TRAPPC12

Chr 2

trafficking protein particle complex subunit 12

Also known as: CGI-87, PEBAS, TTC-15, TTC15

NCBI Gene: 51112 ENSG00000171853 UniProt: Q8WVT3

The TRAPPC12 protein functions in endoplasmic reticulum to Golgi vesicle-mediated transport as part of the TRAPP complex and regulates kinetochore assembly during cell division. Autosomal recessive mutations cause progressive, early-onset encephalopathy with brain atrophy and spasticity. The pathogenic mechanism likely involves disrupted intracellular trafficking and cell division processes essential for normal brain development and function.

ResearchSummary from RefSeq, OMIM, UniProt

Involved in several processes, including endoplasmic reticulum to Golgi vesicle-mediated transport; positive regulation of protein localization to kinetochore; and regulation of kinetochore assembly. Located in several cellular components, including endoplasmic reticulum-Golgi intermediate compartment; kinetochore; and perinuclear region of cytoplasm. Part of TRAPP complex. [provided by Alliance of Genome Resources, Jul 2025]

ResearchGenerating clinical summary…

LOFmechanismLOEUF 1.19

Clinical Summary— TRAPPC12

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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

29 unique Pathogenic / Likely Pathogenic· 203 VUS of 378 total submissions

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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?

1.19LOEUF

pLI 0.000

Z-score 0.71

OE 0.86 (0.63–1.19)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.16Z-score

OE missense 0.98 (0.91–1.06)

457 obs / 466.7 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.86 (0.63–1.19)

0≤0.351.4

Missense OE?0.98 (0.91–1.06)

0≤0.61.4

Synonymous OE?0.97

0≤1.21.6

LoF obs/exp: 26 / 30.2Missense obs/exp: 457 / 466.7Syn Z: 0.37

ClinVar Variant Classifications

378 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic13

Likely Pathogenic16

VUS203

Likely Benign86

Benign29

Conflicting8

Pathogenic

Likely Pathogenic

203

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	10	0	3	0	13
Likely Pathogenic	14	1	1	0	16
VUS	4	191	7	1	203
Likely Benign	0	14	22	50	86
Benign	0	5	8	16	29
Conflicting	—				8
Total	28	211	41	67	355

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

View in ClinVar →

26 pathogenic / likely-pathogenic (of 48) ClinVar copy-number / structural variants overlap TRAPPC12 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →