EOMES
protein-codingeomesodermin, the group of T-box transcription factors
Gene summary
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. [provided by RefSeq, May 2013]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~6.8 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:0001149
Submitter: PanelApp Australia
Inheritance Pattern: AR
Disease ID:MONDO:0015745
Submitter: Orphanet
Inheritance Pattern: AR
Disease ID:MONDO:0015745
Submitter: G2P
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to EOMES variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001278182.2. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 1 | 17 | 1 | 19 | ||
| missense | 92 | 4 | 1 | 97 | ||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 93 | 21 | 2 | 116 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001265111.1 | 6 | MANE Select | |
| Ensembl | ENSP00000388620.1 | 6 | MANE Select | |
| RefSeq | NP_001265112.1 | 5 | Standard | |
| RefSeq | NP_005433.2 | 6 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| eomesa | Danio rerio | Structure: blastodisc Quality: crowded abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Endoderm Differentiation
- Mesodermal Commitment Pathway
- POU5F1 (OCT4), SOX2, NANOG repress genes related to differentiation
- Olfactory bulb development and olfactory learning
- Development and heterogeneity of the ILC family
Biological Process
- negative regulation of transcription by RNA polymerase II
- endoderm formation
- mesoderm formation
- endodermal cell fate specification
- trophectodermal cell differentiation
Molecular Function
- RNA polymerase II regulatory region sequence-specific DNA binding
- DNA-binding transcription factor activity, RNA polymerase II-specific
- RNA polymerase II activating transcription factor binding
- DNA binding
- chromatin binding
Cellular Component
- nuclear chromatin
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000295743
- Coding exons
- 6
- Length
- 6767
- Individuals with no LoFs
- 125699
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 49
- Defined
- 125748
- p
- 0.000195
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.861 | 303 | 348 | 0.870 | 0.0000177 | 4363 |
| Missense (PolyPhen) | 98 | 150.55 | 0.65094 | 1821 | ||
| Synonymous | -1.09 | 163 | 146 | 1.12 | 0.00000790 | 1427 |
| Loss of Function | 4.17 | 3 | 25.9 | 0.116 | 0.00000141 | 289 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.000087 | 0.000087 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00011 | 0.00011 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.00033 | 0.00033 | rare |
| South Asian | 0.00016 | 0.00016 | rare |
| Other | 0.00016 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- Function
- 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. Also involved in the differentiation of CD8+ T-cells during immune response regulating the expression of lytic effector genes. {ECO:0000269|PubMed:17353897, ECO:0000269|PubMed:17566017}.;
- Disease
- DISEASE: Note=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.;
Recessive Scores
- pRec
- 0.330
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.633
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |