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Relevance to Autism

Rare mutations in the RAB39B gene have been identified with autism (Giannandrea et al., 2010).

Molecular Function

This gene encodes a member of the Rab family of proteins. Rab proteins are small GTPases that are involved in vesicular trafficking.

External Links

        

References

Type
Title
Type of Disorder
Associated Disorders
Author, Year
Primary
Mutations in the small GTPase gene RAB39B are responsible for X-linked mental retardation associated with autism, epilepsy, and macrocephaly.
ASD
X-linked MR, epilepsy
Support
Whole-genome sequencing of quartet families with autism spectrum disorder.
ASD
Support
A novel RAB39B mutation and concurrent de novo NF1 mutation in a boy with neurofibromatosis type 1, intellectual disability, and autism: a case report
X-linked mental retardation-72 (MRX72)
ASD, ID, epilepsy/seizures
Support
A de novo paradigm for mental retardation.
ID
Support
Cerebral organoid and mouse models reveal a RAB39b-PI3K-mTOR pathway-dependent dysregulation of cortical development leading to macrocephaly/autism phenotypes
Support
Characterization of intellectual disability and autism comorbidity through gene panel sequencing.
ID, ASD or autistic traits
Support
The Clinical and Genetic Features of Co-occurring Epilepsy and Autism Spectrum Disorder in Chinese Children.
ASD, epilepsy/seizures
Support
Mutations in RAB39B in individuals with intellectual disability, autism spectrum disorder, and macrocephaly.
ASD, ID
Macrocephaly
Support
Targeted sequencing and functional analysis reveal brain-size-related genes and their networks in autism spectrum disorders.
ASD
Highly Cited
Isolation and characterization of a human novel RAB (RAB39B) gene.
Recent Recommendation
The intellectual disability protein RAB39B selectively regulates GluA2 trafficking to determine synaptic AMPAR composition.
Recent Recommendation
Mutations in RAB39B cause X-linked intellectual disability and early-onset Parkinson disease with -synuclein pathology.
ID, early-onset parkinson disease
Recent Recommendation
Increased dosage of RAB39B affects neuronal development and could explain the cognitive impairment in male patients with distal Xq28 copy number ga...
ID
SCZ
Recent Recommendation
Gene expression profiling identifies new biological markers of neoplastic germ cells.

Rare

Variant ID
Variant Type
Allele Change
Residue Change
Inheritance Pattern
Inheritance Association
Family Type
Author, Year
 GEN207R001 
 stop_gained 
 c.21C>A 
 p.Tyr7Ter 
 Familial 
 Maternal 
 Multi-generational 
 GEN207R002 
 splice_site_variant 
 c.215+1G>A 
  
 Familial 
 Maternal 
 Multi-generational 
 GEN207R003 
 copy_number_gain 
  
  
 Familial 
 Maternal 
 Multiplex 
 GEN207R004 
 copy_number_gain 
  
  
 Familial 
 Maternal 
 Simplex 
 GEN207R005 
 copy_number_gain 
  
  
 Unknown 
 Mother not tested 
 Simplex 
 GEN207R006 
 copy_number_loss 
  
  
 Familial 
 Maternal 
 Multiplex 
 GEN207R007 
 missense_variant 
 c.503C>A 
 p.Thr168Lys 
 Familial 
 Maternal 
 Extended multiplex 
 GEN207R008 
 stop_gained 
 c.559G>T 
 p.Glu187Ter 
 Familial 
 Maternal 
 Multiplex 
 GEN207R009 
 stop_gained 
 c.557G>A 
 p.Trp186Ter 
 De novo 
 NA 
 Simplex 
 GEN207R010 
 missense_variant 
 c.31C>T 
 p.Leu11Phe 
 Familial 
  
 Simplex 
 GEN207R011 
 missense_variant 
 c.473T>C 
 p.Ile158Thr 
 Familial 
 Maternal 
  
 GEN207R012 
 missense_variant 
 c.579T>G 
 p.Phe193Leu 
 Familial 
 Maternal 
 Multi-generational 
 GEN207R013 
 inframe_deletion 
 c.436_447del 
 p.Gly146_Tyr149del 
 Familial 
 Maternal 
 Extended multiplex 

Common

No Common Variants Available
Chromosome
CNV Locus
CNV Type
# of studies
Animal Model
X
Deletion
 1
 
X
Duplication
 1
 
X
Deletion-Duplication
 18
 
X
Deletion
 2
 
X
Deletion
 1
 
X
Deletion
 1
 
X
Deletion-Duplication
 1
 
X
Deletion
 2
 
X
Deletion-Duplication
 1
 
X
Deletion
 7
 
X
Deletion-Duplication
 65
 

Model Summary

Rab39b hemizygous knockout mice exhibit cortical neurogenesis impairment, macrocephaly, decreased body weight, no change in anxiety, increased ambulation, no change in social approach, decreased social memory, decreased motor learning, no change in self-grooming, and no change in marble-burying.

References

Type
Title
Author, Year
Primary
Cerebral organoid and mouse models reveal a RAB39b-PI3K-mTOR pathway-dependent dysregulation of cortical development leading to macrocephaly/autism phenotypes

M_RAB39B_1_KO_HE

Model Type: Genetic
Model Genotype: Hemizygous
Mutation: Male mice with hemizygous deletion of Rab39b generated using two CRISPRCas 9 guide RNAs targeting to delete 397 bps in exon 2 in C57BL/N6 oocytes.
Allele Type: Hemizygous
Strain of Origin: C57BL/N6
Genetic Background: C57BL/6N
ES Cell Line: NA
Mutant ES Cell Line: C57BL/N6
Model Source: PMID 32115408

M_RAB39B_2_KO_HM

Model Type: Genetic
Model Genotype: Homozygous
Mutation: Female mice with homozygous deletion of Rab39b generated using two CRISPRCas 9 guide RNAs targeting to delete 397 bps in exon 2 in C57BL/N6 oocytes.
Allele Type: Hemizygous
Strain of Origin: C57BL/N6
Genetic Background: C57BL/6N
ES Cell Line: NA
Mutant ES Cell Line: C57BL/N6
Model Source: PMID 32115408

M_RAB39B_1_KO_HE

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
General locomotor activity: ambulatory activity1
Increased
Description: Increase in distance travelled
Exp Paradigm: NA
 Open field test
 2 months
Motor learning1
Decreased
Description: Absence of increase in latency to fall off in progressive trials
Exp Paradigm: NA
 Accelerating rotarod test
 2 months
Cell proliferation: neural precursors1
Increased
Description: Increase in percentage of brdu-positive cells out of total cells in the vz/svz regions
Exp Paradigm: Brdu
 Immunohistochemistry
 E14.5
Neuronal number1
Increased
Description: Increase in the number of tbr1 positive cells in the cerebral cortex at e16.5, increase in the numbers of tbr1 and ctip2 positive cells at e18.5, increase in cux1 positive cells at p20, increase in the number of tbr2 positive ipcs in the ventricular and subventricular zones, increase in sox2 positive cells
Exp Paradigm: Tbr1, ctip2, cux1, tbr2, sox2
 Immunofluorescence staining
 E14.5, e16.5, e18.5, p20
Cell proliferation: neural precursors1
Decreased
Description: Decrease in the number of precursor neurons exiting the cell cycle measured by counting dual brdu positive and ki67 negative colabelled cells and dual brdu positive and tuj1 positive colabelled cells, indicating delayed differentiation
Exp Paradigm: Brdu, ki67, tuj1
 Pulse-chase analysis
 E13.5-14.5
Neocortex morphology1
Increased
Description: Increased hemisphere length, increased cortical area
Exp Paradigm: NA
 Histomorphometry
 P20
Brain size1
Increased
Description: Increased brain weight
Exp Paradigm: NA
 Measurement of tissue weight
 P20, e18.5
Cell proliferation: neural precursors1
Increased
Description: Increase in percentage of p-h3- and pax6-double-positive cells
Exp Paradigm: P-h3, pax6
 Immunohistochemistry
 E14.5
Social memory1
Decreased
Description: Decrease in time spent with the unfamiliar over the familiar mouse
Exp Paradigm: NA
 Three-chamber social approach test
 2 months
Size/growth1
Decreased
Description: Decrease in body weight
Exp Paradigm: NA
 Body weight measurement
 P20
Targeted expression1
Decreased
Description: Absence of rab39b protein expression in brain lysates
Exp Paradigm: NA
 Western blot
 Not reported
Signaling: mtor pathway1
Increased
Description: Increased expression of ps6 protein levels in mitotic neural precursor cells identified using phospho-vimentin, increase in percentage of ps6 positive neural precursors cells among all mitotic neural precursor cells
Exp Paradigm: Ps6, pvim
 Immunohistochemistry
 E14.5
General characteristics1
 No change
 General observations
 Not reported
Mortality/lethality1
 No change
 General observations
 Not reported
Anxiety1
 No change
 Open field test
 2 months
Motor coordination and balance1
 No change
 Accelerating rotarod test
 2 months
Cortical lamination1
 No change
 Immunofluorescence staining
 E14.5, e18.5. p20
Cortical thickness1
 No change
 Histomorphometry
 P20
Neuronal number1
 No change
 Immunofluorescence staining
 E14.5, e18.5
Reproductive function1
 No change
 General observations
 Not reported
Repetitive digging1
 No change
 Marble-burying test
 2 months
Self grooming: perseveration1
 No change
 Grooming behavior assessments
 2 months
Social approach1
 No change
 Three-chamber social approach test
 2 months
 Not Reported:

M_RAB39B_2_KO_HM

Category
Entity
Quantity
Experimental Paradigm
Age at Testing
Neocortex morphology1
Increased
Description: Increased hemisphere length, increased cortical area
Exp Paradigm: NA
 Histomorphometry
 P20
Brain size1
Increased
Description: Increased brain weight
Exp Paradigm: NA
 Measurement of tissue weight
 P20
Size/growth1
Decreased
Description: Decreased body weight
Exp Paradigm: NA
 Body weight measurement
 P20
Cortical thickness1
 No change
 Histomorphometry
 P20
 Not Reported:


Interactor Symbol Interactor Name Interactor Organism Entrez ID Uniprot ID Interaction Type Evidence Reference
ALPI Intestinal-type alkaline phosphatase 248 P09923 IP; LC-MS/MS
Huttlin EL , et al. 2015
C9orf72 chromosome 9 open reading frame 72 203228 Q96LT7 IP/WB; IP; LC-MS/MS; in vitro GDP release assay
Sellier C , et al. 2016
CARM1 coactivator-associated arginine methyltransferase 1 10498 Q86X55 IP; LC-MS/MS
Huttlin EL , et al. 2015
CBL Cas-Br-M (murine) ecotropic retroviral transforming sequence 867 P22681 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
GOLGA2 golgin A2 2801 Q08379 Y2H; bimolecular fluorescence complementation assay
Rolland T , et al. 2014
HBS1L HBS1-like (S. cerevisiae) 10767 Q9Y450 IP; LC-MS/MS
Huttlin EL , et al. 2015
KLK8 Kallikrein-8 11202 O60259-2 IP; LC-MS/MS
Huttlin EL , et al. 2015
KPNA2 karyopherin alpha 2 (RAG cohort 1, importin alpha 1) 3838 P52292 IP; LC-MS/MS
Huttlin EL , et al. 2015
LAMP3 Lysosome-associated membrane glycoprotein 3 27074 Q9UQV4 IP; LC-MS/MS
Huttlin EL , et al. 2015
PICK1 protein interacting with PRKCA 1 9463 Q9NRD5 Y2H; IP/WB; in vitro binding assay; Co-localization
Mignogna ML , et al. 2015
PMEL Melanocyte protein PMEL 6490 P40967-2 IP; LC-MS/MS
Huttlin EL , et al. 2015
RAB33B RAB33B, member RAS oncogene family 83452 Q9H082 IP; LC-MS/MS
Huttlin EL , et al. 2015
RAB3GAP1 RAB3 GTPase activating protein subunit 1 (catalytic) 22930 C9J837 Y2H; GST
Itoh T , et al. 2006
RABGAP1L RAB GTPase activating protein 1-like 9910 Q5R372 Y2H; GST
Itoh T , et al. 2006
RAD50 RAD50 homolog (S. cerevisiae) 10111 Q92878 IP; LC-MS/MS
Huttlin EL , et al. 2015
RUFY1 RUN and FYVE domain containing 1 80230 A8K7B1 Y2H; bimolecular fluorescence complementation assay
Rolland T , et al. 2014
SGSM3 small G protein signaling modulator 3 NM_015705 B9A6J5 Y2H; GST
Itoh T , et al. 2006
SLC15A1 Solute carrier family 15 member 1 6564 P46059 IP; LC-MS/MS
Huttlin EL , et al. 2015
SMCR8 Smith-Magenis syndrome chromosome region, candidate 8 140775 Q8TEV9 IP/WB; in vitro GDP release assay
Sellier C , et al. 2016
SQSTM1 sequestosome 1 8878 Q13501 IP/WB
Sellier C , et al. 2016
TNFSF8 tumor necrosis factor (ligand) superfamily, member 8 944 P32971 IP; LC-MS/MS
Huttlin EL , et al. 2015
TOMM22 translocase of outer mitochondrial membrane 22 homolog (yeast) NM_020243 Q549C5 IP; LC-MS/MS
Huttlin EL , et al. 2015
TRIM4 tripartite motif containing 4 89122 Q9C037 IP; LC-MS/MS
Huttlin EL , et al. 2015
TRIP6 thyroid hormone receptor interactor 6 7205 Q15654 IP; LC-MS/MS
Huttlin EL , et al. 2015
WDR41 WD repeat domain 41 55255 Q9HAD4 in vitro GDP release assay
Sellier C , et al. 2016
WHAMM WAS protein homolog associated with actin, golgi membranes and microtubules 123720 Q8TF30 IP; LC-MS/MS
Huttlin EL , et al. 2015
Arx aristaless related homeobox 11878 O35085 ChIP-qPCR
Quill ML , et al. 2011

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