TRAPPC10

protein-coding

trafficking protein particle complex subunit 10, the group of Trafficking protein particle complex subunits

Gene summary

The protein encoded by this gene is a transmembrane protein found in the cis-Golgi complex. The encoded protein is part of the multisubunit transport protein particle (TRAPP) complex and may be involved in vesicular transport from the endoplasmic reticulum to the Golgi. Mutations in this gene could be responsible for the Unverricht-Lundborg type of progressive myoclonus epilepsy, or for autoimmune polyglandular disease type 1. [provided by RefSeq, Jul 2008]

Previous symbols:

TMEM1

MANE transcript

NM_003274.5

Inheritance

ClinVar variants

P:6U:166B:28

Top phenotype

neurodevelopmental disorder with microcephaly, short stature, and speech delay

gnomAD constraint

pLI —, LoF o/e 0.11

Max pathogenic AF

—

Genomic locus

chr21:44,012,309-44,106,552

External References & Databases

Ensembl (ENSG00000160218)

Transcript & Mutation Effects

hg38 • Region Span ~94.2 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

neurodevelopmental disorder with microcephaly, short stature, and speech delayMODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0859285

Submitter: Ambry Genetics

neurodevelopmental disorder with microcephaly, short stature, and speech delayLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0859285

Submitter: Ambry Genetics

neurodevelopmental disorder with microcephaly, short stature, and speech delayLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0859285

Submitter: G2P

neurodevelopmental disorder with microcephaly, short stature, and speech delaySTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0859285

Submitter: Labcorp Genetics (formerly Invitae)

neurodevelopmental disorder with microcephaly, short stature, and speech delaySTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0859285

Submitter: PanelApp Australia

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to TRAPPC10 variants in ClinVar

7 Conditions Cataloged

not specifiedTotal: 169

not providedTotal: 22

Neurodevelopmental disorder with microcephaly, short stature, and speech delayTotal: 8

TRAPPC10-related disorderTotal: 3

TRAPPopathy microcephalicTotal: 1

NEURODEVELOPMENTAL DISORDER WITH MICROCEPHALY, SHORT STATURE, SPEECH DELAY, AND BEHAVIORAL ABNORMALITIESTotal: 1

Intellectual disabilityTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_003274.5. 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	17 clinvar		19
missense		1 clinvar	158 clinvar	11 clinvar		170
nonsense		2 clinvar	4 clinvar			6
start loss						0
frameshift	1 clinvar	1 clinvar				2
splice donor/acceptor (+/-2bp)		1 clinvar	2 clinvar			3
Total	1	5	166	28	0	200

Highest pathogenic variant AF is 6.842351e-7

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 55 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_003274.5	RefSeq	NP_003265.3	23	MANE Select
ENST00000291574.9	Ensembl	ENSP00000291574.4	23	MANE Select
NM_001351709.1	RefSeq	NP_001338638.1	13	Standard
ENST00000380221.7	Ensembl	ENSP00000369570.3	7	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

intra-Golgi vesicle-mediated transport
early endosome to Golgi transport
COPII vesicle coating
protein complex oligomerization

Molecular Function

protein binding
Rab guanyl-nucleotide exchange factor activity

Cellular Component

Golgi membrane
cytosol
TRAPP complex
TRAPPII protein complex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000291574
Coding exons: 23
Length: 94234
Individuals with no LoFs: 125735
Homozygous LoFs: 0
Heterozygous LoFs: 13
Defined: 125748
p: 0.0000517

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.56	600	718	0.836	0.0000415	8277
Missense (PolyPhen)		111	208.47	0.53246		2400
Synonymous	-0.111	312	310	1.01	0.0000217	2446
Loss of Function	6.63	7	64.4	0.109	0.00000331	734

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000058	0.000058	rare
Ashkenazi Jewish	0.000099	0.000099	rare
East Asian	0	0.0	absent
Finnish	0.000047	0.000046	rare
European (Non-Finnish)	0.000071	0.000070	rare
South Asian	0.000033	0.000033	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.;

Recessive Scores

pRec: 0.143

Intolerance Scores

LoFtool: 0.240
RVIS EVS: -1.59
RVIS percentile EVS: 3.12

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.518

Gene Damage Prediction

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