TRAPPC12

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

Basic information

Region (hg38): 2:3379675-3485094

Previous symbols: [ "TTC15" ]

Links

ENSG00000171853 ∙ NCBI:51112 ∙ OMIM:614139 ∙ HGNC:24284 ∙ Uniprot:Q8WVT3 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• early-onset progressive encephalopathy-hearing loss-pons hypoplasia-brain atrophy syndrome (Limited), mode of inheritance: AR
• early-onset progressive encephalopathy-hearing loss-pons hypoplasia-brain atrophy syndrome (Strong), mode of inheritance: AR
• early-onset progressive encephalopathy-hearing loss-pons hypoplasia-brain atrophy syndrome (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Encephalopathy, progressive, early-onset, with brain atrophy and spasticity (PEBAS)	AR	General	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	Neurologic	28777934

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the TRAPPC12 gene.

• Inborn_genetic_diseases (148 variants)
• not_provided (140 variants)
• Early-onset_progressive_encephalopathy-hearing_loss-pons_hypoplasia-brain_atrophy_syndrome (36 variants)
• TRAPPC12-related_disorder (24 variants)
• not_specified (4 variants)
• Progressive_childhood_encephalopathy (2 variants)
• See_cases (2 variants)
• Severe_hydrocephalus (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TRAPPC12 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000016030.6. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			1	43	7	51
missense		1	168	18	5	192
nonsense	4	2	2			8
start loss						0
frameshift	3	5	1			9
splice donor/acceptor (+/-2bp)	1	4	1			6
Total	8	12	173	61	12

Highest pathogenic variant AF is 0.000014889132

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TRAPPC12	protein_coding	protein_coding	ENST00000324266	11	105420

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
5.36e-16	0.0492	125685	0	63	125748	0.000251

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.160	457	467	0.979	0.0000318	4744
Missense in 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

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000770	0.000765
Ashkenazi Jewish	0.000512	0.000496
East Asian	0.000167	0.000163
Finnish	0.00	0.00
European (Non-Finnish)	0.000262	0.000237
Middle Eastern	0.000167	0.000163
South Asian	0.000251	0.000229
Other	0.000163	0.000163

dbNSFP

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}.
• Pathway: Vesicle-mediated transport;Membrane Trafficking;Rab regulation of trafficking;RAB GEFs exchange GTP for GDP on RABs (Consensus)

Recessive Scores

• pRec: 0.102

Intolerance Scores

• rvis_EVS: -0.39
• rvis_percentile_EVS: 27.05

Haploinsufficiency Scores

• pHI: 0.0838
• hipred: N
• hipred_score: 0.251
• ghis: 0.529

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.114

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Trappc12

Gene ontology

• Biological process: proteolysis;endoplasmic reticulum to Golgi vesicle-mediated transport;Golgi organization;protein complex oligomerization;metaphase plate congression;regulation of kinetochore assembly;positive regulation of protein localization to kinetochore
• Cellular component: kinetochore;nucleus;endoplasmic reticulum-Golgi intermediate compartment;cytosol;TRAPP complex;perinuclear region of cytoplasm
• Molecular function: endopeptidase activity;protein binding;Rab guanyl-nucleotide exchange factor activity