VPS35L

Chr 16AR

VPS35 endosomal protein sorting factor like

Also known as: C16orf62, EC97, RTSC3

NCBI Gene: 57020ENSG00000103544UniProt: Q7Z3J2

Involved in Golgi to plasma membrane transport and endocytic recycling. Located in endosome. Implicated in Ritscher-Schinzel syndrome. [provided by Alliance of Genome Resources, Jul 2025]

Primary Disease Associations & Inheritance

Ritscher-Schinzel syndrome 3MIM #619135
AR
58
ClinVar variants
22
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— VPS35L
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
22 Pathogenic / Likely Pathogenic· 25 VUS of 58 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.57LOEUF
pLI 0.000
Z-score 4.31
OE 0.41 (0.30–0.57)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.69Z-score
OE missense 0.92 (0.86–0.99)
562 obs / 610.1 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.41 (0.30–0.57)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.92 (0.86–0.99)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.99
0≤1.21.6
LoF obs/exp: 26 / 62.9Missense obs/exp: 562 / 610.1Syn Z: 0.16

ClinVar Variant Classifications

58 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic19
Likely Pathogenic3
VUS25
Likely Benign7
Benign4
19
Pathogenic
3
Likely Pathogenic
25
VUS
7
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
1
1
1
0
3
VUS
0
15
10
0
25
Likely Benign
0
0
2
5
7
Benign
0
1
2
1
4
Total31930658

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.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Ritscher-Schinzel syndrome 3

MIM #619135

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC

No open access results found

Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools