JOSD1

Chr 22

Josephin domain containing 1

Also known as: dJ508I15.2

NCBI Gene: 9929ENSG00000100221UniProt: Q15040

Predicted to enable cysteine-type deubiquitinase activity. Predicted to be involved in proteolysis. Predicted to act upstream of or within several processes, including endocytosis; membrane biogenesis; and protein deubiquitination. Located in membrane. [provided by Alliance of Genome Resources, Apr 2025]

47
ClinVar variants
20
Pathogenic / LP
0.04
pLI score
0
Active trials
Clinical Summary— JOSD1
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.04) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
20 Pathogenic / Likely Pathogenic· 19 VUS of 47 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
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.
0.83LOEUF
pLI 0.045
Z-score 1.97
OE 0.36 (0.18–0.83)
Tolerant

Typical tolerance to LoF variation

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.
1.81Z-score
OE missense 0.53 (0.43–0.66)
63 obs / 118.5 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.0.36 (0.18–0.83)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.53 (0.43–0.66)
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.1.32
0≤1.21.6
LoF obs/exp: 4 / 11.1Missense obs/exp: 63 / 118.5Syn Z: -1.75

ClinVar Variant Classifications

47 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic18
Likely Pathogenic2
VUS19
Benign1
Conflicting1
18
Pathogenic
2
Likely Pathogenic
19
VUS
1
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
18
0
18
Likely Pathogenic
0
0
2
0
2
VUS
0
15
4
0
19
Likely Benign
0
0
0
0
0
Benign
0
0
1
0
1
Conflicting
—1
Total01525041

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

View in ClinVar →

Protein Context — Lollipop Plot

JOSD1 · 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
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