleotide Excision Repair (GG-NER)	1
Epigenetic regulation by WDR5-containing histone modifying complexes	1
Gene expression (Transcription)	1
Chromatin organization	1
Post-translational protein modification	1
DNA Repair	1
Nucleotide Excision Repair	1
Metabolism of proteins	1
Epigenetic regulation of gene expression	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
intracellular membraneless organelle	5
cellular anatomical structure	5
DNA metabolic process	3
regulation of DNA metabolic process	3
DNA repair	2
positive regulation of response to stimulus	2
nuclear lumen	2
telomere organization	1
DNA replication	1
DNA damage response	1
regulation of cellular response to stress	1
chromatin organization	1
regulation of organelle organization	1
chromosome organization	1
protein metabolic process	1
macromolecule modification	1
regulation of DNA repair	1
positive regulation of DNA metabolic process	1
DNA-templated transcription	1
regulation of DNA-templated transcription	1
positive regulation of RNA biosynthetic process	1
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
positive regulation of DNA-templated transcription	1
embryo development	1
regulation of multicellular organismal development	1
cell cycle	1
regulation of cellular process	1
DNA strand elongation	1
telomere maintenance via telomere lengthening	1
negative regulation of telomere maintenance	1
regulation of telomere maintenance via telomere lengthening	1
positive regulation of telomere maintenance	1
telomere maintenance in response to DNA damage	1
regulation of telomere maintenance in response to DNA damage	1
positive regulation of protein localization to nucleus	1
protein localization to nucleolus	1
regulation of protein localization to nucleolus	1
cellular component organization	1
cellular response to stress	1

Protein interactions and networks

STRING

1394 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MCRS1	KANSL2	Q9H9L4	993
MCRS1	KANSL3	Q9P2N6	990
MCRS1	PHF20	Q9BVI0	953
MCRS1	OGT	O15294	948
MCRS1	WDR5	P61964	901
MCRS1	CHD4	Q14839	888
MCRS1	KANSL1	Q7Z3B3	888
MCRS1	HCFC1	P51610	830
MCRS1	DAXX	Q9UER7	767
MCRS1	UBTF	P17480	736
MCRS1	TRIM27	P14373	716
MCRS1	KAT8	Q9H7Z6	678
MCRS1	NOP2	P46087	663
MCRS1	NDE1	Q9NXR1	595
MCRS1	PTEN	P60484	581

IntAct

532 interactions, top by confidence:

A	B	Type	Score
WASHC3	MCRS1	psi-mi:“MI:0915”(physical association)	0.880
MCRS1	WASHC3	psi-mi:“MI:0915”(physical association)	0.880
ZBTB22	MCRS1	psi-mi:“MI:0915”(physical association)	0.720
MCRS1	USHBP1	psi-mi:“MI:0915”(physical association)	0.720
USHBP1	MCRS1	psi-mi:“MI:0915”(physical association)	0.720
GPBP1	MCRS1	psi-mi:“MI:0915”(physical association)	0.700
TRIM37	MCRS1	psi-mi:“MI:0915”(physical association)	0.670
MCRS1	IKZF1	psi-mi:“MI:0915”(physical association)	0.670
MCRS1	TRIM37	psi-mi:“MI:0915”(physical association)	0.670
IKZF1	MCRS1	psi-mi:“MI:0915”(physical association)	0.670
MCRS1	GCC1	psi-mi:“MI:0915”(physical association)	0.620
GCC1	MCRS1	psi-mi:“MI:0915”(physical association)	0.620
MCRS1	KIAA1958	psi-mi:“MI:0915”(physical association)	0.560
KIAA1958	MCRS1	psi-mi:“MI:0915”(physical association)	0.560
ZNF23	MCRS1	psi-mi:“MI:0915”(physical association)	0.560
CCNH	MCRS1	psi-mi:“MI:0915”(physical association)	0.560
BRD8	MCRS1	psi-mi:“MI:0915”(physical association)	0.560
SNAPC5	MCRS1	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (354): MCRS1 (Two-hybrid), MCRS1 (Two-hybrid), MCRS1 (Two-hybrid), CCDC53 (Two-hybrid), USHBP1 (Two-hybrid), KIAA1958 (Two-hybrid), BRCA1 (Two-hybrid), BRCA1 (Affinity Capture-Western), MCRS1 (Affinity Capture-Western), MCRS1 (Affinity Capture-Western), MCRS1 (Two-hybrid), MCRS1 (Affinity Capture-MS), MCRS1 (Affinity Capture-MS), KXD1 (Two-hybrid), CEP44 (Two-hybrid)

