VPS51

VPS51 subunit of GARP complex, the group of Golgi associated retrograde protein (GARP) complex|Endosome-associated recycling protein (EARP) complex

Basic information

Region (hg38): 11:65089324-65111862

Previous symbols: [ "C11orf3", "C11orf2" ]

Links

ENSG00000149823 ∙ NCBI:738 ∙ OMIM:615738 ∙ HGNC:1172 ∙ Uniprot:Q9UID3 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• pontocerebellar hypoplasia, type 13 (Moderate), mode of inheritance: AR
• pontocerebellar hypoplasia, type 13 (Limited), mode of inheritance: AR
• pontocerebellar hypoplasia, type 13 (Limited), mode of inheritance: Unknown

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Pontocerebellar hypoplasia, type 13	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	Craniofacial; Neurologic; Ophthalmologic	30624672; 31207318

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the VPS51 gene.

• Pontocerebellar hypoplasia, type 13 (1 variants)
• not provided (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the VPS51 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				9		9
missense	1		51	1		53
nonsense			1			1
start loss						0
frameshift						0
inframe indel			1			1
splice donor/acceptor (+/-2bp)						0
splice region				1	2	3
non coding					2	2
Total	1	0	53	10	2

Highest pathogenic variant AF is 0.00000657

Variants in VPS51

This is a list of pathogenic ClinVar variants found in the VPS51 region.

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

Position	Type	Phenotype	Significance	ClinVar
11-65096264-C-T		not specified	Uncertain significance (Nov 29, 2023)
11-65096282-C-T		not specified	Uncertain significance (Mar 29, 2022)
11-65096314-C-T		not specified	Uncertain significance (Jan 04, 2024)
11-65096319-G-C		not specified	Uncertain significance (Feb 05, 2024)
11-65096338-C-T		not specified	Uncertain significance (Dec 09, 2023)
11-65096393-C-T		not specified	Uncertain significance (Jan 10, 2023)
11-65096450-A-T		not specified	Uncertain significance (Jan 17, 2023)
11-65096451-C-G		not specified	Uncertain significance (Aug 13, 2021)
11-65096486-C-T			Likely benign (May 14, 2018)
11-65096497-TG-T			Benign (Aug 21, 2019)
11-65097076-G-A		not specified	Uncertain significance (Jun 17, 2024)
11-65097080-T-C		not specified	Uncertain significance (Jun 02, 2023)
11-65107640-GCCA-G		Pontocerebellar hypoplasia, type 13	Uncertain significance (-)
11-65107642-C-T		VPS51-related disorder	Likely benign (Oct 27, 2020)
11-65107689-C-T		not specified	Uncertain significance (Oct 13, 2023)
11-65107705-C-G		not specified	Uncertain significance (Feb 15, 2023)
11-65107710-G-A		not specified	Uncertain significance (Oct 05, 2023)
11-65107854-G-A		not specified	Uncertain significance (Jan 04, 2024)
11-65107951-G-C			Likely benign (Apr 01, 2022)
11-65107956-G-A		not specified	Uncertain significance (Jun 02, 2023)
11-65107993-C-G			Likely benign (May 01, 2023)
11-65107994-C-A		not specified	Uncertain significance (Aug 03, 2022)
11-65107997-G-T		not specified	Uncertain significance (Jan 30, 2024)
11-65108016-G-A			Uncertain significance (Mar 01, 2024)
11-65108214-C-T		not specified	Uncertain significance (Aug 14, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
VPS51	protein_coding	protein_coding	ENST00000279281	10	22537

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.05e-8	0.928	125685	0	63	125748	0.000251

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.66	347	518	0.670	0.0000364	4920
Missense in Polyphen		99	170.61	0.58026		1602
Synonymous	1.79	200	235	0.851	0.0000173	1699
Loss of Function	1.87	17	27.6	0.616	0.00000126	312

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000359	0.000358
Ashkenazi Jewish	0.000522	0.000397
East Asian	0.000109	0.000109
Finnish	0.000828	0.000739
European (Non-Finnish)	0.000200	0.000193
Middle Eastern	0.000109	0.000109
South Asian	0.000163	0.000163
Other	0.00100	0.000978

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 protein retrieval from endosomes to the TGN, acid hydrolase sorting, lysosome function, endosomal cholesterol traffic and autophagy. VPS51 participates in retrograde transport of acid hydrolase receptors, likely by promoting tethering and SNARE-dependent fusion of endosome-derived carriers to the TGN (PubMed:20685960). Acts as component of the EARP complex that is involved in endocytic recycling. The EARP complex associates with Rab4-positive endosomes and promotes recycling of internalized transferrin receptor (TFRC) to the plasma membrane (PubMed:25799061). {ECO:0000269|PubMed:20685960, 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: 0.183

Intolerance Scores

• rvis_EVS: -0.64
• rvis_percentile_EVS: 16.53

Haploinsufficiency Scores

• pHI: 0.428
• hipred: N
• hipred_score: 0.498
• ghis: 0.544

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: E

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Vps51
• 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); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan)

Zebrafish Information Network

• Gene name: vps51
• Affected structure: cholangiocyte
• Phenotype tag: abnormal
• Phenotype quality: dilated

Gene ontology

• Biological process: lipid transport;autophagy;Golgi organization;lysosomal transport;protein transport;endocytic recycling;retrograde transport, endosome to Golgi;Golgi vesicle transport
• Cellular component: GARP complex;nucleolus;Golgi apparatus;trans-Golgi network;cytosol;membrane;integral component of membrane;trans-Golgi network membrane;intracellular membrane-bounded organelle;recycling endosome;EARP complex
• Molecular function: molecular_function;protein binding