SERPINB12

Chr 18

serpin family B member 12

Also known as: YUKOPIN

NCBI Gene: 89777ENSG00000166634UniProt: Q96P63

SERPINB12 encodes a serine protease inhibitor that inhibits trypsin and plasmin and may play a role in cell differentiation. The gene is not well-constrained against loss-of-function variants (pLI ~0, LOEUF 1.96), and no established human genetic diseases have been reported from mutations in this gene. Based on current knowledge, SERPINB12 is not associated with recognized pediatric neurological conditions.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
5
Pubs (1 yr)
97
P/LP submissions
0%
P/LP missense
1.96
LOEUF
Multiple*
Mechanism· predicted
Clinical Summary— SERPINB12
⚡
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· 77 VUS of 173 total submissions
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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
1.96LOEUF
pLI 0.000
Z-score -2.82
OE 1.73 (1.26–1.96)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-0.71Z-score
OE missense 1.14 (1.02–1.26)
246 obs / 216.4 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE1.73 (1.26–1.96)
0≤0.351.4
Missense OE1.14 (1.02–1.26)
0≤0.61.4
Synonymous OE1.05
0≤1.21.6
LoF obs/exp: 30 / 17.3Missense obs/exp: 246 / 216.4Syn Z: -0.32
DN
0.7229th %ile
GOF
0.6832th %ile
LOF
0.2289th %ile

This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

DNprediction above median
GOFprediction 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

173 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic87
Likely Pathogenic7
VUS77
Likely Benign2
87
Pathogenic
7
Likely Pathogenic
77
VUS
2
Likely 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
70
7
0
77
Likely Benign
0
2
0
0
2
Benign
0
0
0
0
0
Total0721010173

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

View in ClinVar →

Protein Context — Lollipop Plot

SERPINB12 · 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

ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 4 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients