EBF3early B-cell factor 3
Autism Reports / Total Reports
4 / 9Rare Variants / Common Variants
30 / 0Aliases
EBF3, COE3, EBF-3, HADDS, O/E-2, OE-2Associated Syndromes
-Genetic Category
Rare Single Gene Mutation, SyndromicChromosome Band
10q26.3Associated Disorders
DD/NDD, ASD, IDRelevance to Autism
Heterozygous mutations in the EBF3 gene are associated with hypotonia, ataxia, and delayed development syndrome (HADDS; OMIM 617330), a neurodevelopmental syndrome characterized by congenital hypotonia, delayed psychomotor development, variable intellectual disability with speech delay, variable dysmorphic facial features, and ataxia, often associated with cerebellar hypoplasia (Sleven et al., 2017; Chao et al., 2017; Harms et al., 2017; Blackburn et al., 2017); individuals in Chao et al., 2017 were reported as presenting with perseverative social behaviors and motor stereotypies. Tanaka et al., 2017 described seven novel individuals with de novo EBF3 mutations; two of these individuals presented with autism, two individuals presented with autistic features, and two individuals presented with delayed or absent social smile.
Molecular Function
This gene encodes a member of the early B-cell factor (EBF) family of DNA binding transcription factors. EBF proteins are involved in B-cell differentiation, bone development and neurogenesis, and may also function as tumor suppressors. The encoded protein inhibits cell survival through the regulation of genes involved in cell cycle arrest and apoptosis, and aberrant methylation or deletion of this gene may play a role in multiple malignancies including glioblastoma multiforme and gastric carcinoma.
External Links
Reports related to EBF3 (9 Reports)
# | Type | Title | Author, Year | Autism Report | Associated Disorders |
---|---|---|---|---|---|
1 | Support | The contribution of de novo coding mutations to autism spectrum disorder | Iossifov I et al. (2014) | Yes | - |
2 | Support | De Novo Mutations in EBF3 Cause a Neurodevelopmental Syndrome. | Sleven H , et al. (2016) | No | - |
3 | Support | A Syndromic Neurodevelopmental Disorder Caused by De Novo Variants in EBF3. | Chao HT , et al. (2016) | No | - |
4 | Support | Mutations in EBF3 Disturb Transcriptional Profiles and Cause Intellectual Disability, Ataxia, and Facial Dysmorphism. | Harms FL , et al. (2016) | No | - |
5 | Support | Novel de novo variant in EBF3 is likely to impact DNA binding in a patient with a neurodevelopmental disorder and expanded phenotypes: patient repo... | Blackburn PR , et al. (2017) | No | - |
6 | Support | Whole Gene Deletion of EBF3 Supporting Haploinsufficiency of This Gene as a Mechanism of Neurodevelopmental Disease. | Lopes F , et al. (2017) | Yes | DD, ID |
7 | Primary | De novo variants in EBF3 are associated with hypotonia, developmental delay, intellectual disability, and autism. | Tanaka AJ , et al. (2017) | No | Autism or autistic features |
8 | Support | Large-Scale Exome Sequencing Study Implicates Both Developmental and Functional Changes in the Neurobiology of Autism | Satterstrom FK et al. (2020) | Yes | - |
9 | Support | Rare genetic susceptibility variants assessment in autism spectrum disorder: detection rate and practical use. | Husson T , et al. (2020) | Yes | - |
Rare Variants (30)
Status | Allele Change | Residue Change | Variant Type | Inheritance Pattern | Parental Transmission | Family Type | PubMed ID | Author, Year |
---|---|---|---|---|---|---|---|---|
- | - | copy_number_loss | De novo | NA | Simplex | 29062322 | Lopes F , et al. (2017) | |
c.907C>T | p.Arg303Ter | stop_gained | De novo | NA | - | 28017373 | Harms FL , et al. (2016) | |
c.913C>T | p.Gln305Ter | stop_gained | De novo | NA | - | 28017373 | Harms FL , et al. (2016) | |
c.1101+1G>T | - | splice_site_variant | De novo | NA | - | 28017373 | Harms FL , et al. (2016) | |
c.486-1G>A | - | splice_site_variant | De novo | NA | - | 29162653 | Tanaka AJ , et al. (2017) | |
c.-19G>C | - | missense_variant | De novo | NA | Simplex | 28017370 | Sleven H , et al. (2016) | |
c.616C>T | p.Arg206Ter | stop_gained | De novo | NA | - | 29162653 | Tanaka AJ , et al. (2017) | |
c.196A>G | p.Asn66Asp | missense_variant | De novo | NA | - | 28017373 | Harms FL , et al. (2016) | |
c.422A>G | p.Tyr141Cys | missense_variant | De novo | NA | - | 28017373 | Harms FL , et al. (2016) | |
c.512G>A | p.Gly171Asp | missense_variant | De novo | NA | - | 28017373 | Harms FL , et al. (2016) | |
c.530C>T | p.Pro177Leu | missense_variant | De novo | NA | - | 28017373 | Harms FL , et al. (2016) | |
c.191A>C | p.Lys64Thr | missense_variant | De novo | NA | - | 29162653 | Tanaka AJ , et al. (2017) | |
c.232C>T | p.Gln78Ter | stop_gained | De novo | NA | Simplex | 32094338 | Husson T , et al. (2020) | |
c.355+1G>C | - | splice_site_variant | De novo | NA | Simplex | 28017370 | Sleven H , et al. (2016) | |
c.471C>A | p.His157Gln | missense_variant | De novo | NA | - | 29162653 | Tanaka AJ , et al. (2017) | |
c.626G>A | p.Arg209Gln | missense_variant | De novo | NA | - | 29162653 | Tanaka AJ , et al. (2017) | |
c.-38_-37insCTTTCGGCC | - | inframe_insertion | De novo | NA | - | 28017373 | Harms FL , et al. (2016) | |
c.-227_-224del | - | frameshift_variant | De novo | NA | Simplex | 28017370 | Sleven H , et al. (2016) | |
c.487C>T | p.Arg163Trp | missense_variant | De novo | NA | - | 28487885 | Blackburn PR , et al. (2017) | |
c.488G>A | p.Arg163Gln | missense_variant | De novo | NA | Simplex | 28017372 | Chao HT , et al. (2016) | |
c.488G>T | p.Arg163Leu | missense_variant | De novo | NA | Simplex | 28017372 | Chao HT , et al. (2016) | |
c.530C>T | p.Pro177Leu | missense_variant | De novo | NA | Simplex | 28017370 | Sleven H , et al. (2016) | |
c.579G>T | p.Lys193Asn | missense_variant | De novo | NA | Simplex | 28017370 | Sleven H , et al. (2016) | |
c.49G>A | p.Glu17Lys | splice_site_variant | De novo | NA | Simplex | 28017370 | Sleven H , et al. (2016) | |
c.244del | p.Val82TrpfsTer50 | frameshift_variant | De novo | NA | - | 29162653 | Tanaka AJ , et al. (2017) | |
c.1496G>C | p.Gly499Ala | missense_variant | De novo | NA | Simplex | 25363768 | Iossifov I et al. (2014) | |
c.840dup | p.Asp281Ter | frameshift_variant | De novo | NA | Simplex | 31981491 | Satterstrom FK et al. (2020) | |
c.625C>T | p.Arg209Trp | missense_variant | Familial | Maternal | Multiplex | 28017373 | Harms FL , et al. (2016) | |
c.1402_1414del | p.Thr468ProfsTer10 | frameshift_variant | De novo | NA | - | 29162653 | Tanaka AJ , et al. (2017) | |
c.616C>T | p.Arg206Ter | stop_gained | De novo (possible germline mosaicism) | - | Multiplex | 28017370 | Sleven H , et al. (2016) |
Common Variants
No common variants reported.
