TRAPPC8

Chr 18

trafficking protein particle complex subunit 8

Also known as: GSG1, HsT2706, KIAA1012, TRS85

NCBI Gene: 22878ENSG00000153339UniProt: Q9Y2L5OMIM: 614136

The TRAPPC8 protein functions in endoplasmic reticulum to Golgi trafficking, maintains the ATG9 cycling pool required for autophagy initiation, and is involved in collagen secretion. Mutations cause autosomal recessive intellectual developmental disorder with seizures and spasticity, typically presenting in infancy with developmental delays, epilepsy, and progressive spasticity. This gene is highly constrained against loss-of-function variants, indicating that complete loss of protein function is likely incompatible with normal development.

OMIMResearchSummary from RefSeq, UniProt
LOFmechanismLOEUF 0.14
Clinical Summary— TRAPPC8
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
39 unique Pathogenic / Likely Pathogenic· 192 VUS of 284 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint
0.14LOEUF
pLI 1.000
Z-score 7.55
OE 0.07 (0.03–0.14)
Highly constrained

Among the most LoF-intolerant genes (~top 3%)

Missense Constraint
1.21Z-score
OE missense 0.87 (0.82–0.93)
634 obs / 725.8 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.07 (0.03–0.14)
0≤0.351.4
Missense OE0.87 (0.82–0.93)
0≤0.61.4
Synonymous OE1.13
0≤1.21.6
LoF obs/exp: 5 / 76.0Missense obs/exp: 634 / 725.8Syn Z: -1.59
DN
0.2399th %ile
GOF
0.2198th %ile
LOF
0.77top 5%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.14

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

284 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic38
Likely Pathogenic1
VUS192
Likely Benign8
Benign3
38
Pathogenic
1
Likely Pathogenic
192
VUS
8
Likely Benign
3
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
38
0
38
Likely Pathogenic
0
0
1
0
1
VUS
0
181
11
0
192
Likely Benign
0
4
2
2
8
Benign
0
1
2
0
3
Total0186542242

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

TRAPPC8 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients