TRAPPC6Btrafficking protein particle complex 6B
Autism Reports / Total Reports
2 / 9Rare Variants / Common Variants
24 / 0Aliases
TRAPPC6B, TPC6Associated Syndromes
-Chromosome Band
14q21.1Associated Disorders
ASDRelevance 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.
External Links
SFARI Genomic Platforms
Reports related to TRAPPC6B (9 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 consanguineous families | 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 |
3 | Support | Lessons Learned from Large-Scale, First-Tier Clinical Exome Sequencing in a Highly Consanguineous Population | Monies D , et al. (2019) | No | ASD |
4 | Support | Increased diagnostic and new genes identification outcome using research reanalysis of singleton exome sequencing | Bruel AL , et al. (2019) | No | - |
5 | Support | Utility of clinical exome sequencing in a complex Emirati pediatric cohort | Mahfouz NA et al. (2020) | No | - |
6 | Support | - | Levchenko O et al. (2022) | No | - |
7 | Support | - | Zhou X et al. (2022) | Yes | - |
8 | Support | - | Cirnigliaro M et al. (2023) | Yes | - |
9 | Support | - | Hashem Almousa et al. (2024) | No | ASD, epilepsy/seizures, stereotypy |
Rare Variants (24)
Status | Allele Change | Residue Change | Variant Type | Inheritance Pattern | Parental Transmission | Family Type | PubMed ID | Author, Year |
---|---|---|---|---|---|---|---|---|
c.91C>T | p.Arg31Ter | stop_gained | Unknown | - | - | 31231135 | Bruel AL , et al. (2019) | |
c.275A>G | p.Tyr92Cys | missense_variant | De novo | - | - | 35982159 | Zhou X et al. (2022) | |
c.37G>T | p.Glu13Ter | stop_gained | Familial | Both parents | - | 37713627 | Hashem Almousa et al. (2024) | |
c.47C>G | p.Tyr19Ter | stop_gained | Familial | Both parents | - | 37713627 | Hashem Almousa et al. (2024) | |
c.268-2_268-1del | - | splice_site_variant | Unknown | - | Simplex | 37713627 | Hashem Almousa et al. (2024) | |
c.27_29del | p.Leu10del | missense_variant | Unknown | - | Simplex | 37713627 | Hashem Almousa et al. (2024) | |
c.381_382del | p.Gly128TrpfsTer14 | splice_site_variant | Unknown | - | - | 31130284 | Monies D , et al. (2019) | |
c.267+1G>A | - | splice_site_variant | Familial | Both parents | Simplex | 32382396 | Mahfouz NA et al. (2020) | |
c.37G>T | p.Glu13Ter | stop_gained | Familial | Paternal | Multiplex | 37506195 | Cirnigliaro M et al. (2023) | |
c.91C>T | p.Arg31Ter | stop_gained | Familial | Both parents | Simplex | 37713627 | Hashem Almousa et al. (2024) | |
c.124C>T | p.Arg42Ter | stop_gained | Familial | Both parents | Multiplex | 28397838 | Harripaul R , et al. (2017) | |
c.150-1G>A | - | splice_site_variant | Familial | Both parents | Simplex | 37713627 | Hashem Almousa et al. (2024) | |
c.352-2A>G | - | splice_site_variant | Familial | Both parents | Simplex | 37713627 | Hashem Almousa et al. (2024) | |
c.91C>T | p.Arg31Ter | stop_gained | Familial | Both parents | Multiplex | 37713627 | Hashem Almousa et al. (2024) | |
c.124C>T | p.Arg42Ter | stop_gained | Familial | Both parents | Multiplex | 37713627 | Hashem Almousa et al. (2024) | |
c.283C>T | p.Gln95Ter | stop_gained | Familial | Both parents | Multiplex | 37713627 | Hashem Almousa et al. (2024) | |
c.149+2T>A | - | splice_site_variant | Familial | Both parents | Multiplex | 37713627 | Hashem Almousa et al. (2024) | |
c.445+5G>T | - | splice_site_variant | Familial | Both parents | Multiplex | 37713627 | Hashem Almousa et al. (2024) | |
c.454C>T | p.Gln152Ter | stop_gained | Familial | Both parents | Multiplex | 37713627 | Hashem Almousa et al. (2024) | |
c.119G>T | p.Gly40Val | missense_variant | Familial | Both parents | Multiplex | 35887114 | Levchenko O et al. (2022) | |
c.82-2A>G | - | splice_site_variant | Familial | Both parents | Multiplex | 28626029 | Marin-Valencia I , et al. (2017) | |
c.371G>T | p.Gly124Val | missense_variant | Familial | Both parents | Simplex | 37713627 | Hashem Almousa et al. (2024) | |
c.269del | - | splice_site_variant | Familial | Both parents | Extended multiplex | 37713627 | Hashem Almousa et al. (2024) | |
c.416del | p.Val139GlufsTer15 | frameshift_variant | Familial | Both parents | Not simplex (positive family history) | 31130284 | Monies D , et al. (2019) |
Common Variants
No common variants reported.
SFARI Gene score
Syndromic
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).
Score Delta: Score remained at S
criteria met
See SFARI Gene'scoring criteriaThe 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."
4/1/2020
Score remained at S
Description
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).
10/1/2019
Score remained at S
New Scoring Scheme
Description
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).
Reports Added
[New Scoring Scheme]7/1/2019
Score remained at S
Description
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).
Krishnan Probability Score
Score 0.41992685868384
Ranking 21168/25841 scored genes
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ExAC Score
Score 0.021980277629556
Ranking 9319/18225 scored genes
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Sanders TADA Score
Score 0.92776195545174
Ranking 10749/18665 scored genes
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Zhang D Score
Score -0.2623684729846
Ranking 16602/20870 scored genes
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