IMMP2LIMP2 inner mitochondrial membrane peptidase-like (S. cerevisiae)
Autism Reports / Total Reports
10 / 17Rare Variants / Common Variants
17 / 8Aliases
IMMP2L, IMP2Associated Syndromes
-Chromosome Band
7q31.1Associated Disorders
DD/NDD, ADHD, ID, ASDRelevance to Autism
Rare mutation in the IMMP2L gene has been identified with Tourette syndrome (possible syndromic overlap with autism) (Petek et al., 2001). However, a separate study found no coding mutations in IMMP2L in either Tourette syndrome or ASD patients screened (Petek et al., 2007).
Molecular Function
The encoded protein has serine-like peptidase activity.
External Links
SFARI Genomic Platforms
Reports related to IMMP2L (17 Reports)
| # | Type | Title | Author, Year | Autism Report | Associated Disorders |
|---|---|---|---|---|---|
| 1 | Primary | Disruption of a novel gene (IMMP2L) by a breakpoint in 7q31 associated with Tourette syndrome | Petek E , et al. (2001) | No | - |
| 2 | Recent Recommendation | The m-AAA protease defective in hereditary spastic paraplegia controls ribosome assembly in mitochondria | Nolden M , et al. (2005) | No | - |
| 3 | Negative Association | Molecular and genomic studies of IMMP2L and mutation screening in autism and Tourette syndrome | Petek E , et al. (2006) | Yes | - |
| 4 | Positive Association | High-density SNP association study and copy number variation analysis of the AUTS1 and AUTS5 loci implicate the IMMP2L-DOCK4 gene region in autism susceptibility | Maestrini E , et al. (2009) | Yes | - |
| 5 | Support | Translocation breakpoint at 7q31 associated with tics: further evidence for IMMP2L as a candidate gene for Tourette syndrome | Patel C , et al. (2011) | No | - |
| 6 | Support | Social Responsiveness Scale-aided analysis of the clinical impact of copy number variations in autism | van Daalen E , et al. (2011) | Yes | - |
| 7 | Support | Application of array comparative genomic hybridization in 102 patients with epilepsy and additional neurodevelopmental disorders | Bartnik M , et al. (2012) | No | ASD, DD, ID |
| 8 | Support | A discovery resource of rare copy number variations in individuals with autism spectrum disorder | Prasad A , et al. (2013) | Yes | - |
| 9 | Recent Recommendation | Intragenic deletions affecting two alternative transcripts of the IMMP2L gene in patients with Tourette syndrome | Bertelsen B , et al. (2014) | No | ADHD, OCD, ASD |
| 10 | Negative Association | Family-based association study of ZNF533, DOCK4 and IMMP2L gene polymorphisms linked to autism in a northeastern Chinese Han population | Liang S , et al. (2014) | Yes | - |
| 11 | Support | Association of IMMP2L deletions with autism spectrum disorder: A trio family study and meta-analysis | Zhang Y , et al. (2017) | Yes | ID |
| 12 | Positive Association | Common schizophrenia alleles are enriched in mutation-intolerant genes and in regions under strong background selection | Pardias AF , et al. (2018) | No | - |
| 13 | Support | Both rare and common genetic variants contribute to autism in the Faroe Islands | Leblond CS , et al. (2019) | Yes | - |
| 14 | Support | First behavioural assessment of a novel Immp2l knockdown mouse model with relevance for Gilles de la Tourette syndrome and Autism spectrum disorder | Kreilaus F , et al. (2019) | Yes | - |
| 15 | Support | - | Yoshikawa A et al. (2022) | No | ASD or autistic features |
| 16 | Support | - | Zhou X et al. (2022) | Yes | - |
| 17 | Support | - | Leung BK et al. (2023) | Yes | - |
Rare Variants (17)
| Status | Allele Change | Residue Change | Variant Type | Inheritance Pattern | Parental Transmission | Family Type | PubMed ID | Author, Year |
|---|---|---|---|---|---|---|---|---|
| - | - | copy_number_loss | Unknown | - | - | 35776734 | Yoshikawa A et al. (2022) | |
| - | - | copy_number_gain | De novo | - | Simplex | 11254443 | Petek E , et al. (2001) | |
| - | - | copy_number_loss | De novo | - | Simplex | 21386874 | Patel C , et al. (2011) | |
| - | - | copy_number_loss | De novo | - | Simplex | 29152845 | Zhang Y , et al. (2017) | |
| - | - | copy_number_loss | Unknown | - | Unknown | 23275889 | Prasad A , et al. (2013) | |
| - | - | copy_number_loss | Unknown | - | Unknown | 24549057 | Bertelsen B , et al. (2014) | |
| - | - | copy_number_loss | Unknown | Not maternal | - | 22825934 | Bartnik M , et al. (2012) | |
| - | - | copy_number_loss | Familial | Maternal | Simplex | 29152845 | Zhang Y , et al. (2017) | |
| c.343C>T | p.Gln115Ter | missense_variant | De novo | - | - | 35982159 | Zhou X et al. (2022) | |
| - | - | copy_number_loss | Familial | Maternal | Simplex | 30675382 | Leblond CS , et al. (2019) | |
| - | - | copy_number_loss | Familial | Maternal | Simplex | 24549057 | Bertelsen B , et al. (2014) | |
| - | - | copy_number_loss | Familial | Paternal | Simplex | 24549057 | Bertelsen B , et al. (2014) | |
| - | - | copy_number_loss | Familial | Maternal | Unknown | 24549057 | Bertelsen B , et al. (2014) | |
| - | - | copy_number_loss | Familial | Paternal | Unknown | 24549057 | Bertelsen B , et al. (2014) | |
| - | - | copy_number_loss | Familial | Paternal | Simplex | 21837366 | van Daalen E , et al. (2011) | |
| - | - | copy_number_gain | Familial | Paternal | Multiplex | 19401682 | Maestrini E , et al. (2009) | |
| - | - | copy_number_loss | Familial | Maternal | Multiplex | 19401682 | Maestrini E , et al. (2009) |
Common Variants (8)
| Status | Allele Change | Residue Change | Variant Type | Inheritance Pattern | Paternal Transmission | Family Type | PubMed ID | Author, Year |
|---|---|---|---|---|---|---|---|---|
| c.409-20964G>A;c.286-20964G>A;c.306-20964G>A | - | intron_variant | - | - | - | 19401682 | Maestrini E , et al. (2009) | |
| c.239+151030C>G;c.116+151030C>G;c.323+81051C>G | - | intron_variant | - | - | - | 29483656 | Pardias AF , et al. (2018) | |
| c.408+83877T>C;c.285+83877T>C;c.306-138995T>C | - | intron_variant | - | - | - | 19401682 | Maestrini E , et al. (2009) | |
| c.408+84794C>T;c.285+84794C>T;c.306-138078C>T | - | intron_variant | - | - | - | 19401682 | Maestrini E , et al. (2009) | |
| c.409-58981G>A;c.286-58981G>A;c.306-58981G>A | Risk allele, C | intron_variant | - | - | - | 19401682 | Maestrini E , et al. (2009) | |
| c.409-93770C>T;c.286-93770C>T;c.306-93770C>T | Risk allele, A | intron_variant | - | - | - | 19401682 | Maestrini E , et al. (2009) | |
| c.408+47114C>A;c.285+47114C>A;c.305+124021C>A;c.409-3986C>A | Risk allele, T | intron_variant | - | - | - | 19401682 | Maestrini E , et al. (2009) | |
| T>C | - | intergenic_variant | - | - | - | 29483656 | Pardias AF , et al. (2018) |
SFARI Gene score
Strong Candidate
The IMMP2L gene is located within an ASD-associated linkage region on chromosome 7. While sequencing of the IMMP2L gene in 95 multiplex ASD families in Petek et al., 2007 failed to identify any deleterious mutations, deletions affecting the IMMP2L gene have been identified in ASD probands (Maestrini et al., 2010; van Daalen et al., 2011; Prasad et al., 2012). Genotyping of 100 Han Chinese ASD trio families in Zhang et al., 2017 identified three male ASD probands with intragenic IMMP2L deletions; however, meta-analysis in this report using 5,568 cases and 10,279 controls failed to demonstrate statistically significant enrichment of IMMP2L deletions in ASD cases. Common intronic variants in IMMP2L have also been demonstrated to associate with ASD in a case-control analysis (Maestrini et al., 2010). Furthermore, several reports have linked disruption of the IMMP2L gene, either by chromosomal rearrangement or copy number variation, with Tourette syndrome (Petek et al., 2001; Bertelsen et al., 2014) and ADHD (Elia et al., 2010). Moreover, Bertelsen et al., 2014 demonstrated that the frequency of intragenic IMMP2L deletions in Danish Tourette syndrome cases was significantly higher than in Danish controls (3.7% in cases vs. 0.9% in controls; P < 0.05).
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
Decreased from 3 to 2
Description
The IMMP2L gene is located within an ASD-associated linkage region on chromosome 7. While sequencing of the IMMP2L gene in 95 multiplex ASD families in Petek et al., 2007 failed to identify any deleterious mutations, deletions affecting the IMMP2L gene have been identified in ASD probands (Maestrini et al., 2010; van Daalen et al., 2011; Prasad et al., 2012). Genotyping of 100 Han Chinese ASD trio families in Zhang et al., 2017 identified three male ASD probands with intragenic IMMP2L deletions; however, meta-analysis in this report using 5,568 cases and 10,279 controls failed to demonstrate statistically significant enrichment of IMMP2L deletions in ASD cases. Common intronic variants in IMMP2L have also been demonstrated to associate with ASD in a case-control analysis (Maestrini et al., 2010). Furthermore, several reports have linked disruption of the IMMP2L gene, either by chromosomal rearrangement or copy number variation, with Tourette syndrome (Petek et al., 2001; Bertelsen et al., 2014) and ADHD (Elia et al., 2010). Moreover, Bertelsen et al., 2014 demonstrated that the frequency of intragenic IMMP2L deletions in Danish Tourette syndrome cases was significantly higher than in Danish controls (3.7% in cases vs. 0.9% in controls; P < 0.05).
10/1/2019
Decreased from 4 to 3
New Scoring Scheme
Description
The IMMP2L gene is located within an ASD-associated linkage region on chromosome 7. While sequencing of the IMMP2L gene in 95 multiplex ASD families in Petek et al., 2007 failed to identify any deleterious mutations, deletions affecting the IMMP2L gene have been identified in ASD probands (Maestrini et al., 2010; van Daalen et al., 2011; Prasad et al., 2012). Genotyping of 100 Han Chinese ASD trio families in Zhang et al., 2017 identified three male ASD probands with intragenic IMMP2L deletions; however, meta-analysis in this report using 5,568 cases and 10,279 controls failed to demonstrate statistically significant enrichment of IMMP2L deletions in ASD cases. Common intronic variants in IMMP2L have also been demonstrated to associate with ASD in a case-control analysis (Maestrini et al., 2010). Furthermore, several reports have linked disruption of the IMMP2L gene, either by chromosomal rearrangement or copy number variation, with Tourette syndrome (Petek et al., 2001; Bertelsen et al., 2014) and ADHD (Elia et al., 2010). Moreover, Bertelsen et al., 2014 demonstrated that the frequency of intragenic IMMP2L deletions in Danish Tourette syndrome cases was significantly higher than in Danish controls (3.7% in cases vs. 0.9% in controls; P < 0.05).
Reports Added
[New Scoring Scheme]7/1/2019
Decreased from 4 to 4
Description
The IMMP2L gene is located within an ASD-associated linkage region on chromosome 7. While sequencing of the IMMP2L gene in 95 multiplex ASD families in Petek et al., 2007 failed to identify any deleterious mutations, deletions affecting the IMMP2L gene have been identified in ASD probands (Maestrini et al., 2010; van Daalen et al., 2011; Prasad et al., 2012). Genotyping of 100 Han Chinese ASD trio families in Zhang et al., 2017 identified three male ASD probands with intragenic IMMP2L deletions; however, meta-analysis in this report using 5,568 cases and 10,279 controls failed to demonstrate statistically significant enrichment of IMMP2L deletions in ASD cases. Common intronic variants in IMMP2L have also been demonstrated to associate with ASD in a case-control analysis (Maestrini et al., 2010). Furthermore, several reports have linked disruption of the IMMP2L gene, either by chromosomal rearrangement or copy number variation, with Tourette syndrome (Petek et al., 2001; Bertelsen et al., 2014) and ADHD (Elia et al., 2010). Moreover, Bertelsen et al., 2014 demonstrated that the frequency of intragenic IMMP2L deletions in Danish Tourette syndrome cases was significantly higher than in Danish controls (3.7% in cases vs. 0.9% in controls; P < 0.05).
1/1/2019
Decreased from 4 to 4
Description
The IMMP2L gene is located within an ASD-associated linkage region on chromosome 7. While sequencing of the IMMP2L gene in 95 multiplex ASD families in Petek et al., 2007 failed to identify any deleterious mutations, deletions affecting the IMMP2L gene have been identified in ASD probands (Maestrini et al., 2010; van Daalen et al., 2011; Prasad et al., 2012). Genotyping of 100 Han Chinese ASD trio families in Zhang et al., 2017 identified three male ASD probands with intragenic IMMP2L deletions; however, meta-analysis in this report using 5,568 cases and 10,279 controls failed to demonstrate statistically significant enrichment of IMMP2L deletions in ASD cases. Common intronic variants in IMMP2L have also been demonstrated to associate with ASD in a case-control analysis (Maestrini et al., 2010). Furthermore, several reports have linked disruption of the IMMP2L gene, either by chromosomal rearrangement or copy number variation, with Tourette syndrome (Petek et al., 2001; Bertelsen et al., 2014) and ADHD (Elia et al., 2010). Moreover, Bertelsen et al., 2014 demonstrated that the frequency of intragenic IMMP2L deletions in Danish Tourette syndrome cases was significantly higher than in Danish controls (3.7% in cases vs. 0.9% in controls; P < 0.05).
