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Relevance to Autism

De novo variants in this gene were identified in two separate reports using ASD probands from the Simons Simplex Collection (Sanders et al. 2012a, 2012b)

Molecular Function

This gene is a member of the WD40 repeat-containing gene family and shares sequence similarity with transducin (beta)-like 1X-linked (TBL1X). The protein encoded by this gene is thought to be a component of both nuclear receptor corepressor (N-CoR) and histone deacetylase 3 (HDAC 3) complexes, and is required for transcriptional activation by a variety of transcription factors. Mutations in these gene have been associated with some autism spectrum disorders, and one finding suggests that haploinsufficiency of this gene may be a cause of intellectual disability with dysmorphism.

External Links

        

References

Type
Title
Type of Disorder
Associated Disorders
Author, Year
Primary
Sporadic autism exomes reveal a highly interconnected protein network of de novo mutations.
ASD
Support
A new syndrome of intellectual disability with dysmorphism due to TBL1XR1 deletion.
ID
Support
Pierpont syndrome associated with the p.Tyr446Cys missense mutation in TBL1XR1.
Pierpont syndrome
Support
Increased diagnostic and new genes identification outcome using research reanalysis of singleton exome sequencing.
ID
Support
A girl with West syndrome and autistic features harboring a de novo TBL1XR1 mutation.
West syndrome
Epilepsy, autistic features
Support
De novo non-synonymous TBL1XR1 mutation alters Wnt signaling activity.
SCZ
Support
Variantrecurrence in neurodevelopmental disorders: the use of publicly available genomic data identifies clinically relevant pathogenic missense v...
DD
Support
De novo deletion of TBL1XR1 in a child with non-specific developmental delay supports its implication in intellectual disability.
ID
Support
A heritable microduplication encompassing TBL1XR1 causes a genomic sister-disorder for the 3q26.32 microdeletion syndrome.
ASD, ID
Support
Both rare and common genetic variants contribute to autism in the Faroe Islands.
ASD
Support
Multiplex targeted sequencing identifies recurrently mutated genes in autism spectrum disorders.
ASD
Support
Targeted sequencing identifies 91 neurodevelopmental-disorder risk genes with autism and developmental-disability biases.
DD
Support
TBL1XR1 mutations in Pierpont syndrome are not restricted to the recurrent p.Tyr446Cys mutation.
Pierpont syndrome
Autistic features
Support
Meta-analysis of 2,104 trios provides support for 10 new genes for intellectual disability.
ID
Support
Clinical genome sequencing in an unbiased pediatric cohort.
Pierpont syndrome
DD, hypotonia
Support
Large-scale discovery of novel genetic causes of developmental disorders.
DD, ID
Epilpesy/seizures
Support
Improved diagnostic yield compared with targeted gene sequencing panels suggests a role for whole-genome sequencing as a first-tier genetic test.
DD, epilepsy/seizures
Recent Recommendation
Integrating population variation and protein structural analysis to improve clinical interpretation of missense variation: application to the WD40 ...
DD, ASD
Recent Recommendation
Structure of the MeCP2-TBLR1 complex reveals a molecular basis for Rett syndrome and related disorders.
ASD, DD, ID
Recent Recommendation
A specific mutation in TBL1XR1 causes Pierpont syndrome.
Pierpont syndrome
DD, ID

Rare

Variant ID
Variant Type
Allele Change
Residue Change
Inheritance Pattern
Inheritance Association
Family Type
Author, Year
 GEN476R001 
 missense_variant 
 c.845T>C 
 p.Leu282Pro 
 De novo 
 NA 
 Simplex 
 GEN476R002 
 frameshift_variant 
 c.1189del 
 p.Ile397SerfsTer19 
 De novo 
 NA 
 Simplex 
 GEN476R003 
 copy_number_loss 
  
  
 De novo 
 NA 
  
 GEN476R004 
 missense_variant 
 c.209G>A 
 p.Gly70Asp 
 De novo 
 NA 
  
 GEN476R005 
 copy_number_loss 
  
  
 Familial 
 Maternal 
 Multi-generational 
 GEN476R006 
 missense_variant 
 c.1322A>G 
 p.His441Arg 
 De novo 
 NA 
 Simplex 
 GEN476R007 
 missense_variant 
 c.1108G>T 
 p.Asp370Tyr 
 De novo 
 NA 
 Simplex 
 GEN476R008 
 missense_variant 
 c.983A>G 
 p.Asp328Gly 
 De novo 
 NA 
  
 GEN476R009 
 missense_variant 
 c.1331C>G 
 p.Pro444Arg 
 De novo 
 NA 
  
 GEN476R010 
 missense_variant 
 c.639T>A 
 p.His213Gln 
 De novo 
 NA 
  
 GEN476R011 
 frameshift_variant 
 c.800dup 
 p.Ile269TyrfsTer8 
 De novo 
 NA 
  
 GEN476R012 
 missense_variant 
 c.1337A>C 
 p.Tyr446Ser 
 De novo 
 NA 
  
 GEN476R013 
 missense_variant 
 c.1336T>G 
 p.Tyr446Asp 
 De novo 
 NA 
  
 GEN476R014 
 missense_variant 
 c.1379G>A 
 p.Gly460Asp 
 De novo 
 NA 
  
 GEN476R015 
 missense_variant 
 c.1107C>A 
 p.Asp369Glu 
 De novo 
 NA 
  
 GEN476R016 
 copy_number_gain 
  
  
 De novo 
 NA 
 Simplex 
 GEN476R017 
 copy_number_gain 
  
  
 Familial 
 Maternal 
 Multi-generational 
 GEN476R018 
 missense_variant 
 c.30C>G 
 p.Phe10Leu 
 De novo 
 NA 
 Simplex 
 GEN476R019 
 missense_variant 
 c.1337A>G 
 p.Tyr446Cys 
 De novo 
 NA 
  
 GEN476R020 
 missense_variant 
 c.1337A>G 
 p.Tyr446Cys 
 De novo 
 NA 
  
 GEN476R021 
 missense_variant 
 c.1336T>G 
 p.Tyr446Asp 
 De novo 
 NA 
  
 GEN476R022 
 missense_variant 
 c.974G>A 
 p.Cys325Tyr 
 De novo 
 NA 
 Simplex 
 GEN476R023 
 missense_variant 
 c.1336T>C 
 p.Tyr446His 
 De novo 
 NA 
 Simplex 
 GEN476R024 
 copy_number_gain 
  
  
 Familial 
 Maternal 
 Simplex 
 GEN476R025 
 missense_variant 
 c.1336T>C 
 p.Tyr446His 
 De novo 
 NA 
  
 GEN476R026 
 missense_variant 
 c.1336T>C 
 p.Tyr446His 
 De novo 
 NA 
  

Common

No Common Variants Available
Chromosome
CNV Locus
CNV Type
# of studies
Animal Model
3
Duplication
 1
 
3
Duplication
 1
 
3
Duplication
 2
 
3
Duplication
 1
 
3
Duplication
 1
 
3
Duplication
 2
 
3
Deletion-Duplication
 20
 
3
Deletion
 2
 
3
Duplication
 1
 
3
Deletion-Duplication
 14
 

No Animal Model Data Available


Interactor Symbol Interactor Name Interactor Organism Entrez ID Uniprot ID Interaction Type Evidence Reference
ABCF1 ATP-binding cassette, sub-family F (GCN20), member 1 23 Q8NE71 PCP; SILAC
Kristensen AR , et al. 2012
ARL2 ADP-ribosylation factor-like 2 402 G3V184 Y2H; bimolecular fluorescence complementation assay
Rolland T , et al. 2014
AXIN2 axin 2 8313 Q9Y2T1 ChIP
Li J and Wang CY 2008
BCL3 B-cell CLL/lymphoma 3 602 P20749 IP; MS; IP/WB
Keutgens A , et al. 2010
CCND1 cyclin D1 595 P24385 ChIP
Choi HK , et al. 2011
CD2BP2 CD2 (cytoplasmic tail) binding protein 2 10421 O95400 Ion-exchange chromatography; MS
Havugimana PC , et al. 2012
CHD4 chromodomain helicase DNA binding protein 4 1108 Q14839 Ion-exchange chromatography; MS
Havugimana PC , et al. 2012
CHD8 chromodomain helicase DNA binding protein 8 57680 Q9HCK8 ChIP-chip
Subtil-Rodrguez A , et al. 2013
CTNNB1 catenin (cadherin-associated protein), beta 1, 88kDa 1499 Q9WU82 Luciferase reporter assay; IP/WB
Li J and Wang CY 2008
ELAVL1 ELAV (embryonic lethal, abnormal vision, Drosophila)-like 1 (Hu antigen R) 1994 Q15717 RNP IP; Protein microarray
Abdelmohsen K , et al. 2009
EMD emerin 2010 P50402 Affinity chromatography; IP/WB
Holaska JM and Wilson KL 2007
FKBP6 FK506 binding protein 6, 36kDa 8468 O75344 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
GPS2 G protein pathway suppressor 2 2874 Q13227 IP; MS
Bantscheff M , et al. 2011
GPS2 G protein pathway suppressor 2 2874 Q13227 IP; LC-MS/MS
Huttlin EL , et al. 2015
HAO2 Hydroxyacid oxidase 2 51179 Q9NYQ3 IP; LC-MS/MS
Huttlin EL , et al. 2015
HDAC3 Histone deacetylase 3 8841 O15379 Affinity chromatography; MS
Zhang J , et al. 2002
HDAC5 Histone deacetylase 5 10014 Q9UQL6 IP; MS
Greco TM , et al. 2010
HIST2H2BE histone cluster 2, H2be 8349 Q16778 GST
Yoon HG , et al. 2003
HIST2H4A histone cluster 2, H4a 8370 B2R4R0 GST
Yoon HG , et al. 2003
IL17RA interleukin 17 receptor A 23765 Q96F46 IP; LC-MS/MS
Huttlin EL , et al. 2015
KDM1A lysine (K)-specific demethylase 1A 23028 O60341 IP; MS
Bantscheff M , et al. 2011
KLK3 kallikrein-related peptidase 3 354 P07288 ChIP
Zhu P , et al. 2006
MKX Homeobox protein Mohawk 283078 Q8IYA7 IP; LC-MS/MS
Huttlin EL , et al. 2015
MYC v-myc myelocytomatosis viral oncogene homolog (avian) 4609 P01106 ChIP
Li J and Wang CY 2008
NCAPH2 non-SMC condensin II complex, subunit H2 29781 Q6IBW4 IP; LC-MS/MS
Huttlin EL , et al. 2015
NCOR1 nuclear receptor corepressor 1 9611 O75376 Affinity chromatography; MS
Zhang J , et al. 2002
NCOR2 nuclear receptor corepressor 2 9612 Q9Y618 GST; IP/WB
Zhang XM , et al. 2006
NOTCH1 notch 1 4851 P46531 IP; MS
Yatim A , et al. 2012
PSMA3 proteasome (prosome, macropain) subunit, alpha type, 3 5684 P25788 GST
Fedorova OA , et al. 2011
QPRT Nicotinate-nucleotide pyrophosphorylase [carboxylating] 23475 Q15274 IP; LC-MS/MS
Huttlin EL , et al. 2015
RARB retinoic acid receptor, beta 5915 F1D8S6 ChIP
Zhu P , et al. 2006
SENP1 SUMO1/sentrin specific peptidase 1 29843 Q9P0U3 IP/WB
Choi HK , et al. 2011
SKI v-ski sarcoma viral oncogene homolog (avian) 6497 P12755 Affinity chromatography; IP/WB
Tabata T , et al. 2008
SUMO1 SMT3 suppressor of mif two 3 homolog 1 (S. cerevisiae) 7341 P63165 in vitro SUMOylation assay; IP/WB; in vivo SUMOylation assay
Choi HK , et al. 2011
TAB2 TGF-beta activated kinase 1/MAP3K7 binding protein 2 23118 B4DIR9 ChIP
Zhu P , et al. 2006
TBL1X transducin (beta)-like 1X-linked 6907 O60907 IP; MS
Bantscheff M , et al. 2011
TBL1Y F-box-like/WD repeat-containing protein TBL1Y 90665 Q9BQ87 IP; LC-MS/MS
Huttlin EL , et al. 2015
TBL3 transducin (beta)-like 3 10607 Q12788 IP/WB
Choi HK , et al. 2008
THRA thyroid hormone receptor, alpha 7067 P10827 GST; MS
Jeyakumar M , et al. 2007
THRB thyroid hormone receptor, beta 7068 F1D8N7 GST; MS
Jeyakumar M , et al. 2007
TOP3B topoisomerase (DNA) III beta 8940 O95985 HITS-CLIP
Xu D , et al. 2013
UBC ubiquitin C 7316 P63279 Affinity chromatography
Danielsen JM , et al. 2010
UBE2D1 ubiquitin-conjugating enzyme E2D 1 (UBC4/5 homolog, yeast) 7321 P51668 IP/WB
Perissi V , et al. 2004
UBE2E3 ubiquitin-conjugating enzyme E2E 3 10477 Q969T4 IP/WB
Choi HK , et al. 2008
vif Virion infectivity factor 155459 P69720 Affinity chromatography
Jger S , et al. 2011
WNT3A wingless-type MMTV integration site family, member 3A 89780 P56704 IP/WB
Choi HK , et al. 2011
Camk2g calcium/calmodulin-dependent protein kinase II gamma 12325 Q923T9 IP/WB; GST
Huang W , et al. 2009
Sox2 SRY-box containing gene 2 20674 P48432 Affinity chromatography
Engelen E , et al. 2011

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