TRAPPC6B

Chr 14AR

trafficking protein particle complex subunit 6B

Also known as: NEDMEBA, TPC6

NCBI Gene: 122553ENSG00000182400UniProt: Q86SZ2

TRAPPC6B is a component of TRAPP complexes, which are tethering complexes involved in vesicle transport (Kummel et al., 2005 [PubMed 16025134]).[supplied by OMIM, Mar 2008]

Primary Disease Associations & Inheritance

Neurodevelopmental disorder with microcephaly, epilepsy, and brain atrophyMIM #617862
AR
104
ClinVar variants
38
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— TRAPPC6B
🧬
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.
📋
ClinVar Variants
38 Pathogenic / Likely Pathogenic· 37 VUS of 104 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
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?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.11Z-score
OE missense 0.97 (0.81–1.16)
81 obs / 83.7 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.70 (0.40–1.32)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.97 (0.81–1.16)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.33
0≤1.21.6
LoF obs/exp: 7 / 9.9Missense obs/exp: 81 / 83.7Syn Z: -1.47

ClinVar Variant Classifications

104 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic32
Likely Pathogenic6
VUS37
Likely Benign20
Benign9
32
Pathogenic
6
Likely Pathogenic
37
VUS
20
Likely Benign
9
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
4
0
28
0
32
Likely Pathogenic
3
0
3
0
6
VUS
0
27
10
0
37
Likely Benign
0
1
7
12
20
Benign
0
0
7
2
9
Total7285514104

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.

Gene2Phenotype Curations

TRAPPC6B-related neurodevelopmental disorder with microcephaly, epilepsy, and brain atrophy

strong
ARLoss Of FunctionAbsent Gene Product, Altered Gene Product Structure
Dev. Disorders
G2P ↗
splice region variantstop gainedmissense variantframeshift variant NMD escaping

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Neurodevelopmental disorder with microcephaly, epilepsy, and brain atrophy

MIM #617862

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
A Humanized Yeast Model for Studying TRAPP Complex Mutations; Proof-of-Concept Using Variants from an Individual with a TRAPPC1-Associated Neurodevelopmental Syndrome.
Zykaj E et al.·Cells
2024Functional
A TRAPPC6B splicing variant associates to restless legs syndrome.
Aridon P et al.·Parkinsonism Relat Disord
2016
TRAPPC6B biallelic variants cause a neurodevelopmental disorder with TRAPP II and trafficking disruptions.
Almousa H et al.·Brain
2024
A homozygous founder mutation in TRAPPC6B associates with a neurodevelopmental disorder characterised by microcephaly, epilepsy and autistic features.
Marin-Valencia I et al.·J Med Genet
2018
Description of novel variants in consanguineous Pakistani families affected with intellectual disability.
Rasool IG et al.·Genes Genomics
2023
[Analysis of clinical phenotype and gene variation of a child with neurodevelopmental disorder caused by homozygous variation of TRAPPC6B gene].
Li W et al.·Zhonghua Yi Xue Yi Chuan Xue Za Zhi
2025Case report
RAB5A and TRAPPC6B are novel targets for Shiga toxin 2a inactivation in kidney epithelial cells.
Kouzel IU et al.·Sci Rep
2020
Mapping autosomal recessive intellectual disability: combined microarray and exome sequencing identifies 26 novel candidate genes in 192 consanguineous families.
Harripaul R et al.·Mol Psychiatry
2018
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools