VPS35L

protein-coding

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

Gene summary

Involved in Golgi to plasma membrane transport and endocytic recycling. Located in endosome. Part of protein-containing complex. Implicated in Ritscher-Schinzel syndrome. [provided by Alliance of Genome Resources, Jun 2026]

Previous symbols:

C16orf62

MANE transcript

NM_020314.7

Inheritance

ClinVar variants

P:7U:36B:7

Top phenotype

Ritscher-Schinzel syndrome 3

gnomAD constraint

pLI —, LoF o/e 0.41

Max pathogenic AF

—

Genomic locus

chr16:19,555,240-19,706,793

External References & Databases

Ensembl (ENSG00000103544)

Transcript & Mutation Effects

hg38 • Region Span ~151.6 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

Ritscher-Schinzel syndrome 3LIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0030864

Submitter: Ambry Genetics

Ritscher-Schinzel syndromeLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0019078

Submitter: Franklin by Genoox

Two siblings who presented clinical manifestations including cranio-cerebello-cardiac anomalies, coloboma, microphthalmia, chondrodysplasia punctata, complicated skeletal malformation, periventricular nodular heterotopia and proteinuria. Performed exome sequencing and identified compound heterozygous pathogenic variants in VPS35L. VPS35L knockout cells showed decreased autophagic function in nutrient-rich and starvation conditions, as well as following treatment with Torin 1

Clinical Genomic Database (CGD)

Ritscher-Schinzel syndrome 3AR

Manifestation: Craniofacial; Musculoskeletal; Neurologic; Ophthalmologic; Renal

Intervention: General

Rationale: 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

Refs: 31712251; 36113987

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to VPS35L variants in ClinVar

5 Conditions Cataloged

not providedTotal: 13

not specifiedTotal: 12

Ritscher-Schinzel syndrome 3Total: 8

VPS35L-related disorderTotal: 3

Ritscher-Schinzel syndromeTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_020314.7. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			1 clinvar	6 clinvar		7
missense	2 clinvar	1 clinvar	24 clinvar		1 clinvar	28
nonsense		1 clinvar	3 clinvar			4
start loss						0
frameshift	1 clinvar	1 clinvar				2
splice donor/acceptor (+/-2bp)	1 clinvar		8 clinvar			9
Total	4	3	36	6	1	50

Highest pathogenic variant AF is 0.000016183889

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 83 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_020314.7	RefSeq	NP_064710.5	31	MANE Select
ENST00000417362.7	Ensembl	ENSP00000395973.3	31	MANE Select
NM_001300743.3	RefSeq	NP_001287672.2	28	Standard
NM_001365293.2	RefSeq	NP_001352222.1	30	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Neutrophil degranulation
Innate Immune System
Immune System

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000438132
Coding exons: 31
Length: 151554
Individuals with no LoFs: 125655
Homozygous LoFs: 0
Heterozygous LoFs: 93
Defined: 125748
p: 0.000370

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.692	562	610	0.921	0.0000349	6909
Missense (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

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00031	0.00031	rare
Latino/Admixed American	0.00015	0.00014	rare
Ashkenazi Jewish	0.00040	0.00040	rare
East Asian	0.00027	0.00027	rare
Finnish	0.00060	0.00060	rare
European (Non-Finnish)	0.00048	0.00047	rare
South Asian	0.00017	0.00016	rare
Other	0.00033	0.00033	rare

dbNSFP Gene Annotations

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}.;

Intolerance Scores

RVIS EVS: -1.21
RVIS percentile EVS: 5.69