TRAPPC2
protein-codingtrafficking protein particle complex subunit 2, the group of Trafficking protein particle complex subunits
Gene summary
The protein encoded by this gene is thought to be part of a large multi-subunit complex involved in the targeting and fusion of endoplasmic reticulum-to-Golgi transport vesicles with their acceptor compartment. In addition, the encoded protein can bind c-myc promoter-binding protein 1 and block its transcriptional repression capability. Mutations in this gene are a cause of spondyloepiphyseal dysplasia tarda (SEDT). A processed pseudogene of this gene is located on chromosome 19, and other pseudogenes are found on chromosomes 8 and Y. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Mar 2010]
- SEDL
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~22.4 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: XL
Disease ID:MONDO:0010737
Submitter: G2P
Inheritance Pattern: XL
Disease ID:MONDO:0010737
Submitter: PanelApp Australia
Inheritance Pattern: XL
Disease ID:MONDO:0010737
Submitter: Labcorp Genetics (formerly Invitae)
Inheritance Pattern: AD
Disease ID:MONDO:0019667
Submitter: Orphanet
Clinical Genomic Database (CGD)
Manifestation: Musculoskeletal
Intervention: General
Rationale: 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
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to TRAPPC2 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001011658.4. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 2 | 9 | 5 | 16 | ||
| missense | 2 | 23 | 1 | 2 | 28 | |
| nonsense | 6 | 1 | 1 | 8 | ||
| start loss | 1 | 1 | ||||
| frameshift | 14 | 4 | 1 | 19 | ||
| splice donor/acceptor (+/-2bp) | 2 | 4 | 6 | 12 | ||
| Total | 23 | 11 | 33 | 10 | 7 | 84 |
Highest pathogenic variant AF is 0.0000027855256
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001011658.1 | 4 | MANE Select | |
| Ensembl | ENSP00000369953.1 | 4 | MANE Select | |
| RefSeq | NP_001122307.2 | 5 | Standard | |
| RefSeq | NP_055378.1 | 4 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Vesicle-mediated transport
- Membrane Trafficking
- Post-translational protein modification
- Metabolism of proteins
- Transport to the Golgi and subsequent modification
Biological Process
- skeletal system development
- regulation of transcription, DNA-templated
- endoplasmic reticulum to Golgi vesicle-mediated transport
- COPII vesicle coating
Molecular Function
- protein binding
- transcription factor binding
- Rab guanyl-nucleotide exchange factor activity
- ion channel binding
Cellular Component
- Golgi membrane
- nucleus
- nucleoplasm
- endoplasmic reticulum
- endoplasmic reticulum-Golgi intermediate compartment
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000458511
- Coding exons
- 5
- Length
- 22392
- Individuals with no LoFs
- 115758
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 2
- Defined
- 115760
- p
- 0.00000864
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.53 | 24 | 56.4 | 0.426 | 0.00000404 | 1169 |
| Missense (PolyPhen) | 4 | 13.921 | 0.28734 | 333 | ||
| Synonymous | -0.429 | 24 | 21.5 | 1.12 | 0.00000178 | 290 |
| Loss of Function | 0.275 | 4 | 4.64 | 0.862 | 3.36e-7 | 95 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.000081 | 0.000058 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000014 | 0.0000096 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Prevents transcriptional repression and induction of cell death by ENO1 (By similarity). May play a role in vesicular transport from endoplasmic reticulum to Golgi. {ECO:0000250}.;
Recessive Scores
- pRec
- 0.355
Intolerance Scores
- RVIS EVS
- 0.12
- RVIS percentile EVS
- 62.38
Essentials
- Essential (CRISPR)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.824
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Low | Low | Low |
| Primary Immunodeficiency | Medium | Low | Medium |
| Cancer | Low | Low | Low |