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10 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
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SERPINA7
serpin family A member 7
Chromosome X Β· Xq22.3
NCBI Gene: 6906Ensembl: ENSG00000123561.16HGNC: HGNC:11583UniProt: P05543
62PubMed Papers
20Diseases
0Drugs
6Pathogenic Variants
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
thyroid hormone transportextracellular exosomeserine-type endopeptidase inhibitor activityGO:0005615neoplasmhyperinsulinemic hypoglycemia, familial, 4Pallister-Hall syndromeEhlers-Danlos syndrome, musculocontractural type
✦AI Summary

SERPINA7 encodes thyroxine-binding globulin (TBG), the major thyroid hormone transport protein in serum, carrying approximately 75% of circulating T4 and T3 1. As a serpin family member, SERPINA7 functions as a serine-type endopeptidase inhibitor and operates in the extracellular region [GO annotations]. The protein is synthesized in the liver and secreted into circulation where it binds thyroid hormones with high affinity 2. TBG deficiency results from SERPINA7 mutations causing amino acid substitutions, truncations, or alterations in protein stability and secretion 31. Mutations can produce complete or partial deficiency phenotypes, with compound hemizygous variants showing cumulative effects on protein folding and function 3. Clinically, TBG deficiency presents with abnormally low serum total T4 and T3 in euthyroid individuals with normal TSH, potentially leading to misdiagnosis as hypothyroidism if unrecognized 14. Genome-wide association studies identified SERPINA7 variants associated with free T3 levels, highlighting its role in thyroid function regulation 2. Beyond thyroid hormone transport, SERPINA7 levels are downregulated in primary open-angle glaucoma aqueous humor and serve as a prognostic biomarker in idiopathic pulmonary fibrosis 56, suggesting broader physiological significance in ocular and pulmonary pathologies.

Sources cited
1
SERPINA7 encodes TBG; variants cause altered protein stability and secretion
PMID: 33554479
2
TBG carries approximately 75% of serum T4 and T3; encoded by SERPINA7 on X-chromosome; deficiency presents with low T4/T3 in euthyroid subjects with normal TSH
PMID: 19415532
3
SERPINA7 variants associated with free T3 levels in genome-wide association study
PMID: 34524976
4
SERPINA7 mutations result in TBG deficiency; low TBG can be misdiagnosed as hypothyroidism
PMID: 36475360
5
SERPINA7 is one of thirteen most abundant serpins in aqueous humor; downregulated in primary open-angle glaucoma
PMID: 40389884
6
SERPINA7 is a prognostic biomarker for respiratory death or lung transplant risk in idiopathic pulmonary fibrosis
PMID: 41126189
Disease Associationsβ“˜20
neoplasmOpen Targets
0.10Suggestive
hyperinsulinemic hypoglycemia, familial, 4Open Targets
0.07Suggestive
Pallister-Hall syndromeOpen Targets
0.05Suggestive
Ehlers-Danlos syndrome, musculocontractural typeOpen Targets
0.05Suggestive
colorectal cancerOpen Targets
0.04Suggestive
osteoarthritis, kneeOpen Targets
0.04Suggestive
hepatocellular carcinomaOpen Targets
0.04Suggestive
non-alcoholic steatohepatitisOpen Targets
0.04Suggestive
medical procedureOpen Targets
0.03Suggestive
breast cancerOpen Targets
0.03Suggestive
major depressive disorderOpen Targets
0.03Suggestive
infectionOpen Targets
0.02Suggestive
hypothyroidismOpen Targets
0.02Suggestive
liver and intrahepatic bile duct neoplasmOpen Targets
0.02Suggestive
Neoplasm of the liverOpen Targets
0.02Suggestive
Acute hepatic failureOpen Targets
0.02Suggestive
mucopolysaccharidosis type 4AOpen Targets
0.02Suggestive
osteoarthritis, hipOpen Targets
0.02Suggestive
thyroid diseaseOpen Targets
0.02Suggestive
thyroiditisOpen Targets
0.02Suggestive
Pathogenic Variants6
NM_000354.6(SERPINA7):c.1114del (p.Leu372fs)Likely pathogenic
Thyroxine-binding globulin quantitative trait locus
β˜…β˜†β˜†β˜†2025β†’ Residue 372
NM_000354.6(SERPINA7):c.1117_1118delinsCAG (p.Ser373fs)Pathogenic
Thyroxine-binding globulin deficiency
β˜…β˜†β˜†β˜†2025β†’ Residue 373
NM_000354.6(SERPINA7):c.804_805del (p.Phe269fs)Pathogenic
Thyroxine-binding globulin quantitative trait locus
β˜…β˜†β˜†β˜†2019β†’ Residue 269
NM_000354.5(SERPINA7):c.986A>T (p.Tyr329Phe)Pathogenic
Thyroxine-binding globulin, Chicago
β˜†β˜†β˜†β˜†1995β†’ Residue 329
NM_000354.5(SERPINA7):c.571G>A (p.Asp191Asn)Pathogenic
Thyroxine-binding globulin, slow
β˜†β˜†β˜†β˜†1990β†’ Residue 191
NM_000354.5(SERPINA7):c.347T>A (p.Ile116Asn)Pathogenic
Thyroxine-binding globulin deficiency, partial
β˜†β˜†β˜†β˜†1990β†’ Residue 116
View on ClinVar β†—
Related Genes
APOA5Protein interaction100%AFPProtein interaction98%SHBGProtein interaction95%F2Protein interaction89%UGT2B10Protein interaction85%SERPINA11Protein interaction80%
Tissue Expression6 tissues
Liver
100%
Ovary
0%
Brain
0%
Lung
0%
Heart
0%
Bone Marrow
0%
Gene Interaction Network
Click a node to explore
SERPINA7APOA5AFPSHBGF2UGT2B10SERPINA11
PROTEIN STRUCTURE
Preparing viewer…
PDB2XN6 Β· 1.29 Γ… Β· X-ray
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
1.37LoF Tolerant
pLIβ“˜
0.00Tolerant
Observed/Expected LoF0.88 [0.58–1.37]
RankingsWhere SERPINA7 stands among ~20K protein-coding genes
  • #7,506of 20,598
    Most Researched62
  • #3,379of 5,498
    Most Pathogenic Variants6
  • #14,271of 17,882
    Most Constrained (LOEUF)1.37
Genes detectedSERPINA7
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
The unfolded protein response regulates hepatic autophagy by sXBP1-mediated activation of TFEB.
PMID: 32597296
Autophagy Β· 2021
1.00
2
Compound hemizygous variants in SERPINA7 gene cause thyroxine-binding globulin deficiency.
PMID: 33554479
Mol Genet Genomic Med Β· 2021
0.90
3
Unveiling the levels and significance of different serpin family proteins in aqueous humor dynamics.
PMID: 40389884
BMC Ophthalmol Β· 2025
0.80
4
A novel variant in Serpina7 gene in a family with thyroxine-binding globulin deficiency.
PMID: 19415532
Endocrine Β· 2009
0.70
5
Mass spectrometry-based peripheral blood proteomics for biomarker discovery in idiopathic pulmonary fibrosis.
PMID: 41126189
Respir Res Β· 2025
0.60