TRAPPC1

Chr 17

trafficking protein particle complex subunit 1

Also known as: BET5, MUM2

NCBI Gene: 58485 ENSG00000170043 UniProt: Q9Y5R8 OMIM: 610969

TRAPPC1 encodes a component of the transport protein particle (TRAPP) complex that facilitates vesicular transport from the endoplasmic reticulum to the Golgi apparatus. Mutations cause autosomal recessive limb-girdle muscular dystrophy type 18 (LGMDR18), characterized by progressive proximal muscle weakness typically beginning in childhood or adolescence. The gene shows low constraint against loss-of-function variants, consistent with its recessive inheritance pattern.

OMIM ResearchSummary from UniProt

This gene product plays a role in vesicular transport of proteins to the Golgi apparatus from the endoplasmic reticulum. The encoded protein is a component of the multisubunit transport protein particle (TRAPP) complex. Alternative splicing results in multiple transcript variants.[provided by RefSeq, Oct 2009]

OMIM ResearchGenerating clinical summary…

DNmechanismLOEUF 0.90

Clinical Summary— TRAPPC1

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Population Constraint (gnomAD)

Constrained for loss-of-function variants (OE-LoF 0.35) despite low pLI — interpret in context.

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ClinVar Variants

13 VUS of 25 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.90LOEUF

pLI 0.087

Z-score 1.77

OE 0.35 (0.16–0.90)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

1.28Z-score

OE missense 0.62 (0.50–0.77)

55 obs / 89.0 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.35 (0.16–0.90)

0≤0.351.4

Missense OE?0.62 (0.50–0.77)

0≤0.61.4

Synonymous OE?1.17

0≤1.21.6

LoF obs/exp: 3 / 8.6Missense obs/exp: 55 / 89.0Syn Z: -0.82

This gene — mechanism propensity

0.6936th %ile

GOF

0.4776th %ile

LOF

0.3164th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

25 submitted variants in ClinVar

ClinVar

Classification Summary

VUS13

VUS

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Total
Pathogenic	0	0
Likely Pathogenic	0	0
VUS	13	13
Likely Benign	0	0
Benign	0	0
Total	13	13

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

View in ClinVar →

21 pathogenic / likely-pathogenic (of 29) ClinVar copy-number / structural variants overlap TRAPPC1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →