TRAPPC8

Chr 18

trafficking protein particle complex subunit 8

Also known as: GSG1, HsT2706, KIAA1012, TRS85

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.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
1
Pubs (1 yr)
39
P/LP submissions
0%
P/LP missense
0.14
LOEUF· LoF intol.
LOF
Mechanism· predicted
Clinical SummaryTRAPPC8
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
37 unique Pathogenic / Likely Pathogenic· 189 VUS of 279 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.14LOEUF
pLI 1.000
Z-score 7.55
OE 0.07 (0.030.14)
Highly constrained

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

Missense Constraint
1.21Z-score
OE missense 0.87 (0.820.93)
634 obs / 725.8 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.07 (0.030.14)
00.351.4
Missense OE0.87 (0.820.93)
00.61.4
Synonymous OE1.13
01.21.6
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

279 submitted variants in ClinVar

Classification Summary

Pathogenic36
Likely Pathogenic1
VUS189
Likely Benign8
Benign3
36
Pathogenic
1
Likely Pathogenic
189
VUS
8
Likely Benign
3
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
36
0
36
Likely Pathogenic
0
0
1
0
1
VUS
0
178
11
0
189
Likely Benign
0
4
2
2
8
Benign
0
1
2
0
3
Total0183522237

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.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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