TRAPPC2L

protein-coding

trafficking protein particle complex subunit 2L, the group of Trafficking protein particle complex subunits

Gene summary

This gene encodes a protein that interacts with the tethering factor trafficking protein particle (TRAPP complex). TRAPP complexes mediate the contact between vescicles and target membranes, and thus, are involved in vescicle-mediated transport of proteins and lipids. The encoded protein is related to the X-linked trafficking protein particle complex 2. A related pseudogene is located on the X chromosome. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jan 2016]

MANE transcript

NM_001318525.2

Inheritance

ClinVar variants

P:4U:42B:5

Top phenotype

Encephalopathy, progressive, early-onset, with episodic rhabdomyolysis

gnomAD constraint

pLI —, LoF o/e 1.65

Max pathogenic AF

—

Genomic locus

chr16:88,856,220-88,862,686

External References & Databases

Ensembl (ENSG00000167515)

Transcript & Mutation Effects

hg38 • Region Span ~6.5 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

encephalopathy, progressive, early-onset, with episodic rhabdomyolysisLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0032681

Submitter: Ambry Genetics

encephalopathy, progressive, early-onset, with episodic rhabdomyolysisMODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0032681

Submitter: PanelApp Australia

encephalopathy, progressive, early-onset, with episodic rhabdomyolysisSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0032681

Submitter: Labcorp Genetics (formerly Invitae)

encephalopathy, progressive, early-onset, with episodic rhabdomyolysisLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0032681

Submitter: G2P

Clinical Genomic Database (CGD)

Encephalopathy, progressive, early-onset, with episodic rhabdomyolysisAR

Manifestation: Musculoskeletal; Neurologic

Intervention: General

Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing

Refs: 30120216

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to TRAPPC2L variants in ClinVar

5 Conditions Cataloged

not specifiedTotal: 35

Encephalopathy, progressive, early-onset, with episodic rhabdomyolysisTotal: 11

TRAPPC2L-related disorderTotal: 10

not providedTotal: 5

Intellectual disabilityTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001318525.2. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			2 clinvar	3 clinvar		5
missense	1 clinvar	2 clinvar	36 clinvar	1 clinvar	1 clinvar	41
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)		1 clinvar	3 clinvar			4
Total	1	3	42	4	1	51

Highest pathogenic variant AF is 0.000012317563

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 67 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001318525.2	RefSeq	NP_001305454.1	5	MANE Select
ENST00000696289.1	Ensembl	ENSP00000512526.1	5	MANE Select
NM_001318524.2	RefSeq	NP_001305453.1	5	Standard
NM_001318526.2	RefSeq	NP_001305455.1	4	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Vesicle-mediated transport
Membrane Trafficking
Post-translational protein modification
Metabolism of proteins
Transport to the Golgi and subsequent modification

Biological Process

endoplasmic reticulum to Golgi vesicle-mediated transport
COPII vesicle coating
protein complex oligomerization

Molecular Function

protein binding
Rab guanyl-nucleotide exchange factor activity

Cellular Component

Golgi membrane
endoplasmic reticulum
cytosol
TRAPP complex
intracellular membrane-bounded organelle

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000301021
Coding exons: 5
Length: 6467
Individuals with no LoFs: 125701
Homozygous LoFs: 0
Heterozygous LoFs: 43
Defined: 125744
p: 0.000171

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.384	102	91.7	1.11	0.00000565	925
Missense (PolyPhen)		25	26.892	0.92963		335
Synonymous	-2.20	56	38.6	1.45	0.00000278	255
Loss of Function	-1.69	13	7.89	1.65	5.00e-7	80

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00034	0.00031	rare
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00033	0.00033	rare
Finnish	0.00046	0.00046	rare
European (Non-Finnish)	0.00018	0.00018	rare
South Asian	0.000074	0.000065	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: May play a role in vesicular transport from endoplasmic reticulum to Golgi. {ECO:0000269|PubMed:19416478}.;

Recessive Scores

pRec: 0.113

Intolerance Scores

LoFtool: 0.384
RVIS EVS: -0.12
RVIS percentile EVS: 44.89

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.974

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium