MEIS3

Summary

MEIS3 (Meis homeobox 3, HGNC:29537) is a protein-coding gene on chromosome 19q13.32, encoding Homeobox protein Meis3 (Q99687). Transcriptional regulator which directly modulates PDPK1 expression, thus promoting survival of pancreatic beta-cells.

This gene encodes a homeobox protein and probable transcriptional regulator. The orthologous protein in mouse controls expression of 3-phosphoinositide dependent protein kinase 1, which promotes survival of pancreatic beta-cells.

Source: NCBI Gene 56917 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 97 total
• MANE Select transcript: NM_001301059

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29537
Approved symbol	MEIS3
Name	Meis homeobox 3
Location	19q13.32
Locus type	gene with protein product
Status	Approved
Aliases	MRG2, DKFZp547H236
Ensembl gene	ENSG00000105419
Ensembl biotype	protein_coding
OMIM	619443
Entrez	56917

Gene structure

Transcript identifiers

Ensembl transcripts: 27 — 23 protein_coding, 2 protein_coding_CDS_not_defined, 2 retained_intron

ENST00000331559, ENST00000441740, ENST00000557833, ENST00000558555, ENST00000559338, ENST00000559524, ENST00000560245, ENST00000560253, ENST00000561040, ENST00000561096, ENST00000561204, ENST00000561293, ENST00000607330, ENST00000607695, ENST00000877961, ENST00000913844, ENST00000913845, ENST00000913846, ENST00000913847, ENST00000913848, ENST00000913849, ENST00000913850, ENST00000913851, ENST00000913852, ENST00000943575, ENST00000943576, ENST00000943577

RefSeq mRNA: 4 — MANE Select: NM_001301059 NM_001009813, NM_001301059, NM_001346148, NM_020160

CCDS: CCDS33064, CCDS46132, CCDS74406

Canonical transcript exons

ENST00000558555 — 13 exons

Exon	Start	End
ENSE00002543876	47419070	47419527
ENSE00002547662	47403124	47403553
ENSE00003674972	47415051	47415101
ENSE00003694952	47409099	47409247
ENSE00003695376	47409436	47409547
ENSE00003695538	47407079	47407137
ENSE00003697712	47417178	47417350
ENSE00003697848	47414717	47414866
ENSE00003698703	47407352	47407428
ENSE00003699425	47416804	47416963
ENSE00003700392	47416652	47416702
ENSE00003700932	47406460	47406526
ENSE00003702305	47406888	47406971

Expression profiles

Bgee: expression breadth ubiquitous, 171 present calls, max score 97.36.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0463 / max 4.3030, expressed in 11 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
181760	1.5535	751
181759	0.0463	11

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
body of uterus	UBERON:0009853	97.36	gold quality
left uterine tube	UBERON:0001303	96.61	gold quality
anterior cingulate cortex	UBERON:0009835	96.49	gold quality
cortical plate	UBERON:0005343	96.21	gold quality
amygdala	UBERON:0001876	95.83	gold quality
right frontal lobe	UBERON:0002810	95.78	gold quality
ganglionic eminence	UBERON:0004023	95.34	gold quality
prefrontal cortex	UBERON:0000451	95.22	gold quality
stromal cell of endometrium	CL:0002255	94.96	gold quality
Brodmann (1909) area 9	UBERON:0013540	94.59	gold quality
smooth muscle tissue	UBERON:0001135	93.38	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	92.90	gold quality
neocortex	UBERON:0001950	92.85	gold quality
frontal cortex	UBERON:0001870	92.64	gold quality
cerebral cortex	UBERON:0000956	91.18	gold quality
mucosa of stomach	UBERON:0001199	91.12	gold quality
endocervix	UBERON:0000458	91.09	gold quality
myometrium	UBERON:0001296	90.39	gold quality
temporal lobe	UBERON:0001871	90.18	gold quality
hypothalamus	UBERON:0001898	89.44	gold quality
Ammon’s horn	UBERON:0001954	89.28	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	89.07	gold quality
right ovary	UBERON:0002118	88.69	gold quality
right hemisphere of cerebellum	UBERON:0014890	88.44	gold quality
lower esophagus muscularis layer	UBERON:0035833	88.28	gold quality
lower esophagus	UBERON:0013473	88.21	gold quality
cerebellar hemisphere	UBERON:0002245	87.97	gold quality
cerebellar cortex	UBERON:0002129	87.95	gold quality
ventricular zone	UBERON:0003053	87.79	gold quality
left ovary	UBERON:0002119	87.78	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.42
E-MTAB-4850	no	9.99

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

4 targets.

Target	Regulation
MEIS3	Repression
PDK1
SHH	Unknown
TSHZ1

JASPAR motifs

Motif	Name	Family
MA0775.1	MEIS3	TALE-type homeo domain factors
MA0775.2	MEIS3	TALE-type homeo domain factors

JASPAR matrix evidence (PMIDs): PMID:9405651

Upstream regulators (CollecTRI, top): MEIS3, TSHZ1

miRNA regulators (miRDB)

36 targeting MEIS3, 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-4283	100.00	66.42	2097
HSA-MIR-3689D	100.00	66.14	1181
HSA-MIR-6851-5P	100.00	65.63	1294
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-499A-5P	99.98	70.79	1323
HSA-LET-7A-5P	99.98	72.29	1790
HSA-LET-7B-5P	99.98	72.31	1790
HSA-LET-7C-5P	99.98	72.29	1790
HSA-LET-7E-5P	99.98	72.29	1790
HSA-LET-7F-5P	99.98	72.56	1784
HSA-LET-7G-5P	99.98	72.37	1784
HSA-LET-7I-5P	99.98	72.37	1788
HSA-MIR-98-5P	99.98	72.33	1787
HSA-LET-7D-5P	99.96	71.76	1632
HSA-MIR-4458	99.96	71.64	1650
HSA-MIR-6845-3P	99.94	66.88	1439
HSA-MIR-8087	99.90	69.55	1351
HSA-MIR-605-3P	99.88	69.22	1833
HSA-MIR-1321	99.84	65.30	1811
HSA-MIR-4739	99.84	65.25	1832
HSA-MIR-4756-5P	99.84	64.98	1809
HSA-MIR-519D-5P	99.41	69.30	2057
HSA-MIR-4316	99.37	65.75	1360
HSA-MIR-6799-5P	99.14	65.72	2093
HSA-MIR-7854-3P	99.08	66.26	1117
HSA-MIR-6770-5P	98.97	66.76	1853
HSA-MIR-3154	98.94	66.55	1455
HSA-MIR-6887-5P	98.56	68.49	1295
HSA-MIR-6795-5P	98.52	68.51	1277
HSA-MIR-1910-3P	98.44	67.51	1695

Literature-anchored findings (GeneRIF, showing 3)

• This work suggests that the transcriptional activity of all members of the Meis/Prep Hth protein family is subject to autoinhibition by their Hth domains, and that the Meis3.2 splice variant encodes a protein that bypasses this autoinhibitory effect. (PMID:20553494)
• Findings support a model in which Meis3 is required for neural crest proliferation, migration into, and colonization of the gut such that its loss leads to severe defects in enteric nervous system development. (PMID:26354419)
• Inhibition of MEIS3 Generates Cetuximab Resistance through c-Met and Akt. (PMID:33376716)

Cross-species orthologs

10 orthologs

Organism	Symbol	Gene ID
danio_rerio	meis3	ENSDARG00000002795
mus_musculus	Meis3	ENSMUSG00000041420
rattus_norvegicus	Meis3	ENSRNOG00000021390
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): PBX4 (ENSG00000105717), TGIF2 (ENSG00000118707), MEIS2 (ENSG00000134138), MEIS1 (ENSG00000143995), TGIF2LX (ENSG00000153779), PKNOX1 (ENSG00000160199), PKNOX2 (ENSG00000165495), PBX3 (ENSG00000167081), TGIF2LY (ENSG00000176679), TGIF1 (ENSG00000177426), PBX1 (ENSG00000185630), MEIS3P2 (ENSG00000188013), PBX2 (ENSG00000204304)

Protein

Protein identifiers

Homeobox protein Meis3 — Q99687 (reviewed: Q99687)

Alternative names: Meis1-related protein 2

All UniProt accessions (8): Q99687, H0YLL0, H0YMV2, H0YNA8, H3BLU4, Q59FK5, U3KQJ9, U3KQV2

UniProt curated annotations — full annotation on UniProt →

Function. Transcriptional regulator which directly modulates PDPK1 expression, thus promoting survival of pancreatic beta-cells. Also regulates expression of NDFIP1, BNIP3, and CCNG1.

Subcellular location. Nucleus.

Similarity. Belongs to the TALE/MEIS homeobox family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q99687-1	1	yes
Q99687-2	2
Q99687-3	3

RefSeq proteins (4): NP_001009813, NP_001287988, NP_001333077, NP_064545 (=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 (18 total): sequence conflict 8, region of interest 3, compositionally biased region 2, splice variant 2, chain 1, domain 1, DNA-binding region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q99687-F1	66.18	0.26

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 90 (showing top): GOBP_ANIMAL_ORGAN_MORPHOGENESIS, GOBP_EMBRYONIC_PATTERN_SPECIFICATION, GOBP_BLOOD_VESSEL_MORPHOGENESIS, GOBP_HEAD_DEVELOPMENT, GOBP_EMBRYO_DEVELOPMENT, GOBP_SENSORY_ORGAN_DEVELOPMENT, RIZ_ERYTHROID_DIFFERENTIATION_APOBEC2, GOBP_CIRCULATORY_SYSTEM_DEVELOPMENT, GOBP_TUBE_MORPHOGENESIS, GOMF_SEQUENCE_SPECIFIC_DNA_BINDING, GOBP_POSITIVE_REGULATION_OF_CELL_POPULATION_PROLIFERATION, GOBP_POSITIVE_REGULATION_OF_TRANSCRIPTION_BY_RNA_POLYMERASE_II, GOBP_SENSORY_SYSTEM_DEVELOPMENT, LIM_MAMMARY_LUMINAL_MATURE_UP, GOMF_DNA_BINDING_TRANSCRIPTION_ACTIVATOR_ACTIVITY

GO Biological Process (9): angiogenesis (GO:0001525), eye development (GO:0001654), brain development (GO:0007420), positive regulation of cell population proliferation (GO:0008284), embryonic pattern specification (GO:0009880), animal organ morphogenesis (GO:0009887), hemopoiesis (GO:0030097), positive regulation of transcription by RNA polymerase II (GO:0045944), regulation of DNA-templated transcription (GO:0006355)

GO Molecular Function (6): DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), DNA-binding transcription activator activity, RNA polymerase II-specific (GO:0001228), sequence-specific DNA binding (GO:0043565), sequence-specific double-stranded DNA binding (GO:1990837), DNA binding (GO:0003677), protein binding (GO:0005515)

GO Cellular Component (2): chromatin (GO:0000785), nucleus (GO:0005634)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
animal organ development	2
regulation of transcription by RNA polymerase II	2
RNA polymerase II transcription regulatory region sequence-specific DNA binding	2
blood vessel morphogenesis	1
anatomical structure formation involved in morphogenesis	1
sensory organ development	1
visual system development	1
central nervous system development	1
head development	1
cell population proliferation	1
regulation of cell population proliferation	1
positive regulation of cellular process	1
pattern specification process	1
embryo development	1
anatomical structure morphogenesis	1
cell development	1
transcription by RNA polymerase II	1
positive regulation of DNA-templated transcription	1
DNA-templated transcription	1
regulation of gene expression	1
regulation of RNA biosynthetic process	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
DNA binding	1
double-stranded DNA binding	1
sequence-specific DNA binding	1
nucleic acid binding	1
binding	1
chromosome	1
cellular anatomical structure	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

676 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MEIS3	PBX4	Q9BYU1	822
MEIS3	PBX2	P40425	646
MEIS3	PBX3	P40426	596
MEIS3	PBX1	P40424	510
MEIS3	MYBBP1A	Q9BQG0	480
MEIS3	FOXD3	Q9UJU5	452
MEIS3	ZNF676	Q8N7Q3	443
MEIS3	METTL21C	Q5VZV1	437
MEIS3	ALG1L2	C9J202	416
MEIS3	KLF4	P78338	414
MEIS3	HOXB1	P14653	406
MEIS3	FOXL1	Q12952	395
MEIS3	AK1	P00568	353
MEIS3	ALG1	Q9BT22	353
MEIS3	CD96	P40200	353
MEIS3	ADRA1B	P35368	353

IntAct

4 interactions, top by confidence:

A	B	Type	Score
PBX4	MEIS1	psi-mi:“MI:0914”(association)	0.350
TRAF3IP1	MEIS3	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (28): MEIS3 (Affinity Capture-MS), MEIS3 (Affinity Capture-MS), MEIS3 (Affinity Capture-RNA), MEIS3 (Affinity Capture-RNA), MEIS3 (Two-hybrid), MEIS3 (Two-hybrid), MEIS3 (Two-hybrid), LENG1 (Two-hybrid), PRPF31 (Two-hybrid), ENKD1 (Two-hybrid), FAM110A (Two-hybrid), VEZF1 (Two-hybrid), SUOX (Two-hybrid), INTS4 (Two-hybrid), PIP4K2A (Two-hybrid)

ESM2 similar proteins: A0A5N6H279, A6NDR6, A8K0S8, M0R5D6, O15062, P06499, P09015, P09019, P0DH66, P14837, P17481, P29169, P52729, P52730, P70284, P97368, Q02780, Q08820, Q1HKZ5, Q1KKV3, Q28G02, Q3TEL6, Q4ZHW1, Q5R6P2, Q66H65, Q6IR52, Q6PKN7, Q7T1K4, Q7ZY13, Q804R0, Q8BIA3, Q8IYA7, Q8JH55, Q90655, Q90YI8, Q90ZH7, Q90ZH8, Q91848, Q949U2, Q98924

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

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	79
Likely benign	4
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

1725 predictions. Top by Δscore:

Variant	Effect	Δscore
19:47406448:AGAC:A	donor_gain	1.0000
19:47407150:CA:C	acceptor_gain	1.0000
19:47407347:CTCA:C	donor_loss	1.0000
19:47407348:TCACC:T	donor_loss	1.0000
19:47407349:CACC:C	donor_loss	1.0000
19:47407350:A:AC	donor_gain	1.0000
19:47407350:ACCAG:A	donor_loss	1.0000
19:47407351:C:CC	donor_gain	1.0000
19:47409094:CTCAC:C	donor_loss	1.0000
19:47409097:A:AC	donor_gain	1.0000
19:47409098:C:CC	donor_gain	1.0000
19:47409098:C:CG	donor_loss	1.0000
19:47409245:CTC:C	acceptor_gain	1.0000
19:47409247:CCTG:C	acceptor_loss	1.0000
19:47409248:C:CC	acceptor_gain	1.0000
19:47409248:CTGA:C	acceptor_loss	1.0000
19:47409249:T:G	acceptor_loss	1.0000
19:47409543:TTATT:T	acceptor_gain	1.0000
19:47409544:TATT:T	acceptor_gain	1.0000
19:47409545:ATT:A	acceptor_gain	1.0000
19:47409545:ATTC:A	acceptor_loss	1.0000
19:47409546:TT:T	acceptor_gain	1.0000
19:47409547:TCTAG:T	acceptor_loss	1.0000
19:47409548:C:CC	acceptor_gain	1.0000
19:47409548:CTAGA:C	acceptor_loss	1.0000
19:47416799:CCCA:C	donor_loss	1.0000
19:47416800:CCACC:C	donor_loss	1.0000
19:47416801:CAC:C	donor_loss	1.0000
19:47416802:A:AT	donor_loss	1.0000
19:47416803:C:CG	donor_loss	1.0000

AlphaMissense

2460 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:47407111:A:T	V321E	1.000
19:47407114:A:C	I320S	1.000
19:47407114:A:G	I320T	1.000
19:47407114:A:T	I320N	1.000
19:47407117:C:G	R319P	1.000
19:47407118:G:A	R319C	1.000
19:47407118:G:C	R319G	1.000
19:47407118:G:T	R319S	1.000
19:47407119:T:A	R318S	1.000
19:47407119:T:G	R318S	1.000
19:47407120:C:A	R318I	1.000
19:47407120:C:G	R318T	1.000
19:47407121:T:C	R318G	1.000
19:47407124:G:C	R317G	1.000
19:47407126:G:T	A316D	1.000
19:47407127:C:G	A316P	1.000
19:47407128:G:C	N315K	1.000
19:47407128:G:T	N315K	1.000
19:47407129:T:A	N315I	1.000
19:47407129:T:G	N315T	1.000
19:47407130:T:C	N315D	1.000
19:47407132:A:C	I314S	1.000
19:47407132:A:G	I314T	1.000
19:47407132:A:T	I314N	1.000
19:47407134:G:C	F313L	1.000
19:47407134:G:T	F313L	1.000
19:47407135:A:C	F313C	1.000
19:47407135:A:G	F313S	1.000
19:47407136:A:C	F313V	1.000
19:47407136:A:G	F313L	1.000

dbSNP variants (sampled 300 via entrez): RS1000020503 (19:47409726 G>A), RS1000087745 (19:47403890 C>T), RS1000559046 (19:47405770 G>A,C), RS1000980476 (19:47420720 C>A,T), RS1001068292 (19:47420891 C>T), RS1001142758 (19:47416552 G>A,T), RS1001384240 (19:47408991 C>G,T), RS1001633682 (19:47418772 G>A), RS1001705094 (19:47414484 C>A,T), RS1001728574 (19:47418972 A>G), RS1001844293 (19:47423194 C>T), RS1001917032 (19:47404425 C>T), RS1001983247 (19:47403281 G>A), RS1002164999 (19:47414140 C>T), RS1002251183 (19:47410095 T>C)

Disease associations

OMIM: gene MIM:619443 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

24 total (human), top 24 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases methylation	2
bisphenol A	affects cotreatment, increases expression	1
deoxynivalenol	decreases expression, decreases response to substance	1
beta-lapachone	increases expression	1
sodium arsenite	affects cotreatment, decreases expression, increases abundance, increases expression	1
benzo(e)pyrene	decreases methylation	1
aflatoxin B2	decreases methylation	1
2-methyl-2H-pyrazole-3-carboxylic acid (2-methyl-4-o-tolylazophenyl)amide	affects cotreatment, increases expression	1
bisphenol S	increases methylation	1
Arsenic	increases abundance, increases expression, affects cotreatment, decreases expression	1
Dexamethasone	affects cotreatment, increases expression	1
Doxorubicin	decreases expression	1
Estradiol	affects cotreatment, increases expression	1
Gallic Acid	increases expression	1
Indomethacin	affects cotreatment, increases expression	1
Methapyrilene	decreases methylation	1
Niclosamide	increases expression	1
Silicon Dioxide	decreases expression	1
Smoke	decreases expression	1
Tetrachlorodibenzodioxin	increases expression, decreases expression, affects cotreatment	1
Triclosan	increases expression	1
1-Methyl-3-isobutylxanthine	affects cotreatment, increases expression	1
Aflatoxin B1	decreases methylation	1
Acrylamide	decreases expression	1

Clinical trials (associated diseases)

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