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SHBG sex hormone binding globulin [ Homo sapiens (human) ]

Gene ID: 6462, updated on 31-Mar-2024

Summary

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Official Symbol
SHBGprovided by HGNC
Official Full Name
sex hormone binding globulinprovided by HGNC
Primary source
HGNC:HGNC:10839
See related
Ensembl:ENSG00000129214 MIM:182205; AllianceGenome:HGNC:10839
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
ABP; SBP; TEBG
Summary
This gene encodes a steroid binding protein that was first described as a plasma protein secreted by the liver but is now thought to participate in the regulation of steroid responses. The encoded protein transports androgens and estrogens in the blood, binding each steroid molecule as a dimer formed from identical or nearly identical monomers. Polymorphisms in this gene have been associated with polycystic ovary syndrome and type 2 diabetes mellitus. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2014]
Expression
Biased expression in liver (RPKM 11.7), testis (RPKM 2.8) and 3 other tissues See more
Orthologs
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Genomic context

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See SHBG in Genome Data Viewer
Location:
17p13.1
Exon count:
10
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 17 NC_000017.11 (7614064..7633372)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 17 NC_060941.1 (7518285..7537563)
105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 17 NC_000017.10 (7517382..7536690)

Chromosome 17 - NC_000017.11Genomic Context describing neighboring genes Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr17:7492556-7493130 Neighboring gene mannose-P-dolichol utilization defect 1 Neighboring gene SRY-box transcription factor 15 Neighboring gene FMR1 autosomal homolog 2 Neighboring gene uncharacterized LOC124904134 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 8132 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 8133 Neighboring gene MPRA-validated peak2713 silencer Neighboring gene tRNA-undetermined (NNN) 6-1 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 11638 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 8134 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 11639 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 11640 Neighboring gene spermidine/spermine N1-acetyltransferase family member 2 Neighboring gene ReSE screen-validated silencer GRCh37_chr17:7551198-7551407 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr17:7552896-7553396 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr17:7553397-7553897 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr17:7554172-7554814 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr17:7558514-7559332 Neighboring gene ATPase Na+/K+ transporting subunit beta 2 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr17:7571230-7572027 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr17:7580287-7580898 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr17:7580899-7581510 Neighboring gene H3K27ac hESC enhancer GRCh37_chr17:7581511-7582121 Neighboring gene tumor protein p53 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 8136 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 11641 Neighboring gene BRD4-independent group 4 enhancer GRCh37_chr17:7589699-7590898 Neighboring gene WD repeat containing antisense to TP53

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • Project title: HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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Related articles in PubMed

  1. The Association between Inflammation, Testosterone and SHBG in men: A cross-sectional Multi-Ethnic Study of Atherosclerosis. Osmancevic A, et al. Clin Endocrinol (Oxf), 2023 Aug. PMID 37221937,
  2. Sex hormones, SHBG and cognitive performance among older Australian women: an observational study. Sultana F, et al. Climacteric, 2023 Apr. PMID 36716780, Free PMC Article
  3. Sex Hormone-Binding Globulin and Risk of Coronary Heart Disease in Men and Women. Li J, et al. Clin Chem, 2023 Apr 3. PMID 36702572
  4. Estrone, sex hormone binding globulin and lipid profiles in older women: an observational study. Azene ZN, et al. Climacteric, 2023 Apr. PMID 36693423, Free PMC Article
  5. Associations of low sex hormone-binding globulin and androgen excess in early pregnancy with fasting and post-prandial hyperglycaemia, gestational diabetes, and its severity. Mustaniemi S, et al. Diabetes Metab Res Rev, 2023 Feb. PMID 36484476, Free PMC Article