SFARI Gene score
High Confidence


Heterozygous mutations in the EBF3 gene are associated with hypotonia, ataxia, and delayed development syndrome (HADDS; OMIM 617330), a neurodevelopmental syndrome characterized by congenital hypotonia, delayed psychomotor development, variable intellectual disability with speech delay, variable dysmorphic facial features, and ataxia, often associated with cerebellar hypoplasia (Sleven et al., 2017; Chao et al., 2017; Harms et al., 2017; Blackburn et al., 2017); individuals in Chao et al., 2017 were reported as presenting with perseverative social behaviors and motor stereotypies. Tanaka et al., 2017 described seven novel individuals with de novo EBF3 mutations; two of these individuals presented with autism, two individuals presented with autistic features, and two individuals presented with delayed or absent social smile. A de novo missense variant in the EBF3 gene was identified in an ASD proband from the Simons Simplex Collection in Iossifov et al., 2014; while this variant was novel (not present in dbSNP or ESP), it was predicted by PolyPhen-2 to be benign in Sanders et al., 2015.
Score Delta: Score remained at S
criteria met
See SFARI Gene'scoring criteriaWe considered a rigorous statistical comparison between cases and controls, yielding genome-wide statistical significance, with independent replication, to be the strongest possible evidence for a gene. These criteria were relaxed slightly for category 2.
1/1/2020

Score remained at S
Description
Heterozygous mutations in the EBF3 gene are associated with hypotonia, ataxia, and delayed development syndrome (HADDS; OMIM 617330), a neurodevelopmental syndrome characterized by congenital hypotonia, delayed psychomotor development, variable intellectual disability with speech delay, variable dysmorphic facial features, and ataxia, often associated with cerebellar hypoplasia (Sleven et al., 2017; Chao et al., 2017; Harms et al., 2017; Blackburn et al., 2017); individuals in Chao et al., 2017 were reported as presenting with perseverative social behaviors and motor stereotypies. Tanaka et al., 2017 described seven novel individuals with de novo EBF3 mutations; two of these individuals presented with autism, two individuals presented with autistic features, and two individuals presented with delayed or absent social smile. A de novo missense variant in the EBF3 gene was identified in an ASD proband from the Simons Simplex Collection in Iossifov et al., 2014; while this variant was novel (not present in dbSNP or ESP), it was predicted by PolyPhen-2 to be benign in Sanders et al., 2015.
10/1/2019

Increased from S to 1
New Scoring Scheme
Description
Heterozygous mutations in the EBF3 gene are associated with hypotonia, ataxia, and delayed development syndrome (HADDS; OMIM 617330), a neurodevelopmental syndrome characterized by congenital hypotonia, delayed psychomotor development, variable intellectual disability with speech delay, variable dysmorphic facial features, and ataxia, often associated with cerebellar hypoplasia (Sleven et al., 2017; Chao et al., 2017; Harms et al., 2017; Blackburn et al., 2017); individuals in Chao et al., 2017 were reported as presenting with perseverative social behaviors and motor stereotypies. Tanaka et al., 2017 described seven novel individuals with de novo EBF3 mutations; two of these individuals presented with autism, two individuals presented with autistic features, and two individuals presented with delayed or absent social smile. A de novo missense variant in the EBF3 gene was identified in an ASD proband from the Simons Simplex Collection in Iossifov et al., 2014; while this variant was novel (not present in dbSNP or ESP), it was predicted by PolyPhen-2 to be benign in Sanders et al., 2015.
Reports Added
[New Scoring Scheme]Krishnan Probability Score
Score 0.53132184844142
Ranking 1539/25841 scored genes
[Show Scoring Methodology]
ExAC Score
Score 0.99859001376164
Ranking 1157/18225 scored genes
[Show Scoring Methodology]
Sanders TADA Score
Score 0.94010716308957
Ranking 14448/18665 scored genes
[Show Scoring Methodology]
Zhang D Score
Score -0.35346458549528
Ranking 17858/20870 scored genes
[Show Scoring Methodology]