Human Gene Module / Chromosome 2 / ERMN

ERMNermin

Score
3
Suggestive Evidence Criteria 3.1
Autism Reports / Total Reports
1 / 1
Rare Variants / Common Variants
7 / 0
Aliases
ERMN, JN,  KIAA1189
Associated Syndromes
-
Genetic Category
Rare Single Gene Mutation
Chromosome Band
2q24.1
Associated Disorders
-
Relevance to Autism

Analysis of methylation changes in blood DNA from 53 male ASD patients and 757 healthy controls found that hypomethylation caused by rare genetic variants (meSNVs) at six loci significantly associated with ASD (q-value <0.05); among the meSNVs identified was a differentially methylated CpG (DMCpG) at the GALNT5-ERMN locus in two ASD cases, one of whom displayed ERMN overexpression (Homs et al., 2016). Resequencing of top candidate genes in additional ASD cases and reanalysis of 931 previously reported ASD exomes available from dbGAP identified a significant increase in the mutation load of ERMN in ASD cases compared to controls (P=0.046), which became more significant if population-specific variants were excluded (P=7.97E-05).

Molecular Function

The protein encoded by the ERMN gene plays a role in cytoskeletal rearrangements during the late wrapping and/or compaction phases of myelinogenesis as well as in maintenance and stability of myelin sheath in the adult. It may also play an important role in late-stage oligodendroglia maturation, myelin/Ranvier node formation during CNS development, and in the maintenance and plasticity of related structures in the mature CNS.

Reports related to ERMN (1 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Primary Genetic and epigenetic methylation defects and implication of the ERMN gene in autism spectrum disorders. Homs A , et al. (2016) Yes -
Rare Variants   (7)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.7+1G>T - splice_site_variant Unknown - - 27404287 Homs A , et al. (2016)
- - intergenic_variant Familial Maternal Simplex 27404287 Homs A , et al. (2016)
c.565G>A p.Asp189Asn missense_variant Unknown - - 27404287 Homs A , et al. (2016)
c.595A>C p.Ile199Leu missense_variant Unknown - - 27404287 Homs A , et al. (2016)
c.692A>G p.Glu231Gly missense_variant Unknown - - 27404287 Homs A , et al. (2016)
c.823T>G p.Ser275Ala missense_variant Unknown - - 27404287 Homs A , et al. (2016)
c.830G>A p.Arg277Gln missense_variant Unknown - - 27404287 Homs A , et al. (2016)
Common Variants  

No common variants reported.

SFARI Gene score
3

Suggestive Evidence

Analysis of methylation changes in blood DNA from 53 male ASD patients and 757 healthy controls found that hypomethylation caused by rare genetic variants (meSNVs) at six loci significantly associated with ASD (q-value <0.05); among the meSNVs identified was a differentially methylated CpG (DMCpG) at the GALNT5-ERMN locus in two ASD cases, one of whom displayed ERMN overexpression (Homs et al., 2016). Resequencing of top candidate genes in additional ASD cases and reanalysis of 931 previously reported ASD exomes available from dbGAP identified a significant increase in the mutation load of ERMN in ASD cases compared to controls (P=0.046), which became more significant if population-specific variants were excluded (P=7.97E-05).

Score Delta: Score remained at 4

3

Suggestive Evidence

See all Category 3 Genes

The literature is replete with relatively small studies of candidate genes, using either common or rare variant approaches, which do not reach the criteria set out for categories 1 and 2. Genes that had two such lines of supporting evidence were placed in category 3, and those with one line of evidence were placed in category 4. Some additional lines of "accessory evidence" (indicated as "acc" in the score cards) could also boost a gene from category 4 to 3.

10/1/2019
4
icon
3

Decreased from 4 to 3

New Scoring Scheme
Description

Analysis of methylation changes in blood DNA from 53 male ASD patients and 757 healthy controls found that hypomethylation caused by rare genetic variants (meSNVs) at six loci significantly associated with ASD (q-value <0.05); among the meSNVs identified was a differentially methylated CpG (DMCpG) at the GALNT5-ERMN locus in two ASD cases, one of whom displayed ERMN overexpression (Homs et al., 2016). Resequencing of top candidate genes in additional ASD cases and reanalysis of 931 previously reported ASD exomes available from dbGAP identified a significant increase in the mutation load of ERMN in ASD cases compared to controls (P=0.046), which became more significant if population-specific variants were excluded (P=7.97E-05).

Reports Added
[New Scoring Scheme]
7/1/2016
icon
4

Increased from to 4

Description

Analysis of methylation changes in blood DNA from 53 male ASD patients and 757 healthy controls found that hypomethylation caused by rare genetic variants (meSNVs) at six loci significantly associated with ASD (q-value <0.05); among the meSNVs identified was a differentially methylated CpG (DMCpG) at the GALNT5-ERMN locus in two ASD cases, one of whom displayed ERMN overexpression (Homs et al., 2016). Resequencing of top candidate genes in additional ASD cases and reanalysis of 931 previously reported ASD exomes available from dbGAP identified a significant increase in the mutation load of ERMN in ASD cases compared to controls (P=0.046), which became more significant if population-specific variants were excluded (P=7.97E-05).

Krishnan Probability Score

Score 0.49404661784764

Ranking 3855/25841 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.
ExAC Score

Score 0.0031015254764955

Ranking 10962/18225 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
Sanders TADA Score

Score 0.84697229060573

Ranking 3357/18665 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).
Zhang D Score

Score -0.054544977745424

Ranking 10569/20870 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.
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SFARI Gene Update

We are pleased to announce some changes to the ongoing curation of the data in SFARI Gene. In the context of a continued effort to develop the human gene module and its manually curated list of autism risk genes, we are modifying other aspects of the site to focus on the information that is of greatest interest to the research community. The version of SFARI Gene that has been developed until now will be frozen and will remain available as “SFARI Gene Archive”. Please see the announcement for more details.
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