EN2engrailed homolog 2
Autism Reports / Total Reports
13 / 27Rare Variants / Common Variants
4 / 8Aliases
EN2, AUTS1, engrailed 2, engrailed-2Associated Syndromes
-Chromosome Band
7q36.3Associated Disorders
-Relevance to Autism
Several studies have found genetic association between the EN2 gene and autism. In particular, studies have found associations in the Chinese Han population as well as AGRE, NIMH and CPEA cohorts. However, another study found no genetic association between EN2 and autism in an AGRE cohort (Zhong et al., 2003).
Molecular Function
The encoded protein is a transcription factor.
External Links
SFARI Genomic Platforms
Reports related to EN2 (27 Reports)
# | Type | Title | Author, Year | Autism Report | Associated Disorders |
---|---|---|---|---|---|
1 | Negative Association | No association between the EN2 gene and autistic disorder | Zhong H , et al. (2003) | Yes | - |
2 | Primary | Association of the homeobox transcription factor, ENGRAILED 2, 3, with autism spectrum disorder | Gharani N , et al. (2004) | Yes | - |
3 | Positive Association | Support for the homeobox transcription factor gene ENGRAILED 2 as an autism spectrum disorder susceptibility locus | Benayed R , et al. (2005) | Yes | - |
4 | Recent Recommendation | The transcription factor Engrailed-2 guides retinal axons | Brunet I , et al. (2005) | No | - |
5 | Recent Recommendation | En2 knockout mice display neurobehavioral and neurochemical alterations relevant to autism spectrum disorder | Cheh MA , et al. (2006) | No | - |
6 | Recent Recommendation | Physical and functional association of a trimethyl H3K4 demethylase and Ring6a/MBLR, a polycomb-like protein | Lee MG , et al. (2007) | No | - |
7 | Positive Association | Heterogeneous association between engrailed-2 and autism in the CPEA network | Brune CW , et al. (2007) | Yes | - |
8 | Positive Association | Association of the ENGRAILED 2 (EN2) gene with autism in Chinese Han population | Wang L , et al. (2007) | Yes | - |
9 | Positive Association | Association of the homeobox transcription factor gene ENGRAILED 2 with autistic disorder in Chinese children | Yang P , et al. (2008) | Yes | - |
10 | Recent Recommendation | Engrailed-2 regulates genes related to vesicle formation and transport in cerebellar Purkinje cells | Holst MI , et al. (2008) | No | - |
11 | Negative Association | Association study of the CNS patterning genes and autism in Han Chinese in Taiwan | Chien YL , et al. (2011) | Yes | - |
12 | Support | Cut-like homeobox 1 and nuclear factor I/B mediate ENGRAILED2 autism spectrum disorder-associated haplotype function | Choi J , et al. (2011) | No | - |
13 | Negative Association | The association of rs4307059 and rs35678 markers with autism spectrum disorders is replicated in Italian families | Prandini P , et al. (2012) | Yes | - |
14 | Recent Recommendation | Engrailed2 modulates cerebellar granule neuron precursor proliferation, differentiation and insulin-like growth factor 1 signaling during postnatal development | Rossman IT , et al. (2014) | No | - |
15 | Support | Autism associated gene, engrailed2, and flanking gene levels are altered in post-mortem cerebellum | Choi J , et al. (2014) | No | - |
16 | Recent Recommendation | Elevated 5-hydroxymethylcytosine in the Engrailed-2 (EN-2) promoter is associated with increased gene expression and decreased MeCP2 binding in autism cerebellum | James SJ , et al. (2014) | No | - |
17 | Support | Large-scale discovery of novel genetic causes of developmental disorders | Deciphering Developmental Disorders Study (2014) | No | - |
18 | Support | Serotonin abnormalities in Engrailed-2 knockout mice: New insight relevant for a model of Autism Spectrum Disorder | Viaggi C , et al. (2015) | No | - |
19 | Support | Whole-exome sequencing identifies a novel heterozygous missense variant of the EN2 gene in two unrelated patients with autism spectrum disorder | Hnoonual A , et al. (2016) | Yes | - |
20 | Recent Recommendation | Increased signaling by the autism-related Engrailed-2 protein enhances dendritic branching and spine density, alters synaptic structural matching, and exaggerates protein synthesis | Soltani A , et al. (2017) | No | - |
21 | Highly Cited | Expression patterns of the homeo box-containing genes En-1 and En-2 and the proto-oncogene int-1 diverge during mouse development | Davis CA and Joyner AL (1988) | No | - |
22 | Recent Recommendation | Impaired Neuronal Differentiation of Neural Stem Cells Lacking the Engrailed-2 Gene | Boschian C , et al. (2018) | No | - |
23 | Support | - | Zhou J et al. (2019) | Yes | - |
24 | Recent Recommendation | - | Chen X et al. (2021) | Yes | - |
25 | Support | - | Giulia Lazzarini et al. (2024) | Yes | - |
26 | Support | - | Lorenzo Mattioni et al. (2024) | Yes | - |
27 | Highly Cited | Abnormal embryonic cerebellar development and patterning of postnatal foliation in two mouse Engrailed-2 mutants | Millen KJ , et al. (1994) | No | - |
Rare Variants (4)
Status | Allele Change | Residue Change | Variant Type | Inheritance Pattern | Parental Transmission | Family Type | PubMed ID | Author, Year |
---|---|---|---|---|---|---|---|---|
C>T | - | intergenic_variant | De novo | - | Simplex | 31133750 | Zhou J et al. (2019) | |
c.425C>G | p.Pro142Arg | missense_variant | Familial | Paternal | Simplex | 27755371 | Hnoonual A , et al. (2016) | |
c.425C>G | p.Pro142Arg | missense_variant | Familial | Maternal | Multiplex | 27755371 | Hnoonual A , et al. (2016) | |
c.996C>T | p.Ser332= | synonymous_variant | De novo | - | Unknown | 25533962 | Deciphering Developmental Disorders Study (2014) |
Common Variants (8)
Status | Allele Change | Residue Change | Variant Type | Inheritance Pattern | Paternal Transmission | Family Type | PubMed ID | Author, Year |
---|---|---|---|---|---|---|---|---|
c.686-921T>C | C/T | intron_variant | - | - | - | 18424904 | Yang P , et al. (2008) | |
c.686-1568C>T | A/G | intron_variant | - | - | - | 17948901 | Wang L , et al. (2007) | |
c.686-1073G>A | A/G | intron_variant | - | - | - | 18424904 | Yang P , et al. (2008) | |
c.686-1073G>A | A/G | intron_variant | - | - | - | 17948868 | Brune CW , et al. (2007) | |
c.686-921T>C | C/T | intron_variant | - | - | - | 16252243 | Benayed R , et al. (2005) | |
c.686-1073G>A | A/G | intron_variant | - | - | - | 16252243 | Benayed R , et al. (2005) | |
c.686-921T>C | C to T | intron_variant | - | - | - | 15024396 | Gharani N , et al. (2004) | |
c.686-1073G>A | A to G | intron_variant | - | - | - | 15024396 | Gharani N , et al. (2004) |
SFARI Gene score
Strong Candidate
![](https://gene.sfari.org//wp-content/themes/sfari-gene/img/color-band/2.png)
![](https://gene.sfari.org//wp-content/themes/sfari-gene/img/color-band/s-null.png)
EN2 is located in a linkage region with variable evidence for association with autism. For example, studies have found associations in the Chinese Han population as well as AGRE, NIMH and CPEA cohorts. However, another study found no genetic association between EN2 and autism in an AGRE cohort (Zhong et al., 2003).
Score Delta: Score remained at 2
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.
4/1/2022
![icon](https://gene.sfari.org//wp-content/themes/sfari-gene/img/score-down.png)
Decreased from 3 to 2
Description
EN2 is located in a linkage region with variable evidence for association with autism. For example, studies have found associations in the Chinese Han population as well as AGRE, NIMH and CPEA cohorts. However, another study found no genetic association between EN2 and autism in an AGRE cohort (Zhong et al., 2003).
10/1/2019
![icon](https://gene.sfari.org//wp-content/themes/sfari-gene/img/score-down.png)
Decreased from 4 to 3
New Scoring Scheme
Description
EN2 is located in a linkage region with variable evidence for association with autism. For example, studies have found associations in the Chinese Han population as well as AGRE, NIMH and CPEA cohorts. However, another study found no genetic association between EN2 and autism in an AGRE cohort (Zhong et al., 2003).
Reports Added
[New Scoring Scheme]10/1/2018
![icon](https://gene.sfari.org//wp-content/themes/sfari-gene/img/score-same.png)
Decreased from 4 to 4
Description
EN2 is located in a linkage region with variable evidence for association with autism. For example, studies have found associations in the Chinese Han population as well as AGRE, NIMH and CPEA cohorts. However, another study found no genetic association between EN2 and autism in an AGRE cohort (Zhong et al., 2003).
7/1/2018
![icon](https://gene.sfari.org//wp-content/themes/sfari-gene/img/score-same.png)
Decreased from 4 to 4
Description
EN2 is located in a linkage region with variable evidence for association with autism. For example, studies have found associations in the Chinese Han population as well as AGRE, NIMH and CPEA cohorts. However, another study found no genetic association between EN2 and autism in an AGRE cohort (Zhong et al., 2003).
7/1/2017
![icon](https://gene.sfari.org//wp-content/themes/sfari-gene/img/score-same.png)
Decreased from 4 to 4
Description
EN2 is located in a linkage region with variable evidence for association with autism. For example, studies have found associations in the Chinese Han population as well as AGRE, NIMH and CPEA cohorts. However, another study found no genetic association between EN2 and autism in an AGRE cohort (Zhong et al., 2003).
10/1/2016
![icon](https://gene.sfari.org//wp-content/themes/sfari-gene/img/score-same.png)
Decreased from 4 to 4
Description
EN2 is located in a linkage region with variable evidence for association with autism. For example, studies have found associations in the Chinese Han population as well as AGRE, NIMH and CPEA cohorts. However, another study found no genetic association between EN2 and autism in an AGRE cohort (Zhong et al., 2003).
1/1/2015
![icon](https://gene.sfari.org//wp-content/themes/sfari-gene/img/score-same.png)
Decreased from 4 to 4
Description
EN2 is located in a linkage region with variable evidence for association with autism. For example, studies have found associations in the Chinese Han population as well as AGRE, NIMH and CPEA cohorts. However, another study found no genetic association between EN2 and autism in an AGRE cohort (Zhong et al., 2003).
10/1/2014
![icon](https://gene.sfari.org//wp-content/themes/sfari-gene/img/score-same.png)
Decreased from 4 to 4
Description
EN2 is located in a linkage region with variable evidence for association with autism. For example, studies have found associations in the Chinese Han population as well as AGRE, NIMH and CPEA cohorts. However, another study found no genetic association between EN2 and autism in an AGRE cohort (Zhong et al., 2003).
7/1/2014
![icon](https://gene.sfari.org//wp-content/themes/sfari-gene/img/score-up.png)
Increased from No data to 4
Description
EN2 is located in a linkage region with variable evidence for association with autism. For example, studies have found associations in the Chinese Han population as well as AGRE, NIMH and CPEA cohorts. However, another study found no genetic association between EN2 and autism in an AGRE cohort (Zhong et al., 2003).
4/1/2014
![icon](https://gene.sfari.org//wp-content/themes/sfari-gene/img/score-up.png)
Increased from No data to 4
Description
EN2 is located in a linkage region with variable evidence for association with autism. For example, studies have found associations in the Chinese Han population as well as AGRE, NIMH and CPEA cohorts. However, another study found no genetic association between EN2 and autism in an AGRE cohort (Zhong et al., 2003).
Krishnan Probability Score
Score 0.56677281727376
Ranking 1204/25841 scored genes
[Show Scoring Methodology]
ExAC Score
Score 0.43310737895365
Ranking 5802/18225 scored genes
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Sanders TADA Score
Score 0.90504414661926
Ranking 6917/18665 scored genes
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Larsen Cumulative Evidence Score
Score 47.5
Ranking 34/461 scored genes
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Zhang D Score
Score -0.25487339216838
Ranking 16456/20870 scored genes
[Show Scoring Methodology]
External PIN Data
Interactome
- Protein Binding
- DNA Binding
- RNA Binding
- Protein Modification
- Direct Regulation
- ASD-Linked Genes
Interaction Table
Interactor Symbol | Interactor Name | Interactor Organism | Interactor Type | Entrez ID | Uniprot ID |
---|---|---|---|---|---|
Foxa2 | forkhead box A2 | Rat | Protein Binding | 25099 | P32182 |
MIR181A1 | microRNA 181a-1 | Human | RNA Binding | 406995 | N/A |
PAX2 | paired box 2 | Human | DNA Binding | 5076 | Q02962 |
PAX3 | paired box 3 | Human | Protein Binding | 5077 | P23760 |
PAX5 | paired box 5 | Human | DNA Binding | 5079 | Q02548 |
PAX8 | paired box 8 | Human | DNA Binding | 7849 | Q06710 |