TRAPPC12

Chr 2AR

trafficking protein particle complex subunit 12

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

NCBI Gene: 51112 ENSG00000171853 UniProt: Q8WVT3 OMIM: 614139

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.

OMIM 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]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Encephalopathy, progressive, early-onset, with brain atrophy and spasticityMIM #617669

Clinical highlights

Gene–disease validity

Not independently assessedOMIM lists Encephalopathy, progressive, early-onset, with brain atrophy and spasticity; no ClinGen or GenCC tier

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

1.19

LOEUF

LOF

Mechanism· G2P

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

Background carrier burden — how many people carry a rare variant somewhere in TRAPPC12?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 40

1,238 rare PASS variants

Rare truncating (LoF)

1 in 1,200

177 rare PASS variants

Rare synonymous (reference)

1 in 82

506 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for TRAPPC12. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 48	1 in 1,200
South Asian	~43k	1 in 36	1 in 770
Remaining (unassigned)	~30k	1 in 37	1 in 1,600
European (Finnish)	~27k	1 in 150	1 in 2,800
Admixed American	~22k	1 in 38	1 in 580
African / African American	~21k	1 in 34	1 in 590
East Asian	~20k	1 in 58	1 in 1,400
Ashkenazi Jewish	~13k	1 in 110	1 in 750
Middle Eastern	~2,884	1 in 40	≈ 1 in 720

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): 8 of 11 coding exons well covered in gnomAD exomes; exon 8 poorly covered; exons 3, 10 marginal. Genomes: all 11.? see exons ↓