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Relevance to Autism

Seven rare variants (minor allele frequency < 1%) in the HOMER1 gene were identified in a cohort of 290 non-syndromic ASD cases; none of these variants were observed in 300 ethnically matched controls. Four of the variants in the HOMER1 gene co-segregated with ASD in multiplex families (Kelleher III et al., 2012).

Molecular Function

This gene encodes a member of the homer family of dendritic proteins. Members of this family regulate group 1 metabotrophic glutamate receptor function.

External Links

        

References

Type
Title
Type of Disorder
Associated Disorders
Author, Year
Primary
High-throughput sequencing of mGluR signaling pathway genes reveals enrichment of rare variants in autism.
Non-syndromic ASD
Support
Homer1a regulates Shank3 expression and underlies behavioral vulnerability to stress in a model of Phelan-McDermid syndrome
Phelan-McDermid syndrome
Support
Large-scale discovery of novel genetic causes of developmental disorders.
Unknown diagnosis
Recent Recommendation
Overexpression of Homer1a in the basal and lateral amygdala impairs fear conditioning and induces an autism-like social impairment.
Recent Recommendation
Impairment of fragile X mental retardation protein-metabotropic glutamate receptor 5 signaling and its downstream cognates ras-related C3 botulinum...
ASD
Recent Recommendation
Disrupted Homer scaffolds mediate abnormal mGluR5 function in a mouse model of fragile X syndrome.

Rare

Variant ID
Variant Type
Allele Change
Residue Change
Inheritance Pattern
Inheritance Association
Family Type
Author, Year
 GEN356R001 
 intron_variant 
 c.162+19G>T 
  
  
  
 Multiplex 
 GEN356R002 
 missense_variant 
 c.195G>T 
 p.Met65Ile 
 Familial 
 Maternal 
 Multiplex 
 GEN356R003 
 missense_variant 
 c.290C>T 
 p.Ser97Leu 
 Familial 
 Maternal 
 Multiplex 
 GEN356R004 
 missense_variant 
 c.425C>T 
 p.Pro142Leu 
 Familial 
 Paternal 
 Multiplex 
 GEN356R005 
 intron_variant 
 c.528-11T>G 
  
  
  
 Multiplex 
 GEN356R006 
 missense_variant 
 c.968G>A 
 p.Arg323His 
 De novo 
  
 Multiplex 
 GEN356R007 
 3_prime_UTR_variant 
 c.*197C>T 
  
 Familial 
 Paternal 
 Multiplex 
 GEN356R008 
 missense_variant 
 c.634A>G 
 p.Lys212Glu 
 De novo 
  
 Unknown 

Common

No Common Variants Available
Chromosome
CNV Locus
CNV Type
# of studies
Animal Model
5
Duplication
 1
 
5
Duplication
 4
 
5
Duplication
 1
 
5
Deletion-Duplication
 18
 
5
Duplication
 1
 

Model Summary

Overexpression of Homer1a, which is a dominant negative regulator of the critical synaptic scaffolding protein Homer1, and is upregulated in the basal and lateral amygdala (BLA) of VPA-exposed animals.

References

Type
Title
Author, Year
Primary
Overexpression of Homer1a in the basal and lateral amygdala impairs fear conditioning and induces an autism-like social impairment.

R_HOMER1_1_TG

Model Type: Genetic
Model Genotype: Transgenic
Mutation: AAV plasmid infused into BLA. Plasmid contains 1.1-kb CBA promoter (266 bp CMV immediate early gene enhancer, 410 bp exon 1 of CBA, hybrid CBA/rabbit beta-globin intron, 5' end of beta-globin exon) to control expression of HA-tagged Homer1a. Plasmid contains Woodchuck posttranscriptional element (WPRE) and bovine growth hormone poly A sequence. Control plasmid is GFP gene. Canulae were implanted bilaterally in BLA. A total of 1 microL of virus (1.5E13 GC/mL) was injected in each side.
Allele Type: Transgenic
Strain of Origin: Sprague Dawley
Genetic Background: Sprague Dawley
ES Cell Line:
Mutant ES Cell Line:
Model Source:

