TRAPPC6A

protein-coding

trafficking protein particle complex subunit 6A, the group of Trafficking protein particle complex subunits

Gene summary

This gene encodes a component of the trafficking protein particle complex, which tethers transport vesicles to the cis-Golgi membrane. Loss of expression of the related gene in mouse affects coat and eye pigmentation, suggesting that the encoded protein may be involved in melanosome biogenesis. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Aug 2012]

MANE transcript

NM_001270891.2

Inheritance

ClinVar variants

U:30B:10

Top phenotype

TRAPPC6A-related disorder

gnomAD constraint

pLI —, LoF o/e 1.26

Max pathogenic AF

—

Genomic locus

chr19:45,162,928-45,178,237

External References & Databases

Ensembl (ENSG00000007255)

Transcript & Mutation Effects

hg38 • Region Span ~15.3 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

complex neurodevelopmental disorderLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0100038

Submitter: Ambry Genetics

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to TRAPPC6A variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 33

TRAPPC6A-related disorderTotal: 11

not providedTotal: 1

Neurodevelopmental disorderTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001270891.2. 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			1 clinvar	3 clinvar	1 clinvar	5
missense			27 clinvar	5 clinvar	1 clinvar	33
nonsense						0
start loss			1 clinvar			1
frameshift						0
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	30	8	2	40

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 31 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001270891.2	RefSeq	NP_001257820.1	6	MANE Select
ENST00000585934.1	Ensembl	ENSP00000468612.1	6	MANE Select
NM_001270892.2	RefSeq	NP_001257821.1	4	Standard
NM_001270893.2	RefSeq	NP_001257822.1	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
regulation of GTPase activity
COPII vesicle coating
melanosome assembly

Molecular Function

protein binding
Rab guanyl-nucleotide exchange factor activity

Cellular Component

Golgi membrane
endoplasmic reticulum
cis-Golgi network
trans-Golgi network
cytosol

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000006275
Coding exons: 6
Length: 15310
Individuals with no LoFs: 125716
Homozygous LoFs: 0
Heterozygous LoFs: 28
Defined: 125744
p: 0.000111

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.0215	105	104	1.01	0.00000612	1100
Missense (PolyPhen)		23	29.219	0.78716		354
Synonymous	-0.0581	47	46.5	1.01	0.00000298	347
Loss of Function	-0.676	10	7.94	1.26	3.38e-7	94

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00014	0.00012	rare
Latino/Admixed American	0.00024	0.00023	rare
Ashkenazi Jewish	0.000099	0.000099	rare
East Asian	0	0.0	absent
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.000063	0.000062	rare
South Asian	0.00030	0.00029	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: May play a role in vesicular transport during the biogenesis of melanosomes. {ECO:0000250|UniProtKB:Q78XR0}.;

Recessive Scores

pRec: 0.105

Intolerance Scores

LoFtool: 0.597
RVIS EVS: -0.05
RVIS percentile EVS: 50.01

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.890

Gene Damage Prediction

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