VPS54

VPS54 subunit of GARP complex, the group of Protein phosphatase 1 regulatory subunits|Golgi associated retrograde protein (GARP) complex

Basic information

Region (hg38): 2:63892146-64019428

Links

ENSG00000143952

∙ NCBI:51542 ∙ OMIM:614633 ∙ HGNC:18652 ∙ Uniprot:Q9P1Q0 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the VPS54 gene.

not_specified (98 variants)
not_provided (8 variants)
Tooth_agenesis (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the VPS54 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000016516.3. 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	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous			1 clinvar		1 clinvar	2
missense			98 clinvar	4 clinvar	1 clinvar	103
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	99	4	2

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
VPS54	protein_coding	protein_coding	ENST00000272322	22	126927

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.999	0.000706	125714	0	17	125731	0.0000676

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.951	425	484	0.878	0.0000229	6419
Missense in Polyphen		78	153.68	0.50756		2062
Synonymous	-0.374	177	171	1.04	0.00000846	1804
Loss of Function	5.77	7	51.8	0.135	0.00000256	691

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000162	0.000155
Ashkenazi Jewish	0.000100	0.0000993
East Asian	0.0000545	0.0000544
Finnish	0.000139	0.0000924
European (Non-Finnish)	0.0000897	0.0000879
Middle Eastern	0.0000545	0.0000544
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

Function: FUNCTION: Acts as component of the GARP complex that is involved in retrograde transport from early and late endosomes to the trans-Golgi network (TGN). The GARP complex is required for the maintenance of the cycling of mannose 6-phosphate receptors between the TGN and endosomes, this cycling is necessary for proper lysosomal sorting of acid hydrolases such as CTSD (PubMed:18367545). Within the GARP complex, required to tether the complex to the TGN. Not involved in endocytic recycling (PubMed:25799061). {ECO:0000269|PubMed:18367545, ECO:0000269|PubMed:25799061}.;
Pathway: Vesicle-mediated transport;Membrane Trafficking;Retrograde transport at the Trans-Golgi-Network;Intra-Golgi and retrograde Golgi-to-ER traffic (Consensus)

Recessive Scores

pRec: 0.108

Intolerance Scores

loftool: 0.610
rvis_EVS: -0.91
rvis_percentile_EVS: 10.07

Haploinsufficiency Scores

pHI: 0.257
hipred: Y
hipred_score: 0.653
ghis: 0.602

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: E
essential_gene_gene_trap: K
gene_indispensability_pred: N
gene_indispensability_score: 0.105

Gene Damage Prediction

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

Mouse Genome Informatics

Gene name: Vps54
Phenotype: endocrine/exocrine gland phenotype; growth/size/body region phenotype; craniofacial phenotype; muscle phenotype; cellular phenotype; immune system phenotype; homeostasis/metabolism phenotype; liver/biliary system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); embryo phenotype; reproductive system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); hematopoietic system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan);

Gene ontology

Biological process: Golgi to vacuole transport;lysosomal transport;protein transport;regulation of growth;retrograde transport, endosome to Golgi;homeostasis of number of cells within a tissue;musculoskeletal movement;neurofilament cytoskeleton organization
Cellular component: GARP complex;nucleoplasm;Golgi apparatus;trans-Golgi network;cytosol;trans-Golgi network membrane;perinuclear region of cytoplasm
Molecular function: protein binding;syntaxin binding