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Relevance 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

        

References

Type
Title
Type of Disorder
Associated Disorders
Author, Year
Primary
Disruption of a novel gene (IMMP2L) by a breakpoint in 7q31 associated with Tourette syndrome.
TS
Positive Association
Common schizophrenia alleles are enriched in mutation-intolerant genes and in regions under strong background selection.
SCZ
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 ...
ASD
Negative Association
Family-based association study of ZNF533, DOCK4 and IMMP2L gene polymorphisms linked to autism in a northeastern Chinese Han population.
ASD
Negative Association
Molecular and genomic studies of IMMP2L and mutation screening in autism and Tourette syndrome.
ASD, TS
Support
First behavioural assessment of a novel Immp2l knockdown mouse model with relevance for Gilles de la Tourette syndrome and Autism spectrum disorder.
ASD, TS
Support
Both rare and common genetic variants contribute to autism in the Faroe Islands.
ASD
Support
Association of IMMP2L deletions with autism spectrum disorder: A trio family study and meta-analysis.
ASD
ID
Support
A discovery resource of rare copy number variations in individuals with autism spectrum disorder.
ASD
Support
ASD, TS
Support
Application of array comparative genomic hybridization in 102 patients with epilepsy and additional neurodevelopmental disorders.
Epilepsy
ASD, DD, ID
Support
Integrating de novo and inherited variants in 42
ASD
Support
Social Responsiveness Scale-aided analysis of the clinical impact of copy number variations in autism.
ASD
Support
Exonic deletions in IMMP2L in schizophrenia with enhanced glycation stress subtype
SCZ
ASD or autistic features
Support
Translocation breakpoint at 7q31 associated with tics: further evidence for IMMP2L as a candidate gene for Tourette syndrome.
TS
Recent Recommendation
Intragenic deletions affecting two alternative transcripts of the IMMP2L gene in patients with Tourette syndrome.
TS
ADHD, OCD, ASD
Recent Recommendation
The m-AAA protease defective in hereditary spastic paraplegia controls ribosome assembly in mitochondria.

Rare

Variant ID
Variant Type
Allele Change
Residue Change
Inheritance Pattern
Inheritance Association
Family Type
Author, Year
 GEN134R001 
 copy_number_gain 
  
  
 De novo 
  
 Simplex 
 GEN134R002 
 copy_number_loss 
  
  
 Familial 
 Paternal 
 Simplex 
 GEN134R003 
 copy_number_loss 
  
  
 Unknown 
 Not maternal 
  
 GEN134R004 
 copy_number_loss 
  
  
 Unknown 
  
 Unknown 
 GEN134R005 
 copy_number_loss 
  
  
 Familial 
 Paternal 
 Simplex 
 GEN134R006 
 copy_number_loss 
  
  
 Familial 
 Maternal 
 Simplex 
 GEN134R007 
 copy_number_loss 
  
  
 Familial 
 Maternal 
 Unknown 
 GEN134R008 
 copy_number_loss 
  
  
 Familial 
 Paternal 
 Simplex 
 GEN134R009 
 copy_number_loss 
  
  
 Unknown 
  
 Unknown 
 GEN134R010 
 copy_number_loss 
  
  
 Familial 
 Paternal 
 Simplex 
 GEN134R011 
 copy_number_loss 
  
  
 Familial 
 Paternal 
 Unknown 
 GEN134R012 
 copy_number_loss 
  
  
 Familial 
 Maternal 
 Multiplex 
 GEN134R013 
 copy_number_gain 
  
  
 Familial 
 Paternal 
 Multiplex 
 GEN134R014 
 copy_number_loss 
  
  
 De novo 
  
 Simplex 
 GEN134R015 
 copy_number_loss 
  
  
 De novo 
  
 Simplex 
 GEN134R016 
 copy_number_loss 
  
  
 Familial 
 Maternal 
 Simplex 
 GEN134R017 
 copy_number_loss 
  
  
 Familial 
 Maternal 
 Simplex 
 GEN134R018 
 copy_number_loss 
  
  
 Familial 
 Maternal 
 Simplex 
 GEN134R019 
 copy_number_loss 
  
  
 Unknown 
  
  
 GEN134R020 
 copy_number_loss 
  
  
 Unknown 
  
  
 GEN134R021 
 copy_number_loss 
  
  
 Unknown 
  
  
 GEN134R022 
 copy_number_loss 
  
  
 Unknown 
  
  
 GEN134R023 
 missense_variant 
 c.343C>T 
 p.Gln115Ter 
 De novo 
  
  

Common

Variant ID
Polymorphism
SNP ID
Allele Change
Residue Change
Population Origin
Population Stage
Author, Year
 GEN134C001 
 intron_variant 
 rs1464895 
 c.409-20964G>A;c.286-20964G>A;c.306-20964G>A 
  
 Discovery cohort: 127 ASD families from IMGSAC showing linkage to the AUTS1 region, 188 gender-matched controls 
 Discovery 
 GEN134C002 
 intron_variant 
 rs2030781 
 c.409-58981G>A;c.286-58981G>A;c.306-58981G>A 
 Risk allele, C 
 Combined sample of IMGSAC primary and replication samples (420-421 cases, 368 controls) 
 Discovery 
 GEN134C003 
 intron_variant 
 rs12537269 
 c.409-93770C>T;c.286-93770C>T;c.306-93770C>T 
 Risk allele, A 
 Combined sample of IMGSAC primary and replication samples (420-421 cases, 368 controls) 
 Discovery 
 GEN134C004 
 intron_variant 
 rs10500002 
 c.408+84794C>T;c.285+84794C>T;c.306-138078C>T 
  
 Discovery cohort: 127 ASD families from IMGSAC showing linkage to the AUTS1 region, 188 gender-matched controls 
 Discovery 
 GEN134C005 
 intron_variant 
 rs1528039 
 c.408+83877T>C;c.285+83877T>C;c.306-138995T>C 
  
 Discovery cohort: 127 ASD families from IMGSAC showing linkage to the AUTS1 region, 188 gender-matched controls 
 Discovery 
 GEN134C006 
 intron_variant 
 rs12531640 
 c.408+47114C>A;c.285+47114C>A;c.305+124021C>A;c.409-3986C>A 
 Risk allele, T 
 Discovery cohort: 127 ASD families from IMGSAC showing linkage to the AUTS1 region, 188 gender-matched controls 
 Discovery 
 GEN134C007 
 intron_variant 
 rs12705761 
 c.239+151030C>G;c.116+151030C>G;c.323+81051C>G 
  
 40,675 SCZ cases and 64,643 controls (CLOZUK and independent PGC datasets) 
 Discovery 
 GEN134C008 
 intergenic_variant 
 rs211829 
 T>C 
  
 40,675 SCZ cases and 64,643 controls (CLOZUK and independent PGC datasets) 
 Discovery 
Chromosome
CNV Locus
CNV Type
# of studies
Animal Model
7
Deletion
 2
 
7
Deletion-Duplication
 28
 
7
Deletion
 1
 
7
Deletion
 1
 
7
Deletion-Duplication
 45
 
7
Deletion
 3
 

Model Summary

Novel link between mitochondrial dysfunction and infertility and suggest that superoxide ion targeting agents may prove useful for treating infertility in a subpopulation of infertile patients.

References

Type
Title
Author, Year
Primary
A mutation in the inner mitochondrial membrane peptidase 2-like gene (Immp2l) affects mitochondrial function and impairs fertility in mice.

M_IMMP2L_1_TG_HM

Model Type: Genetic
Model Genotype: Homozygous
Mutation: Random transgenic insertional mutagenesis strategy resulting in a 50 kb deletion on chromosome 12, within the 6th intron of the Immp2l gene.
Allele Type: Random (Deletion)
Strain of Origin: Not Specified
Genetic Background: Not Specified
ES Cell Line: Not Specified
Mutant ES Cell Line: Not Specified
Model Source: Not Specified

M_IMMP2L_2_TG_HT

Model Type: Genetic
Model Genotype: Heterozygous
Mutation: Random transgenic insertional mutagenesis strategy resulting in a 50 kb deletion on chromosome 12, within the 6th intron of the Immp2l gene.
Allele Type: Random (Deletion)
Strain of Origin: Not Specified
Genetic Background: Not Specified
ES Cell Line: Not Specified
Mutant ES Cell Line: Not Specified
Model Source: Not Specified

M_IMMP2L_1_TG_HM

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
Mitochondrial activity1
Increased
Description: Increased rate of superoxide ion generation in mitochondria from testes
Exp Paradigm: Superoxide generation assay
 Superoxide generation assay
 Unreported
Mitochondrial activity1
Decreased
Description: Decreased activity of mitochondrial respiratory complex i and i + iii in testis
Exp Paradigm: Mitochondrial respiratory chain enzyme analysis
 Mitochondrial respiratory chain enzyme analysis
 Unreported
Mitochondrial function1
Abnormal
Description: Abnormal mitochondrial function: hyperpolarization in mitochondria from testis and brain tissue, increased atp levels in testis, brain tissue, spermatozoa and splenic lymphocytes
Exp Paradigm: Spectrophotometry: membrane potential-sensitive dye tetramethylrhodamine ester (tmre)-fluorescence detection (?ex=510 nm, ?em=590 nm)
 Spectrophotometry
 Unreported
Reproductive system development1
Abnormal
Description: Abnormal reproductive system: heterogenous pattern of disorganization of seminiferous tubules, vacuaolation, and reduced germ cell numbers; increased apoptosis of germ cells
Exp Paradigm: Male mice: histological analysis of testis; tunel assay
 Histology
 7 months
Size/growth1
Decreased
Description: Decreased body weight
Exp Paradigm: General observations
 General observations
 4-5 months
Reproductive system development1
Decreased
Description: Decreased reproductive ability demonstrated by severe sufertility
Exp Paradigm: Male mice: general observations
 General observations
 Unreported
Reproductive system development1
Abnormal
Description: Abnormal reproductive system: increased preantral follicles, decreased antral follicles, increased incidence of degenerating follicles, decreased number of eggs
Exp Paradigm: Female mice: histological analysis of ovaries; superovulation
 Histology
 Unreported
Signaling1
Decreased
Description: Decreased processing of cyc1 protein indicated by larger cyc1 protein
Exp Paradigm: Western blot: cyc1
 Western blot
 Unreported
Signaling1
Decreased
Description: Decreased processing of gpd2 protein
Exp Paradigm: Western blot: gpd2
 Western blot
 Unreported
General characteristics1
 No change
 General observations
 Unreported
Reproductive system development1
 No change
 Histology
 2-3 months
Reproductive system development1
 No change
 General observations
 2-3 months
Reproductive system development1
 No change
 Histology
 3 weeks
Mitochondrial biogenesis1
 No change
 Flow cytometric analysis
 Unreported
Protein phosphorylation1
 No change
 Western blot
 Unreported
Mating behavior1
 No change
 Mating behavior test
 Unreported
 Not Reported: Circadian sleep/wake cycle, Communications, Emotion, Immune response, Learning & memory, Maternal behavior, Motor phenotype, Neuroanatomy / ultrastructure / cytoarchitecture, Physiological parameters, Repetitive behavior, Seizure, Sensory

M_IMMP2L_2_TG_HT

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
Signaling1
Decreased
Description: Decreased processing of gpd2 protein
Exp Paradigm: Gpd2 signal peptide processing
 Western blot
 Unreported
Signaling1
 No change
 Western blot
 Unreported
 Not Reported: Circadian sleep/wake cycle, Communications, Developmental profile, Emotion, Immune response, Learning & memory, Maternal behavior, Motor phenotype, Neuroanatomy / ultrastructure / cytoarchitecture, Neurophysiology, Physiological parameters, Repetitive behavior, Seizure, Sensory, Social behavior


Interactor Symbol Interactor Name Interactor Organism Entrez ID Uniprot ID Interaction Type Evidence Reference
Diablo diablo homolog (Drosophila) ?66593 Q9JIQ3 WB
Burri L , et al. 2005
HMGA2 high mobility group AT-hook 2 8091 P52926 Luciferase reporter assay; EMSA; ChIP
Cleynen I , et al. 2007
Nfkb1 nuclear factor of kappa light polypeptide gene enhancer in B-cells 1, p105 18033 P25799 EMSA; Luciferase reporter assay
Cleynen I , et al. 2007

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