HomeAboutRankingsData Sources
© 2026 GeneE
🧬
GeneE
25 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
ⓘGeneE is for informational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment.
SHBG
sex hormone binding globulin
Chromosome 17 · 17p13.1
NCBI Gene: 6462Ensembl: ENSG00000129214.15HGNC: HGNC:10839UniProt: B0FWH2
365PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
RESEARCH IMPACT
Highly StudiedTrending
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
protein bindingextracellular exosomesteroid bindingGO:0005615testicular diseasetype 2 diabetes mellitusAbnormality of the skeletal systemhypogonadism
✦AI Summary

SHBG (sex hormone-binding globulin) is a hepatically-produced glycoprotein that serves as the primary transport protein for sex steroid hormones in plasma 1. The protein functions as a homodimer, with each dimer binding one molecule of steroid hormone, specifically testosterone, dihydrotestosterone, and estradiol with high affinity 2. SHBG regulates steroid hormone bioavailability by controlling their plasma concentrations and metabolic clearance rates 1. Beyond its transport function, emerging evidence suggests SHBG acts as a hepatokine with direct metabolic effects. Low SHBG levels are associated with insulin resistance, non-alcoholic fatty liver disease, and increased androgen bioavailability 1. Genetic variants in the SHBG gene, particularly the rs35785886 polymorphism with eight or more pentanucleotide repeats, are associated with increased polycystic ovary syndrome (PCOS) risk and reduced serum SHBG concentrations 3. SHBG levels correlate inversely with metabolic dysfunction, including dyslipidemia in postmenopausal women 4 and diabetes risk 5. Recent research indicates SHBG may have a causal role in type 2 diabetes pathogenesis, particularly in women, suggesting therapeutic potential for SHBG-raising treatments 5.

Sources cited
1
SHBG is hepatically-produced glycoprotein that binds sex steroids and regulates bioavailability; associated with NAFLD and insulin resistance
PMID: 33139661
2
SHBG functions as homodimer with high-affinity steroid binding
PMID: 34855305
3
SHBG rs35785886 polymorphism associated with PCOS risk and low SHBG levels
PMID: 33168491
4
SHBG levels inversely correlate with dyslipidemia in postmenopausal women
PMID: 40495241
5
SHBG has causal role in type 2 diabetes pathogenesis and potential as hepatokine
PMID: 34052096
Disease Associationsⓘ20
testicular diseaseOpen Targets
0.47Moderate
type 2 diabetes mellitusOpen Targets
0.45Moderate
Abnormality of the skeletal systemOpen Targets
0.45Moderate
hypogonadismOpen Targets
0.35Weak
agingOpen Targets
0.34Weak
smoking cessationOpen Targets
0.33Weak
osteoarthritis, hipOpen Targets
0.31Weak
atrial fibrillationOpen Targets
0.25Weak
metabolic syndromeOpen Targets
0.12Weak
polycystic ovary syndromeOpen Targets
0.12Weak
non-alcoholic fatty liver diseaseOpen Targets
0.11Weak
gestational diabetesOpen Targets
0.11Weak
breast cancerOpen Targets
0.11Weak
diabetes mellitusOpen Targets
0.10Weak
Insulin resistanceOpen Targets
0.10Weak
Alzheimer diseaseOpen Targets
0.10Suggestive
rheumatoid arthritisOpen Targets
0.10Suggestive
coronary artery diseaseOpen Targets
0.10Suggestive
strokeOpen Targets
0.10Suggestive
myeloid sarcomaOpen Targets
0.09Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
NLGN2Protein interaction100%SERPINA6Protein interaction100%LRP2Protein interaction100%NRXN3Protein interaction98%SERPINA7Protein interaction95%NRXN1Protein interaction92%
Tissue Expression6 tissues
Liver
100%
Ovary
3%
Heart
2%
Brain
2%
Lung
1%
Bone Marrow
0%
Gene Interaction Network
Click a node to explore
SHBGNLGN2SERPINA6LRP2NRXN3SERPINA7NRXN1
PROTEIN STRUCTURE
Preparing viewer…
PDB1D2S · 1.55 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
1.10LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.83 [0.64–1.10]
RankingsWhere SHBG stands among ~20K protein-coding genes
  • #847of 20,598
    Most Researched365 · top 5%
  • #11,172of 17,882
    Most Constrained (LOEUF)1.10
Genes detectedSHBG
Sources retrieved25 papers
Response time—
📄 Sources
25▼
1
Sex Hormone-Binding Globulin (SHBG) as an Early Biomarker and Therapeutic Target in Polycystic Ovary Syndrome.
PMID: 33139661
Int J Mol Sci · 2020
1.00
2
Association between human SHBG gene polymorphisms and risk of PCOS: a meta-analysis.
PMID: 33168491
Reprod Biomed Online · 2021
0.90
3
Hypogonadism and diabetes.
PMID: 12934046
Int J Impot Res · 2003
0.80
4
Human sex hormone-binding globulin gene expression- multiple promoters and complex alternative splicing.
PMID: 19416531
BMC Mol Biol · 2009
0.76
5
Sex hormone-binding globulin: biomarker and hepatokine?
PMID: 34052096
Trends Endocrinol Metab · 2021
0.70