TRAPPC6B

Chr 14

trafficking protein particle complex subunit 6B

Also known as: NEDMEBA, TPC6

NCBI Gene: 122553 ENSG00000182400 UniProt: Q86SZ2

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.

ResearchSummary from RefSeq, OMIM, UniProt

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]

ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtNeurodevelopmental disorder with microcephaly, epilepsy, and brain atrophy

Clinical highlights

Gene–disease validity (ClinGen)

Definitive · neurodevelopmental disorder with microcephaly, epilepsy, and brain atrophy · AR · ClinGen 2024

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.32

LOEUF

LOF

Mechanism· G2P

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

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 OE?0.70 (0.40–1.32)

0≤0.351.4

Missense OE?0.97 (0.81–1.16)

0≤0.61.4

Synonymous OE?1.33

0≤1.21.6

LoF obs/exp: 7 / 9.9Missense obs/exp: 81 / 83.7Syn Z: -1.47

Background carrier burden — how many people carry a rare variant somewhere in TRAPPC6B?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 320

225 rare PASS variants

Rare truncating (LoF)

1 in 3,100

52 rare PASS variants

Rare synonymous (reference)

1 in 500

83 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for TRAPPC6B. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 8 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 310	1 in 3,500
South Asian	~43k	1 in 270	1 in 1,500
Remaining (unassigned)	~30k	1 in 300	1 in 4,800
European (Finnish)	~27k	1 in 3,300	≈ 1 in 5,600
Admixed American	~22k	1 in 420	1 in 980
African / African American	~21k	1 in 370	1 in 2,800
East Asian	~20k	1 in 420	1 in 3,300
Middle Eastern	~2,884	1 in 290	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 4 of 6 coding exons well covered in gnomAD exomes; exons 3, 6 marginal. Genomes: all 6.? see exons ↓