TSPAN33

Chr 7

tetraspanin 33

Also known as: PEN, PEN., TSPAN-33

NCBI Gene: 340348ENSG00000158457UniProt: Q86UF1

Enables enzyme binding activity. Involved in pore complex assembly; protein localization to plasma membrane; and protein maturation. Located in plasma membrane. Part of pore complex. [provided by Alliance of Genome Resources, Jul 2025]

49
ClinVar variants
24
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— TSPAN33
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
24 Pathogenic / Likely Pathogenic· 23 VUS of 49 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.
0.99LOEUF
pLI 0.000
Z-score 1.60
OE 0.57 (0.34–0.99)
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.
1.36Z-score
OE missense 0.69 (0.59–0.81)
107 obs / 154.8 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.0.57 (0.34–0.99)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.69 (0.59–0.81)
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.0.84
0≤1.21.6
LoF obs/exp: 9 / 15.9Missense obs/exp: 107 / 154.8Syn Z: 0.99

ClinVar Variant Classifications

49 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic24
VUS23
Likely Benign2
24
Pathogenic
23
VUS
2
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
24
0
24
Likely Pathogenic
0
0
0
0
0
VUS
0
22
1
0
23
Likely Benign
0
0
1
1
2
Benign
0
0
0
0
0
Total02226149

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

View in ClinVar →

Protein Context — Lollipop Plot

TSPAN33 · 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
TETRASPANIN 33; TSPAN33
MIM #610120 · *
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