EBF2
protein-codingEBF transcription factor 2, the group of Early B-cell factors|IPT domain containing
Gene summary
The protein encoded by this gene belongs to the COE (Collier/Olf/EBF) family of non-basic, helix-loop-helix transcription factors that have a well conserved DNA binding domain. The COE family proteins play an important role in variety of developmental processes. Studies in mouse suggest that this gene may be involved in the differentiation of osteoblasts. [provided by RefSeq, Oct 2011]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~203.7 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:0019938
Submitter: LiferaOmics
Genetic evidence – Published: PMID: 29704291 reports a heterozygous variant in EBF2 associated with anorectal malformation in an autosomal dominant (AD) model. Because the reported mode of inheritance is AD and differs from the AR model under current curation, this case is considered supportive context only and is not scored toward the AR gene–disease relationship. Published genetic evidence total (AR model) = 0/12 Genetic evidence – our case: Case-level (biallelic predicted null in AR model; homozygous scored once; −0.5 consanguinity deduction applied) = 1.0 Segregation (carrier parents; unaffected heterozygous sibling; limited informative meioses) = 0.5 Case-control = 0 Our case contribution = 1.5/12 Total genetic evidence (published AR + our case) = 1.5/12 Experimental evidence – Published (AR-focused only) No published functional studies, animal models, or mechanistic data specifically linking EBF2 to anorectal malformation are currently available. Experimental evidence total = 0/6 Overall score = 1.5
Inheritance Pattern: AD
Disease ID:MONDO:0005151
Submitter: Broad Center for Mendelian Genomics
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to EBF2 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_022659.4. 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 | 2 | 1 | 3 | |||
| missense | 65 | 65 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 1 | 1 | ||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 0 | 69 | 0 | 1 | 70 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_073150.2 | 16 | MANE Select | |
| Ensembl | ENSP00000430241.1 | 16 | MANE Select | |
| Ensembl | ENSP00000386178.3 | 12 | Standard | |
| Ensembl | ENSP00000386178.3 | 12 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Biological Process
- cell fate determination
- positive regulation of chromatin binding
- positive regulation of transcription by RNA polymerase II
- brown fat cell differentiation
- adipose tissue development
Molecular Function
- RNA polymerase II proximal promoter sequence-specific DNA binding
- DNA-binding transcription factor activity, RNA polymerase II-specific
- chromatin binding
- metal ion binding
- protein dimerization activity
Cellular Component
- nucleus
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000520164
- Coding exons
- 16
- Length
- 203668
- Individuals with no LoFs
- 124893
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 3
- Defined
- 124896
- p
- 0.0000120
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 2.11 | 221 | 329 | 0.672 | 0.0000168 | 3747 |
| Missense (PolyPhen) | 87 | 162.32 | 0.53599 | 1851 | ||
| Synonymous | -0.435 | 136 | 130 | 1.05 | 0.00000736 | 1120 |
| Loss of Function | 4.97 | 2 | 32.6 | 0.0613 | 0.00000162 | 377 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.000046 | 0.000029 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000018 | 0.000018 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Transcription factor that, in osteoblasts, activates the decoy receptor for RANKL, TNFRSF11B, which in turn regulates osteoclast differentiation. Acts in synergy with the Wnt- responsive LEF1/CTNNB1 pathway. Recognizes variations of the palindromic sequence 5'-ATTCCCNNGGGAATT-3' (By similarity). {ECO:0000250}.;
Intolerance Scores
- LoFtool
- 0.332
- RVIS EVS
- -0.62
- RVIS percentile EVS
- 17.16
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.682
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |