SERPINF1

Chr 17AR

serpin family F member 1

Also known as: EPC-1, OI12, OI6, PEDF, PIG35

NCBI Gene: 5176ENSG00000132386UniProt: P36955OMIM: 172860

The protein is a secreted neurotrophic factor that promotes neuronal differentiation and potently inhibits angiogenesis, functioning as a non-inhibitory member of the serpin family. Mutations cause osteogenesis imperfecta type VI, which follows autosomal recessive inheritance and primarily affects bone formation and mineralization. The gene is highly intolerant to loss-of-function variants, indicating that complete protein loss is likely incompatible with normal development.

OMIMResearchSummary from RefSeq, UniProt
ARLOEUF 1.211 OMIM phenotype
Clinical Summary— SERPINF1
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
102 unique Pathogenic / Likely Pathogenic· 148 VUS of 424 total submissions
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Clinical Trials
3 active or recruiting trials — potential therapeutic options may be available
Explore recent and relevant literature in Research Assistant →
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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
1.21LOEUF
pLI 0.000
Z-score 0.90
OE 0.76 (0.50–1.21)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-0.91Z-score
OE missense 1.17 (1.06–1.29)
275 obs / 235.7 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.76 (0.50–1.21)
0≤0.351.4
Missense OE1.17 (1.06–1.29)
0≤0.61.4
Synonymous OE1.29
0≤1.21.6
LoF obs/exp: 13 / 17.0Missense obs/exp: 275 / 235.7Syn Z: -2.31

ClinVar Variant Classifications

424 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic75
Likely Pathogenic27
VUS148
Likely Benign134
Benign17
Conflicting18
75
Pathogenic
27
Likely Pathogenic
148
VUS
134
Likely Benign
17
Benign
18
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
32
1
42
0
75
Likely Pathogenic
17
2
8
0
27
VUS
3
123
19
3
148
Likely Benign
0
2
47
85
134
Benign
0
1
14
2
17
Conflicting
—18
Total5212913090419

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

View in ClinVar →

Protein Context — Lollipop Plot

SERPINF1 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold
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 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
FTO-Mediated m6A Demethylation of SERPINF1 Attenuates Multiple Myeloma Progression via the Wnt/β-Catenin Pathway.
Dong X et al.·J Microbiol Biotechnol
2026Open Access
Impaired SERPINF1 Expression due to c.[-37C>A];[829_831del] Causes Osteogenesis Imperfecta VI.
Badiger VA et al.·Am J Med Genet A
2026
Endoplasmic reticulum stress and autophagy as potential therapeutic targets in SERPINF1 mutation-induced type VI osteogenesis imperfecta.
Tian Y et al.·Life Sci
2025
Molecular and Clinical Aspects of Osteogenesis Imperfecta Type VI: A Case Series with Novel SERPINF1 Gene Variants.
Merkuryeva ES et al.·Int J Mol Sci
2025Open AccessCohort
SERPINF1 knockdown attenuates chondrocyte senescence, hypertrophy, and inflammation in osteoarthritis to offer a potential therapeutic strategy.
Dong L et al.·Cell Signal
2025
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