VPS35L

Chr 16AR

VPS35 endosomal protein sorting factor like

Also known as: C16orf62, EC97, RTSC3

The protein acts as a component of the retriever complex, which is essential for endosomal cargo retrieval and recycling, including transport of cell surface proteins involved in cell migration, adhesion, and signaling. Mutations cause Ritscher-Schinzel syndrome, which is inherited in an autosomal recessive pattern and typically presents in early childhood with characteristic craniofacial features, cardiac defects, and intellectual disability. This gene is highly constrained against loss-of-function variants (LOEUF 0.573), indicating that complete loss of protein function is likely not tolerated.

OMIMResearchSummary from RefSeq, UniProt
ARLOEUF 0.571 OMIM phenotype
Clinical SummaryVPS35L
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
22 unique Pathogenic / Likely Pathogenic· 26 VUS of 91 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.57LOEUF
pLI 0.000
Z-score 4.31
OE 0.41 (0.300.57)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
0.69Z-score
OE missense 0.92 (0.860.99)
562 obs / 610.1 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.41 (0.300.57)
00.351.4
Missense OE0.92 (0.860.99)
00.61.4
Synonymous OE0.99
01.21.6
LoF obs/exp: 26 / 62.9Missense obs/exp: 562 / 610.1Syn Z: 0.16

ClinVar Variant Classifications

91 submitted variants in ClinVar

Classification Summary

Pathogenic19
Likely Pathogenic3
VUS26
Likely Benign8
Benign4
19
Pathogenic
3
Likely Pathogenic
26
VUS
8
Likely Benign
4
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
2
2
15
0
19
Likely Pathogenic
2
1
0
0
3
VUS
1
17
8
0
26
Likely Benign
0
0
2
6
8
Benign
0
1
2
1
4
Total52127760

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

VPS35L · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
Open Research Assistant →
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC

No open access results found