SHBG

protein-coding

sex hormone binding globulin

Gene 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]

MANE transcript

NM_001040.5

Inheritance

—

ClinVar variants

U:46B:13

Top phenotype

SHBG-related disorder

gnomAD constraint

pLI —, LoF o/e 0.64

Max pathogenic AF

—

Genomic locus

chr17:7,613,946-7,633,382

External References & Databases

Ensembl (ENSG00000129214)

Transcript & Mutation Effects

hg38 • Region Span ~19.4 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to SHBG variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 48

not providedTotal: 8

SHBG-related disorderTotal: 3

Sex Hormone-Binding Globulin DeficiencyTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001040.5. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous				3 clinvar	2 clinvar	5
missense			46 clinvar	5 clinvar	3 clinvar	54
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	46	8	5	59

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 54 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001040.5	RefSeq	NP_001031.2	8	MANE Select
ENST00000380450.9	Ensembl	ENSP00000369816.4	8	MANE Select
NM_001146279.3	RefSeq	NP_001139751.1	8	Standard
NM_001146280.3	RefSeq	NP_001139752.1	7	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Nongenotropic Androgen signaling

Molecular Function

steroid binding
androgen binding
protein binding

Cellular Component

extracellular region
extracellular exosome

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000380450
Coding exons: 8
Length: 19319
Individuals with no LoFs: 125601
Homozygous LoFs: 0
Heterozygous LoFs: 147
Defined: 125748
p: 0.000585

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.195	212	220	0.963	0.0000127	2558
Missense (PolyPhen)		51	55.106	0.92548		716
Synonymous	-0.199	95	92.6	1.03	0.00000513	879
Loss of Function	1.42	12	18.6	0.644	0.00000103	188

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00025	0.00025	rare
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0.0020	0.0020	notable
East Asian	0.00011	0.00011	rare
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.00099	0.00099	rare
South Asian	0.000065	0.000065	rare
Other	0.00065	0.00065	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Functions as an androgen transport protein, but may also be involved in receptor mediated processes. Each dimer binds one molecule of steroid. Specific for 5-alpha-dihydrotestosterone, testosterone, and 17-beta-estradiol. Regulates the plasma metabolic clearance rate of steroid hormones by controlling their plasma concentration.;

Recessive Scores

pRec: 0.0811

Intolerance Scores

LoFtool: 0.226
RVIS EVS: 0.13
RVIS percentile EVS: 63.36

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.218

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium