EOMES

Summary

EOMES (eomesodermin, HGNC:3372) is a protein-coding gene on chromosome 3p24.1, encoding Eomesodermin homolog (O95936). Functions as a transcriptional activator playing a crucial role during development.

This gene belongs to the TBR1 (T-box brain protein 1) sub-family of T-box genes that share the common DNA-binding T-box domain. The encoded protein is a transcription factor which is crucial for embryonic development of mesoderm and the central nervous system in vertebrates. The protein may also be necessary for the differentiation of effector CD8+ T cells which are involved in defense against viral infections. A similar gene disrupted in mice is shown to be essential during trophoblast development and gastrulation. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 8320 — RefSeq curated summary.

At a glance

• Gene–disease (curated): microcephaly-polymicrogyria-corpus callosum agenesis syndrome (Supportive, GenCC) — +1 more curated relationship
• GWAS associations: 29
• Clinical variants (ClinVar): 115 total
• Phenotypes (HPO): 7
• Transcription factor: yes — 28 downstream targets (CollecTRI)
• MANE Select transcript: NM_001278182

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3372
Approved symbol	EOMES
Name	eomesodermin
Location	3p24.1
Locus type	gene with protein product
Status	Approved
Aliases	TBR2
Ensembl gene	ENSG00000163508
Ensembl biotype	protein_coding
OMIM	604615
Entrez	8320

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 3 protein_coding

ENST00000295743, ENST00000449599, ENST00000461503

RefSeq mRNA: 3 — MANE Select: NM_001278182 NM_001278182, NM_001278183, NM_005442

CCDS: CCDS2646, CCDS63584, CCDS63585

Canonical transcript exons

ENST00000449599 — 6 exons

Exon	Start	End
ENSE00003988546	27718587	27718648
ENSE00003988547	27719360	27719481
ENSE00003988548	27718735	27718893
ENSE00003988550	27715953	27717808
ENSE00003988551	27721414	27722323
ENSE00003988554	27720171	27720325

Expression profiles

Bgee: expression breadth ubiquitous, 162 present calls, max score 98.70.

FANTOM5 (CAGE): breadth broad, TPM avg 3.4002 / max 281.4745, expressed in 372 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
41529	2.3250	325
41530	0.9311	117
41524	0.0805	32
41525	0.0635	29

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ganglionic eminence	UBERON:0004023	98.70	gold quality
embryo	UBERON:0000922	98.69	gold quality
ventricular zone	UBERON:0003053	94.79	gold quality
granulocyte	CL:0000094	90.94	gold quality
cerebellar vermis	UBERON:0004720	86.00	gold quality
cerebellum	UBERON:0002037	84.11	gold quality
cerebellar cortex	UBERON:0002129	83.72	gold quality
cerebellar hemisphere	UBERON:0002245	83.58	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	83.53	gold quality
right hemisphere of cerebellum	UBERON:0014890	82.87	gold quality
lymph node	UBERON:0000029	81.59	gold quality
blood	UBERON:0000178	81.08	gold quality
spleen	UBERON:0002106	79.59	gold quality
pancreatic ductal cell	CL:0002079	78.75	silver quality
epithelium of nasopharynx	UBERON:0001951	76.43	gold quality
nasopharynx	UBERON:0001728	76.42	gold quality
superficial temporal artery	UBERON:0001614	74.57	gold quality
ileal mucosa	UBERON:0000331	72.45	gold quality
buccal mucosa cell	CL:0002336	71.71	gold quality
epithelial cell of pancreas	CL:0000083	71.25	gold quality
vermiform appendix	UBERON:0001154	70.76	gold quality
endothelial cell	CL:0000115	69.61	silver quality
tibialis anterior	UBERON:0001385	68.19	silver quality
caecum	UBERON:0001153	67.90	gold quality
palpebral conjunctiva	UBERON:0001812	67.74	gold quality
thymus	UBERON:0002370	66.73	gold quality
cortical plate	UBERON:0005343	66.34	gold quality
trabecular bone tissue	UBERON:0002483	65.71	silver quality
parietal pleura	UBERON:0002400	65.67	gold quality
gall bladder	UBERON:0002110	65.05	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-10485	yes	529.93
E-MTAB-8894	yes	434.35
E-HCAD-5	yes	427.09
E-MTAB-7008	yes	353.26
E-GEOD-75140	yes	322.36
E-CURD-122	yes	44.90
E-ANND-3	yes	9.34
E-CURD-112	yes	4.55

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

28 targets.

Target	Regulation
ALKBH1
CCL3
CD8A
CTNND1
CYFIP1
DKK1
DPPA4
EBF1	Repression
ELAVL2
IFNG	Unknown
IL17A	Activation
IL2
IL21
IL2RB
IL5
INHBA
KAT5
KDM6B
LEFTY2
NES
NOTCH1
PAX6	Repression
PRF1
SUPT7L
TBATA
TH
THY1
TPM1

JASPAR motifs

Motif	Name	Family
MA0800.1	EOMES	TBrain-related factors
MA0800.2	EOMES	TBrain-related factors

JASPAR matrix evidence (PMIDs): PMID:12093383

Upstream regulators (CollecTRI, top): FOXA2, MYCN, NEUROG2, NOTO, PAX6, POU4F2, POU5F1, RUNX3, STAT5A, TBR1, TBX21, TP53

miRNA regulators (miRDB)

65 targeting EOMES, 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-4533	100.00	69.48	2758
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-548C-3P	99.99	74.01	7587
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-25-3P	99.98	74.60	1817
HSA-MIR-32-5P	99.98	75.21	1964
HSA-MIR-363-3P	99.98	74.72	1821
HSA-MIR-367-3P	99.98	74.83	1819
HSA-MIR-92A-3P	99.98	75.21	1960
HSA-MIR-92B-3P	99.98	75.25	1955
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-3605-5P	99.96	67.12	932
HSA-MIR-493-5P	99.96	72.47	2382
HSA-MIR-96-5P	99.95	72.80	2140
HSA-LET-7C-3P	99.95	73.42	2862
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-338-5P	99.92	72.34	2951
HSA-MIR-12133	99.92	71.82	2006
HSA-MIR-450B-5P	99.92	71.48	3175
HSA-MIR-5680	99.91	69.83	3421
HSA-MIR-1271-5P	99.91	71.99	1972
HSA-MIR-498-3P	99.91	71.27	1114
HSA-MIR-605-3P	99.88	69.22	1833
HSA-MIR-182-5P	99.87	74.03	2589

Literature-anchored findings (GeneRIF, showing 40)

• Describes cloning of the human TBR2 gene and compares the human and mouse protein sequences. (PMID:10407135)
• A key transcription factor that links the long-term renewal of memory CD8+ T cells to their characteristic effector potency. (PMID:16273099)
• Breakpoint on chromosome 3 silences the eomesodermin transcript (EOMES) leading to malformative microcephaly syndromes. (PMID:17353897)
• Accessible chromatin-associated (histone 3 lysine 9) acetylation state serves as a cornerstone for differentially high expression of effector gene eomesodermin and its targets perforin 1 and granzyme B in memory CD8 T cells. (PMID:18523274)
• Conditional ablation of Tbr2 transgene in the developing murine forebrain results in loss of intermediate (basal) progenitor cells and their differentiated progeny in the mutant cortex. (PMID:18940588)
• regulates effector CD8+ T cell differentiation into long-term memory cells (PMID:19269192)
• T-bet and Eomes are important transcription factors for the regulation of IFN-gamma production in CD4(+) and CD8(+) T cells. (PMID:20056084)
• CD300a(+) human Th1 cells tend to be polyfunctional and after stimulation up-regulate Eomes. (PMID:20498708)
• ymphoproliferation caused by Fas deficiency is dependent on the transcription factor eomesodermin. (PMID:21076068)
• transcription factors control the expression of EOMESODERMIN (EOMES), which marks the onset of endoderm specification and EOMES interacts with SMAD2/3 to initiate the transcriptional network governing endoderm formation (PMID:21245162)
• Chronic HIV infection affects the expression of the 2 transcription factors required for CD8 T-cell differentiation into cytolytic effectors. (PMID:22490682)
• Methylation levels of EOMES, HOXA9, POU4F2, TWIST1, VIM, and ZNF154 in urine specimens are promising diagnostic biomarkers for bladder cancer recurrence surveillance (PMID:23056278)
• these results provide the evidence that transcription factors CDX2 and EOMES may play critical roles in human induced trophoblast progenitor cell generation. (PMID:23313847)
• T-bet and Eomes are likely regulated at the level of subcellular localization, potentially via different mechanisms. (PMID:23455505)
• a novel pathway by which TIP60 and ThPOK synergistically suppresses Eomes function and IFNgamma production, which could contribute to the regulation of inflammation. (PMID:23609452)
• CD127 is downregulated at a transcriptional level in memory CD8 T cells in association with upregulation of Eomes expression in HIV infected patients. (PMID:23965471)
• The autoimmune disease-associated transcription factors EOMES and TBX21 are dysregulated in multiple sclerosis and define a molecular subtype of disease. (PMID:24495857)
• HHEX promotes hepatic specification by repressing EOMES expression. (PMID:24651531)
• This study supports the concept that poor human viral-specific CD8(+) T cell functionality is due to an inverse expression balance between T-bet and Eomes (PMID:25032686)
• Report a global loss of 5hmC identified three new genes (ECM1, ATF5, and EOMES) with potential anti-cancer functions that may promote the understanding of the molecular mechanisms of hepatocellular carcinoma development and progression. (PMID:25517360)
• This study showed that EOMES (rs2724509; flanking) associated with Alzheimer disease. (PMID:25649652)
• Eomes(+) CD4(+) T cells are increased in the peripheral blood and cerebrospinal fluid from patients in a progressive state of multiple sclerosis. (PMID:26436530)
• the level of T-bet and Eomesodermin, two T-box transcription factors regulating lymphocyte effector functions, is strongly reduced in NK cells from allogeneic hematopoietic stem cell transplantation recipients compared with healthy control subjects. (PMID:26438526)
• we identified a higher Eomes mRNA expression as an independent good prognostic factor for OS and PFS in mRCC patients treated with sorafenib. (PMID:26753694)
• EOMES expression was low in multiple sclerosis (MS), and stable over time. The low EOMES/TBX21 phenotype in MS reflects cd56+ cell dysregulation. (PMID:26762769)
• Reciprocal regulation of BMF and BIRC5 is linked to Eomes overexpression in colorectal cancer. (PMID:27539959)
• Eomes(hi) NK cells can be recruited from the circulation during adult life and that circulating Eomes(lo) NK cells are able to upregulate Eomes and molecules mediating liver retention under cytokine conditions similar to those in the liver. (PMID:27798170)
• The single-cell pattern of Eomes and T-bet expression during ontogeny, however, revealed a stereotyped pattern of reciprocal dominance, with immature NK cells expressing higher amounts of Eomes and more mature NK cells marked by greater abundance of T-bet (PMID:28289707)
• Studies suggest there are two nonoverlapping NK cell populations that are potentially liver resident in humans: CD49a+ NK cells and Eomes hi. (PMID:28318877)
• our exploratory study suggests that EOMES, BCL6 and GZMB gene expression are aberrant within the PB T cell transcriptome of HT patients. The association of this transcription signature with the heterogeneity of HT and disease control is suggested. (PMID:29319368)
• EOMES specifically activates a cardiogenic program in human embryonic stem cells. (PMID:29382828)
• Eomesodermin (EOMES) was increased in T cells from healthy donors homozygous for the PTPN22 risk allele and correlated with a decreased number of naive CD4(+) T cells. An accumulation of EOMES(+) CD4(+) T cells was observed in synovial fluid of RA patients. (PMID:29388193)
• The authors propose that NK cells are defined by coexpression of T-bet and Eomes, while ILC1s express only one of these factors, either T-bet or Eomes, depending on the tissue or the species. (PMID:29424438)
• This study enhances the knowledge that the variant of EOMES is associated with increasing risk in Chinese RRMS patients and provides a potential therapeutic target in RRMS. (PMID:29521285)
• Eomes expression associates to a highly inflammatory phenotype also in patients with juvenile idiopathic arthritis (PMID:30144030)
• this study shows that an elevated incidence of donor-stimulated CD8+T cells co-expressing high levels of Eomes and T-bet before kidney transplantation, may correlate with an increased incidence of acute cellular rejection (PMID:30246373)
• this study shows that eomesodermin controls a unique differentiation program in human IL-10 and IFN-gamma coproducing regulatory T cells (PMID:30431161)
• Intermediate progenitors and Tbr2 in cortical development. (PMID:30677129)
• findings reveal that a high frequency of Eomes(+)T-bet(low) CD8(+) T cells predicts poor clinical outcome in acute myeloid leukemia (AML) and that targeting Eomes may provide a therapeutic benefit against AML (PMID:30709927)
• Metformin Enhances the Antitumor Activity of CD8(+) T Lymphocytes via the AMPK-miR-107-Eomes-PD-1 Pathway. (PMID:32221038)

Cross-species orthologs

15 orthologs

Organism	Symbol	Gene ID
danio_rerio	eomesa	ENSDARG00000006640
danio_rerio	eomesb	ENSDARG00000104243
mus_musculus	Eomes	ENSMUSG00000032446
rattus_norvegicus	Eomes	ENSRNOG00000042140
drosophila_melanogaster	H15	FBGN0016660
drosophila_melanogaster	mid	FBGN0261963
drosophila_melanogaster	ocm	FBGN0266083
caenorhabditis_elegans		WBGENE00003106
caenorhabditis_elegans		WBGENE00004750
caenorhabditis_elegans		WBGENE00006545
caenorhabditis_elegans		WBGENE00006546
caenorhabditis_elegans		WBGENE00006556
caenorhabditis_elegans		WBGENE00006557
caenorhabditis_elegans		WBGENE00006559
caenorhabditis_elegans		WBGENE00044798

Paralogs (16): TBX21 (ENSG00000073861), TBX5 (ENSG00000089225), TBX15 (ENSG00000092607), TBX18 (ENSG00000112837), TBX2 (ENSG00000121068), TBX4 (ENSG00000121075), TBX22 (ENSG00000122145), TBX3 (ENSG00000135111), TBR1 (ENSG00000136535), TBX19 (ENSG00000143178), TBX6 (ENSG00000149922), TBXT (ENSG00000164458), TBX20 (ENSG00000164532), TBX10 (ENSG00000167800), MGA (ENSG00000174197), TBX1 (ENSG00000184058)

Protein

Protein identifiers

Eomesodermin homolog — O95936 (reviewed: O95936)

Alternative names: T-box brain protein 2

All UniProt accessions (1): O95936

UniProt curated annotations — full annotation on UniProt →

Function. Functions as a transcriptional activator playing a crucial role during development. Functions in trophoblast differentiation and later in gastrulation, regulating both mesoderm delamination and endoderm specification. Plays a role in brain development being required for the specification and the proliferation of the intermediate progenitor cells and their progeny in the cerebral cortex. Required for differentiation and migration of unipolar dendritic brush cells. Also involved in the differentiation of CD8+ T-cells during immune response regulating the expression of lytic effector genes.

Subcellular location. Nucleus.

Tissue specificity. Expressed in CD8+ T-cells.

Disease relevance. A translocation t(3;10)(p24;q23) located 215 kb 3’ to the EOMES gene but leading to loss of its expression was identified in a large consanguineous family. Homozygous silencing produces microcephaly associated with corpus callosum agenesis, bilateral polymicrogyria, ventricular dilatation and a small cerebellum.

Induction. Up-regulated in CD8+ T-cells simultaneously stimulated with TGFB1 and IL4/interleukin-4.

Miscellaneous. Dubious isoform produced through aberrant splice sites.

Isoforms (4)

UniProt ID	Names	Canonical?
O95936-1	1	yes
O95936-2	2
O95936-3	3
O95936-4	4

RefSeq proteins (3): NP_001265111, NP_001265112, NP_005433 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001699	TF_T-box	Family
IPR008967	p53-like_TF_DNA-bd_sf	Homologous_superfamily
IPR018186	TF_T-box_CS	Conserved_site
IPR032385	T-box_assoc	Domain
IPR036960	T-box_sf	Homologous_superfamily
IPR046360	T-box_DNA-bd	Domain

Pfam: PF00907, PF16176

UniProt features (24 total): sequence conflict 10, splice variant 3, region of interest 3, compositionally biased region 3, sequence variant 2, chain 1, DNA-binding region 1, modified residue 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O95936-F1	56.74	0.25

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 (1): 107

Function

Pathways and Gene Ontology

Reactome pathways

6 pathways

ID	Pathway
R-HSA-9733709	Cardiogenesis
R-HSA-9754189	Germ layer formation at gastrulation
R-HSA-9758919	Epithelial-Mesenchymal Transition (EMT) during gastrulation
R-HSA-9823730	Formation of definitive endoderm
R-HSA-9827857	Specification of primordial germ cells
R-HSA-2892245	POU5F1 (OCT4), SOX2, NANOG repress genes related to differentiation

MSigDB gene sets: 343 (showing top): GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, GOBP_MUSCLE_TISSUE_DEVELOPMENT, BENPORATH_ES_WITH_H3K27ME3, GOBP_FORMATION_OF_PRIMARY_GERM_LAYER, GOBP_T_CELL_ACTIVATION_INVOLVED_IN_IMMUNE_RESPONSE, GOLDRATH_IMMUNE_MEMORY, GOBP_ALPHA_BETA_T_CELL_DIFFERENTIATION, GOBP_NEUROGENESIS, GOBP_BLASTOCYST_FORMATION, CAGCTG_AP4_Q5, GOBP_FOREBRAIN_DEVELOPMENT, SHEPARD_BMYB_MORPHOLINO_DN, GOBP_FOREBRAIN_REGIONALIZATION, GOBP_FOREBRAIN_GENERATION_OF_NEURONS, GOBP_CELL_DIFFERENTIATION_INVOLVED_IN_EMBRYONIC_PLACENTA_DEVELOPMENT

GO Biological Process (35): negative regulation of transcription by RNA polymerase II (GO:0000122), endoderm formation (GO:0001706), mesoderm formation (GO:0001707), endodermal cell fate specification (GO:0001714), neuron migration (GO:0001764), trophectodermal cell differentiation (GO:0001829), adaptive immune response (GO:0002250), CD8-positive, alpha-beta T cell differentiation involved in immune response (GO:0002302), chromatin remodeling (GO:0006338), regulation of transcription by RNA polymerase II (GO:0006357), brain development (GO:0007420), cardioblast differentiation (GO:0010002), gene expression (GO:0010467), stem cell population maintenance (GO:0019827), olfactory bulb development (GO:0021772), cerebral cortex regionalization (GO:0021796), cerebral cortex neuron differentiation (GO:0021895), skeletal muscle cell differentiation (GO:0035914), positive regulation of DNA-templated transcription (GO:0045893), positive regulation of transcription by RNA polymerase II (GO:0045944), mesendoderm development (GO:0048382), astrocyte differentiation (GO:0048708), cell differentiation involved in embryonic placenta development (GO:0060706), mesodermal to mesenchymal transition involved in gastrulation (GO:0060809), blastocyst development (GO:0001824), immune system process (GO:0002376), regulation of DNA-templated transcription (GO:0006355), gastrulation (GO:0007369), endoderm development (GO:0007492), anatomical structure morphogenesis (GO:0009653), regulation of gene expression (GO:0010468), cerebral cortex development (GO:0021987), neurogenesis (GO:0022008), cell differentiation (GO:0030154), neuron differentiation (GO:0030182)

GO Molecular Function (12): 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 (GO:0003677), transcription corepressor activity (GO:0003714), chromatin DNA binding (GO:0031490), sequence-specific DNA binding (GO:0043565), RNA polymerase II-specific DNA-binding transcription factor binding (GO:0061629), sequence-specific double-stranded DNA binding (GO:1990837), RNA polymerase II transcription regulatory region sequence-specific DNA binding (GO:0000977), chromatin binding (GO:0003682), DNA-binding transcription factor activity (GO:0003700), protein binding (GO:0005515)

GO Cellular Component (3): chromatin (GO:0000785), nucleus (GO:0005634), nucleoplasm (GO:0005654)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
Gastrulation	3
Developmental Biology	1
Reproduction	1
Transcriptional regulation of pluripotent stem cells	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
regulation of transcription by RNA polymerase II	3
transcription by RNA polymerase II	3
regulation of DNA-templated transcription	3
negative regulation of DNA-templated transcription	2
formation of primary germ layer	2
cell differentiation	2
immune response	2
RNA polymerase II transcription regulatory region sequence-specific DNA binding	2
DNA binding	2
transcription cis-regulatory region binding	2
binding	2
cellular anatomical structure	2
endoderm development	1
mesoderm morphogenesis	1
cell fate specification	1
endodermal cell fate commitment	1
cell migration	1
generation of neurons	1
blastocyst formation	1
alpha-beta T cell activation involved in immune response	1
T cell differentiation involved in immune response	1
CD8-positive, alpha-beta T cell differentiation	1
chromatin organization	1
central nervous system development	1
animal organ development	1
head development	1
cardiocyte differentiation	1
stem cell differentiation	1
macromolecule biosynthetic process	1
multicellular organismal process	1
maintenance of cell number	1
olfactory lobe development	1
anatomical structure development	1
regionalization	1
telencephalon regionalization	1
cerebral cortex development	1
forebrain neuron differentiation	1
skeletal muscle tissue development	1
DNA-templated transcription	1
positive regulation of RNA biosynthetic process	1

Protein interactions and networks

STRING

2748 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
EOMES	CD8A	P01732	843
EOMES	SMAD2	Q15796	820
EOMES	GATA3	P23771	818
EOMES	PAX6	P26367	803
EOMES	CDX2	Q99626	791
EOMES	KLRG1	Q96E93	781
EOMES	CUX1	P39880	781
EOMES	MIXL1	Q9H2W2	775
EOMES	GZMB	P10144	771
EOMES	WDR62	O43379	762
EOMES	NCAM1	P13591	752
EOMES	NFIL3	Q16649	749
EOMES	ELF5	Q9UKW6	747
EOMES	SOX17	Q9H6I2	746
EOMES	GATA4	P43694	745

IntAct

4 interactions, top by confidence:

A	B	Type	Score
EOMES	PFDN1	psi-mi:“MI:0915”(physical association)	0.370
EOMES	sgrR	psi-mi:“MI:0915”(physical association)	0.000
	EOMES	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (5): OTP (Two-hybrid), EOMES (Proximity Label-MS), EOMES (Proximity Label-MS), EOMES (Proximity Label-MS), EOMES (Two-hybrid)

ESM2 similar proteins: A2AHG0, A5D962, A5PK23, A7XYH9, A7XYI6, A7XYQ1, E9Q1P8, O14529, O15169, O35615, O75081, O95402, O95936, P60622, P70298, Q0P5V2, Q14135, Q15742, Q1LV17, Q2MJS2, Q5EIC4, Q61127, Q66IY8, Q6DIH5, Q6NZT6, Q6PCG7, Q7T2G1, Q7T3H2, Q7Z5L9, Q7ZXS3, Q80V24, Q863A2, Q8C3Q5, Q8IU81, Q8IXK0, Q8K1Q4, Q8K3X4, Q8R3Y8, Q96NU1, Q96PX6

Diamond homologs: A1YF56, A2AWL7, D3ZJK7, E1BEA8, O01409, O13161, O15119, O15178, O17212, O43435, O54839, O60806, O70306, O73718, O75333, O95935, O95936, O95947, P20293, P24781, P55965, P56158, P57082, P70323, P70324, P70325, P70326, P70327, P79742, P79777, P79778, P79779, P79944, P80492, P87377, P90971, Q07998, Q13207, Q16650, Q17134

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
POU5F1	“down-regulates quantity by repression”	EOMES	“transcriptional regulation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	90
Likely benign	15
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

717 predictions. Top by Δscore:

Variant	Effect	Δscore
3:27717805:CATG:C	acceptor_gain	1.0000
3:27717809:C:CC	acceptor_gain	1.0000
3:27718585:A:AC	donor_gain	1.0000
3:27718586:C:CT	donor_gain	1.0000
3:27718586:CGA:C	donor_gain	1.0000
3:27718586:CGAA:C	donor_gain	1.0000
3:27718586:CGAAT:C	donor_gain	1.0000
3:27718733:A:AC	donor_gain	1.0000
3:27718733:ACAT:A	donor_gain	1.0000
3:27718734:C:CC	donor_gain	1.0000
3:27718734:CA:C	donor_gain	1.0000
3:27718734:CAT:C	donor_gain	1.0000
3:27718734:CATC:C	donor_gain	1.0000
3:27718734:CATCG:C	donor_gain	1.0000
3:27718891:CAT:C	acceptor_gain	1.0000
3:27718894:C:CC	acceptor_gain	1.0000
3:27720169:AC:A	donor_gain	1.0000
3:27720170:CC:C	donor_gain	1.0000
3:27720170:CCCTG:C	donor_gain	1.0000
3:27717763:C:CT	acceptor_gain	0.9900
3:27717807:TG:T	acceptor_gain	0.9900
3:27718500:T:TA	donor_gain	0.9900
3:27718525:G:A	donor_gain	0.9900
3:27718578:TGCAC:T	donor_loss	0.9900
3:27718579:GCACT:G	donor_loss	0.9900
3:27718580:CACT:C	donor_loss	0.9900
3:27718581:ACTTA:A	donor_loss	0.9900
3:27718582:CTTAC:C	donor_loss	0.9900
3:27718583:TTA:T	donor_loss	0.9900
3:27718584:TACG:T	donor_loss	0.9900

AlphaMissense

4571 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:27718599:T:A	D456V	1.000
3:27718600:C:G	D456H	1.000
3:27718601:T:A	R455S	1.000
3:27718601:T:G	R455S	1.000
3:27718602:C:A	R455I	1.000
3:27718602:C:G	R455T	1.000
3:27718603:T:C	R455G	1.000
3:27718604:G:C	F454L	1.000
3:27718604:G:T	F454L	1.000
3:27718605:A:C	F454C	1.000
3:27718605:A:G	F454S	1.000
3:27718606:A:C	F454V	1.000
3:27718606:A:G	F454L	1.000
3:27718606:A:T	F454I	1.000
3:27718608:C:A	G453V	1.000
3:27718608:C:T	G453D	1.000
3:27718609:C:A	G453C	1.000
3:27718609:C:G	G453R	1.000
3:27718609:C:T	G453S	1.000
3:27718610:T:A	K452N	1.000
3:27718610:T:G	K452N	1.000
3:27718611:T:A	K452I	1.000
3:27718611:T:G	K452T	1.000
3:27718612:T:C	K452E	1.000
3:27718612:T:G	K452Q	1.000
3:27718614:G:A	A451V	1.000
3:27718614:G:T	A451E	1.000
3:27718615:C:G	A451P	1.000
3:27718615:C:T	A451T	1.000
3:27718616:A:C	F450L	1.000

dbSNP variants (sampled 300 via entrez): RS1000824129 (3:27719048 C>G), RS1001625550 (3:27716920 T>G), RS1001937519 (3:27719014 T>A), RS1002833728 (3:27722435 G>C,T), RS1003681652 (3:27720647 CT>C), RS1003946566 (3:27718278 G>A), RS1003947676 (3:27723482 TTTATTCCCCACAA>T), RS1004060565 (3:27724686 G>C), RS1004968665 (3:27718121 G>C), RS1005754358 (3:27721131 C>CTA), RS1006193458 (3:27716889 G>A), RS1006356658 (3:27723648 G>A), RS1006409182 (3:27723322 G>T), RS1006698767 (3:27716499 A>G), RS1006814393 (3:27715608 A>G)

Disease associations

OMIM: gene MIM:604615 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
microcephaly-polymicrogyria-corpus callosum agenesis syndrome	Supportive	Autosomal recessive
microcephaly	Limited	Autosomal recessive

Mondo (2): microcephaly-polymicrogyria-corpus callosum agenesis syndrome (MONDO:0015745), microcephaly (MONDO:0001149)

Orphanet (1): Microcephaly-polymicrogyria-corpus callosum agenesis syndrome (Orphanet:171703)

HPO phenotypes

7 total (7 of 7 shown, HPO-id order):

HPO	Term
HP:0001274	Agenesis of corpus callosum
HP:0001321	Cerebellar hypoplasia
HP:0002098	Respiratory distress
HP:0002119	Ventriculomegaly
HP:0002126	Polymicrogyria
HP:0002719	Recurrent infections
HP:0011451	Primary microcephaly

GWAS associations

29 associations (top):

Study	Trait	p-value
GCST001198_18	Multiple sclerosis	1.000000e-09
GCST001341_15	Multiple sclerosis	2.000000e-08
GCST002237_5	Hodgkin’s lymphoma	1.000000e-12
GCST002318_123	Rheumatoid arthritis	9.000000e-09
GCST002318_73	Rheumatoid arthritis	3.000000e-08
GCST003340_2	Epstein Barr virus nuclear antigen 1 IgG levels or multiple sclerosis	4.000000e-09
GCST003468_20	Chronic lymphocytic leukemia	3.000000e-11
GCST003622_23	Systemic lupus erythematosus	5.000000e-06
GCST004099_2	B-cell malignancies (chronic lymphocytic leukemia, Hodgkin lymphoma or multiple myeloma) (pleiotropy)	7.000000e-09
GCST004146_6	Chronic lymphocytic leukemia	2.000000e-09
GCST005529_66	Ankylosing spondylitis	1.000000e-07
GCST005529_9	Ankylosing spondylitis	9.000000e-08
GCST005531_108	Multiple sclerosis	2.000000e-15
GCST005979_10	Systolic blood pressure	1.000000e-12
GCST006009_14	Pulse pressure	5.000000e-11
GCST006010_23	Mean arterial pressure	6.000000e-09
GCST006048_33	Rheumatoid arthritis (ACPA-positive)	3.000000e-08
GCST006959_102	Rheumatoid arthritis	5.000000e-08
GCST006959_33	Rheumatoid arthritis	6.000000e-08
GCST006976_48	Macular thickness	7.000000e-14
GCST007045_20	PR interval	2.000000e-08
GCST007094_82	Diastolic blood pressure	7.000000e-09
GCST009597_137	Multiple sclerosis	2.000000e-16
GCST009597_290	Multiple sclerosis	2.000000e-49
GCST009597_61	Multiple sclerosis	9.000000e-08
GCST012251_13	Macular telangiectasia type 2	2.000000e-07
GCST012252_4	Macular telangiectasia type 2	6.000000e-09
GCST90002388_188	Lymphocyte count	2.000000e-30
GCST90002407_43	White blood cell count	7.000000e-20

EFO canonical traits (8, from GWAS)

EFO ID	Trait name
EFO:0007790	Epstein Barr virus nuclear antigen 1 IgG measurement
EFO:0006335	systolic blood pressure
EFO:0005763	pulse pressure measurement
EFO:0006340	mean arterial pressure
EFO:0004462	PR interval
EFO:0006336	diastolic blood pressure
EFO:1002009	macular telangiectasia type 2
EFO:0004587	lymphocyte count

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D008831	Microcephaly	C05.660.207.620; C10.500.507.400.500; C16.131.621.207.620; C16.131.666.507.400.500

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs2371108	EOMES		0.00	0

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases expression, affects expression	3
methylmercuric chloride	increases expression	2
Nickel	decreases expression, increases expression	2
FR900359	increases phosphorylation	1
triphenyl phosphate	affects expression	1
propionaldehyde	increases expression	1
arsenite	increases methylation	1
sodium arsenite	affects methylation	1
butyraldehyde	increases expression	1
ferrous chloride	decreases expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression, affects cotreatment, decreases expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
nutlin 3	affects cotreatment, increases expression	1
abrine	increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
(+)-JQ1 compound	decreases expression	1
Temozolomide	increases expression	1
Acetaminophen	decreases expression	1
Air Pollutants, Occupational	decreases expression	1
Arsenicals	increases methylation	1
Benzo(a)pyrene	decreases methylation, increases methylation	1
Cadmium	decreases expression	1
Calcitriol	increases expression	1
Camptothecin	increases expression	1
Carbamazepine	affects expression	1
Cisplatin	increases expression	1
Dactinomycin	increases expression, affects cotreatment	1
Demecolcine	decreases expression	1

Cellosaurus cell lines

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

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

Cellosaurus	Name	Category	Sex
CVCL_A1J8	SEES3-1V human EOMES, clone1	Embryonic stem cell	Male
CVCL_A1J9	SEES3-1V human EOMES, clone2	Embryonic stem cell	Male
CVCL_A1K0	SEES3-1V human EOMES, clone3	Embryonic stem cell	Male
CVCL_B8FA	Abcam HCT 116 EOMES KO	Cancer cell line	Male
CVCL_B9HI	Abcam A-549 EOMES KO	Cancer cell line	Male
CVCL_D2F2	Abcam MCF-7 EOMES KO	Cancer cell line	Female
CVCL_F1N5	HyCyte BT-549 KO-hEOMES	Cancer cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT05518188	PHASE1/PHASE2	RECRUITING	Melpida: Recombinant Adeno-associated Virus (serotype 9) Encoding a Codon Optimized Human AP4M1 Transgene (hAP4M1opt)
NCT00001639	Not specified	COMPLETED	Evaluation of Patients With Unresolved Chromosome Abnormalities
NCT01151462	Not specified	WITHDRAWN	Postnatal HCMV Infection in Very Preterm Infants. Implications, Morbidity, Growth and Neurodevelopmental Outcomes.
NCT01565005	Not specified	COMPLETED	Microcephaly Genetic Deficiency in Neural Progenitors
NCT02510170	Not specified	COMPLETED	Fetal and Maternal Head Circumference During Pregnancy in Israeli Population
NCT02741882	Not specified	COMPLETED	Zika and Microcephaly: Case-control Study
NCT02943304	Not specified	COMPLETED	Neurodevelopment Outcome of Newborns Exposed to Zika Virus (ZIKV) in Utero
NCT03255369	Not specified	UNKNOWN	Vertical Exposure to Zika Virus and Its Consequences for Child Neurodevelopment (ZIKVIRUSIFF)
NCT03325946	Not specified	RECRUITING	The FBRI VTC Neuromotor Research Clinic
NCT03330600	Not specified	COMPLETED	Efficacy of Aquatic Physiotherapy in Children With Microcephaly by Zika Virus Congenital Syndrome
NCT03548779	Not specified	COMPLETED	North Carolina Genomic Evaluation by Next-generation Exome Sequencing, 2
NCT03651687	Not specified	COMPLETED	Guangzhou Surveillance and Clinical Study in Microcephaly (GSCSM)
NCT03922594	Not specified	TERMINATED	Surveillance of Zika-related Microcephaly in Sub-Saharan Africa and Asia
NCT04816175	Not specified	COMPLETED	Intensive Therapy for Children With Microcephaly, Hyperkinetic Movements, or Global Developmental Delay
NCT05322980	Not specified	COMPLETED	Summary of Infants Weighing 500 Grams or Less
NCT06019182	Not specified	RECRUITING	MEHMO Natural History and Biomarkers
NCT06566066	Not specified	RECRUITING	Register for Patients With Thyroid Hormone Resistance.