MIS18BP1

Summary

MIS18BP1 (MIS18 binding protein 1, HGNC:20190) is a protein-coding gene on chromosome 14q21.2, encoding Mis18-binding protein 1 (Q6P0N0). Required for recruitment of CENPA to centromeres and normal chromosome segregation during mitosis. It is a common-essential gene (DepMap: required in 96.7% of cancer cell lines).

Predicted to enable DNA binding activity. Predicted to be involved in cell division. Predicted to be located in nucleoplasm. Predicted to be part of CENP-A recruiting complex. Predicted to be active in chromosome, centromeric region.

Source: NCBI Gene 55320 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 179 total
• Cancer dependency (DepMap): dependent in 96.7% of screened cell lines (common-essential)
• MANE Select transcript: NM_018353

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:20190
Approved symbol	MIS18BP1
Name	MIS18 binding protein 1
Location	14q21.2
Locus type	gene with protein product
Status	Approved
Aliases	M18BP1, FLJ11186, KIAA1903, KNL2
Ensembl gene	ENSG00000129534
Ensembl biotype	protein_coding
OMIM	618139
Entrez	55320

Gene structure

Transcript identifiers

Ensembl transcripts: 23 — 14 protein_coding, 4 retained_intron, 3 nonsense_mediated_decay, 2 protein_coding_CDS_not_defined

ENST00000310806, ENST00000451174, ENST00000453142, ENST00000454990, ENST00000469020, ENST00000470424, ENST00000492652, ENST00000494512, ENST00000496413, ENST00000554093, ENST00000555653, ENST00000627697, ENST00000901126, ENST00000919495, ENST00000919496, ENST00000919497, ENST00000919498, ENST00000919499, ENST00000919500, ENST00000919501, ENST00000919502, ENST00000919503, ENST00000952537

RefSeq mRNA: 1 — MANE Select: NM_018353 NM_018353

CCDS: CCDS9684

Canonical transcript exons

ENST00000310806 — 17 exons

Exon	Start	End
ENSE00000889895	45223918	45224746
ENSE00000889896	45226743	45226836
ENSE00000995473	45210380	45210528
ENSE00000995480	45235814	45235944
ENSE00000995481	45206083	45206170
ENSE00001092761	45242034	45242518
ENSE00001092767	45237648	45237721
ENSE00001092774	45242761	45242874
ENSE00001221980	45203190	45204212
ENSE00001333739	45246743	45247377
ENSE00003510437	45231141	45231298
ENSE00003597820	45227663	45227814
ENSE00003627577	45217019	45217179
ENSE00003657030	45232733	45232820
ENSE00003687530	45218282	45218454
ENSE00003694124	45204399	45204453
ENSE00003848233	45253035	45253202

Expression profiles

Bgee: expression breadth ubiquitous, 239 present calls, max score 96.01.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 19.8508 / max 435.5910, expressed in 1744 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
143045	18.6713	1737
143044	0.8214	523
143046	0.2164	94
143047	0.1417	40

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
monocyte	CL:0000576	96.01	gold quality
mononuclear cell	CL:0000842	95.59	gold quality
ventricular zone	UBERON:0003053	95.47	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	95.45	gold quality
leukocyte	CL:0000738	95.20	gold quality
colonic epithelium	UBERON:0000397	93.60	gold quality
tendon of biceps brachii	UBERON:0008188	93.06	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	92.63	gold quality
ganglionic eminence	UBERON:0004023	92.14	gold quality
buccal mucosa cell	CL:0002336	91.84	gold quality
calcaneal tendon	UBERON:0003701	91.61	gold quality
tendon	UBERON:0000043	91.31	gold quality
adrenal tissue	UBERON:0018303	91.02	gold quality
rectum	UBERON:0001052	90.24	gold quality
right lung	UBERON:0002167	89.81	gold quality
left ovary	UBERON:0002119	89.59	gold quality
granulocyte	CL:0000094	89.52	gold quality
bone marrow	UBERON:0002371	89.08	gold quality
minor salivary gland	UBERON:0001830	88.91	gold quality
lymph node	UBERON:0000029	88.70	gold quality
right ovary	UBERON:0002118	88.24	gold quality
spleen	UBERON:0002106	88.00	gold quality
sural nerve	UBERON:0015488	87.69	gold quality
trabecular bone tissue	UBERON:0002483	87.66	gold quality
body of uterus	UBERON:0009853	87.54	gold quality
ectocervix	UBERON:0012249	87.24	gold quality
endocervix	UBERON:0000458	87.20	gold quality
omental fat pad	UBERON:0010414	87.13	gold quality
peritoneum	UBERON:0002358	87.08	gold quality
upper lobe of left lung	UBERON:0008952	86.78	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-MTAB-11121	yes	580.32
E-ANND-3	yes	17.54
E-MTAB-6678	no	3.37

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

83 targeting MIS18BP1, 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-5011-5P	100.00	83.46	5820
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-6740-5P	100.00	65.64	932
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-511-3P	99.99	68.85	1467
HSA-MIR-1184	99.99	68.19	1458
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-6755-5P	99.95	65.59	464
HSA-MIR-548A-5P	99.94	71.27	3482
HSA-MIR-548AD-5P	99.94	71.23	3502
HSA-MIR-548AE-5P	99.94	71.23	3502
HSA-MIR-548AK	99.94	71.24	3488
HSA-MIR-548AM-5P	99.94	71.24	3488
HSA-MIR-548AP-5P	99.94	71.14	3489
HSA-MIR-548AQ-5P	99.94	71.34	3426
HSA-MIR-548AR-5P	99.94	71.28	3515
HSA-MIR-548AS-5P	99.94	71.22	3482
HSA-MIR-548AU-5P	99.94	71.24	3488
HSA-MIR-548AY-5P	99.94	71.23	3502
HSA-MIR-548B-5P	99.94	71.23	3502
HSA-MIR-548BB-5P	99.94	71.27	3509
HSA-MIR-548C-5P	99.94	71.24	3488
HSA-MIR-548D-5P	99.94	71.23	3502

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 96.7% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 4)

• Three human proteins essential for centromere/kinetochore structure and function, hMis18alpha, hMis18beta, and M18BP1, the complex of which is accumulated specifically at the telophase-G1 centromere, are identified.[Mis18alpha, Mis18beta, M18BP1] (PMID:17199038)
• CENP-C works as an important factor for centromeric M18BP1 recruitment (PMID:22540025)
• The authors demonstrate that CDK1 controls Mis18 complex recruitment to centromeres by regulating oligomerization of M18BP1 through the Mis18alpha:Mis18beta scaffold. (PMID:28059702)
• Results confirm the regulation of MIS18BP1 via SUMO-ubiquitin crosstalk during mitosis. (PMID:28951443)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	mis18bp1	ENSDARG00000042563
mus_musculus	Mis18bp1	ENSMUSG00000047534
rattus_norvegicus	Mis18bp1	ENSRNOG00000023093
caenorhabditis_elegans	knl-2	WBGENE00019432

Protein

Protein identifiers

Mis18-binding protein 1 — Q6P0N0 (reviewed: Q6P0N0)

Alternative names: Kinetochore-associated protein KNL-2 homolog, P243

All UniProt accessions (5): Q6P0N0, C9J2Q8, G5E9K5, H0YJM1, H7C1S6

UniProt curated annotations — full annotation on UniProt →

Function. Required for recruitment of CENPA to centromeres and normal chromosome segregation during mitosis.

Subunit / interactions. Interacts with SP1. Interacts with MIS18A. Identified in a complex containing MIS18A, OIP5/MIS18B, MIS18BP1, RBBP7 and RBBP4. Interacts with KAT7/HBO1. Interacts (via N-terminus) with FLNA (via N-terminus).

Subcellular location. Nucleus. Chromosome. Centromere.

Isoforms (2)

UniProt ID	Names	Canonical?
Q6P0N0-1	1	yes
Q6P0N0-2	2

RefSeq proteins (1): NP_060823* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001005	SANT/Myb	Domain
IPR009057	Homeodomain-like_sf	Homologous_superfamily
IPR015216	SANTA	Domain
IPR017884	SANT_dom	Domain
IPR039110	KNL2-like	Family

Pfam: PF09133

UniProt features (62 total): modified residue 20, cross-link 16, region of interest 5, compositionally biased region 4, sequence variant 4, strand 4, helix 3, domain 2, chain 1, splice variant 1, sequence conflict 1, turn 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
8S31	X-RAY DIFFRACTION	2.13
9R6H	X-RAY DIFFRACTION	2.42
9F5W	ELECTRON MICROSCOPY	7.5
1WGX	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6P0N0-F1	48.76	0.08

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 (36): 9, 110, 131, 135, 172, 192, 299, 365, 653, 772, 773, 821, 824, 860, 1008, 1086, 1087, 1089, 1104, 1116 …

Function

Pathways and Gene Ontology

Reactome pathways

5 pathways

ID	Pathway
R-HSA-606279	Deposition of new CENPA-containing nucleosomes at the centromere
R-HSA-69273	Cyclin A/B1/B2 associated events during G2/M transition
R-HSA-1640170	Cell Cycle
R-HSA-73886	Chromosome Maintenance
R-HSA-774815	Nucleosome assembly

MSigDB gene sets: 223 (showing top): GOBP_CHROMOSOME_ORGANIZATION, WU_APOPTOSIS_BY_CDKN1A_VIA_TP53, GOLDRATH_ANTIGEN_RESPONSE, WEI_MYCN_TARGETS_WITH_E_BOX, GOBP_NEGATIVE_REGULATION_OF_GENE_EXPRESSION_EPIGENETIC, CREIGHTON_ENDOCRINE_THERAPY_RESISTANCE_1, RUTELLA_RESPONSE_TO_HGF_VS_CSF2RB_AND_IL4_DN, GOBP_ORGANELLE_ASSEMBLY, ZHOU_INFLAMMATORY_RESPONSE_LIVE_DN, FISCHER_DREAM_TARGETS, ZHANG_BREAST_CANCER_PROGENITORS_UP, MARKEY_RB1_ACUTE_LOF_UP, GOBP_CHROMATIN_REMODELING, GOBP_HETEROCHROMATIN_ORGANIZATION, IVANOVA_HEMATOPOIESIS_EARLY_PROGENITOR

GO Biological Process (3): CENP-A containing chromatin assembly (GO:0034080), cell division (GO:0051301), obsolete pericentric heterochromatin organization (GO:0140462)

GO Molecular Function (2): DNA binding (GO:0003677), protein binding (GO:0005515)

GO Cellular Component (5): chromosome, centromeric region (GO:0000775), nucleoplasm (GO:0005654), CENP-A recruiting complex (GO:0098654), nucleus (GO:0005634), chromosome (GO:0005694)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
Nucleosome assembly	1
G2/M Transition	1
Cell Cycle	1
Chromosome Maintenance	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
chromatin organization	1
kinetochore assembly	1
protein localization to CENP-A containing chromatin	1
cellular process	1
nucleic acid binding	1
binding	1
chromosomal region	1
nuclear lumen	1
cellular anatomical structure	1
nuclear protein-containing complex	1
intracellular membrane-bounded organelle	1
intracellular membraneless organelle	1

Protein interactions and networks

STRING

910 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MIS18BP1	MIS18A	Q9NYP9	998
MIS18BP1	OIP5	O43482	996
MIS18BP1	CENPC	Q03188	817
MIS18BP1	RACGAP1	Q9H0H5	809
MIS18BP1	CENPI	Q92674	774
MIS18BP1	HJURP	Q8NCD3	771
MIS18BP1	RBBP7	Q16576	751
MIS18BP1	CENPA	P49450	720
MIS18BP1	RBBP4	P31149	655
MIS18BP1	PLK1	P53350	651
MIS18BP1	KAT7	O95251	625
MIS18BP1	CENPS	Q8N2Z9	599
MIS18BP1	CENPT	Q96BT3	584
MIS18BP1	CENPN	Q96H22	576
MIS18BP1	INCENP	Q9NQS7	576

IntAct

60 interactions, top by confidence:

A	B	Type	Score
MIS18A	OIP5	psi-mi:“MI:0914”(association)	0.950
MIS18BP1	OIP5	psi-mi:“MI:0915”(physical association)	0.770
OIP5	MIS18BP1	psi-mi:“MI:0915”(physical association)	0.770
MIS18A	DCTN6	psi-mi:“MI:0914”(association)	0.640
CACNG5	ZNF316	psi-mi:“MI:0914”(association)	0.530
DLK1	TCAF2	psi-mi:“MI:0914”(association)	0.530
OIP5	CYTH3	psi-mi:“MI:0914”(association)	0.530
KCNE3	RIOK3	psi-mi:“MI:0914”(association)	0.530
PNMA2	CCDC85C	psi-mi:“MI:0914”(association)	0.530
MIS18BP1	E7	psi-mi:“MI:0915”(physical association)	0.370
PCBD1	MIS18BP1	psi-mi:“MI:0915”(physical association)	0.370
Dctn3		psi-mi:“MI:0914”(association)	0.350
Nedd1		psi-mi:“MI:0914”(association)	0.350
Flot2	ACTG1	psi-mi:“MI:0914”(association)	0.350
RBM7	ZC3H18	psi-mi:“MI:0914”(association)	0.350
CAV3	SHTN1	psi-mi:“MI:0914”(association)	0.350
NCAPH2	MYO9A	psi-mi:“MI:0914”(association)	0.350
LZTS2	MYO9A	psi-mi:“MI:0914”(association)	0.350
GOPC	ZBTB5	psi-mi:“MI:0914”(association)	0.350
OIP5	CYTH3	psi-mi:“MI:0914”(association)	0.350

BioGRID (97): MIS18BP1 (Affinity Capture-MS), MIS18BP1 (Affinity Capture-MS), MIS18BP1 (Proximity Label-MS), MIS18BP1 (Proximity Label-MS), MIS18BP1 (Proximity Label-MS), MIS18BP1 (Affinity Capture-MS), MIS18BP1 (Affinity Capture-MS), MIS18BP1 (Affinity Capture-MS), MIS18BP1 (Affinity Capture-MS), MIS18BP1 (Affinity Capture-MS), MIS18BP1 (Affinity Capture-MS), MIS18BP1 (Affinity Capture-MS), MIS18BP1 (Affinity Capture-MS), MIS18BP1 (Affinity Capture-MS), MIS18BP1 (Affinity Capture-MS)

ESM2 similar proteins: A0A3Q2UEI8, A0JNH9, A2BIL8, A8PUI7, B1H1S4, B2GUZ2, E7FAP1, E9Q309, F1R983, O60284, P49452, P51960, P86345, Q0P5H2, Q3T0A6, Q3T8J9, Q4KLP8, Q4QY64, Q4R731, Q535K8, Q563C3, Q58EL7, Q5FBB7, Q5QJE6, Q5VT06, Q5XG21, Q65Z40, Q6KAQ7, Q6NWJ0, Q6P0N0, Q6P6I6, Q76FK4, Q7YQM1, Q7YQM2, Q80WQ8, Q8C263, Q8C551, Q8IYH5, Q8NA57, Q8R2M2

Diamond homologs: Q6P0N0, Q80WQ8

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
MIS18BP1	“form complex”	“CENP-A recruiting complex”	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	141
Likely benign	6
Benign	10

Top pathogenic / likely-pathogenic (0)

SpliceAI

3090 predictions. Top by Δscore:

Variant	Effect	Δscore
14:45218453:CA:C	acceptor_gain	1.0000
14:45218455:C:CC	acceptor_gain	1.0000
14:45224757:A:C	acceptor_gain	1.0000
14:45226176:TAA:T	donor_gain	1.0000
14:45226177:AAA:A	donor_gain	1.0000
14:45226737:TATTA:T	donor_loss	1.0000
14:45226739:TTAC:T	donor_loss	1.0000
14:45226740:TAC:T	donor_loss	1.0000
14:45226741:A:AT	donor_loss	1.0000
14:45226833:ATTCC:A	acceptor_loss	1.0000
14:45226834:TTCC:T	acceptor_loss	1.0000
14:45226835:TCCT:T	acceptor_loss	1.0000
14:45226837:C:CA	acceptor_loss	1.0000
14:45226838:T:A	acceptor_loss	1.0000
14:45227657:CCTTA:C	donor_loss	1.0000
14:45227658:CTTA:C	donor_loss	1.0000
14:45227659:TTA:T	donor_loss	1.0000
14:45227660:TACC:T	donor_loss	1.0000
14:45227810:CAGTT:C	acceptor_gain	1.0000
14:45227813:TT:T	acceptor_gain	1.0000
14:45227815:C:CC	acceptor_gain	1.0000
14:45231139:A:AC	donor_gain	1.0000
14:45231140:C:CC	donor_gain	1.0000
14:45231148:A:AC	donor_gain	1.0000
14:45231298:CCTT:C	acceptor_gain	1.0000
14:45235940:CGTCT:C	acceptor_gain	1.0000
14:45235943:CT:C	acceptor_gain	1.0000
14:45235945:C:CC	acceptor_gain	1.0000
14:45237718:CTAC:C	acceptor_gain	1.0000
14:45242890:T:C	acceptor_gain	1.0000

AlphaMissense

7576 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
14:45237703:A:G	W388R	0.998
14:45237703:A:T	W388R	0.998
14:45235852:A:G	L437S	0.997
14:45232770:A:G	W467R	0.996
14:45232770:A:T	W467R	0.996
14:45232781:A:G	F463S	0.996
14:45235917:A:C	S415R	0.996
14:45235917:A:T	S415R	0.996
14:45235919:T:G	S415R	0.996
14:45232792:A:C	F459L	0.995
14:45232792:A:T	F459L	0.995
14:45232794:A:G	F459L	0.995
14:45237701:C:A	W388C	0.995
14:45237701:C:G	W388C	0.995
14:45232793:A:G	F459S	0.994
14:45237658:C:G	G403R	0.993
14:45237658:C:T	G403R	0.993
14:45232784:C:T	G462E	0.992
14:45237702:C:G	W388S	0.992
14:45232780:A:C	F463L	0.991
14:45232780:A:T	F463L	0.991
14:45232782:A:G	F463L	0.991
14:45217112:C:A	R970S	0.990
14:45217112:C:G	R970S	0.990
14:45223949:A:G	W880R	0.990
14:45223949:A:T	W880R	0.990
14:45232768:C:A	W467C	0.990
14:45232768:C:G	W467C	0.990
14:45235882:A:T	L427H	0.990
14:45237657:C:T	G403E	0.990

dbSNP variants (sampled 300 via entrez): RS1000016330 (14:45251534 T>A,C), RS1000046073 (14:45229133 G>C), RS1000048 (14:45235806 T>A), RS1000104929 (14:45222544 T>G), RS1000155957 (14:45208643 T>C), RS1000172149 (14:45245817 C>T), RS1000267149 (14:45246147 A>C,G), RS1000346106 (14:45240398 T>C), RS1000385836 (14:45214673 G>A), RS1000453754 (14:45252702 T>C), RS1000512552 (14:45204565 A>G,T), RS1000559411 (14:45251831 T>A,C), RS1000566749 (14:45233039 G>C), RS1000781101 (14:45240127 T>A,C), RS1000991106 (14:45213367 G>A,C)

Disease associations

OMIM: gene MIM:618139 | 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
GCST004061_9	Sjögren’s syndrome	7.000000e-07
GCST90014054_4	Shoulder impingement	1.000000e-09

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	3
trichostatin A	affects cotreatment, decreases expression	2
perfluorooctane sulfonic acid	decreases expression	2
Resveratrol	increases expression, affects cotreatment	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Quercetin	decreases expression, increases phosphorylation	2
Testosterone	affects cotreatment, decreases expression	2
Valproic Acid	decreases expression	2
Cadmium Chloride	decreases expression	2
aristolochic acid I	decreases expression	1
FR900359	affects phosphorylation	1
bisphenol F	affects cotreatment, increases methylation	1
TAK-243	increases sumoylation	1
dicrotophos	decreases expression	1
geldanamycin	increases expression	1
propionaldehyde	decreases expression	1
bisphenol A	decreases expression	1
arsenite	decreases reaction, affects binding	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
sodium arsenite	decreases expression	1
ochratoxin A	decreases expression	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	increases expression, affects cotreatment	1
coumarin	increases phosphorylation	1
di-n-butylphosphoric acid	affects expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
ICG 001	decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
jinfukang	decreases expression	1
Dasatinib	decreases expression	1
Sunitinib	decreases expression	1

Clinical trials (associated diseases)

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