TRAPPC4

trafficking protein particle complex subunit 4, the group of Trafficking protein particle complex subunits|MicroRNA protein coding host genes

Basic information

Region (hg38): 11:119018762-119025454

Links

ENSG00000196655 ∙ NCBI:51399 ∙ OMIM:610971 ∙ HGNC:19943 ∙ Uniprot:Q9Y296 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• neurodevelopmental disorder with epilepsy, spasticity, and brain atrophy (Definitive), mode of inheritance: AR
• syndromic intellectual disability (Supportive), mode of inheritance: AD
• neurodevelopmental disorder with epilepsy, spasticity, and brain atrophy (Limited), mode of inheritance: AR
• neurodevelopmental disorder with epilepsy, spasticity, and brain atrophy (Strong), mode of inheritance: AR
• neurodevelopmental disorder with epilepsy, spasticity, and brain atrophy (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Neurodevelopmental disorder with epilepsy, spasticity, 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	Craniofacial; Musculoskeletal; Neurologic	31794024

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the TRAPPC4 gene.

• not provided (20 variants)
• Inborn genetic diseases (10 variants)
• Neurodevelopmental disorder with epilepsy, spasticity, and brain atrophy (7 variants)
• Neurodevelopmental disorder with progressive microcephaly, spasticity, and brain anomalies (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TRAPPC4 gene is commonly pathogenic or not.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous					3	3
missense		1	14			15
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region		1	1	1		3
non coding					15	15
Total	0	1	14	0	18

Variants in TRAPPC4

This is a list of pathogenic ClinVar variants found in the TRAPPC4 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
11-119018802-A-G		not specified	Uncertain significance (Oct 04, 2022)
11-119018805-T-G		not specified	Uncertain significance (Dec 16, 2021)
11-119018811-G-A		not specified	Uncertain significance (Jan 17, 2024)
11-119018859-T-C		Neurodevelopmental disorder with epilepsy, spasticity, and brain atrophy	Uncertain significance (Aug 02, 2022)
11-119018893-G-C		not specified	Uncertain significance (Jan 19, 2024)
11-119018905-A-G		not specified	Uncertain significance (Sep 22, 2023)
11-119018978-A-G		TRAPPC4-related disorder	Likely benign (Jan 05, 2022)
11-119019100-C-T			Benign (May 15, 2021)
11-119019103-C-G			Benign (May 15, 2021)
11-119019112-C-G			Benign (May 15, 2021)
11-119019140-C-T		Neurodevelopmental disorder with epilepsy, spasticity, and brain atrophy	Uncertain significance (Mar 12, 2021)
11-119019158-T-C		Neurodevelopmental disorder with epilepsy, spasticity, and brain atrophy	Uncertain significance (-)
11-119019161-C-T		not specified	Uncertain significance (Apr 07, 2023)
11-119019174-G-A		not specified	Uncertain significance (Aug 17, 2022)
11-119019193-A-G		not specified	Uncertain significance (Mar 24, 2023)
11-119019227-G-A		Neurodevelopmental disorder with epilepsy, spasticity, and brain atrophy	Uncertain significance (Dec 20, 2021)
11-119019245-C-T		Neurodevelopmental disorder with epilepsy, spasticity, and brain atrophy	Uncertain significance (Jan 20, 2020)
11-119019266-G-C		not specified	Uncertain significance (May 18, 2022)
11-119019267-G-A			Benign (May 06, 2021)
11-119019312-C-T			Benign (May 05, 2021)
11-119019375-C-T			Benign (May 15, 2021)
11-119019446-T-C			Benign (May 22, 2021)
11-119020092-C-A			Benign (May 16, 2021)
11-119020173-T-C		Neurodevelopmental disorder with epilepsy, spasticity, and brain atrophy	Likely pathogenic (-)
11-119020198-C-T			Benign (May 05, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TRAPPC4	protein_coding	protein_coding	ENST00000533632	5	7023

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00000412	0.394	125711	0	36	125747	0.000143

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.428	106	119	0.890	0.00000526	1407
Missense in Polyphen		36	43.975	0.81864		550
Synonymous	-2.49	69	47.2	1.46	0.00000218	446
Loss of Function	0.448	9	10.6	0.851	5.49e-7	116

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000456	0.000456
Ashkenazi Jewish	0.00	0.00
East Asian	0.000217	0.000217
Finnish	0.00	0.00
European (Non-Finnish)	0.000123	0.000123
Middle Eastern	0.000217	0.000217
South Asian	0.000261	0.000261
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: May play a role in vesicular transport from endoplasmic reticulum to Golgi.
• Pathway: Vesicle-mediated transport;Membrane Trafficking;Post-translational protein modification;Metabolism of proteins;Extracellular matrix organization;Transport to the Golgi and subsequent modification;Asparagine N-linked glycosylation;Rab regulation of trafficking;Syndecan interactions;Non-integrin membrane-ECM interactions;RAB GEFs exchange GTP for GDP on RABs;COPII-mediated vesicle transport;ER to Golgi Anterograde Transport;Syndecan-2-mediated signaling events (Consensus)

Recessive Scores

• pRec: 0.145

Intolerance Scores

• loftool: 0.580
• rvis_EVS: -0.27
• rvis_percentile_EVS: 33.97

Haploinsufficiency Scores

• pHI: 0.0542
• hipred: Y
• hipred_score: 0.576
• ghis: 0.653

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.842

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Trappc4

Gene ontology

• Biological process: endoplasmic reticulum to Golgi vesicle-mediated transport;dendrite development;COPII vesicle coating
• Cellular component: Golgi membrane;endoplasmic reticulum;Golgi stack;cytosol;synaptic vesicle;TRAPP complex;dendrite;synapse
• Molecular function: protein binding;Rab guanyl-nucleotide exchange factor activity