VPS50

VPS50 subunit of EARP/GARPII complex, the group of Endosome-associated recycling protein (EARP) complex

Basic information

Region (hg38): 7:93232339-93361123

Previous symbols: [ "CCDC132" ]

Links

ENSG00000004766 ∙ NCBI:55610 ∙ OMIM:616465 ∙ HGNC:25956 ∙ Uniprot:Q96JG6 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• neurodevelopmental disorder with microcephaly, seizures, and neonatal cholestasis (Limited), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Neurodevelopmental disorder with microcephaly, seizures, and neonatal cholestasis	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	Gastrointestinal; Neurologic	34037727

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the VPS50 gene.

• Inborn genetic diseases (21 variants)
• not provided (3 variants)
• not specified (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the VPS50 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			21		1	22
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)			1			1
splice region						0
non coding						0
Total	0	0	22	1	2

Variants in VPS50

This is a list of pathogenic ClinVar variants found in the VPS50 region.

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

Position	Type	Phenotype	Significance	ClinVar
7-93239920-C-T		not specified	Uncertain significance (Jan 08, 2024)
7-93239921-G-A		not specified	Uncertain significance (Apr 13, 2022)
7-93252662-A-G		not specified	Uncertain significance (Jun 06, 2023)
7-93256533-A-G		not specified	Uncertain significance (Jun 12, 2023)
7-93258194-C-A		not specified	Uncertain significance (Dec 14, 2021)
7-93258226-C-T		not specified	Uncertain significance (Aug 13, 2021)
7-93259557-A-G		not specified	Uncertain significance (Jan 04, 2022)
7-93259622-A-C		not specified	Uncertain significance (Mar 06, 2023)
7-93272711-A-G		not specified	Uncertain significance (Oct 17, 2023)
7-93276250-G-A		not specified	Uncertain significance (Nov 19, 2022)
7-93291707-T-G		not specified	Uncertain significance (Mar 01, 2023)
7-93291827-C-T		not specified	Uncertain significance (Dec 01, 2022)
7-93294571-G-A		not specified	Uncertain significance (Jan 20, 2023)
7-93296765-C-G			Likely benign (Mar 01, 2024)
7-93296790-A-G		not specified	Uncertain significance (Jun 22, 2021)
7-93297177-G-C		not specified	Uncertain significance (May 01, 2022)
7-93297244-G-T		not specified	Uncertain significance (May 12, 2023)
7-93305916-T-C		not specified	Uncertain significance (Mar 01, 2024)
7-93305997-C-T		not specified	Uncertain significance (Dec 08, 2023)
7-93308864-A-G		not specified	Uncertain significance (Oct 04, 2022)
7-93308885-C-T		not specified	Uncertain significance (Jan 04, 2022)
7-93308899-C-T		Neurodevelopmental disorder with microcephaly, seizures, and neonatal cholestasis	Likely pathogenic (Mar 25, 2024)
7-93308917-C-T		Neurodevelopmental disorder with microcephaly, seizures, and neonatal cholestasis	Likely pathogenic (May 04, 2022)
7-93311171-C-A		not specified	Uncertain significance (Mar 11, 2022)
7-93311237-TAAC-T		Neurodevelopmental disorder with microcephaly, seizures, and neonatal cholestasis	Pathogenic (Jan 05, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
VPS50	protein_coding	protein_coding	ENST00000305866	28	126686

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.814	0.186	125727	0	21	125748	0.0000835

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.50	325	479	0.678	0.0000233	6352
Missense in Polyphen		80	144.4	0.55401		1968
Synonymous	-0.246	167	163	1.02	0.00000782	1719
Loss of Function	5.63	12	58.4	0.205	0.00000281	755

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000131	0.000123
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.000147	0.000141
Middle Eastern	0.00	0.00
South Asian	0.000102	0.0000980
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: 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. Within the EARP complex, required to tether the complex to recycling endosomes. Not involved in retrograde transport from early and late endosomes to the trans-Golgi network (TGN). {ECO:0000269|PubMed:25799061}.

Intolerance Scores

• rvis_EVS: -0.18
• rvis_percentile_EVS: 40.56

Haploinsufficiency Scores

• pHI: 0.222
• hipred: Y
• hipred_score: 0.614
• ghis: 0.590

Essentials

• essential_gene_gene_trap: N

Mouse Genome Informatics

• Gene name: Vps50

Gene ontology

• Biological process: protein transport;endocytic recycling;retrograde transport, endosome to Golgi
• Cellular component: cytosol;membrane;recycling endosome;extracellular exosome;EARP complex
• Molecular function: SNARE binding;protein binding