SERPINH1

Chr 11MultiAR

serpin family H member 1

Also known as: AsTP3, CBP1, CBP2, HSP47, OI10, PIG14, PPROM, RA-A47

NCBI Gene: 871ENSG00000149257UniProt: P50454

This gene encodes a member of the serpin superfamily of serine proteinase inhibitors. The encoded protein is localized to the endoplasmic reticulum and plays a role in collagen biosynthesis as a collagen-specific molecular chaperone. Autoantibodies to the encoded protein have been found in patients with rheumatoid arthritis. Expression of this gene may be a marker for cancer, and nucleotide polymorphisms in this gene may be associated with preterm birth caused by preterm premature rupture of membranes. Alternatively spliced transcript variants have been observed for this gene, and a pseudogene of this gene is located on the short arm of chromosome 9. [provided by RefSeq, May 2011]

Primary Disease Associations & Inheritance

{Preterm premature rupture of the membranes, susceptibility to}MIM #610504
Multi
Osteogenesis imperfecta, type XMIM #613848
AR
303
ClinVar variants
21
Pathogenic / LP
0.03
pLI score
2
Active trials
Clinical Summary— SERPINH1
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.03) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
21 Pathogenic / Likely Pathogenic· 155 VUS of 303 total submissions
💊
Clinical Trials
2 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.
0.75LOEUF
pLI 0.028
Z-score 2.25
OE 0.35 (0.18–0.75)
Tolerant

Typical tolerance to LoF variation

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.
0.05Z-score
OE missense 0.99 (0.90–1.10)
269 obs / 271.2 exp
Tolerant

Mild missense constraint

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.0.35 (0.18–0.75)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.99 (0.90–1.10)
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.1.09
0≤1.21.6
LoF obs/exp: 5 / 14.1Missense obs/exp: 269 / 271.2Syn Z: -0.78

ClinVar Variant Classifications

303 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic19
Likely Pathogenic2
VUS155
Likely Benign85
Benign18
Conflicting24
19
Pathogenic
2
Likely Pathogenic
155
VUS
85
Likely Benign
18
Benign
24
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
4
1
14
0
19
Likely Pathogenic
0
2
0
0
2
VUS
0
131
21
3
155
Likely Benign
0
4
21
60
85
Benign
0
0
12
6
18
Conflicting
—24
Total41386869303

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

View in ClinVar →

Protein Context — Lollipop Plot

SERPINH1 · 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

{Preterm premature rupture of the membranes, susceptibility to}

MIM #610504

Molecular basis of disorder known

Multifactorial

Osteogenesis imperfecta, type X

MIM #613848

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Single-cell transcriptomic analysis reveals the landscape of epithelial-mesenchymal transition molecular heterogeneity in esophageal squamous cell carcinoma.
Guo D et al.·Cancer Lett
2024
SERPINH1 secretion by cancer-associated fibroblasts promotes hepatocellular carcinoma malignancy through SENP3-mediated SP1/SQLE pathway.
Xiao H et al.·Int Immunopharmacol
2025
SERPINH1 promotes malignant progression of laryngeal squamous cell carcinoma via COL7A1-mediated Wnt/β-catenin signaling.
He F et al.·Cell Signal
2025
Genotype and Phenotype Correlation of Patients with Osteogenesis Imperfecta.
Aliyeva L et al.·J Mol Diagn
2024Cohort
Integrated analysis of tumor and adjacent non-tumor proteomic data reveals SERPINH1 as a recurrence biomarker and drug target in hepatocellular carcinoma.
Hou Y et al.·Int J Biol Sci
2024
Hub gene target of glioblastoma: LOX, SERPINH1 and TGFBI.
Zhang S et al.·Medicine (Baltimore)
2022
What is new in genetics and osteogenesis imperfecta classification?
Valadares ER et al.·J Pediatr (Rio J)
2014Review
Alteration of SERPINH1 is associated with elevated expression in head and neck squamous cell carcinomas and its clinicopathological significance.
Murugesan D et al.·J Stomatol Oral Maxillofac Surg
2024
SERPINH1 and CTSZ are Key Markers of Glioma Angiogenesis.
Wei H et al.·J Mol Neurosci
2025
Genetic analysis of osteogenesis imperfecta in a large Brazilian cohort.
Holtz AP et al.·Bone
2023Cohort
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
Osteogenesis Imperfecta

Urinary Biomarkers of OI Pathobiology

ACTIVE NOT RECRUITING
NCT02531087Baylor College of MedicineStarted 2015-08-17
Hip Fracture of Intertrochanteric TypeThromboembolic EventOsteopenia

Diffrence in Thromboprofilaksis in Elderly Ostoepenic Hip Fractures According to Mobility Status by Genetic Analysis

ACTIVE NOT RECRUITING
NCT06959017Phase NASaglik Bilimleri UniversitesiStarted 2024-11-01
Gene Expression Analysis

External Resources

Links to major genomics databases and tools