VPS50

Chr 7AR

VPS50 subunit of EARP/GARPII complex

Also known as: CCDC132, NEDMSC, VPS54L

NCBI Gene: 55610ENSG00000004766UniProt: Q96JG6

Enables SNARE binding activity. Acts upstream of or within endocytic recycling. Located in recycling endosome. Part of EARP complex. [provided by Alliance of Genome Resources, Jul 2025]

Primary Disease Associations & Inheritance

Neurodevelopmental disorder with microcephaly, seizures, and neonatal cholestasisMIM #619685
AR
121
ClinVar variants
22
Pathogenic / LP
0.81
pLI score
0
Active trials
Clinical Summary— VPS50
⚡
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.81) — some intolerance to loss-of-function variants.
📋
ClinVar Variants
22 Pathogenic / Likely Pathogenic· 92 VUS of 121 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
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.
0.33LOEUF
pLI 0.814
Z-score 5.63
OE 0.21 (0.13–0.33)
Highly constrained

Highly LoF-intolerant (top ~10% 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.
2.50Z-score
OE missense 0.68 (0.62–0.74)
325 obs / 479.1 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

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.0.21 (0.13–0.33)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.68 (0.62–0.74)
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.1.02
0≤1.21.6
LoF obs/exp: 12 / 58.4Missense obs/exp: 325 / 479.1Syn Z: -0.25

ClinVar Variant Classifications

121 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic16
Likely Pathogenic6
VUS92
Likely Benign5
Benign2
16
Pathogenic
6
Likely Pathogenic
92
VUS
5
Likely Benign
2
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
1
0
15
0
16
Likely Pathogenic
3
0
3
0
6
VUS
1
87
4
0
92
Likely Benign
0
2
0
3
5
Benign
0
1
0
1
2
Total590224121

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

View in ClinVar →

Protein Context — Lollipop Plot

VPS50 · 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

Neurodevelopmental disorder with microcephaly, seizures, and neonatal cholestasis

MIM #619685

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
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