Intellectual disability
Gene: TRAPPC2L

TRAPPC2L (trafficking protein particle complex 2 like)
EnsemblGeneIds (GRCh38): ENSG00000167515
EnsemblGeneIds (GRCh37): ENSG00000167515
OMIM: 610970, Gene2Phenotype
TRAPPC2L is in 4 panels

2 reviews

Ida Ertmanska (Genomics England Curator)

Green List (high evidence)

Comment on list classification: There are now 4 unrelated families with biallelic TRAPPC2L variants (3 with missense and 1 with nonsense variants), with syndromic neurodevelopmental delay. Hence, this gene can be promoted to Green on Intellectual disability at the next update.
Created: 17 Jun 2026, 1:32 p.m. | Last Modified: 17 Jun 2026, 1:32 p.m.

Panel Version: 10.20

FOURTH FAMILY
PMID: 36849228 Abaji et al., 2023
2 sibs (boy and girl) with a neurodevelopmental disorder - both had severe developmental delay (absent speech, walking absent in IV-3, sister IV-4 started walking at 7-9 years old), hypotonia, mild dysmorphic features, non-specific MRI changes (e.g., thin corpus callosum, delayed myelination), stereotyped hand movements. No regression of skills was noted. WES revealed a homozygous c.367C>T, p.Gln123Ter variant in TRAPPC2L. Unaffected family members confirmed WT / het. Both patients had elevated CK, but muscle biopsy in patient IV-4 showed normal morphology and no histoenzymatic alterations. Authors argue it may be too early in life to see musculary dystrophy features on biopsy.

TRAPPC2L is associated with AR Encephalopathy, progressive, early-onset, with episodic rhabdomyolysis, MIM:618331 (OMIM accessed 17th Jun 2026).
Created: 17 Jun 2026, 1:30 p.m. | Last Modified: 17 Jun 2026, 1:30 p.m.

Panel Version: 10.19

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
encephalopathy, progressive, early-onset, with episodic rhabdomyolysis, MONDO:0032681; Encephalopathy, progressive, early-onset, with episodic rhabdomyolysis, OMIM:618331

Publications

36849228

Created: 17 Jun 2026, 1:30 p.m.
Last Modified: 17 Jun 2026, 1:30 p.m.
Panel version: 10.19

Arina Puzriakova (Genomics England Curator)

I don't know

Comment on list classification: Rating Amber as additional cases required to delineate the genotype-phenotype relationship. Total of three families, but two share a founder variant, and there are some disparities between the clinical presentations reported in the two publications.
Created: 2 Sep 2020, 4:03 p.m. | Last Modified: 2 Sep 2020, 4:03 p.m.

Panel Version: 3.281

Gene is associated with Encephalopathy, progressive, early-onset, with episodic rhabdomyolysis in OMIM, but not in G2P.

PMID: 30120216 (2018) - Two unrelated probands with an identical homozygous missense (c.109G>T, p.Asp37Tyr) variant in TRAPPC2L. Both individuals presented neurodevelopmental delay, febrile illness-induced encephalopathy, and episodic rhabdomyolysis, followed by developmental arrest, seizures and tetraplegia. The variant segregated with the phenotype in each family, and haplotype analysis suggested a founder effect.

The mutant protein was expressed in patient fibroblasts, but displayed membrane trafficking delays. Studies in yeast showed that the variant impaired interaction with TRAPPC10, and increased levels of the active RAB11.

PMID: 32843486 (2020) - In an Ashkenazi Jewish family with three affected sibs with GDD/ID, WGS revealed a segregating homozygous missense variant (c.5G>C, p.Ala2Gly) in the TRAPPC2L gene. No seizures, brain MRI abnormalities, or illness provoked regression were documented in this family.

Comparable to the previous study, the variant resulted in delayed ER-to-Golgi trafficking and elevated levels of active RAB11. Studies using yeast and in vitro binding, showed that the variant disrupted interaction with another core TRAPP protein, TRAPPC6a.
Sources: Literature
Created: 2 Sep 2020, 3:53 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Encephalopathy, progressive, early-onset, with episodic rhabdomyolysis, 618331

Publications

Created: 2 Sep 2020, 3:53 p.m.

Panel version: 3.280

Details

Mode of Inheritance

BIALLELIC, autosomal or pseudoautosomal

Sources

Expert Review Amber
Literature

Phenotypes

encephalopathy, progressive, early-onset, with episodic rhabdomyolysis, MONDO:0032681
Encephalopathy, progressive, early-onset, with episodic rhabdomyolysis, OMIM:618331

Tags

Q2_26_promote_green

OMIM

610970

Clinvar variants

Variants in TRAPPC2L

Penetrance

None

Publications

Panels with this gene