TRAPPC4

Chr 11AR

trafficking protein particle complex subunit 4

Also known as: CGI-104, HSPC172, NEDESBA, PTD009, SBDN, SYNBINDIN, TRS23

NCBI Gene: 51399ENSG00000196655UniProt: Q9Y296

Involved in autophagy and endoplasmic reticulum to Golgi vesicle-mediated transport. Part of TRAPP complex. [provided by Alliance of Genome Resources, Jul 2025]

Primary Disease Associations & Inheritance

Neurodevelopmental disorder with epilepsy, spasticity, and brain atrophyMIM #618741
AR
0
ClinVar variants
0
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— TRAPPC4
🧬
Gene-Disease Validity (ClinGen)
neurodevelopmental disorder with epilepsy, spasticity, and brain atrophy · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

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

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.
1.48LOEUF
pLI 0.000
Z-score 0.45
OE 0.85 (0.51–1.48)
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.
0.43Z-score
OE missense 0.89 (0.76–1.04)
106 obs / 119.1 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.0.85 (0.51–1.48)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.89 (0.76–1.04)
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.1.46
0≤1.21.6
LoF obs/exp: 9 / 10.6Missense obs/exp: 106 / 119.1Syn Z: -2.49

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

TRAPPC4 · protein map & ClinVar variants

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

Gene2Phenotype Curations

TRAPPC4-related neurodevelopmental disorder with epilepsy, spasticity, and brain atrophy

definitive
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

Neurodevelopmental disorder with epilepsy, spasticity, and brain atrophy

MIM #618741

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
TRAPPC4 regulates the intracellular trafficking of PD-L1 and antitumor immunity.
Ren Y et al.·Nat Commun
2021
Further evidence of muscle involvement in neurodevelopmental disorder with epilepsy, spasticity, and brain atrophy.
Majethia P et al.·Ann Hum Genet
2022
A relatively common homozygous TRAPPC4 splicing variant is associated with an early-infantile neurodegenerative syndrome.
Ghosh SG et al.·Eur J Hum Genet
2021
Deficiencies in vesicular transport mediated by TRAPPC4 are associated with severe syndromic intellectual disability.
Van Bergen NJ et al.·Brain
2020
Child Neurology: TRAPPC4-Related Neurodevelopmental Disorder.
Forno A et al.·Neurology
2025Case report
Generation and heterozygous repair of human iPSC lines from two individuals with the neurodevelopmental disorder, TRAPPC4 deficiency.
Hall R et al.·Stem Cell Res
2025
TRAPPing a neurological disorder: from yeast to humans.
Lipatova Z et al.·Autophagy
2020
Recurrent bi-allelic splicing variant c.454+3A>G in TRAPPC4 is associated with progressive encephalopathy and muscle involvement.
Kaur P et al.·Brain
2020
Reply: Recurrent bi-allelic splicing variant c.454+3A>G in TRAPPC4 is associated with progressive encephalopathy and muscle involvement.
Van Bergen NJ et al.·Brain
2020
An interaction quantitative trait loci tool implicates epistatic functional variants in an apoptosis pathway in smallpox vaccine eQTL data.
Lareau CA et al.·Genes Immun
2016Functional
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