TRAPPC3

Chr 1

trafficking protein particle complex subunit 3

Also known as: BET3

NCBI Gene: 27095 ENSG00000054116 UniProt: O43617 OMIM: 610955

The protein is a component of the trafficking protein particle complex that tethers transport vesicles to the cis-Golgi membrane and regulates transport from the endoplasmic reticulum to the Golgi apparatus. Mutations cause spondyloepiphyseal dysplasia tarda, an X-linked skeletal dysplasia characterized by short stature and spinal abnormalities that typically manifest in late childhood or adolescence. The gene shows X-linked inheritance.

OMIM ResearchSummary from RefSeq, UniProt

This gene encodes a component of the trafficking protein particle complex, which tethers transport vesicles to the cis-Golgi membrane. The encoded protein participates in the regulation of transport from the endoplasmic reticulum to the Golgi apparatus. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2012]

OMIM ResearchGenerating clinical summary…

DNmechanismLOEUF 0.83

Clinical Summary— TRAPPC3

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Population Constraint (gnomAD)

Constrained for loss-of-function variants (OE-LoF 0.27) despite low pLI — interpret in context.

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ClinVar Variants

1 unique Pathogenic / Likely Pathogenic· 34 VUS of 55 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?

0.83LOEUF

pLI 0.251

Z-score 1.87

OE 0.27 (0.11–0.83)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

1.20Z-score

OE missense 0.67 (0.55–0.81)

69 obs / 103.4 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.27 (0.11–0.83)

0≤0.351.4

Missense OE?0.67 (0.55–0.81)

0≤0.61.4

Synonymous OE?0.73

0≤1.21.6

LoF obs/exp: 2 / 7.5Missense obs/exp: 69 / 103.4Syn Z: 1.31

This gene — mechanism propensity

0.6452th %ile

GOF

0.5758th %ile

LOF

0.3452th %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

55 submitted variants in ClinVar

ClinVar

Classification Summary

Likely Pathogenic1

VUS34

Likely Benign10

Benign4

Likely Pathogenic

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	0	0	0
Likely Pathogenic	0	1	0	0	1
VUS	2	31	1	0	34
Likely Benign	0	0	6	4	10
Benign	0	0	2	2	4
Total	2	32	9	6	49

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

View in ClinVar →

8 pathogenic / likely-pathogenic (of 14) ClinVar copy-number / structural variants overlap TRAPPC3 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →