VPS35L

VPS35 endosomal protein sorting factor like, the group of Retriever complex

Basic information

Region (hg38): 16:19555240-19706793

Previous symbols: [ "C16orf62" ]

Links

ENSG00000103544 ∙ NCBI:57020 ∙ OMIM:618981 ∙ HGNC:24641 ∙ Uniprot:Q7Z3J2 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Ritscher-Schinzel syndrome (Limited), mode of inheritance: AR
• Ritscher-Schinzel syndrome 3 (Limited), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Ritscher-Schinzel syndrome 3	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; Musculoskeletal; Neurologic; Ophthalmologic; Renal	31712251; 36113987

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the VPS35L gene.

• not_provided (12 variants)
• not_specified (11 variants)
• Ritscher-Schinzel_syndrome_3 (7 variants)
• VPS35L-related_disorder (3 variants)
• Ritscher-Schinzel_syndrome (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the VPS35L gene is commonly pathogenic or not. These statistics are base on transcript: NM_000020314.7. 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				5		5
missense	2		15		1	18
nonsense		1	1			2
start loss						0
frameshift	1	1				2
splice donor/acceptor (+/-2bp)	1					1
Total	4	2	16	5	1

Highest pathogenic variant AF is 0.000016183889

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
VPS35L	protein_coding	protein_coding	ENST00000438132	31	151554

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
2.23e-9	1.00	125655	0	93	125748	0.000370

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.692	562	610	0.921	0.0000349	6909
Missense in Polyphen		136	160.1	0.84946		1796
Synonymous	0.164	239	242	0.987	0.0000148	2014
Loss of Function	4.31	26	62.9	0.413	0.00000320	716

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000465	0.000459
Ashkenazi Jewish	0.000397	0.000397
East Asian	0.000272	0.000272
Finnish	0.000605	0.000601
European (Non-Finnish)	0.000480	0.000475
Middle Eastern	0.000272	0.000272
South Asian	0.000167	0.000163
Other	0.000330	0.000326

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Involved in copper-dependent ATP7A trafficking between the trans-Golgi network and vesicles in the cell periphery; the function is proposed to depend on its association within the CCC complex and cooperation with the WASH complex on early endosomes. Seems not to be required for CCC complex stability (PubMed:25355947). {ECO:0000269|PubMed:25355947}.
• Pathway: Neutrophil degranulation;Innate Immune System;Immune System (Consensus)

Intolerance Scores

• rvis_EVS: -1.21
• rvis_percentile_EVS: 5.69

Haploinsufficiency Scores

• pHI: 0.175
• hipred: N
• hipred_score: 0.478
• ghis: 0.569

Mouse Genome Informatics

• Gene name: Vps35l