Human Gene Module / Chromosome 14 / TRAPPC6B

TRAPPC6Btrafficking protein particle complex 6B

Score
S
Syndromic Syndromic
Autism Reports / Total Reports
0 / 2
Rare Variants / Common Variants
2 / 0
Aliases
TRAPPC6B, TPC6
Associated Syndromes
-
Genetic Category
Rare Single Gene Mutation, Syndromic
Chromosome Band
14q21.1
Associated Disorders
ASD
Relevance to Autism

A homozygous founder splice-site variant in the TRAPPC6B gene was identified in six individuals from three unrelated Egyptian families presenting with a neurodevelopmental disorder characterized by autistic features (poor social interaction and motor stereotypies such as hand flapping), motor delay, delayed or absent speech, epilepsy, and microcephaly (Marin-Valencia et al., 2017). In the same report, zebrafish trappc6b morphants were found to exhibit reduced head size and lowered seizure threshold, thereby replicating the human phenotype. A homozygous nonsense variant in the TRAPPC6B gene had previously been identified in a consanguineous family with two individuals presenting with autosomal-recessive intellectual disability (Harripaul et al., 2017).

Molecular Function

TRAPPC6B is a component of TRAPP complexes, which are tethering complexes involved in vesicle transport. It may play a role in vesicular transport from endoplasmic reticulum to Golgi.

Reports related to TRAPPC6B (2 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Support Mapping autosomal recessive intellectual disability: combined microarray and exome sequencing identifies 26 novel candidate genes in 192 consanguin... Harripaul R , et al. (2017) No -
2 Primary A homozygous founder mutation in TRAPPC6B associates with a neurodevelopmental disorder characterised by microcephaly, epilepsy and autistic features. Marin-Valencia I , et al. (2017) No Autistic features (poor social interaction, motor
Rare Variants   (2)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.[124C>T];[124C>T] p.[Arg42Ter];[Arg42Ter] stop_gained;stop_gained Familial Both parents Multiplex 28397838 Harripaul R , et al. (2017)
c.[82-2A>G];[82-2A>G] p.[Glu28ValfsTer11];[Glu28ValfsTer11] splice_site_variant;splice_site_variant Familial Both parents Multiplex 28626029 Marin-Valencia I , et al. (2017)
Common Variants  

No common variants reported.

SFARI Gene score
S

Syndromic

S

Score Delta: Score remained at S

The syndromic category includes mutations that are associated with a substantial degree of increased risk and consistently linked to additional characteristics not required for an ASD diagnosis. If there is independent evidence implicating a gene in idiopathic ASD, it will be listed as "#S" (e.g., 2S, 3S, etc.). If there is no such independent evidence, the gene will be listed simply as "S."

Krishnan Probability Score

Score 0.41992685868384

Ranking 21168/25841 scored genes


[Show Scoring Methodology]
Krishnan and colleagues generated probability scores genome-wide by using a machine learning approach on a human brain-specific gene network. The method was first presented in Nat Neurosci 19, 1454-1462 (2016), and scores for more than 25,000 RefSeq genes can be accessed in column G of supplementary table 3 (see: http://www.nature.com/neuro/journal/v19/n11/extref/nn.4353-S5.xlsx). A searchable browser, with the ability to view networks of associated ASD risk genes, can be found at asd.princeton.edu.
ExAC Score

Score 0.021980277629556

Ranking 9319/18225 scored genes


[Show Scoring Methodology]
The Exome Aggregation Consortium (ExAC) is a summary database of 60,706 exomes that has been widely used to estimate 'constraint' on mutation for individual genes. It was introduced by Lek et al. Nature 536, 285-291 (2016), and the ExAC browser can be found at exac.broadinstitute.org. The pLI score was developed as measure of intolerance to loss-of- function mutation. A pLI > 0.9 is generally viewed as highly constrained, and thus any loss-of- function mutations in autism in such a gene would be more likely to confer risk. For a full list of pLI scores see: ftp://ftp.broadinstitute.org/pub/ExAC_release/release0.3.1/functional_gene_constraint/fordist_cle aned_exac_nonTCGA_z_pli_rec_null_data.txt
Sanders TADA Score

Score 0.92776195545174

Ranking 10749/18665 scored genes


[Show Scoring Methodology]
The TADA score ('Transmission and De novo Association') was introduced by He et al. PLoS Genet 9(8):e1003671 (2013), and is a statistic that integrates evidence from both de novo and transmitted mutations. It forms the basis for the claim of 65 individual genes being strongly associated with autism risk at a false discovery rate of 0.1 (Sanders et al. Neuron 87, 1215-1233 (2015)). The calculated TADA score for 18,665 RefSeq genes can be found in column P of Supplementary Table 6 in the Sanders et al. paper (the column headed 'tadaFdrAscSscExomeSscAgpSmallDel'), which represents a combined analysis of exome data and small de novo deletions (see www.cell.com/cms/attachment/2038545319/2052606711/mmc7.xlsx).
Zhang D Score

Score -0.2623684729846

Ranking 16602/20870 scored genes


[Show Scoring Methodology]
The DAMAGES score (disease-associated mutation analysis using gene expression signatures), or D score, was developed to combine evidence from de novo loss-of- function mutation with evidence from cell-type- specific gene expression in the mouse brain (specifically translational profiles of 24 specific mouse CNS cell types isolated from 6 different brain regions). Genes with positive D scores are more likely to be associated with autism risk, with higher-confidence genes having higher D scores. This statistic was first presented by Zhang & Shen (Hum Mutat 38, 204- 215 (2017), and D scores for more than 20,000 RefSeq genes can be found in column M in supplementary table 2 from that paper.
CNVs associated with TRAPPC6B(1 CNVs)
14q21.1 12 Deletion-Duplication 19  /  52
Submit New Gene

Report an Error