10/1/2017
Decreased from 5 to 4
Description
The IMMP2L gene is located within an ASD-associated linkage region on chromosome 7. While sequencing of the IMMP2L gene in 95 multiplex ASD families in Petek et al., 2007 failed to identify any deleterious mutations, deletions affecting the IMMP2L gene have been identified in ASD probands (Maestrini et al., 2010; van Daalen et al., 2011; Prasad et al., 2012). Genotyping of 100 Han Chinese ASD trio families in Zhang et al., 2017 identified three male ASD probands with intragenic IMMP2L deletions; however, meta-analysis in this report using 5,568 cases and 10,279 controls failed to demonstrate statistically significant enrichment of IMMP2L deletions in ASD cases. Common intronic variants in IMMP2L have also been demonstrated to associate with ASD in a case-control analysis (Maestrini et al., 2010). Furthermore, several reports have linked disruption of the IMMP2L gene, either by chromosomal rearrangement or copy number variation, with Tourette syndrome (Petek et al., 2001; Bertelsen et al., 2014) and ADHD (Elia et al., 2010). Moreover, Bertelsen et al., 2014 demonstrated that the frequency of intragenic IMMP2L deletions in Danish Tourette syndrome cases was significantly higher than in Danish controls (3.7% in cases vs. 0.9% in controls; P < 0.05).
1/1/2016
Decreased from 5 to 5
Description
The IMMPL2 gene is located within a linkage region on chromosome 7. There is one report of a disruptive chromosome rearrangement in a patient with Tourette syndrome and autism (Petak et al., 2001). The same group sequenced the gene in 95 multiplex autism families and 39 Tourette families but did not identify any mutations. Copy number variants involving the IMMP2L gene have been reported in attention deficit hyperactivity disorder (ADHD), but not specifically in autism spectrum disorder.
Reports Added
[High-density SNP association study and copy number variation analysis of the AUTS1 and AUTS5 loci implicate the IMMP2L-DOCK4 gene region in autism ...2009] [Social Responsiveness Scale-aided analysis of the clinical impact of copy number variations in autism.2011] [A discovery resource of rare copy number variations in individuals with autism spectrum disorder.2013] [Family-based association study of ZNF533, DOCK4 and IMMP2L gene polymorphisms linked to autism in a northeastern Chinese Han population.2014] [Molecular and genomic studies of IMMP2L and mutation screening in autism and Tourette syndrome.2006] [Application of array comparative genomic hybridization in 102 patients with epilepsy and additional neurodevelopmental disorders.2012] [Disruption of a novel gene (IMMP2L) by a breakpoint in 7q31 associated with Tourette syndrome.2001] [Intragenic deletions affecting two alternative transcripts of the IMMP2L gene in patients with Tourette syndrome.2014] [The m-AAA protease defective in hereditary spastic paraplegia controls ribosome assembly in mitochondria.2005] [Translocation breakpoint at 7q31 associated with tics: further evidence for IMMP2L as a candidate gene for Tourette syndrome.2011]7/1/2014
Increased from No data to 5
Description
The IMMPL2 gene is located within a linkage region on chromosome 7. There is one report of a disruptive chromosome rearrangement in a patient with Tourette syndrome and autism (Petak et al., 2001). The same group sequenced the gene in 95 multiplex autism families and 39 Tourette families but did not identify any mutations. Copy number variants involving the IMMP2L gene have been reported in attention deficit hyperactivity disorder (ADHD), but not specifically in autism spectrum disorder.
4/1/2014
Increased from No data to 5
Description
The IMMPL2 gene is located within a linkage region on chromosome 7. There is one report of a disruptive chromosome rearrangement in a patient with Tourette syndrome and autism (Petak et al., 2001). The same group sequenced the gene in 95 multiplex autism families and 39 Tourette families but did not identify any mutations. Copy number variants involving the IMMP2L gene have been reported in attention deficit hyperactivity disorder (ADHD), but not specifically in autism spectrum disorder.
Krishnan Probability Score
Score 0.44607231041822
Ranking 15018/25841 scored genes
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ExAC Score
Score 0.04076091785976
Ranking 8774/18225 scored genes
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Sanders TADA Score
Score 0.94395974471748
Ranking 15889/18665 scored genes
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Larsen Cumulative Evidence Score
Score 8
Ranking 226/461 scored genes
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Zhang D Score
Score -0.043618901682875
Ranking 10186/20870 scored genes
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