ESM2 similar proteins: A4FVD8, A5D7H2, O14795, O43237, O55047, O70585, O75446, O88574, P58405, P84060, Q02241, Q0VA03, Q13033, Q14161, Q28H91, Q2TAD4, Q4KUS2, Q4R5P6, Q5EA89, Q5HYJ3, Q5R7U7, Q5RE09, Q5SQF8, Q5ZJ65, Q62768, Q6NYV5, Q6PBM7, Q6PDL0, Q80XP8, Q80YA9, Q811S7, Q86UE8, Q8BIK4, Q8C0V0, Q8CBY8, Q8TAV0, Q8WXI2, Q90ZY6, Q922G2, Q96EZ8

Diamond homologs: Q96EZ8, Q99L90

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
MCRS1	“form complex”	“NSL histone acetyltransferase”	binding
MCRS1	“form complex”	“INO80 complex”	binding
AURKA	“up-regulates activity”	MCRS1	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 115 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.

GO biological processes:

GO term	Partners	Fold	FDR
regulation of apoptotic process	8	6.7×	8e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	47
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2599 predictions. Top by Δscore:

Variant	Effect	Δscore
12:49557256:GGCG:G	donor_gain	1.0000
12:49557257:GCGG:G	donor_gain	1.0000
12:49558837:GCTCA:G	donor_loss	1.0000
12:49558838:CTCA:C	donor_loss	1.0000
12:49558839:TCA:T	donor_loss	1.0000
12:49558840:CACC:C	donor_loss	1.0000
12:49558841:ACC:A	donor_loss	1.0000
12:49558842:C:A	donor_loss	1.0000
12:49558844:T:TA	donor_gain	1.0000
12:49558966:GACAC:G	acceptor_gain	1.0000
12:49558967:ACAC:A	acceptor_gain	1.0000
12:49558968:CAC:C	acceptor_gain	1.0000
12:49558968:CACC:C	acceptor_gain	1.0000
12:49558969:AC:A	acceptor_gain	1.0000
12:49558970:CC:C	acceptor_gain	1.0000
12:49558971:C:CC	acceptor_gain	1.0000
12:49558971:C:T	acceptor_gain	1.0000
12:49558973:G:C	acceptor_gain	1.0000
12:49558973:G:GC	acceptor_gain	1.0000
12:49558980:C:CT	acceptor_gain	1.0000
12:49558981:A:T	acceptor_gain	1.0000
12:49559209:GATAC:G	donor_loss	1.0000
12:49559210:ATACC:A	donor_loss	1.0000
12:49559211:TACCT:T	donor_loss	1.0000
12:49559302:C:CC	acceptor_gain	1.0000
12:49559448:CTCA:C	donor_loss	1.0000
12:49559450:CACC:C	donor_loss	1.0000
12:49559533:TGC:T	acceptor_gain	1.0000
12:49559535:CCTGG:C	acceptor_loss	1.0000
12:49559536:C:CC	acceptor_gain	1.0000

AlphaMissense

3010 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:49558707:A:G	F442S	1.000
12:49558865:A:T	L427H	1.000
12:49558922:C:A	G408V	1.000
12:49558922:C:T	G408D	1.000
12:49558923:C:G	G408R	1.000
12:49558927:A:C	N406K	1.000
12:49558927:A:T	N406K	1.000
12:49558958:A:G	L396P	1.000
12:49558964:A:T	I394N	1.000
12:49558970:C:T	G392D	1.000
12:49559214:C:G	G392R	1.000
12:49559222:C:A	R389L	1.000
12:49559228:A:C	I387R	1.000
12:49559228:A:T	I387K	1.000
12:49559237:G:T	A384D	1.000
12:49559243:C:T	G382D	1.000
12:49559244:C:A	G382C	1.000
12:49559244:C:G	G382R	1.000
12:49559245:C:A	E381D	1.000
12:49559245:C:G	E381D	1.000
12:49559246:T:A	E381V	1.000
12:49559247:C:T	E381K	1.000
12:49559249:A:G	L380P	1.000
12:49559255:A:C	L378R	1.000
12:49559255:A:G	L378P	1.000
12:49559255:A:T	L378Q	1.000
12:49559261:A:T	V376E	1.000
12:49559287:T:A	R367S	1.000
12:49559287:T:G	R367S	1.000
12:49559288:C:A	R367I	1.000

dbSNP variants (sampled 300 via entrez): RS1000227936 (12:49567684 C>T), RS1000387562 (12:49566605 C>A,G), RS1000404251 (12:49561329 T>A,G), RS1000797809 (12:49562109 G>A), RS1000996014 (12:49568040 G>T), RS1001260426 (12:49568439 G>A), RS1001333911 (12:49568683 A>G), RS1001438810 (12:49562688 T>C), RS1001439744 (12:49566389 A>C), RS1001890250 (12:49562377 G>A), RS1002364428 (12:49562041 G>C), RS1002804675 (12:49564570 G>A,T), RS1002851068 (12:49564275 A>G), RS1002954405 (12:49559437 G>A,T), RS1003446332 (12:49565874 G>A)

Disease associations

OMIM: gene MIM:609504 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): multiple congenital anomalies/dysmorphic syndrome (MONDO:0019042)

Orphanet (1): Multiple congenital anomalies/dysmorphic syndrome (Orphanet:68341)

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5724632 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 1,538 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1232461	MOLIBRESIB	2	1,538

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

ChEMBL bioactivities

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

pChembl	Type	Value	Unit	Molecule
7.00	IC50	100	nM	MOLIBRESIB

PubChem BioAssay actives

1 with measured affinity, of 6 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
2-[(4S)-6-(4-chlorophenyl)-8-methoxy-1-methyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-4-yl]-N-ethylacetamide	2178978: Inhibition of MCRS1 (unknown origin) incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	ic50	0.1000	uM

CTD chemical–gene interactions

27 total (human), top 27 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases expression	2
Aflatoxin B1	increases methylation, decreases methylation	2
FR900359	affects phosphorylation	1
bisphenol F	increases expression, affects cotreatment	1
triphenyl phosphate	affects expression	1
trichostatin A	affects expression	1
beta-lapachone	increases expression	1
cobaltous chloride	decreases expression	1
beta-methylcholine	affects expression	1
CGP 52608	increases reaction, affects binding	1
jinfukang	increases expression	1
Sunitinib	decreases expression	1
Caffeine	affects phosphorylation	1
Cannabidiol	decreases expression	1
Dexamethasone	affects cotreatment, increases expression	1
Diuron	decreases expression	1
Indomethacin	increases expression, affects cotreatment	1
Lead	affects expression	1
Selenium	increases expression, affects cotreatment	1
Silicon Dioxide	decreases expression	1
Smoke	decreases expression	1
Urethane	decreases expression	1
Valproic Acid	decreases expression, increases methylation	1
Vitamin E	increases expression, affects cotreatment	1
1-Methyl-3-isobutylxanthine	affects cotreatment, increases expression	1
Chlorodiphenyl (54% Chlorine)	increases expression	1
tert-Butylhydroperoxide	decreases 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
CHEMBL5697708	Binding	Inhibition of MCRS1 (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.