SERPINF1

Chr 17AR

serpin family F member 1

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

NCBI Gene: 5176ENSG00000132386UniProt: P36955

This gene encodes a member of the serpin family that does not display the serine protease inhibitory activity shown by many of the other serpin proteins. The encoded protein is secreted and strongly inhibits angiogenesis. In addition, this protein is a neurotrophic factor involved in neuronal differentiation in retinoblastoma cells. Mutations in this gene were found in individuals with osteogenesis imperfecta, type VI. [provided by RefSeq, Aug 2016]

Primary Disease Associations & Inheritance

Osteogenesis imperfecta, type VIMIM #613982
AR
520
ClinVar variants
120
Pathogenic / LP
0.00
pLI score
3
Active trials
Clinical Summary— SERPINF1
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
120 Pathogenic / Likely Pathogenic· 160 VUS of 520 total submissions
💊
Clinical Trials
3 active or recruiting trials — potential therapeutic options may be available

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

Tolerant to missense variation

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.0.76 (0.50–1.21)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.17 (1.06–1.29)
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.1.29
0≤1.21.6
LoF obs/exp: 13 / 17.0Missense obs/exp: 275 / 235.7Syn Z: -2.31

ClinVar Variant Classifications

520 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic88
Likely Pathogenic32
VUS160
Likely Benign147
Benign38
Conflicting30
88
Pathogenic
32
Likely Pathogenic
160
VUS
147
Likely Benign
38
Benign
30
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
16
0
72
0
88
Likely Pathogenic
12
2
18
0
32
VUS
3
124
29
4
160
Likely Benign
0
3
51
93
147
Benign
0
5
29
4
38
Conflicting
—30
Total31134199101495

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.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Osteogenesis imperfecta, type VI

MIM #613982

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Genotype-phenotype relationship and comparison between eastern and western patients with osteogenesis imperfecta.
Lin X et al.·J Endocrinol Invest
2024Cohort
SERPINF1 Mediates Tumor Progression and Stemness in Glioma.
Song L et al.·Genes (Basel)
2023
DNA sequence analysis in 598 individuals with a clinical diagnosis of osteogenesis imperfecta: diagnostic yield and mutation spectrum.
Bardai G et al.·Osteoporos Int
2016
The comparison of pathogenic role and mechanism of Kallistatin and PEDF in tumors.
Lyu J et al.·Biochim Biophys Acta Rev Cancer
2025Review
Developing serum proteomics based prediction models of disease progression in ADPKD.
Aydogan Balaban HÖ et al.·Nat Commun
2025Functional
Restoration of the serum level of SERPINF1 does not correct the bone phenotype in Serpinf1 null mice.
Rajagopal A et al.·Mol Genet Metab
2016
Characterization of three adults and an adolescent with Osteogenesis Imperfecta type VI and a novel founder SERPINF1 variant.
Travessa AM et al.·Eur J Med Genet
2023
Rare Association Between Osteogenesis Imperfecta and Chondrosarcoma: Could a Pathogenic Variant in the Gene SERPINF1 Explain It?
Amorim DMR et al.·Calcif Tissue Int
2023
Endoplasmic reticulum stress and autophagy as potential therapeutic targets in SERPINF1 mutation-induced type VI osteogenesis imperfecta.
Tian Y et al.·Life Sci
2025
Normal bone density and fat mass in heterozygous SERPINF1 mutation carriers.
Al-Jallad H et al.·J Clin Endocrinol Metab
2014
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
Ischemic Stroke

Strategy for Improving Stroke Treatment Response

RECRUITING
NCT05948566Phase PHASE2Translational Sciences, Inc.Started 2024-03-18
TS23
Wet Age-related Macular Degeneration

Pharmacogenomics of antiVEGF in Patients With Age-Associated Macular Degeneration (AMD)

RECRUITING
NCT06952452Phase PHASE3Parc de Salut MarStarted 2022-11-18
BevacizumabRanibizumab Ophthalmic
Osteogenesis Imperfecta

Urinary Biomarkers of OI Pathobiology

ACTIVE NOT RECRUITING
NCT02531087Baylor College of MedicineStarted 2015-08-17

External Resources

Links to major genomics databases and tools