Human Gene Module / Chromosome 1 / EPHB2

EPHB2EPH receptor B2

SFARI Gene Score
2
Strong Candidate Criteria 2.1
Autism Reports / Total Reports
9 / 9
Rare Variants / Common Variants
58 / 0
Aliases
EPHB2, CAPB,  DRT,  EK5,  EPHT3,  ERK,  Hek5,  PCBC,  Tyro5
Associated Syndromes
-
Chromosome Band
1p36.12
Associated Disorders
-
Relevance to Autism

Two de novo variants (one nonsense, one missense) in the EPHB2 gene were identified in separate next-generation sequencing reports using ASD probands (Sanders et al., 2012; Kong et al., 2012).

Molecular Function

This gene encodes a member of the Eph receptor family of receptor tyrosine kinase transmembrane glycoproteins. These receptors are composed of an N-terminal glycosylated ligand-binding domain, a transmembrane region and an intracellular kinase domain. They bind ligands called ephrins and are involved in diverse cellular processes including motility, division, and differentiation. A distinguishing characteristic of Eph-ephrin signaling is that both receptors and ligands are competent to transduce a signaling cascade, resulting in bidirectional signaling. This protein belongs to a subgroup of the Eph receptors called EphB. Proteins of this subgroup are distinguished from other members of the family by sequence homology and preferential binding affinity for membrane-bound ephrin-B ligands.

External Links
Gene CardOpen Targets PlatformgnomAD browserSynGO portalPubMed
Human
Entrez GeneOMIMUniProtHumanBaseVariCarta
Mouse
Entrez GeneMouse Genome InformaticsAllen Brain Atlas
Fruit fly
Entrez Gene
SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to EPHB2 (9 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Primary De novo mutations revealed by whole-exome sequencing are strongly associated with autism Sanders SJ , et al. (2012) Yes -
2 Support Rate of de novo mutations and the importance of father's age to disease risk Kong A , et al. (2012) Yes -
3 Support De novo genic mutations among a Chinese autism spectrum disorder cohort Wang T , et al. (2016) Yes -
4 Support Inherited and multiple de novo mutations in autism/developmental delay risk genes suggest a multifactorial model Guo H , et al. (2018) Yes -
5 Support Large-scale targeted sequencing identifies risk genes for neurodevelopmental disorders Wang T et al. (2020) Yes -
6 Support - Alonso-Gonzalez A et al. (2021) Yes -
7 Support - Woodbury-Smith M et al. (2022) Yes -
8 Support - Zhou X et al. (2022) Yes -
9 Recent Recommendation - He LN et al. (2023) Yes -
Rare Variants   (58)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.1591+3369C>T - missense_variant Unknown - - 33004838 Wang T et al. (2020)
G>A p.Gly900Ser missense_variant De novo - - 22914163 Kong A , et al. (2012)
c.241C>T p.Arg81Cys missense_variant Unknown - - 33004838 Wang T et al. (2020)
c.880C>T p.Arg294Trp missense_variant Unknown - - 33004838 Wang T et al. (2020)
c.916C>T p.Arg306Cys missense_variant Unknown - - 33004838 Wang T et al. (2020)
c.595C>T p.Arg199Cys missense_variant De novo - - 35982159 Zhou X et al. (2022)
c.1552C>T p.Arg518Cys missense_variant Unknown - - 33004838 Wang T et al. (2020)
c.1702C>T p.Arg568Trp missense_variant Unknown - - 33004838 Wang T et al. (2020)
c.1715G>A p.Arg572His missense_variant Unknown - - 33004838 Wang T et al. (2020)
c.1828C>T p.Arg610Trp missense_variant Unknown - - 33004838 Wang T et al. (2020)
c.1850A>G p.Asp617Gly missense_variant Unknown - - 33004838 Wang T et al. (2020)
c.1882G>A p.Gly628Arg missense_variant Unknown - - 33004838 Wang T et al. (2020)
c.1924G>A p.Glu642Lys missense_variant Unknown - - 33004838 Wang T et al. (2020)
c.1994G>A p.Arg665Gln missense_variant Unknown - - 33004838 Wang T et al. (2020)
c.2017G>A p.Ala673Thr missense_variant Unknown - - 33004838 Wang T et al. (2020)
c.2065G>A p.Val689Met missense_variant Unknown - - 33004838 Wang T et al. (2020)
c.2098G>A p.Glu700Lys missense_variant Unknown - - 33004838 Wang T et al. (2020)
c.2117C>T p.Ser706Phe missense_variant Unknown - - 33004838 Wang T et al. (2020)
c.2134C>T p.Arg712Trp missense_variant Unknown - - 33004838 Wang T et al. (2020)
c.2170G>T p.Val724Leu missense_variant Unknown - - 33004838 Wang T et al. (2020)
c.2191G>A p.Ala731Thr missense_variant Unknown - - 33004838 Wang T et al. (2020)
c.2240C>T p.Ser747Leu missense_variant Unknown - - 33004838 Wang T et al. (2020)
c.2356G>A p.Gly786Arg missense_variant Unknown - - 33004838 Wang T et al. (2020)
c.2402G>A p.Arg801Gln missense_variant Unknown - - 33004838 Wang T et al. (2020)
c.2408A>G p.Asp803Gly missense_variant Unknown - - 33004838 Wang T et al. (2020)
c.2414C>T p.Ser805Leu missense_variant Unknown - - 33004838 Wang T et al. (2020)
c.2531G>A p.Arg844Gln missense_variant Unknown - - 33004838 Wang T et al. (2020)
c.2582A>G p.Asp861Gly missense_variant Unknown - - 33004838 Wang T et al. (2020)
c.2599A>T p.Ile867Phe missense_variant Unknown - - 33004838 Wang T et al. (2020)
c.2600G>A p.Arg867His missense_variant Unknown - - 33004838 Wang T et al. (2020)
c.2609G>A p.Arg870Gln missense_variant Unknown - - 33004838 Wang T et al. (2020)
c.2654G>A p.Arg885His missense_variant Unknown - - 33004838 Wang T et al. (2020)
c.2723C>T p.Thr908Met missense_variant Unknown - - 33004838 Wang T et al. (2020)
c.2750C>T p.Thr917Met missense_variant Unknown - - 33004838 Wang T et al. (2020)
c.2773A>T p.Ile925Phe missense_variant Unknown - - 33004838 Wang T et al. (2020)
c.2864G>A p.Arg955Gln missense_variant Unknown - - 33004838 Wang T et al. (2020)
c.690G>A p.Ala230%3D synonymous_variant De novo - - 35982159 Zhou X et al. (2022)
c.2043C>T p.Asn681%3D synonymous_variant De novo - - 35982159 Zhou X et al. (2022)
c.254G>A p.Arg85His missense_variant Familial Maternal - 33004838 Wang T et al. (2020)
c.384del p.Asn129ThrfsTer8 frameshift_variant Unknown - - 33004838 Wang T et al. (2020)
c.2530C>G p.Arg844Gly missense_variant Unknown - Simplex 33004838 Wang T et al. (2020)
c.2653C>T p.Arg885Cys missense_variant Unknown - Simplex 33004838 Wang T et al. (2020)
c.2572C>T p.Gln858Ter stop_gained De novo - Simplex 22495306 Sanders SJ , et al. (2012)
c.438del p.Phe147SerfsTer11 frameshift_variant Unknown - - 33004838 Wang T et al. (2020)
c.2012C>G p.Ala671Gly missense_variant Familial Maternal - 33004838 Wang T et al. (2020)
c.2185C>T p.Arg729Trp missense_variant Familial Maternal - 33004838 Wang T et al. (2020)
c.2308C>T p.Arg770Cys missense_variant Familial Maternal - 33004838 Wang T et al. (2020)
c.3096dup p.Arg1033AlafsTer9 frameshift_variant Unknown - - 33004838 Wang T et al. (2020)
c.174G>A p.Thr58%3D synonymous_variant De novo - Multiplex 35982159 Zhou X et al. (2022)
c.3013C>T p.Arg1005Ter stop_gained Unknown Not maternal - 27824329 Wang T , et al. (2016)
c.668G>A p.Arg223Gln missense_variant Familial Paternal - 27824329 Wang T , et al. (2016)
c.2531G>A p.Arg844Gln missense_variant Familial Maternal - 27824329 Wang T , et al. (2016)
c.2731G>A p.Asp911Asn missense_variant Familial Paternal - 27824329 Wang T , et al. (2016)
c.2976G>A p.Arg992%3D synonymous_variant Unknown - - 35205252 Woodbury-Smith M et al. (2022)
c.2437G>A p.Gly813Ser missense_variant Unknown Not maternal - 27824329 Wang T , et al. (2016)
c.1058G>A p.Arg353Gln missense_variant Familial Maternal Simplex 30564305 Guo H , et al. (2018)
c.2405G>A p.Arg802Gln missense_variant Familial Paternal Simplex 30564305 Guo H , et al. (2018)
c.979G>C p.Ala327Pro missense_variant De novo - Simplex 33431980 Alonso-Gonzalez A et al. (2021)
Common Variants  

No common variants reported.

SFARI Gene score
2

Strong Candidate

Two de novo variants (one nonsense, one missense) in the EPHB2 gene were identified in separate next-generation sequencing reports using ASD probands (Sanders et al., 2012; Kong et al., 2012). Four damaging missense variants (CADD score > 30) that were not present in dbSNP were identified in probands from the Autism Clinical and Genetic Resources in China (ACGC) cohort in Wang et al., 2016; a nonsense variant of unknown origin that was reported in dbSNP was also identified in an ASD proband in this study.

Score Delta: Score remained at 2

criteria met
See SFARI Gene'scoring criteria
2

Strong Candidate

See all Category 2 Genes

We 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.

4/1/2022
3
icon
2

Decreased from 3 to 2

Description

Two de novo variants (one nonsense, one missense) in the EPHB2 gene were identified in separate next-generation sequencing reports using ASD probands (Sanders et al., 2012; Kong et al., 2012). Four damaging missense variants (CADD score > 30) that were not present in dbSNP were identified in probands from the Autism Clinical and Genetic Resources in China (ACGC) cohort in Wang et al., 2016; a nonsense variant of unknown origin that was reported in dbSNP was also identified in an ASD proband in this study.

1/1/2021
3
icon
3

Decreased from 3 to 3

Description

Two de novo variants (one nonsense, one missense) in the EPHB2 gene were identified in separate next-generation sequencing reports using ASD probands (Sanders et al., 2012; Kong et al., 2012). Four damaging missense variants (CADD score > 30) that were not present in dbSNP were identified in probands from the Autism Clinical and Genetic Resources in China (ACGC) cohort in Wang et al., 2016; a nonsense variant of unknown origin that was reported in dbSNP was also identified in an ASD proband in this study.

Reports Added
[Exploring the biological role of postzygotic and germinal de novo mutations in ASD2021]
10/1/2020
3
icon
3

Decreased from 3 to 3

Description

Two de novo variants (one nonsense, one missense) in the EPHB2 gene were identified in separate next-generation sequencing reports using ASD probands (Sanders et al., 2012; Kong et al., 2012). Four damaging missense variants (CADD score > 30) that were not present in dbSNP were identified in probands from the Autism Clinical and Genetic Resources in China (ACGC) cohort in Wang et al., 2016; a nonsense variant of unknown origin that was reported in dbSNP was also identified in an ASD proband in this study.

Reports Added
[Large-scale targeted sequencing identifies risk genes for neurodevelopmental disorders2020]
10/1/2019
4
icon
3

Decreased from 4 to 3

New Scoring Scheme
Description

Two de novo variants (one nonsense, one missense) in the EPHB2 gene were identified in separate next-generation sequencing reports using ASD probands (Sanders et al., 2012; Kong et al., 2012). Four damaging missense variants (CADD score > 30) that were not present in dbSNP were identified in probands from the Autism Clinical and Genetic Resources in China (ACGC) cohort in Wang et al., 2016; a nonsense variant of unknown origin that was reported in dbSNP was also identified in an ASD proband in this study.

Reports Added
[New Scoring Scheme]
1/1/2019
4
icon
4

Decreased from 4 to 4

Description

Two de novo variants (one nonsense, one missense) in the EPHB2 gene were identified in separate next-generation sequencing reports using ASD probands (Sanders et al., 2012; Kong et al., 2012). Four damaging missense variants (CADD score > 30) that were not present in dbSNP were identified in probands from the Autism Clinical and Genetic Resources in China (ACGC) cohort in Wang et al., 2016; a nonsense variant of unknown origin that was reported in dbSNP was also identified in an ASD proband in this study.

Reports Added
[Inherited and multiple de novo mutations in autism/developmental delay risk genes suggest a multifactorial model.2018]
7/1/2018
icon
4

Increased from to 4

Description

Two de novo variants (one nonsense, one missense) in the EPHB2 gene were identified in separate next-generation sequencing reports using ASD probands (Sanders et al., 2012; Kong et al., 2012). Four damaging missense variants (CADD score > 30) that were not present in dbSNP were identified in probands from the Autism Clinical and Genetic Resources in China (ACGC) cohort in Wang et al., 2016; a nonsense variant of unknown origin that was reported in dbSNP was also identified in an ASD proband in this study.

Krishnan Probability Score

Score 0.60789314363908

Ranking 298/25841 scored genes


[Show Scoring Methodology]
Krishnan and colleagues generated probability scores genome-wide by using a machine learning approach on a human brain-specific gene network. The method was first presented in Nat Neurosci 19, 1454-1462 (2016), and scores for more than 25,000 RefSeq genes can be accessed in column G of supplementary table 3 (see: http://www.nature.com/neuro/journal/v19/n11/extref/nn.4353-S5.xlsx). A searchable browser, with the ability to view networks of associated ASD risk genes, can be found at asd.princeton.edu.
Original Source
ExAC Score

Score 0.99994863523136

Ranking 588/18225 scored genes


[Show Scoring Methodology]
The Exome Aggregation Consortium (ExAC) is a summary database of 60,706 exomes that has been widely used to estimate 'constraint' on mutation for individual genes. It was introduced by Lek et al. Nature 536, 285-291 (2016), and the ExAC browser can be found at exac.broadinstitute.org. The pLI score was developed as measure of intolerance to loss-of- function mutation. A pLI > 0.9 is generally viewed as highly constrained, and thus any loss-of- function mutations in autism in such a gene would be more likely to confer risk. For a full list of pLI scores see: ftp://ftp.broadinstitute.org/pub/ExAC_release/release0.3.1/functional_gene_constraint/fordist_cle aned_exac_nonTCGA_z_pli_rec_null_data.txt
Original Source
Sanders TADA Score

Score 0.72292346645744

Ranking 1317/18665 scored genes


[Show Scoring Methodology]
The TADA score ('Transmission and De novo Association') was introduced by He et al. PLoS Genet 9(8):e1003671 (2013), and is a statistic that integrates evidence from both de novo and transmitted mutations. It forms the basis for the claim of 65 individual genes being strongly associated with autism risk at a false discovery rate of 0.1 (Sanders et al. Neuron 87, 1215-1233 (2015)). The calculated TADA score for 18,665 RefSeq genes can be found in column P of Supplementary Table 6 in the Sanders et al. paper (the column headed 'tadaFdrAscSscExomeSscAgpSmallDel'), which represents a combined analysis of exome data and small de novo deletions (see www.cell.com/cms/attachment/2038545319/2052606711/mmc7.xlsx).
Original Source
Larsen Cumulative Evidence Score

Score 10

Ranking 184/461 scored genes


[Show Scoring Methodology]
Larsen and colleagues generated gene scores based on the sum of evidence for all available ASD-associated variants in a gene, with assessments based on mode of inheritance, effect size, and variant frequency in the general population. The approach was first presented in Mol Autism 7:44 (2016), and scores for 461 genes can be found in column I in supplementary table 4 from that paper.
Original Source
Zhang D Score

Score 0.23853941854784

Ranking 3642/20870 scored genes


[Show Scoring Methodology]
The DAMAGES score (disease-associated mutation analysis using gene expression signatures), or D score, was developed to combine evidence from de novo loss-of- function mutation with evidence from cell-type- specific gene expression in the mouse brain (specifically translational profiles of 24 specific mouse CNS cell types isolated from 6 different brain regions). Genes with positive D scores are more likely to be associated with autism risk, with higher-confidence genes having higher D scores. This statistic was first presented by Zhang & Shen (Hum Mutat 38, 204- 215 (2017), and D scores for more than 20,000 RefSeq genes can be found in column M in supplementary table 2 from that paper.
Original Source
Submit New Gene

Report an Error