MSI2

Summary

MSI2 (musashi RNA binding protein 2, HGNC:18585) is a protein-coding gene on chromosome 17q22, encoding RNA-binding protein Musashi homolog 2 (Q96DH6). RNA binding protein that regulates the expression of target mRNAs at the translation level.

This gene encodes an RNA-binding protein that is a member of the Musashi protein family. The encoded protein is transcriptional regulator that targets genes involved in development and cell cycle regulation. Mutations in this gene are associated with poor prognosis in certain types of cancers. This gene has also been shown to be rearranged in certain cancer cells.

Source: NCBI Gene 124540 — RefSeq curated summary.

At a glance

• GWAS associations: 32
• Clinical variants (ClinVar): 48 total
• Druggable target: yes
• Cancer driver (intOGen): loss-of-function (tumor-suppressor-like) across 1 cancer types
• MANE Select transcript: NM_138962

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18585
Approved symbol	MSI2
Name	musashi RNA binding protein 2
Location	17q22
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000153944
Ensembl biotype	protein_coding
OMIM	607897
Entrez	124540

Gene structure

Transcript identifiers

Ensembl transcripts: 38 — 18 protein_coding, 8 protein_coding_CDS_not_defined, 7 nonsense_mediated_decay, 5 retained_intron

ENST00000284073, ENST00000322684, ENST00000416426, ENST00000442934, ENST00000577241, ENST00000579180, ENST00000579205, ENST00000579466, ENST00000579483, ENST00000579505, ENST00000579531, ENST00000579590, ENST00000581523, ENST00000581776, ENST00000582453, ENST00000582772, ENST00000583705, ENST00000583821, ENST00000584476, ENST00000674522, ENST00000674574, ENST00000674898, ENST00000674961, ENST00000674964, ENST00000675127, ENST00000675379, ENST00000675656, ENST00000675822, ENST00000676073, ENST00000676105, ENST00000676345, ENST00000851004, ENST00000902708, ENST00000902709, ENST00000902710, ENST00000902711, ENST00000902712, ENST00000940605

RefSeq mRNA: 4 — MANE Select: NM_138962 NM_001322250, NM_001322251, NM_138962, NM_170721

CCDS: CCDS11596, CCDS11597, CCDS82168

Canonical transcript exons

ENST00000284073 — 14 exons

Exon	Start	End
ENSE00001102120	57676987	57677059
ENSE00001157143	57674972	57675126
ENSE00002219180	57256523	57256804
ENSE00003508406	57627229	57627303
ENSE00003532300	57257098	57257138
ENSE00003580062	57652099	57652161
ENSE00003602774	57262151	57262192
ENSE00003606151	57258270	57258354
ENSE00003627192	57596868	57596950
ENSE00003652249	57529676	57529724
ENSE00003688116	57615970	57616084
ENSE00003694227	57257466	57257547
ENSE00003758332	57401379	57401471
ENSE00004283287	57679549	57684689

Expression profiles

Bgee: expression breadth ubiquitous, 261 present calls, max score 99.14.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 16.8678 / max 719.6124, expressed in 1708 samples.

FANTOM5 promoters (20 alternative TSS)

Promoter ID	TPM avg	Samples expressed
161842	8.0646	1544
161844	3.3258	1159
161847	1.8178	738
161843	1.4267	661
161845	1.1750	606
161866	0.2141	47
161875	0.1988	6
161869	0.1849	27
161846	0.1386	51
161860	0.0958	39

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
corpus epididymis	UBERON:0004359	99.14	gold quality
adrenal tissue	UBERON:0018303	99.01	gold quality
medial globus pallidus	UBERON:0002477	98.73	gold quality
oviduct epithelium	UBERON:0004804	98.59	gold quality
substantia nigra pars reticulata	UBERON:0001966	98.55	gold quality
globus pallidus	UBERON:0001875	98.51	gold quality
caput epididymis	UBERON:0004358	98.39	gold quality
renal medulla	UBERON:0000362	98.25	gold quality
bronchial epithelial cell	CL:0002328	98.22	gold quality
substantia nigra pars compacta	UBERON:0001965	98.18	gold quality
bronchus	UBERON:0002185	98.15	gold quality
mucosa of paranasal sinus	UBERON:0005030	98.00	gold quality
kidney epithelium	UBERON:0004819	97.93	gold quality
corpus callosum	UBERON:0002336	97.76	gold quality
buccal mucosa cell	CL:0002336	97.71	gold quality
superior vestibular nucleus	UBERON:0007227	97.60	gold quality
medulla oblongata	UBERON:0001896	97.58	gold quality
right adrenal gland cortex	UBERON:0035827	97.53	gold quality
lateral globus pallidus	UBERON:0002476	97.52	gold quality
adrenal cortex	UBERON:0001235	97.50	gold quality
right adrenal gland	UBERON:0001233	97.40	gold quality
adrenal gland	UBERON:0002369	97.38	gold quality
left adrenal gland	UBERON:0001234	97.36	gold quality
left adrenal gland cortex	UBERON:0035825	97.33	gold quality
colonic epithelium	UBERON:0000397	97.30	gold quality
adenohypophysis	UBERON:0002196	97.04	gold quality
ventricular zone	UBERON:0003053	96.99	gold quality
cardiac muscle of right atrium	UBERON:0003379	96.97	gold quality
pituitary gland	UBERON:0000007	96.88	gold quality
ventral tegmental area	UBERON:0002691	96.68	gold quality

Single-cell (SCXA)

Detected in 14 experiment(s), a significant marker in 10.

Experiment	Marker?	Max mean expression
E-HCAD-35	yes	2213.46
E-HCAD-6	yes	416.04
E-HCAD-4	yes	71.04
E-CURD-119	yes	46.49
E-HCAD-25	yes	30.05
E-MTAB-9067	yes	25.85
E-CURD-112	yes	21.07
E-ANND-3	yes	13.67
E-HCAD-1	yes	11.11
E-CURD-114	yes	9.19
E-CURD-135	no	899.86
E-CURD-79	no	743.28
E-MTAB-6108	no	555.36
E-MTAB-8060	no	71.37

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

1 targets.

Target	Regulation
NUMB	Repression

Upstream regulators (CollecTRI, top): HOXA9

miRNA regulators (miRDB)

474 targeting MSI2, 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-190A-3P	100.00	80.35	5520
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-3613-3P	100.00	76.36	7965
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-3924	100.00	72.09	2394
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-3689D	100.00	66.14	1181
HSA-MIR-6851-5P	100.00	65.63	1294
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-6758-5P	100.00	66.21	1470
HSA-MIR-6856-5P	100.00	65.47	1298
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-6740-5P	100.00	65.64	932
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-7110-3P	100.00	73.18	2486

Literature-anchored findings (GeneRIF, showing 40)

• The EVI1 gene locus was rearranged in all 13 myeloid malignancies patients and was associated with EVI1 overexpression. In 9 out of 13 patients, the 17q breakpoints clustered in a 250 kb region on band 17q22 encompassing the MSI2 gene (PMID:18815193)
• Msi2 expression is not only highly upregulated during human chronic myeloid leukemia progression but is also an early indicator of poorer prognosis (PMID:20639863)
• MSI2 has a crucial role in both normal and malignant hematopoiesis. (PMID:20823875)
• High MSI2 is associated with acute myeloid leukemia. (PMID:21753187)
• Overexpression of MSI2 resulted in a decrease in MSI1 expression. (PMID:22113197)
• Down-modulation of MSI2 is associated with myelodysplastic syndromes and acute myeloid leukemia. (PMID:22784712)
• MSI2 is associated with shorter overall survival in acute myeloid leukemia patients. (PMID:23233047)
• a large set of SOX2-associated proteins in DAOY medulloblastoma cells (PMID:23667531)
• Data suggest that high MSI2 expression could indicate poor prognosis and facilitate risk and treatment stratification in adult BCR-ABL-negative B-cells acute lymphoblastic leukemia (B-ALL). (PMID:23759245)
• Report a statistical difference between the MSI2 gene expression in different gastric tumor grades, of note between grade I and grade II. (PMID:24002004)
• The Msi2 plays an important role in leukemogenesis involving the MAPK signaling pathway, which indicates that Msi2 may be a novel target for leukemia treatment. (PMID:24076374)
• MSI2 correlates with epithelial-mesenchymal transition and has the potential to be a new predictive biomarker of hepatocellular carcinoma prognosis and invasion. (PMID:24305552)
• These results confirm the association of MSI2 expression with outcome in adult B-ALL and demonstrate the utility of MSI2 as a clinical prognostic biomarker. (PMID:25090928)
• Up-regulated MSI2 is associated with more aggressive chronic myeloid leukemia. (PMID:25363400)
• Msi proteins contribute to an epithelial gene expression program in neural and mammary cell types. (PMID:25380226)
• Acute myeloid leukemia patients have a higher level of MSI2 gene expression. (PMID:25449073)
• MSI2 controls efficient translation of the oncogenic leukemic stem cell self-renewal program. (PMID:25664853)
• the MSI2 RNA-binding protein has a role in transformation of intestinal epithelium (PMID:25774828)
• This review highlights both the essential contribution of RBPs to posttranscriptional regulation and the importance of the Musashi family as master regulators of male gamete development–{REVIEW} (PMID:25851660)
• Concomitant loss of function of both MSI1 is sufficient to abrogate the growth of human colorectal cancer cells, and Msi gene deletion inhibits tumorigenesis in several mouse models of intestinal cancer. (PMID:26673327)
• our study indicates that MSI-2 overexpression is associated with an unfavorable prognosis and may be a potential biomarker for liver metastasis in colorectal cancer patients. (PMID:26775684)
• These results indicate that the human MSI2 gene might be a susceptibility gene for schizophrenia and encourage future research on the functional relationship between this gene and schizophrenia. (PMID:27059221)
• High Musashi2 expression is associated with pancreatic cancer. (PMID:27092875)
• MSI2 directly attenuates aryl hydrocarbon receptor (AHR) signalling through post-transcriptional downregulation of canonical AHR pathway components in cord blood haematopoietic stem and progenitor cells (PMID:27121842)
• The notion that regular and close monitoring of MSI2 mRNA levels in chronic myeloid leukemia patients might identify patients at risk of progressing to blast crisis was not supported by this study; an increase in MSI2 transcripts does not precede an increase in BCR-ABL1 mRNA levels. (PMID:27160312)
• MSI2 provides essential support for TGFbetaR1/SMAD3 signaling and contributes to invasive adenocarcinoma of the lung and may serve as a predictive biomarker of NSCLC aggressiveness (PMID:27274057)
• Overexpression of Msi2 significantly increased and silencing of Msi2 reduced the phosphorylation of JAK2 and its downstream effecter STAT3. (PMID:27322953)
• MSI2 expression was markedly increased in both PDAC cell lines and human PDAC specimens, and high MSI2 expression was associated with poor prognosis for PDAC. Forced MSI2 expression promoted PDAC proliferation, migration, and invasion in vitro and growth and metastasis in vivo, whereas knockdown of MSI2 expression did the opposite. Dysregulated KLF4/MSI2 signaling promotes PDAC progression and metastasis. (PMID:27449499)
• our findings identified a novel regulatory mechanism of MSI2 as an upstream regulator of ESR1 and revealed the clinical relevance of the RNA-binding protein MSI2 in breast cancer. (PMID:27593929)
• MSI2 overexpression induces paclitaxel resistance in ovarian cancer. (PMID:27600258)
• MSI2 might play a crucial role in sustaining stemness and chemoresistance of liver cancer stem cells in LIN28A-dependent manner in hepatocellular carcinoma. (PMID:27721018)
• these findings provide evidence that DBC2 suppresses tumorigenesis in breast cancer by ubiquitinating MSI2. (PMID:27941885)
• MSI2 and FLT3 are significantly co-regulated in human AML (PMID:28107692)
• MSI1 and MSI2 bind and regulate the mRNA stability and translation of proteins operating in essential oncogenic signaling pathways..This review provides a current overview of Musashi as a cancer driver and novel therapeutic target. (PMID:28143872)
• MSI2 regulates myeloid leukemia stem cells gene expression. (PMID:28436985)
• Differential methylation of the MSI2 gene (chr17:55484635) in blood and islet cells is strongly related to hyperglycemia. (PMID:28542303)
• Results provide evidence that MSI2 variants may contribute to the age-at-onset in schizophrenia. (PMID:28866849)
• Here, the authors demonstrate that the canonical Musashi2 isoform is subject to regulated site-specific phosphorylation, converting Musashi2 from a repressor to an activator of target mRNA translation. (PMID:28912529)
• High MSI2 expression is associated with esophageal squamous cell carcinoma. (PMID:29054489)
• MSI2 expression is increased in epithelial cells adjacent to breast carcinoma, and increases with increasing proximity. (PMID:29093438)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	msi2b	ENSDARG00000032614
danio_rerio	msi2a	ENSDARG00000033901
mus_musculus	Msi2	ENSMUSG00000069769
rattus_norvegicus	Msi2	ENSRNOG00000025338
drosophila_melanogaster	msi	FBGN0011666
drosophila_melanogaster	Rbp6	FBGN0260943
caenorhabditis_elegans		WBGENE00003423

Paralogs (36): DAZAP1 (ENSG00000071626), CIRBP (ENSG00000099622), RBM23 (ENSG00000100461), RBM3 (ENSG00000102317), NCL (ENSG00000115053), TIA1 (ENSG00000116001), HNRNPA2B1 (ENSG00000122566), RBM19 (ENSG00000122965), RBM39 (ENSG00000131051), MSI1 (ENSG00000135097), HNRNPA1 (ENSG00000135486), HNRNPD (ENSG00000138668), HNRNPA1L2 (ENSG00000139675), RBMX (ENSG00000147274), A1CF (ENSG00000148584), TIAL1 (ENSG00000151923), RBM46 (ENSG00000151962), HNRNPDL (ENSG00000152795), RBM47 (ENSG00000163694), RBMY1F (ENSG00000169800), HNRNPA3 (ENSG00000170144), RBMXL2 (ENSG00000170748), RBM4B (ENSG00000173914), RBM4 (ENSG00000173933), RBMXL3 (ENSG00000175718), HNRNPA0 (ENSG00000177733), TRNAU1AP (ENSG00000180098), HNRNPAB (ENSG00000197451), RBMXL1 (ENSG00000213516), HNRNPA1L3 (ENSG00000224578), RBMY1J (ENSG00000226941), RBMY1A1 (ENSG00000234414), RBMY1E (ENSG00000242389), RBMY1B (ENSG00000242875), RBMY1D (ENSG00000244395), DND1 (ENSG00000256453)

Protein

Protein identifiers

RNA-binding protein Musashi homolog 2 — Q96DH6 (reviewed: Q96DH6)

All UniProt accessions (15): Q96DH6, A0A6Q8PF05, A0A6Q8PFI2, A0A6Q8PFU8, A0A6Q8PGD8, A0A6Q8PGF5, A0A6Q8PH26, A0A6Q8PH41, A0A6Q8PH51, A0A6Q8PHP1, A0A6Q8PHT3, B4DHE8, B4DM51, J3KTC1, J3QKT5

UniProt curated annotations — full annotation on UniProt →

Function. RNA binding protein that regulates the expression of target mRNAs at the translation level. May play a role in the proliferation and maintenance of stem cells in the central nervous system.

Subunit / interactions. Interacts with RHOBTB2; the interaction is necessary for MSI2 ubiquitination and degradation.

Subcellular location. Cytoplasm.

Tissue specificity. Ubiquitous; detected at low levels.

Post-translational modifications. Phosphorylated. Ubiquitinated by the RHOBTB2-CUL3-RBX1 ubiquitin ligase complex.

Disease relevance. Chromosomal aberrations involving MSI2 may contribute to disease progression in chronic myeloid leukemia. Translocation t(7;17)(p15;q23) with HOXA9; translocation t(7;17)(q32-34;q23).

Induction. Up-regulated in astrocytes after brain injury.

Similarity. Belongs to the Musashi family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q96DH6-1	1, A	yes
Q96DH6-2	2
Q96DH6-3	3

RefSeq proteins (4): NP_001309179, NP_001309180, NP_620412, NP_733839 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000504	RRM_dom	Domain
IPR012677	Nucleotide-bd_a/b_plait_sf	Homologous_superfamily
IPR034126	MSI_RRM2	Domain
IPR035979	RBD_domain_sf	Homologous_superfamily

Pfam: PF00076

UniProt features (28 total): modified residue 6, strand 6, splice variant 4, helix 3, domain 2, region of interest 2, chain 1, turn 1, initiator methionine 1, compositionally biased region 1, site 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
6DBP	X-RAY DIFFRACTION	1.6
6NTY	X-RAY DIFFRACTION	2.1
6C8U	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96DH6-F1	67.62	0.26

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): 217–218 (breakpoint for translocation to form msi2/hoxa9 fusion protein)

Post-translational modifications (6): 261, 2, 14, 1, 6, 228

Function

Pathways and Gene Ontology

Reactome pathways

6 pathways

ID	Pathway
R-HSA-9013418	RHOBTB2 GTPase cycle
R-HSA-162582	Signal Transduction
R-HSA-194315	Signaling by Rho GTPases
R-HSA-9012999	RHO GTPase cycle
R-HSA-9706574	RHOBTB GTPase Cycle
R-HSA-9716542	Signaling by Rho GTPases, Miro GTPases and RHOBTB3

MSigDB gene sets: 335 (showing top): RRAGTTGT_UNKNOWN, RORA1_01, NKX25_02, RACCACAR_AML_Q6, TGACCTY_ERR1_Q2, CACCAGC_MIR138, MONNIER_POSTRADIATION_TUMOR_ESCAPE_UP, GOBP_TRANSLATION, GOBP_POST_TRANSCRIPTIONAL_REGULATION_OF_GENE_EXPRESSION, MYLLYKANGAS_AMPLIFICATION_HOT_SPOT_5, CREIGHTON_ENDOCRINE_THERAPY_RESISTANCE_1, SHETH_LIVER_CANCER_VS_TXNIP_LOSS_PAM4, AML_Q6, BRN2_01, HFH3_01

GO Biological Process (3): regulation of translation (GO:0006417), central nervous system development (GO:0007417), stem cell development (GO:0048864)

GO Molecular Function (7): RNA binding (GO:0003723), mRNA binding (GO:0003729), poly(U) RNA binding (GO:0008266), identical protein binding (GO:0042802), nucleic acid binding (GO:0003676), single-stranded RNA binding (GO:0003727), protein binding (GO:0005515)

GO Cellular Component (2): cytoplasm (GO:0005737), cytosol (GO:0005829)

Reactome top-level categories

Rollup of top-5 pathways:

Category	Pathways
RHOBTB GTPase Cycle	1
Signaling by Rho GTPases, Miro GTPases and RHOBTB3	1
Signaling by Rho GTPases	1
RHO GTPase cycle	1
Signal Transduction	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
RNA binding	2
binding	2
cellular anatomical structure	2
translation	1
post-transcriptional regulation of gene expression	1
regulation of protein metabolic process	1
nervous system development	1
system development	1
cell development	1
stem cell differentiation	1
nucleic acid binding	1
poly-pyrimidine tract binding	1
protein binding	1
intracellular anatomical structure	1
cytoplasm	1

Protein interactions and networks

STRING

1520 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MSI2	NUMBL	Q9Y6R0	945
MSI2	NUMB	P49757	930
MSI2	HOXA9	P31269	916
MSI2	NUP98	P52948	844
MSI2	SOX2	P48431	691
MSI2	BCAT1	P54687	628
MSI2	MYC	P01106	578
MSI2	ABL1	P00519	562
MSI2	IKZF2	Q9UKS7	558
MSI2	LIN28A	Q9H9Z2	543
MSI2	KRAS	P01116	535
MSI2	PTEN	P60484	528
MSI2	PBX1	P40424	524
MSI2	NOTCH1	P46531	517
MSI2	CDKN1A	P38936	514

IntAct

64 interactions, top by confidence:

A	B	Type	Score
MSI2	HNRNPH2	psi-mi:“MI:0915”(physical association)	0.720
HNRNPH2	MSI2	psi-mi:“MI:0915”(physical association)	0.720
HNRNPH1	MSI2	psi-mi:“MI:0915”(physical association)	0.670
IGF2BP1	IGF2BP3	psi-mi:“MI:0914”(association)	0.640
MAPT	MSI2	psi-mi:“MI:0407”(direct interaction)	0.590
MSI2	MSI2	psi-mi:“MI:0407”(direct interaction)	0.580
MSI2	MSI2	psi-mi:“MI:0403”(colocalization)	0.580
MEOX2	MSI2	psi-mi:“MI:0915”(physical association)	0.560
MSI2	MEOX2	psi-mi:“MI:0915”(physical association)	0.560
MRPL18	GTPBP10	psi-mi:“MI:0914”(association)	0.530
ESRP1	RGPD8	psi-mi:“MI:0914”(association)	0.530
VCAM1	PSMD11	psi-mi:“MI:0914”(association)	0.530
MSI2	CACNA1C	psi-mi:“MI:0915”(physical association)	0.500
MSI2	TIMM10B	psi-mi:“MI:0915”(physical association)	0.500
CDK1	CHEK1	psi-mi:“MI:0914”(association)	0.350
KIF21A	NCOA4	psi-mi:“MI:0914”(association)	0.350
	NAP1L1	psi-mi:“MI:0914”(association)	0.350
CUL3	PXDNL	psi-mi:“MI:0914”(association)	0.350
	DDX3Y	psi-mi:“MI:0914”(association)	0.350
H2AX	ANXA6	psi-mi:“MI:0914”(association)	0.350
SOX2	CBX4	psi-mi:“MI:0914”(association)	0.350
MSI2	SOX2	psi-mi:“MI:0914”(association)	0.350
SRPK3	SNRPGP15	psi-mi:“MI:0914”(association)	0.350
CPEB1		psi-mi:“MI:0914”(association)	0.350

BioGRID (220): MSI2 (Two-hybrid), MSI2 (Two-hybrid), MSI2 (Affinity Capture-MS), MSI2 (Affinity Capture-MS), MSI2 (Affinity Capture-MS), MSI2 (Affinity Capture-MS), ICK (Affinity Capture-MS), ANXA13 (Affinity Capture-MS), TIMM10B (Affinity Capture-MS), MSI2 (Affinity Capture-MS), FKBP1A (Co-fractionation), MSI2 (Co-fractionation), MSI2 (Co-fractionation), MSI2 (Co-fractionation), MSI2 (Co-fractionation)

ESM2 similar proteins: A0A8M1NHK4, A0AV96, B3M3R5, B4KX02, O22173, O43347, P86049, Q05196, Q15233, Q1LZD9, Q32NN2, Q3UEB3, Q4KLH4, Q5R469, Q5R5P4, Q5R9H4, Q5RFL9, Q5W9D5, Q5W9D6, Q5W9D7, Q5YD48, Q61474, Q66H68, Q6DEY7, Q6GR16, Q6IRN2, Q6P0D0, Q7JJZ8, Q8GZ26, Q8K3P4, Q8MSV2, Q8R326, Q8TBY0, Q8WXF1, Q91WT8, Q91XU1, Q920Q6, Q923K9, Q96DH6, Q96PU8

Diamond homologs: A0A0D1C8Z4, A0A2R8Y4L2, A5A6H4, A7VJC2, D0VWM8, G5EFS2, O14979, O43347, O88569, O89086, O93235, O94432, P04256, P07909, P09405, P09651, P09867, P13383, P17130, P19338, P19682, P19683, P21522, P22626, P28644, P41891, P48809, P48810, P49312, P51968, P51989, P51990, P51991, P51992, P60824, P60825, P60826, P98179, Q02926, Q03878

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
HOXA9	“up-regulates quantity by expression”	MSI2	“transcriptional regulation”
MSI2	“down-regulates quantity by repression”	NUMB	“transcriptional regulation”

Disease & clinical

Cancer significance

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

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	29
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

4200 predictions. Top by Δscore:

Variant	Effect	Δscore
17:57257096:A:AG	acceptor_gain	1.0000
17:57257097:G:GG	acceptor_gain	1.0000
17:57257097:GTA:G	acceptor_gain	1.0000
17:57257097:GTAA:G	acceptor_gain	1.0000
17:57257097:GTAAA:G	acceptor_gain	1.0000
17:57257137:AGGTA:A	donor_loss	1.0000
17:57257139:G:T	donor_loss	1.0000
17:57258351:GACG:G	donor_gain	1.0000
17:57262146:CCCA:C	acceptor_loss	1.0000
17:57262148:CAG:C	acceptor_loss	1.0000
17:57262149:A:AG	acceptor_gain	1.0000
17:57262150:G:A	acceptor_loss	1.0000
17:57262150:G:GA	acceptor_gain	1.0000
17:57262150:GATT:G	acceptor_gain	1.0000
17:57262190:AAGG:A	donor_loss	1.0000
17:57262192:GGTA:G	donor_loss	1.0000
17:57262193:GTAA:G	donor_loss	1.0000
17:57262194:T:G	donor_loss	1.0000
17:57347874:T:A	acceptor_gain	1.0000
17:57401373:TTGCA:T	acceptor_loss	1.0000
17:57401374:TGCA:T	acceptor_loss	1.0000
17:57401375:GCAG:G	acceptor_loss	1.0000
17:57401376:CAGA:C	acceptor_loss	1.0000
17:57401377:A:AG	acceptor_gain	1.0000
17:57401377:A:C	acceptor_loss	1.0000
17:57401377:AGAT:A	acceptor_gain	1.0000
17:57401378:G:GG	acceptor_gain	1.0000
17:57401378:GA:G	acceptor_gain	1.0000
17:57401378:GAT:G	acceptor_gain	1.0000
17:57401378:GATG:G	acceptor_gain	1.0000

AlphaMissense

2166 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:57257101:A:C	K22N	1.000
17:57257101:A:T	K22N	1.000
17:57257103:T:A	M23K	1.000
17:57257103:T:G	M23R	1.000
17:57257105:T:A	F24I	1.000
17:57257105:T:C	F24L	1.000
17:57257105:T:G	F24V	1.000
17:57257106:T:C	F24S	1.000
17:57257106:T:G	F24C	1.000
17:57257107:T:A	F24L	1.000
17:57257107:T:G	F24L	1.000
17:57257109:T:A	I25N	1.000
17:57257111:G:A	G26S	1.000
17:57257111:G:C	G26R	1.000
17:57257111:G:T	G26C	1.000
17:57257112:G:A	G26D	1.000
17:57257112:G:T	G26V	1.000
17:57257114:G:A	G27R	1.000
17:57257114:G:C	G27R	1.000
17:57257115:G:A	G27E	1.000
17:57257115:G:T	G27V	1.000
17:57257118:T:A	L28Q	1.000
17:57257118:T:C	L28P	1.000
17:57257118:T:G	L28R	1.000
17:57257120:A:C	S29R	1.000
17:57257122:C:A	S29R	1.000
17:57257122:C:G	S29R	1.000
17:57257123:T:A	W30R	1.000
17:57257123:T:C	W30R	1.000
17:57257125:G:C	W30C	1.000

dbSNP variants (sampled 300 via entrez): RS1000008848 (17:57528664 T>C), RS1000022412 (17:57647842 A>G), RS1000028316 (17:57475930 T>G), RS1000031570 (17:57418390 A>G), RS1000032850 (17:57567858 G>C), RS1000033199 (17:57614750 C>A,G), RS1000044612 (17:57291531 A>G), RS1000055637 (17:57679963 C>T), RS1000088328 (17:57315511 T>A), RS1000090373 (17:57637688 T>C), RS1000117650 (17:57503939 T>C), RS1000118624 (17:57356302 T>C), RS1000138808 (17:57494989 G>A), RS1000141384 (17:57397732 C>A,T), RS1000144353 (17:57695969 A>G)

Disease associations

OMIM: gene MIM:607897 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

32 associations (top):

Study	Trait	p-value
GCST002097_27	Coronary artery calcification	8.000000e-06
GCST003983_20	Male-pattern baldness	2.000000e-12
GCST004599_127	Mean platelet volume	8.000000e-14
GCST004607_76	Plateletcrit	6.000000e-26
GCST004946_48	Schizophrenia	2.000000e-08
GCST005116_51	Male-pattern baldness	9.000000e-23
GCST006091_7	Freckles	2.000000e-09
GCST006629_12	Pulse pressure	2.000000e-14
GCST007201_254	Schizophrenia	5.000000e-06
GCST007473_2	Rapid automatized naming of pictures	6.000000e-06
GCST007576_75	Chronotype	9.000000e-09
GCST008362_64	Birth weight	4.000000e-08
GCST008476_27	Emphysema annual change measurement in smokers (percent low attenuation area)	5.000000e-06
GCST008477_36	Emphysema annual change measurement in smokers (adjusted lung density)	6.000000e-06
GCST008514_26	Peginterferon alfa-2a treatment response in chronic hepatitis B infection	4.000000e-06
GCST008839_469	Height	7.000000e-14
GCST009391_1176	Metabolite levels	4.000000e-06
GCST009560_1	Decreased low contrast letter acuity in multiple sclerosis	4.000000e-08
GCST010002_126	Refractive error	7.000000e-42
GCST90002381_123	Eosinophil count	2.000000e-13
GCST90002381_124	Eosinophil count	9.000000e-23
GCST90002382_475	Eosinophil percentage of white cells	5.000000e-12
GCST90002382_476	Eosinophil percentage of white cells	5.000000e-13
GCST90002390_119	Mean corpuscular hemoglobin	3.000000e-09
GCST90002392_300	Mean corpuscular volume	3.000000e-09
GCST90002393_526	Monocyte count	4.000000e-13
GCST90002395_264	Mean platelet volume	7.000000e-27
GCST90002395_265	Mean platelet volume	3.000000e-11
GCST90002398_279	Neutrophil count	5.000000e-13
GCST90002400_223	Plateletcrit	1.000000e-64

EFO canonical traits (17, from GWAS)

EFO ID	Trait name
EFO:0004723	coronary artery calcification
EFO:0007985	platelet crit
EFO:0003963	freckles
EFO:0005763	pulse pressure measurement
EFO:0005301	reading and spelling ability
EFO:0008328	chronotype measurement
EFO:0004344	birth weight
EFO:0007626	emphysema imaging measurement
EFO:0010103	response to peginterferon alfa-2a
EFO:0010454	adenosine monophosphate measurement
EFO:0008385	visual acuity measurement
EFO:0004842	eosinophil count
EFO:0007991	eosinophil percentage of leukocytes
EFO:0004527	mean corpuscular hemoglobin
EFO:0005091	monocyte count
EFO:0004833	neutrophil count
EFO:0004309	platelet count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5465344 (SINGLE PROTEIN)

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

ChEMBL bioactivities

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

pChembl	Type	Value	Unit	Molecule
8.91	Kd	1.228	nM	CHEMBL3752910
8.91	ED50	1.235	nM	CHEMBL3752910

PubChem BioAssay actives

1 with measured affinity, of 4 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	2149891: Binding affinity to human MSI2 incubated for 45 mins by Kinobead based pull down assay	kd	0.0012	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression, affects expression, decreases methylation	8
Benzo(a)pyrene	affects expression, affects methylation, decreases expression, increases expression	7
Air Pollutants	increases abundance, increases oxidation, affects expression, increases expression, decreases expression (+1 more)	5
sodium arsenite	increases reaction, decreases expression, affects cotreatment, increases abundance, affects binding	3
Acetaminophen	decreases expression	3
methylmercuric chloride	decreases expression, increases expression	2
Arsenic	affects methylation, affects cotreatment, decreases expression, increases abundance	2
Ozone	affects expression, affects cotreatment, increases oxidation, increases abundance	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression, affects expression	2
Aflatoxin B1	decreases methylation, increases expression	2
Particulate Matter	decreases expression, increases abundance, increases expression	2
aristolochic acid I	decreases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
bisphenol A	affects cotreatment, increases methylation, decreases methylation	1
glycidyl methacrylate	decreases expression	1
trichostatin A	decreases expression	1
arsenite	increases methylation	1
manganese chloride	affects cotreatment, decreases expression, increases abundance	1
aflatoxin B2	decreases methylation	1
cupric oxide	increases expression	1
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	1
beta-methylcholine	affects expression	1
di-n-butylphosphoric acid	affects expression	1
cylindrospermopsin	increases expression	1
CGP 52608	affects binding, increases reaction	1
deguelin	decreases expression	1
fenpyroximate	decreases expression	1
4-chloro-N-((4-(1,1-dimethylethyl)phenyl)methyl)-3-ethyl-1-methyl-1H-pyrazole-5-carboxamide	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1

ChEMBL screening assays

3 unique, capped per target: 3 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5381218	Binding	Inhibition of TGFbeta2-induced Msi2 protein expression in human MDA-MB-231 cells at 10 uM incubated for 48 hrs by Western blotting analysis	Small Molecules Targeting the RNA-Binding Protein HuR Inhibit Tumor Growth in Xenografts. — J Med Chem

Cellosaurus cell lines

3 cell lines: 3 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_SZ05	HAP1 MSI2 (-) 1	Cancer cell line	Male
CVCL_XQ65	HAP1 MSI2 (-) 2	Cancer cell line	Male
CVCL_XQ66	HAP1 MSI2 (-) 3	Cancer cell line	Male

Clinical trials (associated diseases)

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