R_HOMER1_2_TG

Model Type: Genetic
Model Genotype: Transgenic
Mutation: AAV plasmid infused into BLA. Plasmid contains 480 bp human synapsin core promoter to control expression of Venus-tagged Homer1a. Plasmid contains Woodchuck posttranscriptional element (WPRE) and bovine growth hormone poly A sequence. Control plasmid is Homer1a with a point mutation in EVH1 domain (W24A) so that in can't interact with postsynaptic binding partners. Canulae were implanted bilaterally in BLA. A total of 1 microL of virus (1.5E13 GC/mL) was injected in each side.
Allele Type: Transgenic
Strain of Origin: Sprague Dawley
Genetic Background: Sprague Dawley
ES Cell Line:
Mutant ES Cell Line:
Model Source:

R_HOMER1_1_TG

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
Social approach1
Decreased
Description: Decreased amount of time spent in social interaction zone
 Reciprocal social interaction test
 2-3 months
Cued or contextual fear conditioning: memory of cue1
Decreased
Description: Decreased freezing in both short term (1 hour) memory paradigm and long term (24 hours) memory paradigm
Exp Paradigm: 30-s, 5-Hz, 75-dB tone coterminated with 0.75-mA foot shock, test in novel context
 Fear conditioning test
 2-3 months
Targeted expression1
Increased
Description: HA-tagged Homer1a protein is increased
Exp Paradigm: Western blot performed 21 days after vector infusion
 Western blot
 2-3 months
Anxiety1
 No change
 Open field test
 2-3 months
General locomotor activity: ambulatory activity1
 No change
 Open field test
 
Foot shock sensitivity1
 No change
 Fear conditioning test
 2-3 months
 Not Reported: Circadian sleep/wake cycle, Communications, Developmental profile, Immune response, Maternal behavior, Neuroanatomy / ultrastructure / cytoarchitecture, Neurophysiology, Physiological parameters, Repetitive behavior, Seizure

R_HOMER1_2_TG

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
Social approach1
Decreased
Description: Decreased amount of time spent in social interaction zone
 Reciprocal social interaction test
 2-3 months
Cued or contextual fear conditioning: memory of cue1
Decreased
Description: Decreased freezing in long term (24 hours) memory paradigm
Exp Paradigm: 30-s, 5-Hz, 75-dB tone coterminated with 0.75-mA foot shock, test in novel context
 Fear conditioning test
 2-3 months
Foot shock sensitivity1
 No change
 Fear conditioning test
 2-3 months
 Not Reported: Circadian sleep/wake cycle, Communications, Developmental profile, Emotion, Immune response, Maternal behavior, Molecular profile, Motor phenotype, Neuroanatomy / ultrastructure / cytoarchitecture, Neurophysiology, Physiological parameters, Repetitive behavior, Seizure





Download HOMER1's Cytoscape file

Interactor Symbol Interactor Name Interactor Organism Entrez ID Uniprot ID Interaction Type Evidence Reference
ABI3 ABI family, member 3 51225 Q9P2A4 Y2H
Rual JF , et al. 2005
ACTBL2 actin, beta-like 2 345651 Q562R1 IP; LC-MS/MS
Huttlin EL , et al. 2015
C19ORF57 chromosome 19 open reading frame 57 79173 Q0VDD7 Y2H; bimolecular fluorescence complementation assay
Rolland T , et al. 2014
C1orf116 chromosome 1 open reading frame 116 79098 Q9BW04 Y2H
Rual JF , et al. 2005
C1ORF116 chromosome 1 open reading frame 116 79098 Q9BW04 Y2H; bimolecular fluorescence complementation assay
Rolland T , et al. 2014
C22ORF41 synaptonemal complex central element protein 3 644186 A1L190 IP; LC-MS/MS
Huttlin EL , et al. 2015
CEP72 centrosomal protein 72kDa 55722 Q9P209 IP; LC-MS/MS
Huttlin EL , et al. 2015
CHD8 chromodomain helicase DNA binding protein 8 57680 Q9HCK8 ChIP-chip
Subtil-Rodrguez A , et al. 2013
COLEC12 collectin sub-family member 12 81035 Q5KU26 IP; LC-MS/MS
Huttlin EL , et al. 2015
CSPP1 centrosome and spindle pole associated protein 1 NM_024790 Q1MSJ5 IP; LC-MS/MS
Huttlin EL , et al. 2015
DBN1 drebrin 1 1627 Q16643 IP; LC-MS/MS
Huttlin EL , et al. 2015
Dnm3 dynamin 3 171574 Q08877 IP; in vitro kinase assay
Tu JC , et al. 1998
EEF1A2 eukaryotic translation elongation factor 1 alpha 2 1917 Q05639 IP; LC-MS/MS
Huttlin EL , et al. 2015
EMILIN1 elastin microfibril interfacer 1 11117 Q9Y6C2 IP; LC-MS/MS
Huttlin EL , et al. 2015
FAT1 FAT tumor suppressor homolog 1 (Drosophila) 2195 Q14517 Affinity chromatography; MS; Co-localization
AC/MALDI-TOF; GST
Schreiner D , et al. 2006
FAT1 FAT tumor suppressor homolog 1 (Drosophila) 14107 F2Z4A3 IP; LC-MS/MS
Badouel C , et al. 2015
FBXO28 F-box protein 28 23219 E9PEM8 IP; LC-MS/MS
Huttlin EL , et al. 2015
FMR1 fragile X mental retardation 1 2332 G8JLE9 PAR-CLIP
Ascano M Jr , et al. 2012
FRYL FRY-like 285527 O94915 IP; LC-MS/MS
Huttlin EL , et al. 2015
GRAMD3 GRAM domain-containing protein 3 65983 Q96HH9 IP; LC-MS/MS
Huttlin EL , et al. 2015
Grm1 glutamate receptor, metabotropic 1 24414 P23385 Y2H; IP/WB
Brakeman PR , et al. 1997
Grm5 glutamate receptor, metabotropic 5 24418 P31424 Y2H; IP/WB
Y2H; IP/WB; GST
Brakeman PR , et al. 1997
HOMER2 homer homolog 2 (Drosophila) 9455 Q9NSB8 IP; LC-MS/MS
Huttlin EL , et al. 2015
HOMER3 homer homolog 3 (Drosophila) 9454 Q9NSC5 Y2H; bimolecular fluorescence complementation assay
Rolland T , et al. 2014
HOMER3 homer homolog 3 (Drosophila) 9454 Q9NSC5 IP; LC-MS/MS
Huttlin EL , et al. 2015
IFT57 intraflagellar transport 57 homolog (Chlamydomonas) 55081 Q9NWB7 IP; LC-MS/MS
Huttlin EL , et al. 2015
Itpr1 inositol 1,4,5-trisphosphate receptor, type 1 25262 P29994 IP; in vitro kinase assay
Tu JC , et al. 1998
ITPR2 inositol 1,4,5-trisphosphate receptor, type 2 3709 Q14571 IP/WB
Jardin I , et al. 2012
KIF2B Kinesin-like protein KIF2B 84643 Q8N4N8 IP; LC-MS/MS
Huttlin EL , et al. 2015
KIF5B kinesin family member 5B 3799 P33176 IP; LC-MS/MS
Huttlin EL , et al. 2015
MIS18A MIS18 kinetochore protein homolog A (S. pombe) 54069 Q9NYP9 IP; LC-MS/MS
Huttlin EL , et al. 2015
NUP54 nucleoporin 54kDa 53371 Q7Z3B4 IP; LC-MS/MS
Huttlin EL , et al. 2015
OPHN1 oligophrenin 1 4983 O60890 GST
Nadif Kasri N , et al. 2011
Orai1 ORAI calcium release-activated calcium modulator 1 84876 Q96D31 IP/WB
Jardin I , et al. 2012
Ryr1 ryanodine receptor 1-like 114207 F1LMY4 GST; in vitro kinase assay
Feng W , et al. 2002
SHANK1 SH3 and multiple ankyrin repeat domains 1 78957 Q9WV48 Y2H; GST; IP/WB
Tu JC , et al. 1999
SHANK3 SH3 and multiple ankyrin repeat domains 3 59312 Q9JLU4 Y2H; GST; IP/WB
Tu JC , et al. 1999
SPTBN4 spectrin, beta, non-erythrocytic 4 57731 Q9H254 IP; LC-MS/MS
Huttlin EL , et al. 2015
SRGAP2 SLIT-ROBO Rho GTPase activating protein 2 23380 O75044 IP/WB; Co-localization
Fossati M , et al. 2016
STIM1 stromal interaction molecule 1 6786 Q13586 IP/WB
Jardin I , et al. 2012
TCP10L T-complex protein 10A homolog 2 140290 Q8TDR4 IP; LC-MS/MS
Huttlin EL , et al. 2015
TP53BP2 tumor protein p53 binding protein, 2 7159 Q13625 IP; LC-MS/MS
Huttlin EL , et al. 2015
TPM1 tropomyosin 1 (alpha) 7168 D9YZV2 IP; LC-MS/MS
Huttlin EL , et al. 2015
TRAF5 TNF receptor-associated factor 5 7188 O00463 IP; LC-MS/MS
Huttlin EL , et al. 2015
TRPC1 transient receptor potential cation channel, subfamily C, member 1 7220 P48995 IP/WB
Yuan JP , et al. 2003
TRPC2 transient receptor potential cation channel, subfamily C, member 2, pseudogene 7221 N/A IP/WB
Yuan JP , et al. 2003
TRPC5 transient receptor potential cation channel, subfamily C, member 5 7224 Q9UL62 IP/WB
Yuan JP , et al. 2003
ARNT2 aryl hydrocarbon receptor nuclear translocator 2 11864 Q61324 Gene microarray
Liu C , et al. 2003
Camk2a calcium/calmodulin-dependent protein kinase II alpha 12322 P11798 In vivo kinase assay
Guo W , et al. 2015
FAT1 FAT tumor suppressor homolog 1 (Drosophila) 2195 Q14517 Affinity chromatography; MS; Co-localization
AC/MALDI-TOF; GST
Schreiner D , et al. 2006
Grm5 glutamate receptor, metabotropic 5 108071 Q3UVX5 IP/WB; Bioluminescence resonance energy transfer assay
Guo W , et al. 2015
Klk1 kallikrein 1 16612 P15947 IP; MS
Su J , et al. 2012
Trpc3 transient receptor potential cation channel, subfamily C, member 3 22065 Q9QZC1 IP/WB
Woo JS , et al. 2008
Frmpd4 FERM and PDZ domain containing 4 302656 D4A3K7 Y2H; IP/WB
Hu JH , et al. 2012
GRM5 glutamate receptor, metabotropic 5 24418 P31424 Y2H; IP/WB
Y2H; IP/WB; GST
Brakeman PR , et al. 1997
Nfatc1 nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 1 100361818 N/A GST
Salanova M , et al. 2011
PARK2 Parkinson disease (autosomal recessive, juvenile) 2, parkin 56816 Q9JK66 IP/WB
Fallon L , et al. 2001
Plcb1 phospholipase C, beta 1 (phosphoinositide-specific) 24654 P10687 IP/WB
Grubb DR , et al. 2011
SHANK1 SH3 and multiple ankyrin repeat domains 1 78957 Q9WV48 Y2H; GST; IP/WB
Tu JC , et al. 1999
SHANK2 SH3 and multiple ankyrin repeat domains 2 171093 Q9QX74 GST; IP/WB
Hwang JI , et al. 2005
SHANK3 SH3 and multiple ankyrin repeat domains 3 59312 Q9JLU4 Y2H; GST; IP/WB
Tu JC , et al. 1999

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