TRAPPC12

protein-coding

trafficking protein particle complex subunit 12, the group of Trafficking protein particle complex subunits|Tetratricopeptide repeat domain containing

Gene summary

Involved in several processes, including endoplasmic reticulum to Golgi vesicle-mediated transport; positive regulation of protein localization to kinetochore; and regulation of kinetochore assembly. Located in several cellular components, including endoplasmic reticulum-Golgi intermediate compartment; kinetochore; and perinuclear region of cytoplasm. Part of TRAPP complex. [provided by Alliance of Genome Resources, Jul 2025]

Previous symbols:

TTC15

MANE transcript

NM_016030.6

Inheritance

ClinVar variants

P:27U:214B:89

Top phenotype

Encephalopathy, progressive, early-onset, with brain atrophy and spasticity (PEBAS)

gnomAD constraint

pLI —, LoF o/e 0.86

Max pathogenic AF

—

Genomic locus

chr2:3,379,675-3,485,094

External References & Databases

Ensembl (ENSG00000171853)

Transcript & Mutation Effects

hg38 • Region Span ~105.4 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

early-onset progressive encephalopathy-hearing loss-pons hypoplasia-brain atrophy syndromeSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0044696

Submitter: G2P

early-onset progressive encephalopathy-hearing loss-pons hypoplasia-brain atrophy syndromeLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0044696

Submitter: Ambry Genetics

early-onset progressive encephalopathy-hearing loss-pons hypoplasia-brain atrophy syndromeSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0044696

Submitter: PanelApp Australia

early-onset progressive encephalopathy-hearing loss-pons hypoplasia-brain atrophy syndromeSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0044696

Submitter: Labcorp Genetics (formerly Invitae)

Clinical Genomic Database (CGD)

Encephalopathy, progressive, early-onset, with brain atrophy and spasticity (PEBAS)AR

Manifestation: 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: 28777934

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to TRAPPC12 variants in ClinVar

8 Conditions Cataloged

Inborn genetic diseasesTotal: 170

not providedTotal: 163

Early-onset progressive encephalopathy-hearing loss-pons hypoplasia-brain atrophy syndromeTotal: 43

TRAPPC12-related disorderTotal: 31

not specifiedTotal: 20

Progressive childhood encephalopathyTotal: 2

See casesTotal: 2

Severe hydrocephalusTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_016030.6. 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			3 clinvar	56 clinvar	8 clinvar	67
missense		1 clinvar	199 clinvar	22 clinvar	3 clinvar	225
nonsense	4 clinvar	3 clinvar	3 clinvar			10
start loss			1 clinvar			1
frameshift	5 clinvar	8 clinvar	1 clinvar			14
splice donor/acceptor (+/-2bp)	1 clinvar	5 clinvar	7 clinvar			13
Total	10	17	214	78	11	330

Highest pathogenic variant AF is 0.000021344864

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 58 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_016030.6	RefSeq	NP_057114.5	11	MANE Select
ENST00000324266.10	Ensembl	ENSP00000324318.5	11	MANE Select
NM_001321102.2	RefSeq	NP_001308031.1	11	Standard
ENST00000382110.6	Ensembl	ENSP00000371544.2	11	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Vesicle-mediated transport
Membrane Trafficking
Rab regulation of trafficking
RAB GEFs exchange GTP for GDP on RABs

Biological Process

proteolysis
endoplasmic reticulum to Golgi vesicle-mediated transport
Golgi organization
protein complex oligomerization
metaphase plate congression

Molecular Function

endopeptidase activity
protein binding
Rab guanyl-nucleotide exchange factor activity

Cellular Component

kinetochore
nucleus
endoplasmic reticulum-Golgi intermediate compartment
cytosol
TRAPP complex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000324266
Coding exons: 11
Length: 105420
Individuals with no LoFs: 125685
Homozygous LoFs: 0
Heterozygous LoFs: 63
Defined: 125748
p: 0.000251

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.160	457	467	0.979	0.0000318	4744
Missense (PolyPhen)		136	143.54	0.94748		1459
Synonymous	0.371	213	220	0.968	0.0000184	1466
Loss of Function	0.713	26	30.2	0.860	0.00000152	331

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00025	0.00025	rare
Latino/Admixed American	0.00052	0.00046	rare
Ashkenazi Jewish	0.00051	0.00050	rare
East Asian	0.00017	0.00016	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00026	0.00024	rare
South Asian	0.00025	0.00023	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Component of the TRAPP complex, which is involved in endoplasmic reticulum to Golgi apparatus trafficking at a very early stage (PubMed:21525244, PubMed:28777934). Also plays a role in chromosome congression, kinetochore assembly and stability and controls the recruitment of CENPE to the kinetochores (PubMed:25918224). {ECO:0000269|PubMed:21525244, ECO:0000269|PubMed:25918224, ECO:0000269|PubMed:28777934}.;
Disease: DISEASE: Encephalopathy, progressive, early-onset, with brain atrophy and spasticity (PEBAS) [MIM:617669]: An autosomal recessive, progressive encephalopathy characterized by central nervous system atrophy and dysfunction, spasticity, microcephaly, global developmental delay, and hearing loss. {ECO:0000269|PubMed:28777934}. Note=The disease is caused by mutations affecting the gene represented in this entry. Cells display a fragmented Golgi apparatus (PubMed:28777934). {ECO:0000269|PubMed:28777934}.;

Recessive Scores

pRec: 0.102

Intolerance Scores

RVIS EVS: -0.39
RVIS percentile EVS: 27.05

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.114

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	High	High	High
Primary Immunodeficiency	High	High	High
Cancer	High	High	High