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.

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.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			1		1	2
missense			40	1	1	42
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region					1	1
non coding						0
Total	0	0	41	1	2

Variants in VPS54

This is a list of pathogenic ClinVar variants found in the VPS54 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
2-63893491-G-T		not specified	Uncertain significance (May 20, 2024)
2-63893506-G-A		not specified	Uncertain significance (Dec 12, 2023)
2-63897588-C-A		not specified	Benign (-)
2-63899588-G-A			Benign (Aug 20, 2018)
2-63912336-A-T			Likely benign (-)
2-63912577-T-C		not specified	Uncertain significance (Aug 17, 2022)
2-63912610-C-T		not specified	Uncertain significance (Nov 27, 2023)
2-63913259-C-G		not specified	Uncertain significance (Jun 28, 2023)
2-63914195-G-A		not specified	Uncertain significance (May 30, 2024)
2-63914230-G-C		not specified	Uncertain significance (Jul 14, 2021)
2-63916886-A-T		not specified	Benign (-)
2-63916887-A-C		not specified	Benign (-)
2-63916934-G-C		not specified	Uncertain significance (Jul 12, 2022)
2-63920467-T-C		not specified	Uncertain significance (Aug 10, 2021)
2-63920541-G-C		not specified	Uncertain significance (Feb 15, 2023)
2-63920551-G-C			Uncertain significance (Jan 01, 2017)
2-63920564-A-G		not specified	Uncertain significance (Dec 14, 2023)
2-63921211-C-T		not specified	Uncertain significance (Nov 14, 2023)
2-63921228-T-C		not specified	Uncertain significance (Dec 13, 2022)
2-63921237-C-T		not specified	Uncertain significance (Jul 12, 2022)
2-63921305-T-C			Uncertain significance (May 01, 2016)
2-63933691-G-C			Uncertain significance (Aug 01, 2017)
2-63933709-G-A		not specified	Uncertain significance (Feb 14, 2023)
2-63933730-G-C			Benign (Jul 23, 2018)
2-63933817-A-G		not specified	Uncertain significance (Dec 13, 2022)

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