See all (345) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. Longitudinal Changes in Sex Hormone Binding Globulin (SHBG) and Risk of Incident Diabetes: The Study of Women's Health Across the Nation (SWAN).
    Title: Longitudinal Changes in Sex Hormone Binding Globulin (SHBG) and Risk of Incident Diabetes: The Study of Women's Health Across the Nation (SWAN).
  2. Association of Testosterone and Sex Hormone-Binding Globulin With All-Cause and Cardiovascular Disease Mortality in Older Chinese Men.
    Title: Association of Testosterone and Sex Hormone-Binding Globulin With All-Cause and Cardiovascular Disease Mortality in Older Chinese Men.
  3. Sex-Hormone-Binding Globulin Gene Polymorphisms and Breast Cancer Risk in Caucasian Women of Russia.
    Title: Sex-Hormone-Binding Globulin Gene Polymorphisms and Breast Cancer Risk in Caucasian Women of Russia.
  4. The Association Between SHBG and Osteoporosis: A NHANES Cross-Sectional Study and A Bidirectional Mendelian Randomization.
    Title: The Association Between SHBG and Osteoporosis: A NHANES Cross-Sectional Study and A Bidirectional Mendelian Randomization.
  5. Sex Hormone-Binding Globulin and Risk of Incident Dementia in Middle-Aged to Older Women: Results from the UK Biobank Cohort Study.
    Title: Sex Hormone-Binding Globulin and Risk of Incident Dementia in Middle-Aged to Older Women: Results from the UK Biobank Cohort Study.
  6. Sex hormone-binding globulin exerts sex-related causal effects on lower extremity varicose veins: evidence from gender-stratified Mendelian randomization.
    Title: Sex hormone-binding globulin exerts sex-related causal effects on lower extremity varicose veins: evidence from gender-stratified Mendelian randomization.
  7. Associations of bone mineral density with sex hormone-binding globulin (SHBG) and testosterone in middle-aged Saudi men: a cross-sectional study.
    Title: Associations of bone mineral density with sex hormone-binding globulin (SHBG) and testosterone in middle-aged Saudi men: a cross-sectional study.
  8. The relationship between sex hormone-binding protein and non-alcoholic fatty liver disease using Mendelian randomisation.
    Title: The relationship between sex hormone-binding protein and non-alcoholic fatty liver disease using Mendelian randomisation.
  9. Circulating sex hormone-binding globulin levels and ischemic stroke risk: a Mendelian randomization study.
    Title: Circulating sex hormone-binding globulin levels and ischemic stroke risk: a Mendelian randomization study.
  10. Genetic Correlation, Shared Loci, and Causal Association Between Sex Hormone-Binding Globulin and Bone Mineral Density: Insights From a Large-Scale Genomewide Cross-Trait Analysis.
    Title: Genetic Correlation, Shared Loci, and Causal Association Between Sex Hormone-Binding Globulin and Bone Mineral Density: Insights From a Large-Scale Genomewide Cross-Trait Analysis.
Submit: New GeneRIF Correction See all GeneRIFs (299)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

EBI GWAS Catalog

Description
A genome-wide association meta-analysis of circulating sex hormone-binding globulin reveals multiple Loci implicated in sex steroid hormone regulation.
EBI GWAS Catalog
A genome-wide association study identifies protein quantitative trait loci (pQTLs).
EBI GWAS Catalog
Genetic determinants of serum testosterone concentrations in men.
EBI GWAS Catalog
Genome-wide association study identifies a new locus JMJD1C at 10q21 that may influence serum androgen levels in men.
EBI GWAS Catalog
Genome-wide association study of circulating estradiol, testosterone, and sex hormone-binding globulin in postmenopausal women.
EBI GWAS Catalog
Genome-wide association study of sex hormones, gonadotropins and sex hormone-binding protein in Chinese men.
EBI GWAS Catalog

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Genotypes

Pathways from PubChem

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Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

Clone Names

  • MGC126834, MGC138391

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables androgen binding TAS
Traceable Author Statement
more info
 PubMed 
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables steroid binding IBA
Inferred from Biological aspect of Ancestor
more info
  
Component Evidence Code Pubs
located_in extracellular exosome HDA PubMed 
located_in extracellular region NAS
Non-traceable Author Statement
more info
 PubMed 

General protein information

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Preferred Names
sex hormone-binding globulin
Names
sex steroid-binding protein
testis-specific androgen-binding protein
testosterone-binding beta-globulin
testosterone-estradiol-binding globulin
testosterone-estrogen-binding globulin

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

  1. NG_011981.2 RefSeqGene

    Range
    21072..24309
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_001040.5 → NP_001031.2  sex hormone-binding globulin isoform 1 precursor

    See identical proteins and their annotated locations for NP_001031.2

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1), which has also been referred to as SHBG-L, encodes the longest protein (isoform 1).
    Source sequence(s)
    BC101785, EU352659
    Consensus CDS
    CCDS11117.1
    UniProtKB/Swiss-Prot
    B0FWH4, B4DYU0, E9PGW1, F5H5Z8, I3L1N7, P04278, P14689, Q16616, Q3MIL0, Q6ISD2
    Related
    ENSP00000369816.4, ENST00000380450.9
    Conserved Domains (1) summary
    pfam00054
    Location:75 → 205
    Laminin_G_1; Laminin G domain

  2. NM_001146279.3 → NP_001139751.1  sex hormone-binding globulin isoform 2 precursor

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) uses an alternate in-frame splice site in the 3' coding region compared to variant 1. The encoded isoform (2) is shorter compared to isoform 1.
    Source sequence(s)
    CD013957, EU352659
    Consensus CDS
    CCDS58513.1
    UniProtKB/Swiss-Prot
    P04278
    UniProtKB/TrEMBL
    B0FWH2
    Related
    ENSP00000458973.1, ENST00000575903.5
    Conserved Domains (1) summary
    pfam00054
    Location:75 → 199
    Laminin_G_1; Laminin G domain

  3. NM_001146280.3 → NP_001139752.1  sex hormone-binding globulin isoform 3 precursor

    Status: REVIEWED

    Description
    Transcript Variant: This variant (3) lacks an alternate exon in the 3' coding region which results in a frameshift compared to variant 1. Isoform 3 is shorter and has a distinct C-terminus compared to isoform 1.
    Source sequence(s)
    CD013955, EU352659
    Consensus CDS
    CCDS54082.1
    UniProtKB/Swiss-Prot
    P04278
    UniProtKB/TrEMBL
    B0FWH2
    Related
    ENSP00000388867.3, ENST00000416273.7
    Conserved Domains (1) summary
    pfam00054
    Location:75 → 205
    Laminin_G_1; Laminin G domain

  4. NM_001146281.3 → NP_001139753.1  sex hormone-binding globulin isoform 4 precursor

    Status: REVIEWED

    Description
    Transcript Variant: This variant (4) lacks two alternate exons in the 3' coding region but maintains the reading frame compared to variant 1. Isoforzm 4 is shorter compared to isoform 1.
    Source sequence(s)
    EU352659, EU352661, X05403
    Consensus CDS
    CCDS54083.1
    UniProtKB/TrEMBL
    A0A0C4DGN2
    Related
    ENSP00000393426.2, ENST00000441599.6
    Conserved Domains (1) summary
    pfam00054
    Location:75 → 205
    Laminin_G_1; Laminin G domain

  5. NM_001289113.2 → NP_001276042.1  sex hormone-binding globulin isoform 5

    See identical proteins and their annotated locations for NP_001276042.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (5) differs in the 5' UTR, lacks part of the 5' coding region, and uses a downstream start codon, compared to variant 1. The encoded isoform (5) has a shorter N-terminus, compared to isoform 1. Both variants 5 and 6 encode the same isoform.
    Source sequence(s)
    AC007421, AK302603, EU352665, X05403
    Consensus CDS
    CCDS73961.1
    UniProtKB/TrEMBL
    I3L145, I3L2X4
    Related
    ENSP00000345675.6, ENST00000340624.9
    Conserved Domains (1) summary
    pfam00054
    Location:17 → 147
    Laminin_G_1; Laminin G domain

  6. NM_001289114.2 → NP_001276043.1  sex hormone-binding globulin isoform 5

    See identical proteins and their annotated locations for NP_001276043.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (6) differs in the 5' UTR, lacks part of the 5' coding region, and uses a downstream start codon, compared to variant 1. The encoded isoform (5) has a shorter N-terminus, compared to isoform 1. Both variants 5 and 6 encode the same isoform.
    Source sequence(s)
    EU352670, X05403
    Consensus CDS
    CCDS73961.1
    UniProtKB/TrEMBL
    I3L145, I3L2X4
    Related
    ENSP00000458559.1, ENST00000575314.5
    Conserved Domains (1) summary
    pfam00054
    Location:17 → 147
    Laminin_G_1; Laminin G domain

  7. NM_001289115.2 → NP_001276044.1  sex hormone-binding globulin isoform 6

    See identical proteins and their annotated locations for NP_001276044.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (7) differs in the 5' UTR, lacks part of the 5' coding region, uses a downstream start codon, and lacks an exon in the 3' coding region, which results in a frameshift, compared to variant 1. The encoded isoform (6) is shorter, compared to isoform 1.
    Source sequence(s)
    AC007421, AK302603, X05403
    Consensus CDS
    CCDS73962.1
    UniProtKB/Swiss-Prot
    P04278
    UniProtKB/TrEMBL
    B4DYU0
    Related
    ENSP00000458181.1, ENST00000574539.5
    Conserved Domains (1) summary
    pfam00054
    Location:17 → 147
    Laminin_G_1; Laminin G domain

  8. NM_001289116.2 → NP_001276045.1  sex hormone-binding globulin isoform 7

    Status: REVIEWED

    Description
    Transcript Variant: This variant (8) uses two alternate splice sites in the central coding regions, which results in a frameshift and use of an alternate start codon, compared to variant 1. The encoded isoform (7) has a shorter and distinct N-terminus, compared to isoform 1.
    Source sequence(s)
    CD013958, EU352659
    UniProtKB/Swiss-Prot
    P04278
    UniProtKB/TrEMBL
    B0FWH2
    Conserved Domains (1) summary
    cl22861
    Location:34 → 89
    LamG; Laminin G domain; Laminin G-like domains are usually Ca++ mediated receptors that can have binding sites for steroids, beta1 integrins, heparin, sulfatides, fibulin-1, and alpha-dystroglycans. Proteins that contain LamG domains serve a variety of ...

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000017.11 Reference GRCh38.p14 Primary Assembly

    Range
    7614064..7633372
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060941.1 Alternate T2T-CHM13v2.0

    Range
    7518285..7537563
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)
Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
P04278.2 GenPept UniProtKB/Swiss-Prot:P04278

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