MEIS1

Summary

MEIS1 (Meis homeobox 1, HGNC:7000) is a protein-coding gene on chromosome 2p14, encoding Homeobox protein Meis1 (O00470). Acts as a transcriptional regulator of PAX6.

Homeobox genes, of which the most well-characterized category is represented by the HOX genes, play a crucial role in normal development. In addition, several homeoproteins are involved in neoplasia. This gene encodes a homeobox protein belonging to the TALE (’three amino acid loop extension’) family of homeodomain-containing proteins.

Source: NCBI Gene 4211 — RefSeq curated summary.

At a glance

• GWAS associations: 88
• Clinical variants (ClinVar): 31 total
• Druggable target: yes
• Transcription factor: yes — 25 downstream targets (CollecTRI)
• MANE Select transcript: NM_002398

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:7000
Approved symbol	MEIS1
Name	Meis homeobox 1
Location	2p14
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000143995
Ensembl biotype	protein_coding
OMIM	601739
Entrez	4211

Gene structure

Transcript identifiers

Ensembl transcripts: 25 — 14 protein_coding, 9 protein_coding_CDS_not_defined, 2 retained_intron

ENST00000272369, ENST00000398506, ENST00000409517, ENST00000409622, ENST00000437869, ENST00000450027, ENST00000466811, ENST00000475239, ENST00000488550, ENST00000490726, ENST00000491706, ENST00000495021, ENST00000496248, ENST00000498705, ENST00000542964, ENST00000560281, ENST00000606455, ENST00000878432, ENST00000878433, ENST00000951686, ENST00000951687, ENST00000951688, ENST00000951689, ENST00000951690, ENST00000951691

RefSeq mRNA: 1 — MANE Select: NM_002398 NM_002398

CCDS: CCDS46309

Canonical transcript exons

ENST00000272369 — 13 exons

Exon	Start	End
ENSE00001654912	66571246	66573869
ENSE00002312002	66435125	66435868
ENSE00003695022	66440562	66440612
ENSE00003696230	66512149	66512294
ENSE00003697059	66569050	66569145
ENSE00003698752	66437737	66437963
ENSE00003699282	66441414	66441464
ENSE00003701460	66568667	66568756
ENSE00003701724	66442902	66443048
ENSE00003702097	66547943	66548019
ENSE00003702126	66439843	66439984
ENSE00003716167	66567453	66567511
ENSE00003784577	66464109	66464220

Expression profiles

Bgee: expression breadth ubiquitous, 264 present calls, max score 98.54.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 16.1283 / max 651.2898, expressed in 1505 samples.

FANTOM5 promoters (11 alternative TSS)

Promoter ID	TPM avg	Samples expressed
20639	6.2655	1246
20638	5.6336	1258
20644	1.2636	505
20637	0.7046	407
20640	0.6488	341
20641	0.4644	237
20642	0.3701	151
20647	0.3583	191
20643	0.1903	79
20636	0.1752	80

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right uterine tube	UBERON:0001302	98.54	gold quality
mucosa of stomach	UBERON:0001199	98.45	gold quality
body of uterus	UBERON:0009853	98.29	gold quality
endocervix	UBERON:0000458	97.97	gold quality
left uterine tube	UBERON:0001303	97.91	gold quality
stromal cell of endometrium	CL:0002255	97.78	gold quality
ectocervix	UBERON:0012249	97.47	gold quality
lower esophagus muscularis layer	UBERON:0035833	97.43	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	97.43	gold quality
lower esophagus	UBERON:0013473	97.41	gold quality
palpebral conjunctiva	UBERON:0001812	97.32	gold quality
right adrenal gland	UBERON:0001233	97.09	gold quality
adrenal tissue	UBERON:0018303	97.08	gold quality
myometrium	UBERON:0001296	97.06	gold quality
left adrenal gland cortex	UBERON:0035825	96.87	gold quality
left adrenal gland	UBERON:0001234	96.80	gold quality
muscle layer of sigmoid colon	UBERON:0035805	96.80	gold quality
adrenal cortex	UBERON:0001235	96.65	gold quality
right adrenal gland cortex	UBERON:0035827	96.64	gold quality
uterus	UBERON:0000995	96.28	gold quality
body of pancreas	UBERON:0001150	96.24	gold quality
cauda epididymis	UBERON:0004360	96.21	gold quality
vagina	UBERON:0000996	96.12	gold quality
adrenal gland	UBERON:0002369	96.07	gold quality
endometrium	UBERON:0001295	95.81	gold quality
right ovary	UBERON:0002118	95.54	gold quality
seminal vesicle	UBERON:0000998	95.42	gold quality
colonic epithelium	UBERON:0000397	95.05	gold quality
left ovary	UBERON:0002119	94.87	gold quality
female reproductive system	UBERON:0000474	94.57	gold quality

Single-cell (SCXA)

Detected in 13 experiment(s), a significant marker in 12.

Experiment	Marker?	Max mean expression
E-MTAB-9067	yes	430.26
E-GEOD-76312	yes	430.13
E-HCAD-10	yes	43.29
E-CURD-112	yes	35.90
E-MTAB-6678	yes	29.29
E-ANND-3	yes	23.13
E-CURD-119	yes	19.13
E-MTAB-5061	yes	14.25
E-MTAB-9388	yes	10.39
E-GEOD-93593	yes	6.82
E-GEOD-81608	yes	5.04
E-GEOD-83139	yes	3.97
E-GEOD-100618	no	1103.06

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

25 targets.

Target	Regulation
AR	Unknown
ASCL1	Unknown
CCL3	Repression
CCL4	Repression
CCND1	Unknown
CDKN1A	Activation
CYBB
FLT3	Activation
FOXN4
GFI1
GFM1
HIF1A	Activation
IL10	Activation
ITGA9	Unknown
KRT19	Activation
MYB	Unknown
MYC	Unknown
NFYA
PAX6	Unknown
PF4	Activation
POU5F1	Activation
PTCH1	Activation
SOX3	Unknown
TGFBR2	Activation
ZIC3

JASPAR motifs

Motif	Name	Family
MA0498.2	MEIS1	TALE-type homeo domain factors
MA0498.3	MEIS1	TALE-type homeo domain factors
MA1639.1	MEIS1	TALE-type homeo domain factors
MA1639.2	MEIS1	TALE-type homeo domain factors

JASPAR matrix evidence (PMIDs): PMID:9405651, PMID:23602564

Upstream regulators (CollecTRI, top): ARX, CREB1, DNMT3A, DOT1L, E2F1, ELF1, GFI1B, HOXA7, HOXA9, KMT2A, MYC, PBX2, PKNOX1, POU5F1, RARG, RNF2, SPI1, TFAP2A, TLX1

miRNA regulators (miRDB)

116 targeting MEIS1, 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-3646	100.00	73.56	5283
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-6758-5P	100.00	66.21	1470
HSA-MIR-6856-5P	100.00	65.47	1298
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-507	99.97	70.11	1915
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-557	99.96	70.01	1640
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163
HSA-MIR-23C	99.95	73.92	3192
HSA-MIR-3912-5P	99.95	66.11	925
HSA-MIR-9718	99.94	68.91	918
HSA-MIR-4302	99.89	67.94	1187
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-6124	99.87	69.78	3551
HSA-MIR-3151-5P	99.86	63.83	1069
HSA-MIR-221-5P	99.86	65.45	1052
HSA-MIR-8073	99.86	65.21	1118
HSA-MIR-369-3P	99.85	70.52	2264
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-6844	99.82	70.69	2423
HSA-MIR-4760-5P	99.80	69.88	1619
HSA-MIR-3156-3P	99.76	66.72	939
HSA-MIR-623	99.76	68.16	1170
HSA-MIR-1976	99.74	65.48	1127
HSA-MIR-4755-5P	99.71	70.34	2716

Literature-anchored findings (GeneRIF, showing 40)

• these studies demonstrate that the homeodomain proteins, MEIS1, PBX1B, and PBX2, play an important role in megakaryocytic gene expression (PMID:12609849)
• Hoxa9 and Hoxa7 as well as the Hox coregulators Meis1 and Pbx3 among the targets upregulated by MLL-ENL-ERtm in conditionally transformed cells (PMID:14701735)
• Data report novel nucleoporin 98 fusions with homeobox (HOX)A10, HOXB3 and HOXB4, and describe the results of coexpression of these proteins with the Hox cofactor Meis1 in leukemic induction. (PMID:14966272)
• found a constant downregulation of the Meis 1 gene mRNA in AML1-ETO acute myeloid leukemias and in those cases harboring in frame mutations in the bZIP domain of CEBPalpha (PMID:15103390)
• suggest that MLL aberrations may regulate MEIS1 and HOXA9 gene expression in ALL-derived cell lines, while AML-derived cell lines express these genes independently of the MLL status (PMID:15160920)
• advantage to Meis1-HoxA9 coexpressing cells in vivo, leading to leukemogenesis. (PMID:15479723)
• MEIS C termini possess transcriptional regulatory domains that respond to cell signaling and confer functional differences between MEIS and PREP proteins (PMID:15654074)
• CYBB is a common target gene repressed by HoxA10 and activated by HoxA9, and Meis1 and Nup98-hoxA9 have roles in repressing myeloid-specific gene transcription (PMID:15681849)
• pre B-cell leukemia transcription factor 1 is mostly cytoplasmic in epithelial endometrial cells of the developing female genital tract despite the nuclear localization of MEIS1 (PMID:16172981)
• In CREB-overexpressing control cells, Meis1 RNA expression was 3-fold higher than in untransfected cells. In AML cells, it was 5- to 10-fold higher than in the control cells. Persistent Meis1 expression may cause leukemia. (PMID:17805329)
• MLL-FRYL did not increase MEIS1 expression, conferred a proliferative advantage without altering differentiation, and had protracted latency to disease. (PMID:18195096)
• MEIS1 polymorphism is associated with Nocturnal Myoclonus Syndrome. (PMID:18216367)
• analysis of the role of deregulated PcG genes in acute myeloid leukemia, and the downstream PcG targets HOXA4, HOXA9 and MEIS1 (PMID:18410541)
• MEIS1 and LBXCOR1 are developmental factors and raise new pathophysiologic questions for RLS. (PMID:18541116)
• co-expression of PBX1 and MEIS1/2 in granulosa cells in normal human ovaries suggested that MEIS1/2 might control PBX1 sublocalization, as seen in other systems (PMID:18973687)
• results show that MEIS1 expression is important for MLL-rearranged leukemias and suggest that MEIS1 promotes cell-cycle entry (PMID:19109563)
• Reduced expression of the MEIS1 gene, possibly through intronic cis-regulatory element(s), predisposes to restless legs syndrome. (PMID:19126776)
• From the result of this study suggested there was no evidence for an over-transmission of the at-risk haplotype in MEIS1 (G-A-G, 51 transmissions versus 59 non-transmissions, nominal p-value = 0.381). (PMID:19223043)
• MEIS1A transactivation in response to protein kinase A signaling requires the transducers of regulated CREB family of CREB co-activators (PMID:19473990)
• co-operation between TLX1 and MEIS proteins may have a significant role in T-cell leukemogenesis. (PMID:19559479)
• combination of low HOXA4 and low MEIS1 gene expression is a favourable predictor for outcome in all AML patients and that the expression levels are governed by the methylation state of these genes. (PMID:19563517)
• CREB1 may mediate HOXA9 modulation of Meis1 expression. (PMID:19620287)
• We report a MEIS1 p.R272H mutation in familial restless legs syndrome. (PMID:19620614)
• MEIS1 may be a useful tumor marker for favorable prognosis in breast cancer. (PMID:19776672)
• Data demonstrated that overexpressed PBX1 and MEIS1 increased endogenous SOX3 protein expression in both uninduced and RA-induced NT2/D1 cells. (PMID:19799567)
• GSK-3 maintains the MLL leukemia stem cell transcriptional program by promoting the conditional association of CREB and its coactivators TORC and CBP with homedomain protein MEIS1, which in turn facilitates HOX-mediated transcription and transformation. (PMID:20541704)
• ETS transcription factor ELF1 is an important positive regulator of MEIS1 expression (PMID:20600580)
• Screening of the coding regions of MEIS1 in patients with RLS revealed 3 novel variants. (PMID:21422461)
• Several targets of MLL fusions, MEIS1, HOXA7, HOXA9, and HOXA10 are functionally related and have been implicated in leukemias. Each of the four genes was knocked down separately in the precursor B-cell leukemic line RS4;11 expressing MLL-AF4. (PMID:21518888)
• In the German sample, variants in MEIS1 and BTBD9 were associated with Restless legs syndrome in end stage renal disease (PMID:21572129)
• These findings indicate that Meis1 works as a transcription factor for mitochondrial genes in pancreatic cancer cells. (PMID:21703237)
• A link is established between the restless legs syndrome-associated MEIS1 gene and iron metabolism. (PMID:21710629)
• Data show that MEIS1D, a Meis1 isoform, is expressed in colon. (PMID:21858198)
• Variants in MEIS1, BTBD9, and MAP2K5/SKOR1 confer a significant risk of restless legs syndrome in a United States population. (PMID:21925394)
• the cellular context in which HOX/MEIS1 is overexpressed appears to be very important, and other relevant genes are most likely required as well to maintain the expanding capacity of the CD34thorn NPMcthorn acute myeloid leukemia cells (PMID:21986840)
• up-regulation of MEIS1 is important for sustaining proliferation of leukemic cells and that down-regulation of MEIS1 (PMID:22185299)
• findings show that HOXA9 and MEIS1 are direct targets of miRNA-196b, a microRNA located adjacent to and co-expressed with HOXA9, in MLL-rearranged leukaemic cells (PMID:22353710)
• Data indicate that dynamin 3 (DNM3) harbors MEIS1 binding sites and is associated with differences in mean platelet volume (MPV). (PMID:22972982)
• Hoxa7, Hoxa9 and Hox cofactor Meis1 were identified as AP-2alpha target genes, which are involved in myeloid leukemogenesis. (PMID:23660297)
• [review] It is possible that Meis1 contributes to the quiescent state of adult cardiomyocytes by regulating redox homeostasis. (PMID:23868827)

Cross-species orthologs

10 orthologs

Organism	Symbol	Gene ID
danio_rerio	meis1b	ENSDARG00000012078
mus_musculus	Meis1	ENSMUSG00000020160
rattus_norvegicus	Meis1	ENSRNOG00000004606
drosophila_melanogaster	exd	FBGN0000611
drosophila_melanogaster	hth	FBGN0001235
drosophila_melanogaster	vis	FBGN0033748
drosophila_melanogaster	achi	FBGN0033749
caenorhabditis_elegans		WBGENE00000443
caenorhabditis_elegans		WBGENE00006796
caenorhabditis_elegans		WBGENE00017690

Paralogs (13): MEIS3 (ENSG00000105419), PBX4 (ENSG00000105717), TGIF2 (ENSG00000118707), MEIS2 (ENSG00000134138), TGIF2LX (ENSG00000153779), PKNOX1 (ENSG00000160199), PKNOX2 (ENSG00000165495), PBX3 (ENSG00000167081), TGIF2LY (ENSG00000176679), TGIF1 (ENSG00000177426), PBX1 (ENSG00000185630), MEIS3P2 (ENSG00000188013), PBX2 (ENSG00000204304)

Protein

Protein identifiers

Homeobox protein Meis1 — O00470 (reviewed: O00470)

All UniProt accessions (5): O00470, E9PDC4, F5GYS8, H0YNY8, U3KPR8

UniProt curated annotations — full annotation on UniProt →

Function. Acts as a transcriptional regulator of PAX6. Acts as a transcriptional activator of PF4 in complex with PBX1 or PBX2. Required for hematopoiesis, megakaryocyte lineage development and vascular patterning. May function as a cofactor for HOXA7 and HOXA9 in the induction of myeloid leukemias.

Subunit / interactions. Interacts with the N-terminal region of PBX1 to form a heterodimer which binds DNA including a cAMP-responsive sequence in CYP17. Also forms heterodimers with PBX2. Forms heterotrimers with PBX1 or PBX2 and a number of HOX proteins including HOXA9, HOXD4 and HOXD9 where it acts as a non-DNA-binding partner. Also forms heterotrimers with PBX1 and HOX proteins including HOXD9 and HOXD10 where PBX1 is the non-DNA-binding partner. Heterodimer with DLX3. Heterodimer with HOXB13.

Subcellular location. Nucleus.

Tissue specificity. Expressed at low level in normal immunohepatopoietic tissues, including the fetal liver. Expressed in a subset of myeloid leukemia cell lines, with the highest expression seen in those with a megakaryocytic-erythroid phenotype. Also expressed at high levels in the cerebellum.

Disease relevance. Restless legs syndrome 7 (RLS7) [MIM:612853] A neurologic sleep/wake disorder characterized by uncomfortable and unpleasant sensations in the legs that appear at rest, usually at night, inducing an irresistible desire to move the legs. The disorder results in nocturnal insomnia and chronic sleep deprivation. The majority of patients also have periodic limb movements in sleep, which are characterized by involuntary, highly stereotypical, regularly occurring limb movements that occur during sleep. Disease susceptibility may be associated with variants affecting the gene represented in this entry.

Similarity. Belongs to the TALE/MEIS homeobox family.

Isoforms (2)

UniProt ID	Names	Canonical?
O00470-1	1	yes
O00470-2	2

RefSeq proteins (1): NP_002389* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001356	HD	Domain
IPR008422	KN_HD	Domain
IPR009057	Homeodomain-like_sf	Homologous_superfamily
IPR032453	PKNOX/Meis_N	Domain
IPR050224	TALE_homeobox	Family

Pfam: PF05920, PF16493

UniProt features (16 total): helix 3, region of interest 3, turn 2, compositionally biased region 2, splice variant 2, chain 1, domain 1, sequence variant 1, DNA-binding region 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
5EGO	X-RAY DIFFRACTION	2.54
4XRS	X-RAY DIFFRACTION	3.5

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O00470-F1	66.38	0.25

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-5617472	Activation of anterior HOX genes in hindbrain development during early embryogenesis
R-HSA-1266738	Developmental Biology
R-HSA-5619507	Activation of HOX genes during differentiation

MSigDB gene sets: 332 (showing top): GOBP_MYELOID_CELL_DIFFERENTIATION, MULLIGHAN_NPM1_SIGNATURE_3_UP, BROWNE_HCMV_INFECTION_6HR_DN, JI_RESPONSE_TO_FSH_UP, GOBP_NEGATIVE_REGULATION_OF_NEURON_DIFFERENTIATION, BENPORATH_ES_WITH_H3K27ME3, WWTAAGGC_UNKNOWN, GOBP_BEHAVIOR, GOBP_MYELOID_CELL_DEVELOPMENT, GGGNRMNNYCAT_UNKNOWN, YAO_HOXA10_TARGETS_VIA_PROGESTERONE_UP, chr2p14, TATTATA_MIR374, LINDGREN_BLADDER_CANCER_CLUSTER_3_DN, GOBP_NEUROGENESIS

GO Biological Process (17): angiogenesis (GO:0001525), eye development (GO:0001654), lens morphogenesis in camera-type eye (GO:0002089), brain development (GO:0007420), locomotory behavior (GO:0007626), positive regulation of cell population proliferation (GO:0008284), embryonic pattern specification (GO:0009880), animal organ morphogenesis (GO:0009887), hemopoiesis (GO:0030097), megakaryocyte development (GO:0035855), negative regulation of myeloid cell differentiation (GO:0045638), negative regulation of neuron differentiation (GO:0045665), positive regulation of transcription by RNA polymerase II (GO:0045944), definitive hemopoiesis (GO:0060216), cell growth involved in cardiac muscle cell development (GO:0061049), regulation of DNA-templated transcription (GO:0006355), blood vessel morphogenesis (GO:0048514)

GO Molecular Function (7): 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), DNA binding (GO:0003677), chromatin binding (GO:0003682), protein binding (GO:0005515), sequence-specific DNA binding (GO:0043565)

GO Cellular Component (3): chromatin (GO:0000785), nucleus (GO:0005634), transcription regulator complex (GO:0005667)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Activation of HOX genes during differentiation	1
Developmental Biology	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
anatomical structure morphogenesis	2
animal organ development	2
negative regulation of cell differentiation	2
regulation of transcription by RNA polymerase II	2
binding	2
blood vessel morphogenesis	1
anatomical structure formation involved in morphogenesis	1
sensory organ development	1
visual system development	1
lens development in camera-type eye	1
camera-type eye morphogenesis	1
central nervous system development	1
head development	1
behavior	1
cell population proliferation	1
regulation of cell population proliferation	1
positive regulation of cellular process	1
pattern specification process	1
embryo development	1
cell development	1
megakaryocyte differentiation	1
myeloid cell development	1
myeloid cell differentiation	1
regulation of myeloid cell differentiation	1
neuron differentiation	1
regulation of neuron differentiation	1
transcription by RNA polymerase II	1
positive regulation of DNA-templated transcription	1
hemopoiesis	1
physiological cardiac muscle hypertrophy	1
developmental cell growth	1
cardiac muscle cell development	1
DNA-templated transcription	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
blood vessel development	1
tube morphogenesis	1
cis-regulatory region sequence-specific DNA binding	1
chromatin	1

Protein interactions and networks

STRING

2246 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MEIS1	HOXA9	P31269	996
MEIS1	PBX1	P40424	983
MEIS1	NUP98	P52948	909
MEIS1	HOXA7	P31268	898
MEIS1	HOXA10	P31260	849
MEIS1	HOXB3	P14651	776
MEIS1	FCRLA	Q7L513	766
MEIS1	BTBD9	Q96Q07	760
MEIS1	PAX6	P26367	733
MEIS1	MLLT3	P42568	727
MEIS1	EYA1	Q99502	715
MEIS1	PHF23	Q9BUL5	695
MEIS1	MLLT1	Q03111	693
MEIS1	CREB1	P16220	685
MEIS1	MAP2K5	Q13163	668

IntAct

55 interactions, top by confidence:

A	B	Type	Score
MEIS1	CREB1	psi-mi:“MI:0914”(association)	0.680
MEIS1	CREB1	psi-mi:“MI:0915”(physical association)	0.680
CREB1	MEIS1	psi-mi:“MI:0915”(physical association)	0.680
CREB1	MEIS1	psi-mi:“MI:0914”(association)	0.680
CCDC120	AIP	psi-mi:“MI:0914”(association)	0.640
MEIS1	PBX1	psi-mi:“MI:0915”(physical association)	0.550
DNAAF8	CCDC85C	psi-mi:“MI:0914”(association)	0.530
MAB21L1	MEIS1	psi-mi:“MI:0914”(association)	0.530
FAM222A	MEIS1	psi-mi:“MI:0914”(association)	0.530
C5orf24	MEIS1	psi-mi:“MI:0914”(association)	0.530
MAB21L2	MEIS1	psi-mi:“MI:0914”(association)	0.530
TLX1	MEIS1	psi-mi:“MI:0915”(physical association)	0.510
MEIS1	TLX1	psi-mi:“MI:0915”(physical association)	0.510
MEIS1	ETS1	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (53): MEIS1 (Affinity Capture-RNA), MEIS1 (Affinity Capture-MS), MEIS1 (Affinity Capture-MS), MEIS1 (Affinity Capture-MS), MEIS1 (Affinity Capture-MS), MEIS1 (Affinity Capture-MS), MEIS1 (Affinity Capture-MS), MEIS1 (Affinity Capture-MS), MEIS1 (Affinity Capture-MS), MEIS1 (Affinity Capture-MS), MEIS1 (Affinity Capture-MS), MEIS1 (Affinity Capture-MS), MEIS1 (Affinity Capture-MS), MEIS1 (Affinity Capture-MS), MEIS1 (Affinity Capture-MS)

ESM2 similar proteins: A0A0A7HJC7, A0A0A7HMS2, A2Q9L8, B0XYJ1, B0Y8Y9, B0Y9W4, B2AR36, B2W978, B6H7F3, C0STD9, C7YM38, D1ZRZ5, E9EMI7, E9ES99, E9RD40, G4N2B2, G4NEE4, G5EFT5, I1S0E2, I1S4T3, J5JPY5, K9GDC6, O00167, O00470, O16850, P20945, P22022, P45815, P93755, Q00333, Q01870, Q0U7C8, Q28CH2, Q2GW22, Q2UJJ4, Q2UUM2, Q4PD88, Q4WN10, Q4WQL4, Q4WW99

Diamond homologs: A1YER0, A2D5H2, A6NDR6, A8K0S8, A8WL06, B3DM47, B4F6V6, O00470, O04134, O04135, O14770, O17894, O22299, O35317, O35984, O42406, O46339, O65034, O73916, O80416, O93307, O95343, O95475, P10842, P24345, P40424, P40425, P40426, P40427, P41778, P41779, P41817, P46608, P46609, P46639, P46640, P48731, P53147, P56661, P56662

SIGNOR signaling

16 interactions.

A	Effect	B	Mechanism
HOXD9	“up-regulates activity”	MEIS1	binding
MEIS1	up-regulates	Proliferation
MEIS1	down-regulates	Apoptosis
MLL-ENL	“up-regulates quantity by expression”	MEIS1	“transcriptional regulation”
MEIS1	down-regulates	Differentiation
SPI1	“up-regulates quantity by expression”	MEIS1	“transcriptional regulation”
DNMT3A	“down-regulates quantity by repression”	MEIS1	“transcriptional regulation”
DOT1L	“up-regulates quantity by expression”	MEIS1	“transcriptional regulation”
“AEP complex”	“up-regulates quantity by expression”	MEIS1
MEIS1	down-regulates	Cell_death
miR-155	“down-regulates quantity by repression”	MEIS1	“post transcriptional regulation”
HOXA9	“up-regulates activity”	MEIS1	binding
HOXD10	“up-regulates activity”	MEIS1	binding
HOXD11	“up-regulates activity”	MEIS1	binding
HOXD12	“up-regulates activity”	MEIS1	binding
HOXD13	“up-regulates activity”	MEIS1	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 34 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
eye development	6	72.6×	6e-08

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	18
Likely benign	1
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

3274 predictions. Top by Δscore:

Variant	Effect	Δscore
2:66437735:A:AG	acceptor_gain	1.0000
2:66437736:G:GG	acceptor_gain	1.0000
2:66437964:G:GG	donor_gain	1.0000
2:66442897:TGTA:T	acceptor_loss	1.0000
2:66442901:G:GA	acceptor_loss	1.0000
2:66443045:CCAGG:C	donor_loss	1.0000
2:66443046:CAGGT:C	donor_loss	1.0000
2:66443047:AGGT:A	donor_loss	1.0000
2:66443048:GGTA:G	donor_loss	1.0000
2:66443049:G:A	donor_loss	1.0000
2:66443050:T:A	donor_loss	1.0000
2:66464107:A:AG	acceptor_gain	1.0000
2:66464108:G:GA	acceptor_gain	1.0000
2:66464108:GCC:G	acceptor_gain	1.0000
2:66464108:GCCCT:G	acceptor_gain	1.0000
2:66464217:CAAG:C	donor_loss	1.0000
2:66464218:AAGG:A	donor_loss	1.0000
2:66464221:G:GA	donor_loss	1.0000
2:66464222:T:A	donor_loss	1.0000
2:66512292:ACA:A	donor_gain	1.0000
2:66512292:ACAG:A	donor_loss	1.0000
2:66512293:CA:C	donor_gain	1.0000
2:66512294:AG:A	donor_loss	1.0000
2:66512295:G:GG	donor_gain	1.0000
2:66512296:TA:T	donor_loss	1.0000
2:66512297:AAGTG:A	donor_loss	1.0000
2:66547931:A:AG	acceptor_gain	1.0000
2:66547932:T:G	acceptor_gain	1.0000
2:66547939:TCA:T	acceptor_loss	1.0000
2:66547940:CA:C	acceptor_loss	1.0000

AlphaMissense

2612 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:66437957:T:A	I78N	1.000
2:66439845:A:G	H81R	1.000
2:66439846:C:A	H81Q	1.000
2:66439846:C:G	H81Q	1.000
2:66439851:T:C	L83P	1.000
2:66439853:T:C	F84L	1.000
2:66439854:T:C	F84S	1.000
2:66439855:C:A	F84L	1.000
2:66439855:C:G	F84L	1.000
2:66439860:T:A	L86H	1.000
2:66439860:T:C	L86P	1.000
2:66439863:T:C	L87S	1.000
2:66439869:T:C	L89P	1.000
2:66439875:T:C	F91S	1.000
2:66439879:G:C	E92D	1.000
2:66439879:G:T	E92D	1.000
2:66439880:A:C	K93Q	1.000
2:66439880:A:G	K93E	1.000
2:66439881:A:T	K93I	1.000
2:66439882:A:C	K93N	1.000
2:66439882:A:T	K93N	1.000
2:66439883:T:C	C94R	1.000
2:66439884:G:A	C94Y	1.000
2:66439884:G:T	C94F	1.000
2:66439885:T:G	C94W	1.000
2:66439890:T:C	L96S	1.000
2:66439892:G:C	A97P	1.000
2:66439893:C:A	A97D	1.000
2:66439896:C:T	T98I	1.000
2:66439937:T:C	C112R	1.000

dbSNP variants (sampled 300 via entrez): RS1000036660 (2:66553493 A>G), RS1000061351 (2:66486509 C>T), RS1000088489 (2:66553784 A>G), RS1000100562 (2:66510237 G>T), RS1000106744 (2:66538733 A>G), RS1000139446 (2:66538922 C>T), RS1000184243 (2:66467976 T>C), RS1000189726 (2:66566951 C>G), RS1000194763 (2:66511258 A>G), RS1000197122 (2:66522875 A>T), RS1000223773 (2:66482609 A>G), RS1000231598 (2:66557390 T>A), RS1000243380 (2:66437134 A>G), RS1000246724 (2:66480405 T>C,G), RS1000252032 (2:66563636 C>T)

Disease associations

OMIM: gene MIM:601739 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

88 associations (top):

Study	Trait	p-value
GCST000056_1	Restless legs syndrome	3.000000e-28
GCST000562_4	PR interval	5.000000e-11
GCST000971_3	PR interval	3.000000e-09
GCST001159_1	Restless legs syndrome	3.000000e-49
GCST001735_3	PR interval	1.000000e-11
GCST002415_9	Colorectal cancer (diet interaction)	7.000000e-07
GCST002456_2	PR segment duration	5.000000e-09
GCST002690_2	Very long-chain saturated fatty acid levels (fatty acid 20:0)	7.000000e-06
GCST002782_221	Waist-to-hip ratio adjusted for body mass index	2.000000e-07
GCST002782_222	Waist-to-hip ratio adjusted for body mass index	2.000000e-09
GCST002782_223	Waist-to-hip ratio adjusted for body mass index	3.000000e-06
GCST002782_224	Waist-to-hip ratio adjusted for body mass index	1.000000e-08
GCST003818_75	Resting heart rate	2.000000e-07
GCST003819_1	Endometriosis	4.000000e-07
GCST003981_2	Insomnia	9.000000e-19
GCST003982_4	Sleep traits (multi-trait analysis)	4.000000e-16
GCST003992_49	Photic sneeze reflex	1.000000e-11
GCST004288_4	Adolescent idiopathic scoliosis	1.000000e-13
GCST004505_83	Waist-to-hip ratio adjusted for BMI (adjusted for smoking behaviour)	3.000000e-07
GCST004567_58	Waist-to-hip ratio adjusted for BMI (joint analysis for main effect and physical activity interaction)	1.000000e-06
GCST004567_67	Waist-to-hip ratio adjusted for BMI (joint analysis for main effect and physical activity interaction)	4.000000e-08
GCST004576_108	Waist-to-hip ratio adjusted for body mass index	2.000000e-08
GCST004576_66	Waist-to-hip ratio adjusted for body mass index	1.000000e-06
GCST004578_13	Waist-to-hip ratio adjusted for BMI in active individuals	9.000000e-07
GCST004578_69	Waist-to-hip ratio adjusted for BMI in active individuals	7.000000e-08
GCST004695_1	Insomnia complaints	4.000000e-19
GCST004701_1	Insomnia complaints (continuous)	6.000000e-22
GCST004702_1	Insomnia complaints (dichotomous)	2.000000e-19
GCST005042_3	Restless legs syndrome	2.000000e-280
GCST005042_4	Restless legs syndrome	1.000000e-58

EFO canonical traits (28, from GWAS)

EFO ID	Trait name
EFO:0004462	PR interval
EFO:0008111	diet measurement
EFO:0005095	PR segment
EFO:0006796	very long-chain saturated fatty acid measurement
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0007876	insomnia measurement
EFO:0007875	excessive daytime sleepiness measurement
EFO:0007887	autosomal dominant compelling helio-ophthalmic outburst syndrome
EFO:0004318	smoking behavior
EFO:0008002	physical activity measurement
EFO:0008007	age at assessment
EFO:0008343	sex interaction measurement
EFO:0004695	intraocular pressure measurement
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0004530	triglyceride measurement
EFO:0006335	systolic blood pressure
EFO:0009270	heel bone mineral density
EFO:0008328	chronotype measurement
EFO:0006917	spontaneous preterm birth
EFO:0006781	coffee consumption measurement
EFO:0010379	phosphatidylcholine 36:1 measurement
EFO:0004614	apolipoprotein A 1 measurement
EFO:0004327	electrocardiography
EFO:0007874	gut microbiome measurement
EFO:0004531	urate measurement
EFO:0004348	hematocrit
EFO:0004509	hemoglobin measurement
EFO:0004309	platelet count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4879409 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Tretinoin	affects cotreatment, increases expression	4
Valproic Acid	increases methylation, affects expression, increases expression	4
trichostatin A	increases expression, affects cotreatment, decreases expression	3
bisphenol F	affects cotreatment, increases methylation, increases expression	2
bisphenol A	increases expression, affects methylation, affects cotreatment, decreases methylation	2
entinostat	decreases expression, affects cotreatment	2
Arsenic	affects methylation, affects cotreatment, decreases expression, increases abundance	2
Tobacco Smoke Pollution	decreases expression, increases methylation	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	affects expression, decreases expression	2
Cyclosporine	decreases expression	2
Aflatoxin B1	decreases methylation, decreases expression	2
aristolochic acid I	decreases expression	1
FR900359	increases phosphorylation	1
sotorasib	increases expression, affects cotreatment	1
4-oxoretinoic acid	increases expression	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
titanium dioxide	increases methylation	1
2,4,5,2’,4’,5’-hexachlorobiphenyl	decreases expression	1
arsenite	affects binding, increases reaction	1
sodium arsenite	affects cotreatment, decreases expression, increases abundance	1
manganese chloride	increases abundance, affects cotreatment, decreases expression	1
potassium chromate(VI)	decreases expression	1
S-(1,2-dichlorovinyl)cysteine	decreases expression	1
4-oxoretinol	increases expression	1
evodiamine	decreases expression	1
perfluorooctane sulfonic acid	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
dorsomorphin	affects cotreatment, decreases expression	1
licochalcone B	decreases expression	1

ChEMBL screening assays

5 unique, capped per target: 5 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4831197	Binding	Inhibition of MEIS1 (unknown origin) expressed in HEK293T cells co-expressing MEIS-Luc-pGL2 assessed as luciferase activity at 10 uM incubated for 48 hrs by luciferase reporter assay related to protein content	Lead Optimization and Structure-Activity Relationship Studies on Myeloid Ecotropic Viral Integration Site 1 Inhibitor. — J Med Chem

Cellosaurus cell lines

7 cell lines: 4 embryonic stem cell, 3 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_A4C5	SEES3-1V human MEIS1, clone1	Embryonic stem cell	Male
CVCL_A4C6	SEES3-1V human MEIS1, clone2	Embryonic stem cell	Male
CVCL_A4C7	SEES3-1V human MEIS1, clone3	Embryonic stem cell	Male
CVCL_A4EH	WAe001-A-49	Embryonic stem cell	Male
CVCL_SX77	HAP1 MEIS1 (-) 1	Cancer cell line	Male
CVCL_XQ40	HAP1 MEIS1 (-) 2	Cancer cell line	Male
CVCL_XQ41	HAP1 MEIS1 (-) 3	Cancer cell line	Male

Clinical trials (associated diseases)

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