SERPINB5

Chr 18

serpin family B member 5

Also known as: PI5, maspin

The protein functions as a tumor suppressor that blocks growth, invasion, and metastatic properties of mammary tumors, though it lacks serine protease inhibitory activity despite its serpin classification. Mutations in this gene have not been established to cause any recognized Mendelian neurological or developmental disorders. The gene shows tolerance to loss-of-function variants (pLI = 0.004, LOEUF = 0.903), suggesting heterozygous loss alone may not be sufficient to cause disease.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
20
Pubs (1 yr)
97
P/LP submissions
0%
P/LP missense
0.90
LOEUF
DN
Mechanism· predicted
Clinical SummarySERPINB5
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
94 unique Pathogenic / Likely Pathogenic· 53 VUS of 158 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.90LOEUF
pLI 0.004
Z-score 1.82
OE 0.46 (0.250.90)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.39Z-score
OE missense 0.92 (0.811.04)
178 obs / 193.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.46 (0.250.90)
00.351.4
Missense OE0.92 (0.811.04)
00.61.4
Synonymous OE0.92
01.21.6
LoF obs/exp: 6 / 13.1Missense obs/exp: 178 / 193.2Syn Z: 0.56
DN
0.75top 25%
GOF
0.6053th %ile
LOF
0.2190th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

158 submitted variants in ClinVar

Classification Summary

Pathogenic87
Likely Pathogenic7
VUS53
Benign2
87
Pathogenic
7
Likely Pathogenic
53
VUS
2
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
87
0
87
Likely Pathogenic
0
0
7
0
7
VUS
0
46
7
0
53
Likely Benign
0
0
0
0
0
Benign
0
0
2
0
2
Total0461030149

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

View in ClinVar →

Protein Context — Lollipop Plot

SERPINB5 · protein map & ClinVar variants

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
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