SHBG: Sex Hormone-Binding Globulin
A key plasma glycoprotein regulating steroid hormone bioavailability and signaling.
Gene Information Card
| Symbol | SHBG |
|---|---|
| Full Name | Sex Hormone-Binding Globulin |
| Gene Type | Protein coding |
| Chromosomal Location | 17p13.1 |
| NCBI Gene ID | 6462 ncbi.nlm.nih.gov/gene/6462 |
| Ensembl ID | ENSG00000129214 |
| UniProt ID | P04278 |
| OMIM ID | 182205 |
| HGNC ID | 10819 |
| Aliases | ABP, SBP, TEBG |
Description
The SHBG gene encodes sex hormone-binding globulin, a homodimeric plasma glycoprotein that binds and transports sex steroids, primarily testosterone and estradiol, regulating their bioavailability and access to target tissues. SHBG is produced mainly in the liver and circulates in the blood, modulating steroid hormone signaling and influencing various physiological processes including reproduction, metabolism, and cancer risk.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| SHBG Deficiency | Loss-of-function mutations reduce steroid binding, leading to altered androgen/estrogen ratios and potential infertility or metabolic disorders. | ClinVar, OMIM |
| Polycystic Ovary Syndrome (PCOS) | Low SHBG levels are associated with hyperandrogenism and insulin resistance, contributing to PCOS pathophysiology. | NCBI Gene, ClinVar |
| Endometrial Cancer | Reduced SHBG levels may increase free estradiol, promoting estrogen-driven endometrial proliferation. | NCBI Gene, COSMIC |
| Prostate Cancer | SHBG polymorphisms and altered levels influence androgen availability and prostate cancer risk. | NCBI Gene, COSMIC |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 12.5 | High |
| Testis | 2.1 | Medium |
| Kidney | 0.8 | Low |
| Brain | 0.3 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 | 15.0 | Hepatocellular carcinoma cell line, high SHBG expression |
| MCF7 | 0.5 | Breast cancer cell line, low expression |
| LNCaP | 0.2 | Prostate cancer cell line, very low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1A>G (p.Met1?) | Missense | Rare | Loss of start codon, reduced protein expression |
| c.326G>A (p.Arg109His) | Missense | <0.01% | Impaired steroid binding affinity |
| c.533C>T (p.Pro178Leu) | Missense | <0.01% | Altered dimerization and secretion |
Mutation functional classification
Loss of Function (LOF)
Mutations such as p.Met1? and p.Arg109His reduce SHBG production or steroid-binding capacity, leading to decreased transport of sex hormones.
Gain of Function (GOF)
No well-characterized gain-of-function mutations reported in SHBG.
Dominant Negative (DN)
No dominant-negative mutations described for SHBG; the protein functions as a homodimer, but dominant effects are not established.
View complete mutation data：
Gene Ontology (GO)
| • steroid binding (GO:0005496) | • testosterone binding (GO:0005523) |
| • estradiol binding (GO:0030285) | • extracellular region (GO:0005576) |
| • extracellular space (GO:0005615) |
Pathways
• Steroid hormone biosynthesis
• Sex hormone signaling pathway
Protein Summary
SHBG is a 373-amino-acid homodimeric glycoprotein (UniProt P04278) synthesized primarily in hepatocytes. It circulates in plasma as a homodimer, binding testosterone and estradiol with high affinity, thereby regulating their free concentrations and tissue delivery. SHBG also interacts with cell surface receptors (e.g., megalin) to mediate steroid uptake in target tissues. Its levels are modulated by hormones, metabolic status, and genetic variants, influencing conditions such as PCOS, infertility, and hormone-sensitive cancers.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| SHBG Knockout HEK293 Cell Line | EDJ-KQ2131 | Human | 6462 | Details Get a Quote |
| SHBG Knockout HeLa Cell Line | EDJ-KQ54462 | Human | 6462 | Details Get a Quote |
| SHBG Knockout A-549 Cell Line | EDJ-KQ62950 | Human | 6462 | Details Get a Quote |
| SHBG Knockout HCT 116 Cell Line | EDJ-KQ71422 | Human | 6462 | Details Get a Quote |
Displaying Records 1 To 4 Of 4 Records
