MYBL2

Summary

MYBL2 (MYB proto-oncogene like 2, HGNC:7548) is a protein-coding gene on chromosome 20q13.12, encoding Myb-related protein B (P10244). Transcription factor involved in the regulation of cell survival, proliferation, and differentiation. It is a selective cancer dependency (DepMap: 51.4% of cell lines).

The protein encoded by this gene, a member of the MYB family of transcription factor genes, is a nuclear protein involved in cell cycle progression. The encoded protein is phosphorylated by cyclin A/cyclin-dependent kinase 2 during the S-phase of the cell cycle and possesses both activator and repressor activities. It has been shown to activate the cell division cycle 2, cyclin D1, and insulin-like growth factor-binding protein 5 genes. Two transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 4605 — RefSeq curated summary.

At a glance

• GWAS associations: 7
• Clinical variants (ClinVar): 114 total
• Cancer dependency (DepMap): dependent in 51.4% of screened cell lines
• Transcription factor: yes — 57 downstream targets (CollecTRI)
• MANE Select transcript: NM_002466

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:7548
Approved symbol	MYBL2
Name	MYB proto-oncogene like 2
Location	20q13.12
Locus type	gene with protein product
Status	Approved
Aliases	BMYB, B-MYB
Ensembl gene	ENSG00000101057
Ensembl biotype	protein_coding
OMIM	601415
Entrez	4605

Gene structure

Transcript identifiers

Ensembl transcripts: 29 — 29 protein_coding

ENST00000217026, ENST00000396863, ENST00000868544, ENST00000913813, ENST00000913814, ENST00000913815, ENST00000913816, ENST00000913817, ENST00000913818, ENST00000913819, ENST00000913820, ENST00000913821, ENST00000913822, ENST00000913823, ENST00000913824, ENST00000913825, ENST00000913826, ENST00000913827, ENST00000913828, ENST00000913829, ENST00000913830, ENST00000913831, ENST00000913832, ENST00000913833, ENST00000913834, ENST00000913835, ENST00000913836, ENST00000913837, ENST00000913838

RefSeq mRNA: 2 — MANE Select: NM_002466 NM_001278610, NM_002466

CCDS: CCDS13322, CCDS63276

Canonical transcript exons

ENST00000217026 — 14 exons

Exon	Start	End
ENSE00000662204	43681784	43681855
ENSE00000662205	43682794	43682886
ENSE00000662207	43692157	43692319
ENSE00000662208	43699757	43700044
ENSE00000662209	43702490	43702903
ENSE00000662210	43705219	43705358
ENSE00000662211	43709963	43710062
ENSE00000662212	43711488	43711601
ENSE00000662213	43713002	43713106
ENSE00000662214	43715134	43715283
ENSE00000844841	43686852	43687072
ENSE00001380593	43667114	43667303
ENSE00001390215	43673806	43673899
ENSE00001660340	43715959	43716482

Expression profiles

Bgee: expression breadth ubiquitous, 171 present calls, max score 95.88.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 62.9608 / max 902.9948, expressed in 1510 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
184675	46.8006	1482
184674	16.1602	1262

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	95.88	gold quality
endometrium epithelium	UBERON:0004811	94.43	gold quality
ganglionic eminence	UBERON:0004023	90.73	gold quality
ventricular zone	UBERON:0003053	90.30	gold quality
embryo	UBERON:0000922	88.66	gold quality
type B pancreatic cell	CL:0000169	88.10	silver quality
bone marrow	UBERON:0002371	87.66	gold quality
bone marrow cell	CL:0002092	87.09	gold quality
vermiform appendix	UBERON:0001154	86.54	gold quality
mucosa of transverse colon	UBERON:0004991	85.16	gold quality
lymph node	UBERON:0000029	85.05	gold quality
cervix squamous epithelium	UBERON:0006922	84.46	gold quality
trabecular bone tissue	UBERON:0002483	84.45	gold quality
caecum	UBERON:0001153	83.92	gold quality
spleen	UBERON:0002106	83.91	gold quality
oocyte	CL:0000023	83.82	gold quality
secondary oocyte	CL:0000655	83.49	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	83.13	gold quality
olfactory bulb	UBERON:0002264	83.08	silver quality
tongue squamous epithelium	UBERON:0006919	82.12	silver quality
right testis	UBERON:0004534	81.40	gold quality
triceps brachii	UBERON:0001509	81.13	gold quality
left testis	UBERON:0004533	81.06	gold quality
testis	UBERON:0000473	80.54	gold quality
gluteal muscle	UBERON:0002000	80.40	gold quality
stromal cell of endometrium	CL:0002255	80.32	gold quality
body of pancreas	UBERON:0001150	78.81	gold quality
superficial temporal artery	UBERON:0001614	78.27	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	77.69	gold quality
diaphragm	UBERON:0001103	77.41	gold quality

Single-cell (SCXA)

Detected in 8 experiment(s), a significant marker in 8.

Experiment	Marker?	Max mean expression
E-MTAB-6819	yes	381.65
E-MTAB-9467	yes	300.32
E-HCAD-32	yes	242.60
E-MTAB-8530	yes	235.67
E-CURD-122	yes	22.89
E-MTAB-9067	yes	13.20
E-ANND-3	yes	6.31
E-CURD-88	yes	4.35

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

57 targets.

Target	Regulation
ADAM2
ADRA1D
ANPEP	Activation
AR	Activation
BCL2
BIRC5	Activation
CCNA1	Unknown
CCNB1	Activation
CCNB2	Unknown
CCND1	Unknown
CCND2
CDC25B
CDK1	Activation
CDK2
CDK9
CDKN2A
CEL
CLU	Activation
CNTN2
COL1A1	Unknown
COL5A2	Repression
DLST
DYM
E2F1	Activation
ELN	Repression
ERBB2	Repression
ERVK-11
FGF2
FGF4	Activation
GJA1

JASPAR motifs

Motif	Name	Family
MA0777.1	MYBL2	Myb/SANT domain factors

JASPAR matrix evidence (PMIDs): PMID:21998171

Upstream regulators (CollecTRI, top): CTNNB1, E2F1, E2F4, FOXC1, KAT6B, MYBL2, MYC, MYCN, NCOR1, PARP1, SP1, SSRP1, TCF7L2, TFDP1

miRNA regulators (miRDB)

32 targeting MYBL2, 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-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-5682	99.89	72.56	1005
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-6875-3P	99.82	70.26	2983
HSA-MIR-6763-5P	99.76	64.68	1767
HSA-MIR-143-3P	99.49	69.05	1457
HSA-MIR-4770	99.49	69.09	1451
HSA-MIR-4251	99.40	69.19	3363
HSA-MIR-501-3P	99.33	66.12	651
HSA-MIR-502-3P	99.33	66.12	651
HSA-MIR-6761-5P	98.71	68.03	1504
HSA-MIR-423-5P	98.69	67.48	1522
HSA-MIR-4700-5P	98.63	67.43	1915
HSA-MIR-3184-5P	98.56	67.13	1491
HSA-MIR-3661	97.83	67.30	705
HSA-MIR-10398-5P	97.12	64.94	1051
HSA-MIR-3622A-3P	97.06	66.43	1000
HSA-MIR-631	97.05	66.93	602
HSA-MIR-3622B-3P	96.82	66.36	988

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 51.4% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 40)

• B-Myb transactivates the IGFBP-5 promoter (PMID:11973331)
• ZPR9 plays an important role in modulation of the transactivation by B-MYB and cellular growth of neuroblastoma cells (PMID:12645566)
• B-Myb repressor function is regulated by cyclin A phosphorylation and sequences within the C-terminal domain. (PMID:12673206)
• it is evident that B-Myb protein may promote cell proliferation by a non-transcriptional mechanism that involves release of active cyclin/cyclin dependent kinase 2 from cyclin-dependent inhibitor 1C p57(KIP2) (PMID:12947099)
• MRGX can repress or activate the B-myb promoter depending on the cell type studied, suggesting that there may be tissue-specific functions of this protein (PMID:14506250)
• B-Myb has a role in regulation of c-Myc expression by cytosolic phospholipase A2 (PMID:14769798)
• Human B-Myb reduces neointima formation after vascular injury in transgenic mice. (PMID:15256398)
• regulated by temperature to activate genes required for cell survival. (PMID:15618219)
• overexpressed during the S phase of the cell cycle compared with the G0/1 phase (PMID:16476973)
• Chromosomal fragmentation and other aberrations, including shorter, thicker chromatids, end-to-end fusion, and loss of a chromatid, suggest that reduced B-Myb activity is also associated with structural chromosomal instability. (PMID:16551698)
• Mip/LIN-9 is required for the expression of B-Myb, and both proteins collaborate in the control of the cell cycle progression via the regulation of S phase and cyclin A, cyclin B, and CDK1 (PMID:17098733)
• human LIN-9, together with B-MYB, has a critical role in the activation of genes that are essential for progression into mitosis (PMID:17159899)
• The repressor complex that Mip/LIN-9 forms with p107 takes functional precedence over the transcriptional activation linked to the Mip/LIN-9 and B-Myb interaction. (PMID:17563750)
• The expression of stable, hypophosphorylated B-MYB in neuroblastoma may promote cell survival and induce aggressive tumour growth. (PMID:17588787)
• Some B-MYB alleles might be associated with a reduced risk of developing neoplastic disease. (PMID:18026132)
• MYBL2 gene expression was significantly higher in colorectal cancer patients than in healthy volunteers. (PMID:19016757)
• Insight into the influence of B-Myb in human breast cancer, which is of potential clinical importance for determining disease risk and for guiding treatment. (PMID:19043454)
• B-MYB fails to dissociate from LINC in p53 mutant cells, that this contributes to increased G(2)-M gene expression in response to DNA damage, and that B-MYB is required for recovery from the G(2) DNA damage checkpoint in p53-negative cells. (PMID:19383908)
• Study identified an overrepresentation of focal amplifications of known (FGFR3, CCND1, MYC, MDM2) and novel candidate genes (MYBL2, YWHAB and SDC4) in stage Ta bladder carcinoma. (PMID:19821490)
• B-MYB represses p16(INK4alpha)by binding to a MYB-binding site within the promoter region. (PMID:20734103)
• These data suggest that Mybl2 plays a subtle but key role in linking specific aspects of cell-cycle progression with generation of signals for differentiation. (PMID:20857481)
• Data show that that ANCCA is crucial for proliferation and survival of triple-negative/basal-like cancer cells and that it controls the expression of B-Myb and histone methyltransferase EZH2. (PMID:20864510)
• B-MYB acts as a positive regulator of STRAP (PMID:21148321)
• miR-29 and miR-30 regulate B-Myb expression by binding to its 3’UTR; these microRNAs play an important role in Rb-driven cellular senescence (PMID:21187425)
• study concludes that MYCN and B-MYB are engaged in a reciprocal regulatory loop whose pharmacological targeting could be beneficial to patients with the aggressive forms of cancer in which MYCN is amplified (PMID:21304178)
• Owing to the role of B-Myb and E2F1 transcription factors in controlling cell-cycle progression of leukemic cells, the downregulation of these oncogenes by miR-34a suggests the usefulness of therapeutic approaches aimed to modulate the levels of miR-34a. (PMID:21367750)
• Mybl2 upregulation induces fast growth and progression of premalignant and malignant liver, through cell cycle deregulation and activation of genes and pathways related to tumor progression. (PMID:21419759)
• MYBL2 activation is crucial for human HCC progression. In particular, our data indicate that MYBL2-LIN9 complex integrity contributes to survival of DNA damaged p53(-/-) cells. (PMID:21480327)
• Low MYBL2 expression is associated with haematopoietic neoplasia. (PMID:22910183)
• A novel role for B-Myb in S-phase that appears to be independent of its sequence-specific DNA-binding activity and its ability to stimulate the expression of bona fide B-Myb target genes. (PMID:23032261)
• MALAT1-depleted cells display reduced expression of B-MYB (Mybl2), an oncogenic transcription factor involved in G2/M progression, due to altered binding of splicing factors on B-MYB pre-mRNA and aberrant alternative splicing (PMID:23555285)
• conclude that downregulation of MYBL2 activity below levels predicted by classical haploinsufficiency underlies the clonal expansion of hematopoietic progenitors in a large fraction of human myeloid malignancies (PMID:23878725)
• Results show that E7 interacts with the B-Myb, FoxM1 and LIN9 components of this activator complex, leading to cooperative transcriptional activation of mitotic genes in primary cells and E7 recruitment to the corresponding promoters. (PMID:24141769)
• MYBL2 expression analysis could be useful to define subgroups of patients with poor prognosis. (PMID:24199710)
• B-Myb plays a role in suppression of keratinocyte differentiation and maintenance of the undifferentiated proliferative phenotype by modulating the expression levels of cell cycle regulatory proteins, expressed in the S and G2/M phases of the cell cycle (PMID:24515894)
• We found that B-Myb upregulated expression of the key epithelial-to-mesenchymal transition regulator snail and that it mediated epithelial-to-mesenchymal transition activation and cell invasion by B-Myb. (PMID:25502082)
• Data indicate that gene expression alterations in endometrial carcinoma samples with high ATAD2 expression showed upregulation of several cancer-related genes including B-MYB gene. (PMID:26308378)
• Study identified B-Myb as a substrate of the pVHL ubiquitin ligase complex, which targets it for degradation via the ubiquitin-proteasome pathway. It also, provide evidence that the regulation of B-Myb by pVHL plays a critical role in von Hippel-Lindau disease. (PMID:27090638)
• The MuvB multiprotein complex, together with B-MYB and FOXM1 (MMB-FOXM1) regulate the expression of mitotic kinesins in breast cancer cells. (PMID:28061449)
• results suggest that B-Myb-A3B contributes to DNA damage and could be targeted by inhibiting EGF receptor. (PMID:28276478)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	mybl2b	ENSDARG00000032264
mus_musculus	Mybl2	ENSMUSG00000017861
rattus_norvegicus	Mybl2	ENSRNOG00000007805

Paralogs (6): CDC5L (ENSG00000096401), MYB (ENSG00000118513), TTF1 (ENSG00000125482), DMTF1 (ENSG00000135164), SNAPC4 (ENSG00000165684), MYBL1 (ENSG00000185697)

Protein

Protein identifiers

Myb-related protein B — P10244 (reviewed: P10244)

Alternative names: Myb-like protein 2

All UniProt accessions (1): P10244

UniProt curated annotations — full annotation on UniProt →

Function. Transcription factor involved in the regulation of cell survival, proliferation, and differentiation. Transactivates the expression of the CLU gene.

Subunit / interactions. Component of the DREAM complex (also named LINC complex) at least composed of E2F4, E2F5, LIN9, LIN37, LIN52, LIN54, MYBL1, MYBL2, RBL1, RBL2, RBBP4, TFDP1 and TFDP2. The complex exists in quiescent cells where it represses cell cycle-dependent genes. It dissociates in S phase when LIN9, LIN37, LIN52 and LIN54 form a subcomplex that binds to MYBL22. Interacts with CCNF (via the Cyclin N-terminal domain).

Subcellular location. Nucleus.

Post-translational modifications. Phosphorylated by cyclin A/CDK2 during S-phase. Phosphorylation at Thr-520 is probably involved in transcriptional activity.

Isoforms (2)

UniProt ID	Names	Canonical?
P10244-1	1	yes
P10244-2	2

RefSeq proteins (2): NP_001265539, NP_002457* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001005	SANT/Myb	Domain
IPR009057	Homeodomain-like_sf	Homologous_superfamily
IPR015395	C-myb_C	Domain
IPR017930	Myb_dom	Domain
IPR050560	MYB_TF	Family

Pfam: PF00249, PF09316, PF13921

UniProt features (48 total): cross-link 17, modified residue 11, sequence variant 4, domain 3, DNA-binding region 3, short sequence motif 2, helix 2, region of interest 2, chain 1, compositionally biased region 1, splice variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
6C48	X-RAY DIFFRACTION	2.32

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P10244-F1	57.69	0.23

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 (28): 241, 266, 282, 393, 440, 444, 487, 494, 505, 520, 577, 104, 194, 197, 275, 411, 447, 482, 499, 509 …

Function

Pathways and Gene Ontology

Reactome pathways

13 pathways

ID	Pathway
R-HSA-1362300	Transcription of E2F targets under negative control by p107 (RBL1) and p130 (RBL2) in complex with HDAC1
R-HSA-156711	Polo-like kinase mediated events
R-HSA-8869496	TFAP2A acts as a transcriptional repressor during retinoic acid induced cell differentiation
R-HSA-1538133	G0 and Early G1
R-HSA-1640170	Cell Cycle
R-HSA-212436	Generic Transcription Pathway
R-HSA-453274	Mitotic G2-G2/M phases
R-HSA-453279	Mitotic G1 phase and G1/S transition
R-HSA-69275	G2/M Transition
R-HSA-69278	Cell Cycle, Mitotic
R-HSA-73857	RNA Polymerase II Transcription
R-HSA-74160	Gene expression (Transcription)
R-HSA-8864260	Transcriptional regulation by the AP-2 (TFAP2) family of transcription factors

MSigDB gene sets: 318 (showing top): FERRANDO_TAL1_NEIGHBORS, TGGTGCT_MIR29A_MIR29B_MIR29C, GOBP_CHROMOSOME_ORGANIZATION, MODULE_52, HORIUCHI_WTAP_TARGETS_DN, MODULE_451, TSENG_IRS1_TARGETS_UP, GNF2_CENPF, GOBP_RESPONSE_TO_PEPTIDE, CROONQUIST_NRAS_SIGNALING_DN, HOFMANN_CELL_LYMPHOMA_UP, DACOSTA_UV_RESPONSE_VIA_ERCC3_UP, MITSIADES_RESPONSE_TO_APLIDIN_DN, MODULE_16, MODULE_308

GO Biological Process (4): mitotic cell cycle (GO:0000278), positive regulation of transcription by RNA polymerase II (GO:0045944), mitotic spindle assembly (GO:0090307), cellular response to leukemia inhibitory factor (GO:1990830)

GO Molecular Function (6): RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), DNA-binding transcription activator activity, RNA polymerase II-specific (GO:0001228), sequence-specific double-stranded DNA binding (GO:1990837), DNA binding (GO:0003677), protein binding (GO:0005515)

GO Cellular Component (4): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytosol (GO:0005829), Myb complex (GO:0031523)

Reactome top-level categories

Rollup of top-10 pathways:

Category	Pathways
Cell Cycle, Mitotic	2
G0 and Early G1	1
G2/M Transition	1
Transcriptional regulation by the AP-2 (TFAP2) family of transcription factors	1
Mitotic G1 phase and G1/S transition	1
RNA Polymerase II Transcription	1
Mitotic G2-G2/M phases	1
Cell Cycle	1
Gene expression (Transcription)	1
Generic Transcription Pathway	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
RNA polymerase II transcription regulatory region sequence-specific DNA binding	3
mitotic nuclear division	2
regulation of transcription by RNA polymerase II	2
cellular anatomical structure	2
cell cycle	1
transcription by RNA polymerase II	1
positive regulation of DNA-templated transcription	1
mitotic sister chromatid segregation	1
mitotic spindle organization	1
spindle assembly	1
cellular response to cytokine stimulus	1
response to leukemia inhibitory factor	1
cis-regulatory region sequence-specific DNA binding	1
chromatin	1
DNA-binding transcription factor activity	1
DNA-binding transcription factor activity, RNA polymerase II-specific	1
DNA-binding transcription activator activity	1
positive regulation of transcription by RNA polymerase II	1
double-stranded DNA binding	1
sequence-specific DNA binding	1
nucleic acid binding	1
binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
cytoplasm	1
nuclear protein-containing complex	1

Protein interactions and networks

STRING

3362 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MYBL2	LIN9	Q5TKA1	994
MYBL2	LIN54	Q6MZP7	992
MYBL2	FOXM1	Q08050	981
MYBL2	LIN37	Q96GY3	978
MYBL2	ZNF622	Q969S3	914
MYBL2	RBBP4	P31149	865
MYBL2	CCNA2	P20248	856
MYBL2	E2F4	Q16254	840
MYBL2	LIN52	Q52LA3	815
MYBL2	MELK	Q14680	806
MYBL2	CCNB1	P14635	774
MYBL2	AURKA	O14965	742
MYBL2	TP53	P04637	730
MYBL2	CCNA1	P78396	717
MYBL2	BCL2	P10415	697

IntAct

97 interactions, top by confidence:

A	B	Type	Score
RBBP4	CDK2AP1	psi-mi:“MI:0914”(association)	0.790
LIN37	MYBL2	psi-mi:“MI:0914”(association)	0.730
LIN9	MYBL2	psi-mi:“MI:0914”(association)	0.720
LIN9	MYBL2	psi-mi:“MI:0915”(physical association)	0.720
MYBL2	LIN9	psi-mi:“MI:0915”(physical association)	0.720
LIN37	MYBL1	psi-mi:“MI:0914”(association)	0.640
LIN54	MYBL2	psi-mi:“MI:0914”(association)	0.560
LIN54	MYBL2	psi-mi:“MI:0915”(physical association)	0.560
NUF2	SPC24	psi-mi:“MI:0914”(association)	0.530
LIN52	MYBL2	psi-mi:“MI:0914”(association)	0.530
LIN9	MYBL1	psi-mi:“MI:0914”(association)	0.530
RPN1	APBB1	psi-mi:“MI:0914”(association)	0.530
RBBP4	TNRC18	psi-mi:“MI:0914”(association)	0.530
PNMA2	CCDC85C	psi-mi:“MI:0914”(association)	0.530
MYBL2	H1-5	psi-mi:“MI:0915”(physical association)	0.400
MYBL2	H1-4	psi-mi:“MI:0915”(physical association)	0.400
Lin54	MYBL1	psi-mi:“MI:0915”(physical association)	0.400
MYBL2	E2F3	psi-mi:“MI:0915”(physical association)	0.400
E2F4	MYBL2	psi-mi:“MI:0915”(physical association)	0.400
HDAC2	MYBL2	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (237): MYBL2 (Affinity Capture-MS), MYBL2 (Two-hybrid), MYBL2 (Proximity Label-MS), MYBL2 (Affinity Capture-MS), MYBL2 (Affinity Capture-MS), MYBL2 (Affinity Capture-MS), MYBL2 (Affinity Capture-MS), MYBL2 (Affinity Capture-MS), MYBL2 (Affinity Capture-MS), CCNF (Affinity Capture-Western), MYBL2 (Affinity Capture-Western), MYBL2 (Reconstituted Complex), MYBL2 (Affinity Capture-MS), MYBL2 (Affinity Capture-Western), PLA2G4A (Affinity Capture-Western)

ESM2 similar proteins: A0A1W2PPF3, A1YGI6, F1MJR8, O08686, O60284, P09015, P10244, P23497, P31538, P48972, P52551, P52729, P52730, P70284, Q04891, Q08050, Q28G02, Q2M1Z3, Q5DW34, Q5EXX3, Q5W1J6, Q6IR42, Q76I76, Q76I79, Q7M6U3, Q804R0, Q8AXQ4, Q8C0C0, Q8C0Y1, Q8IUE0, Q8IUE1, Q8MIB7, Q8MIB8, Q8MIC2, Q8MID1, Q8MID6, Q8MID8, Q8MIE6, Q8MIE9, Q90655

Diamond homologs: A0A1U8QIH0, A0A1U8QVN4, A0A6S6AAU0, A2WW87, A7SD85, B0G0Y5, B4FNX4, C8VBH3, E0CJS3, F1B281, F4IRB4, K7UPS5, O04192, O13493, O49608, O49782, O80883, P01103, P01104, P04197, P06876, P0CO94, P10242, P10243, P10244, P20025, P22035, P34127, P39964, P46200, P48972, P51960, P52550, P52551, P81393, P81394, P92948, P9WEF9, Q03237, Q05935

SIGNOR signaling

21 interactions.

A	Effect	B	Mechanism
CyclinA2/CDK2	up-regulates	MYBL2	phosphorylation
CDK2	“up-regulates activity”	MYBL2	phosphorylation
E2F1	“up-regulates quantity by expression”	MYBL2	“transcriptional regulation”
TFDP1	“up-regulates quantity by expression”	MYBL2	“transcriptional regulation”
ZMYM2	“up-regulates activity”	MYBL2	binding
SKP2	“down-regulates quantity by destabilization”	MYBL2	polyubiquitination
CDK2	up-regulates	MYBL2	phosphorylation
CDK2	unknown	MYBL2	phosphorylation
MYBL2	“up-regulates quantity by expression”	CLU	“transcriptional regulation”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 93 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
Transcription of E2F targets under negative control by DREAM complex	7	55.2×	1e-08
Polo-like kinase mediated events	6	55.2×	8e-08
Transcription of E2F targets under negative control by p107 (RBL1) and p130 (RBL2) in complex with HDAC1	6	52.3×	9e-08
G0 and Early G1	7	44.6×	2e-08
PD-L1(CD274) glycosylation and translocation to plasma membrane	5	37.6×	1e-05
Cyclin E associated events during G1/S transition	8	33.1×	2e-08
G1/S-Specific Transcription	6	31.0×	3e-06
Cyclin A:Cdk2-associated events at S phase entry	8	30.8×	2e-08

GO biological processes:

GO term	Partners	Fold	FDR
positive regulation of miRNA transcription	5	16.3×	2e-03
protein N-linked glycosylation	5	14.8×	2e-03
transcription by RNA polymerase II	9	7.1×	8e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	72
Likely benign	4
Benign	5

Top pathogenic / likely-pathogenic (0)

SpliceAI

2919 predictions. Top by Δscore:

Variant	Effect	Δscore
20:43673804:A:AG	acceptor_gain	1.0000
20:43673805:G:GG	acceptor_gain	1.0000
20:43673805:GC:G	acceptor_gain	1.0000
20:43673805:GCGA:G	acceptor_gain	1.0000
20:43673896:GGAG:G	donor_gain	1.0000
20:43673897:GAGG:G	donor_gain	1.0000
20:43673898:AGG:A	donor_loss	1.0000
20:43673900:GTGA:G	donor_loss	1.0000
20:43673901:T:A	donor_loss	1.0000
20:43681856:G:GG	donor_gain	1.0000
20:43682875:G:GT	donor_gain	1.0000
20:43682887:G:GG	donor_gain	1.0000
20:43682916:G:GG	donor_gain	1.0000
20:43686849:A:AG	acceptor_gain	1.0000
20:43686849:AAG:A	acceptor_gain	1.0000
20:43686850:A:G	acceptor_gain	1.0000
20:43687068:GGGAG:G	donor_gain	1.0000
20:43687069:GGAG:G	donor_gain	1.0000
20:43687069:GGAGG:G	donor_gain	1.0000
20:43687070:G:T	donor_gain	1.0000
20:43687070:GAG:G	donor_gain	1.0000
20:43687070:GAGG:G	donor_gain	1.0000
20:43687073:G:GA	donor_loss	1.0000
20:43687073:G:GG	donor_gain	1.0000
20:43687074:T:A	donor_loss	1.0000
20:43692316:CCAG:C	donor_loss	1.0000
20:43692321:T:A	donor_loss	1.0000
20:43699751:TTACA:T	acceptor_loss	1.0000
20:43699752:TACAG:T	acceptor_loss	1.0000
20:43699754:CA:C	acceptor_loss	1.0000

AlphaMissense

4587 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
20:43673885:T:A	W34R	1.000
20:43673885:T:C	W34R	1.000
20:43673886:G:C	W34S	1.000
20:43673887:G:C	W34C	1.000
20:43673887:G:T	W34C	1.000
20:43681794:T:C	L42P	1.000
20:43681829:T:A	W54R	1.000
20:43681829:T:C	W54R	1.000
20:43682797:C:A	R64S	1.000
20:43682812:T:C	C69R	1.000
20:43682821:A:G	R72G	1.000
20:43682822:G:C	R72T	1.000
20:43682822:G:T	R72M	1.000
20:43682823:G:C	R72S	1.000
20:43682823:G:T	R72S	1.000
20:43682824:T:A	W73R	1.000
20:43682824:T:C	W73R	1.000
20:43682857:G:A	G84R	1.000
20:43682857:G:C	G84R	1.000
20:43682863:T:A	W86R	1.000
20:43682863:T:C	W86R	1.000
20:43682864:G:C	W86S	1.000
20:43682865:G:C	W86C	1.000
20:43682865:G:T	W86C	1.000
20:43682876:A:T	E90V	1.000
20:43682878:G:C	D91H	1.000
20:43682878:G:T	D91Y	1.000
20:43682879:A:C	D91A	1.000
20:43682879:A:G	D91G	1.000
20:43682879:A:T	D91V	1.000

dbSNP variants (sampled 300 via entrez): RS1000040800 (20:43665272 C>A,T), RS1000072888 (20:43670875 A>G), RS1000073365 (20:43693485 C>A,T), RS1000128444 (20:43670489 A>T), RS1000135141 (20:43709898 G>A,T), RS1000171155 (20:43669865 C>G), RS1000211568 (20:43710952 C>A,T), RS1000320109 (20:43694442 T>C), RS1000333765 (20:43688423 A>T), RS1000416136 (20:43676676 G>A), RS1000417970 (20:43715857 G>A,C), RS1000468577 (20:43676457 C>T), RS1000469710 (20:43677023 C>T), RS1000474051 (20:43711814 T>C), RS1000542582 (20:43666981 C>A,G)

Disease associations

OMIM: gene MIM:601415 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

7 associations (top):

Study	Trait	p-value
GCST90002385_537	High light scatter reticulocyte count	1.000000e-10
GCST90002386_516	High light scatter reticulocyte percentage of red cells	2.000000e-11
GCST90002390_669	Mean corpuscular hemoglobin	2.000000e-11
GCST90002392_106	Mean corpuscular volume	5.000000e-12
GCST90002397_165	Mean spheric corpuscular volume	2.000000e-13
GCST90002404_579	Red cell distribution width	2.000000e-13
GCST90002406_554	Reticulocyte fraction of red cells	5.000000e-09

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0007986	reticulocyte count
EFO:0004527	mean corpuscular hemoglobin
EFO:0009188	Red cell distribution width

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases expression	5
bisphenol A	decreases expression, increases expression, affects expression	4
Estradiol	decreases expression, increases expression	4
Cyclosporine	decreases expression	4
Benzo(a)pyrene	decreases expression, increases expression, increases mutagenesis	3
Tretinoin	decreases expression	3
Valproic Acid	affects cotreatment, increases expression, decreases expression, increases methylation	3
(+)-JQ1 compound	decreases expression	2
Calcitriol	decreases expression, affects cotreatment	2
Cisplatin	increases expression, decreases expression	2
Fluorouracil	increases expression, affects response to substance	2
FR900359	affects phosphorylation	1
bisphenol F	affects cotreatment, decreases expression	1
TAK-243	increases sumoylation	1
dicrotophos	increases expression	1
lasiocarpine	increases expression	1
geraniol	decreases expression	1
methylselenic acid	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
cobaltous chloride	decreases expression	1
tanshinone	increases expression	1
zinc chromate	decreases expression, increases abundance	1
4-hydroxy-2-nonenal	decreases expression	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, increases expression	1
coumarin	increases phosphorylation	1
diallyl trisulfide	decreases expression	1
exemestane	increases expression	1
phenethyl isothiocyanate	decreases expression	1
chromium hexavalent ion	decreases expression, increases abundance	1
perfluorooctane sulfonic acid	decreases expression	1

Cellosaurus cell lines

3 cell lines: 3 embryonic stem cell

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_A4H3	SEES3-1V human MYBL2, clone1	Embryonic stem cell	Male
CVCL_A4H4	SEES3-1V human MYBL2, clone2	Embryonic stem cell	Male
CVCL_A4H5	SEES3-1V human MYBL2, clone3	Embryonic stem cell	Male

Clinical trials (associated diseases)

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