TRAPPC6B

trafficking protein particle complex subunit 6B, the group of Trafficking protein particle complex subunits

Basic information

Region (hg38): 14:39147811-39170532

Links

ENSG00000182400 ∙ NCBI:122553 ∙ OMIM:610397 ∙ HGNC:23066 ∙ Uniprot:Q86SZ2 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• neurodevelopmental disorder with microcephaly, epilepsy, and brain atrophy (Moderate), mode of inheritance: AR
• neurodevelopmental disorder with microcephaly, epilepsy, and brain atrophy (Moderate), mode of inheritance: AR
• neurodevelopmental disorder with microcephaly, epilepsy, and brain atrophy (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Neurodevelopmental disorder with microcephaly, epilepsy, and brain atrophy	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Neurologic	28397838; 28626029

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the TRAPPC6B gene.

• not_provided (34 variants)
• Inborn_genetic_diseases (19 variants)
• Neurodevelopmental_disorder_with_microcephaly,_epilepsy,_and_brain_atrophy (8 variants)
• TRAPPC6B-related_disorder (7 variants)
• TRAPPC6B-related_neurodevelopmental_disorder (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TRAPPC6B gene is commonly pathogenic or not. These statistics are base on transcript: NM_001079537.2. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				10	2	12
missense			25	1		26
nonsense	2	2				4
start loss			1			1
frameshift	1					1
splice donor/acceptor (+/-2bp)	2	2				4
Total	5	4	26	11	2

Highest pathogenic variant AF is 0.000021182243

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TRAPPC6B	protein_coding	protein_coding	ENST00000330149	6	22722

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.000153	0.684	125715	0	31	125746	0.000123

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.107	81	83.7	0.967	0.00000417	1035
Missense in Polyphen		31	26.911	1.1519		383
Synonymous	-1.47	42	31.5	1.33	0.00000172	276
Loss of Function	0.864	7	9.94	0.704	4.83e-7	126

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000505	0.000499
Ashkenazi Jewish	0.00	0.00
East Asian	0.000228	0.000217
Finnish	0.00	0.00
European (Non-Finnish)	0.0000623	0.0000615
Middle Eastern	0.000228	0.000217
South Asian	0.000145	0.000131
Other	0.000169	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Component of a transport protein particle (TRAPP) complex that may function in specific stages of inter-organelle traffic (PubMed:16025134, PubMed:16828797). Specifically involved in the early development of neural circuitry, likely by controlling the frequency and amplitude of intracellular calcium transients implicated in the regulation of neuron differentiation and survival (Probable). {ECO:0000269|PubMed:16025134, ECO:0000269|PubMed:16828797, ECO:0000305|PubMed:28626029}.
• Pathway: Vesicle-mediated transport;Membrane Trafficking;Post-translational protein modification;Metabolism of proteins;Transport to the Golgi and subsequent modification;Asparagine N-linked glycosylation;Rab regulation of trafficking;RAB GEFs exchange GTP for GDP on RABs;COPII-mediated vesicle transport;ER to Golgi Anterograde Transport (Consensus)

Recessive Scores

• pRec: 0.118

Intolerance Scores

• loftool: 0.533
• rvis_EVS: -0.21
• rvis_percentile_EVS: 38.28

Haploinsufficiency Scores

• pHI: 0.205
• hipred: N
• hipred_score: 0.335
• ghis: 0.634

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.973

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Trappc6b

Gene ontology

• Biological process: endoplasmic reticulum to Golgi vesicle-mediated transport;nervous system development;regulation of GTPase activity;COPII vesicle coating
• Cellular component: Golgi membrane;endoplasmic reticulum;cis-Golgi network;trans-Golgi network;cytosol
• Molecular function: protein binding;Rab guanyl-nucleotide exchange factor activity