SERPINB5

Chr 18

serpin family B member 5

Also known as: PI5, maspin

NCBI Gene: 5268 ENSG00000206075 UniProt: P36952 OMIM: 154790

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.

OMIM ResearchSummary from RefSeq, UniProt

Predicted to enable serine-type endopeptidase inhibitor activity. Predicted to act upstream of or within several processes, including extracellular matrix organization; prostate gland morphogenesis; and regulation of epithelial cell proliferation. Located in cytoplasm. Biomarker of hepatocellular carcinoma. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.90

LOEUF

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.90LOEUF

pLI 0.004

Z-score 1.82

OE 0.46 (0.25–0.90)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.39Z-score

OE missense 0.92 (0.81–1.04)

178 obs / 193.2 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.46 (0.25–0.90)

0≤0.351.4

Missense OE?0.92 (0.81–1.04)

0≤0.61.4

Synonymous OE?0.92

0≤1.21.6

LoF obs/exp: 6 / 13.1Missense obs/exp: 178 / 193.2Syn Z: 0.56

Background carrier burden — how many people carry a rare variant somewhere in SERPINB5?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 110

487 rare PASS variants

Rare truncating (LoF)

1 in 2,900

62 rare PASS variants

Rare synonymous (reference)

1 in 270

190 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for SERPINB5. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 130	1 in 3,500
South Asian	~43k	1 in 120	1 in 940
Remaining (unassigned)	~30k	1 in 120	1 in 2,500
European (Finnish)	~27k	1 in 650	none seen
Admixed American	~22k	1 in 150	1 in 3,700
African / African American	~21k	1 in 130	1 in 2,500
East Asian	~20k	1 in 150	1 in 4,000
Ashkenazi Jewish	~13k	1 in 1,600	≈ 1 in 4,300
Middle Eastern	~2,884	1 in 160	≈ 1 in 1,400

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.