TRAPPC6B

Chr 14AR

trafficking protein particle complex subunit 6B

Also known as: NEDMEBA, TPC6

NCBI Gene: 122553 ENSG00000182400 UniProt: Q86SZ2 OMIM: 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.

OMIM 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]

OMIM ResearchGenerating clinical summary…

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

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

11 unique Pathogenic / Likely Pathogenic· 31 VUS of 81 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 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

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

strongTRAPPC6B-related neurodevelopmental disorder with microcephaly, epilepsy, and brain atrophyLOFAR

This gene — mechanism propensity

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

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

81 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic6

Likely Pathogenic5

VUS31

Likely Benign20

Benign9

Pathogenic

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	6	0	0	0	6
Likely Pathogenic	5	0	0	0	5
VUS	0	28	3	0	31
Likely Benign	0	1	7	12	20
Benign	0	0	7	2	9
Total	11	29	17	14	71

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

View in ClinVar →

28 pathogenic / likely-pathogenic (of 36) ClinVar copy-number / structural variants overlap TRAPPC6B — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →