TRAPPC12

Chr 2AR

trafficking protein particle complex subunit 12

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

NCBI Gene: 51112ENSG00000171853UniProt: Q8WVT3

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]

Primary Disease Associations & Inheritance

Encephalopathy, progressive, early-onset, with brain atrophy and spasticityMIM #617669
AR
394
ClinVar variants
51
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— TRAPPC12
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
51 Pathogenic / Likely Pathogenic· 220 VUS of 394 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.
1.19LOEUF
pLI 0.000
Z-score 0.71
OE 0.86 (0.63–1.19)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?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.
0.16Z-score
OE missense 0.98 (0.91–1.06)
457 obs / 466.7 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.0.86 (0.63–1.19)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.98 (0.91–1.06)
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.0.97
0≤1.21.6
LoF obs/exp: 26 / 30.2Missense obs/exp: 457 / 466.7Syn Z: 0.37

ClinVar Variant Classifications

394 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic36
Likely Pathogenic15
VUS220
Likely Benign87
Benign29
Conflicting7
36
Pathogenic
15
Likely Pathogenic
220
VUS
87
Likely Benign
29
Benign
7
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
4
0
32
0
36
Likely Pathogenic
10
1
4
0
15
VUS
3
187
29
1
220
Likely Benign
0
14
24
49
87
Benign
0
5
8
16
29
Conflicting
—7
Total172079766394

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

View in ClinVar →

Protein Context — Lollipop Plot

TRAPPC12 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

TRAPPC12-related progressive childhood encephalopathy and Golgi dysfunction

strong
ARLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Encephalopathy, progressive, early-onset, with brain atrophy and spasticity

MIM #617669

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Expanding Clinical Phenotype of TRAPPC12-Related Childhood Encephalopathy: Two Cases and Review of Literature.
Aslanger AD et al.·Neuropediatrics
2020Review
Mutations in TRAPPC12 Manifest in Progressive Childhood Encephalopathy and Golgi Dysfunction.
Milev MP et al.·Am J Hum Genet
2017
Genetic insights into CRP levels in Indian adolescents: confirming adult genetic associations.
Nair JM et al.·Mol Genet Genomics
2025
Comparison of methods for multivariate gene-based association tests for complex diseases using common variants.
Chung J et al.·Eur J Hum Genet
2019
Hydrocephaly associated with compound heterozygous alterations in TRAPPC12.
Gass JM et al.·Birth Defects Res
2020Case report
RNA sequencing to support intronic variant interpretation: A case report of TRAPPC12-related disorder.
Bhola PT et al.·Am J Med Genet A
2023Case report
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