TRAPPC6B

Chr 14AR

trafficking protein particle complex subunit 6B

Also known as: NEDMEBA, TPC6

NCBI Gene: 122553ENSG00000182400UniProt: Q86SZ2OMIM: 610397

TRAPPC6B encodes a component of transport protein particle (TRAPP) complexes that function in vesicle transport between cellular organelles and regulate intracellular calcium transients critical for neuron differentiation and survival. Biallelic mutations cause autosomal recessive neurodevelopmental disorder with microcephaly, epilepsy, and brain atrophy. The gene is not highly constrained against loss-of-function variants, consistent with its recessive inheritance pattern.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismARLOEUF 1.321 OMIM phenotype
Clinical Summary— TRAPPC6B
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Gene-Disease Validity (ClinGen)
neurodevelopmental disorder with microcephaly, epilepsy, and brain atrophy · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
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ClinVar Variants
38 unique Pathogenic / Likely Pathogenic· 38 VUS of 116 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
1.32LOEUF
pLI 0.000
Z-score 0.86
OE 0.70 (0.40–1.32)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.11Z-score
OE missense 0.97 (0.81–1.16)
81 obs / 83.7 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.70 (0.40–1.32)
0≤0.351.4
Missense OE0.97 (0.81–1.16)
0≤0.61.4
Synonymous OE1.33
0≤1.21.6
LoF obs/exp: 7 / 9.9Missense obs/exp: 81 / 83.7Syn Z: -1.47
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
strongTRAPPC6B-related neurodevelopmental disorder with microcephaly, epilepsy, and brain atrophyLOFAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.78top 25%
GOF
0.4480th %ile
LOF
0.2968th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

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

ClinVar Variant Classifications

116 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic32
Likely Pathogenic6
VUS38
Likely Benign20
Benign9
32
Pathogenic
6
Likely Pathogenic
38
VUS
20
Likely Benign
9
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
6
0
26
0
32
Likely Pathogenic
5
0
1
0
6
VUS
0
28
10
0
38
Likely Benign
0
1
7
12
20
Benign
0
0
7
2
9
Total11295114105

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

View in ClinVar →

Protein Context — Lollipop Plot

TRAPPC6B · 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