Steroidogenic factor 1
Encyclopedia
The steroidogenic factor 1 (SF1) protein
controls sexual development in the embryo and at puberty.
SF1 is a member of the nuclear receptor
family of intracellular
transcription factor
s and is encoded by the NR5A1 gene
(nuclear receptor subfamily 5, group A, member 1).
s at every level of the hypothalamic-pituitary-gonadal axis
, as well as many genes involved in gonadal and adrenal steroidogenesis.
Missense
, in-frame and frameshift mutation
s of NR5A1 have been found in families with 46,XY disorders of sex development, 46,XX gonadal dysgenesis
and 46,XX primary ovarian insufficiency
. 46,XY individuals may have ambiguous or female genitals. Individuals of either karyotype
may not enter puberty, although expression of the phenotype
, penetrance
, fertility, and modes of inheritance can vary. Some mutations are dominant, some are recessive.
with:
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
controls sexual development in the embryo and at puberty.
SF1 is a member of the nuclear receptor
Nuclear receptor
In the field of molecular biology, nuclear receptors are a class of proteins found within cells that are responsible for sensing steroid and thyroid hormones and certain other molecules...
family of intracellular
Intracellular
Not to be confused with intercellular, meaning "between cells".In cell biology, molecular biology and related fields, the word intracellular means "inside the cell".It is used in contrast to extracellular...
transcription factor
Transcription factor
In molecular biology and genetics, a transcription factor is a protein that binds to specific DNA sequences, thereby controlling the flow of genetic information from DNA to mRNA...
s and is encoded by the NR5A1 gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
(nuclear receptor subfamily 5, group A, member 1).
Function
SF-1 is a critical regulator of reproduction, regulating the transcription of key genes involved in sexual development and reproduction. Its targets include geneGene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
s at every level of the hypothalamic-pituitary-gonadal axis
Hypothalamic-pituitary-gonadal axis
The hypothalamic–pituitary–gonadal axis refers to the effects of the hypothalamus, pituitary gland, and gonads as if these individual endocrine glands were a single entity as a whole...
, as well as many genes involved in gonadal and adrenal steroidogenesis.
Clinical significance
Mutations in NR5A1 can produce intersex genitals, absence of puberty, and infertility. It is one cause of arrest of ovarian function in women <40 years of age, which occurs in 1% of all women.Missense
Missense mutation
In genetics, a missense mutation is a point mutation in which a single nucleotide is changed, resulting in a codon that codes for a different amino acid . This can render the resulting protein nonfunctional...
, in-frame and frameshift mutation
Frameshift mutation
A frameshift mutation is a genetic mutation caused by indels of a number of nucleotides that is not evenly divisible by three from a DNA sequence...
s of NR5A1 have been found in families with 46,XY disorders of sex development, 46,XX gonadal dysgenesis
Gonadal dysgenesis
Gonadal dysgenesis is a term used to describe multiple reproductive system development disorders. They are conditions of genetic origin. It is characterized by a progressive loss of primordial germ cells on the developing gonads of an embryo....
and 46,XX primary ovarian insufficiency
Premature ovarian failure
Premature Ovarian Failure , also known as premature ovarian insufficiency, primary ovarian insufficiency , premature menopause, hypergonadotropic hypogonadism, is the loss of function of the ovaries before age 40...
. 46,XY individuals may have ambiguous or female genitals. Individuals of either karyotype
Karyotype
A karyotype is the number and appearance of chromosomes in the nucleus of an eukaryotic cell. The term is also used for the complete set of chromosomes in a species, or an individual organism.p28...
may not enter puberty, although expression of the phenotype
Phenotype
A phenotype is an organism's observable characteristics or traits: such as its morphology, development, biochemical or physiological properties, behavior, and products of behavior...
, penetrance
Penetrance
Penetrance in genetics is the proportion of individuals carrying a particular variant of a gene that also express an associated trait . In medical genetics, the penetrance of a disease-causing mutation is the proportion of individuals with the mutation who exhibit clinical symptoms...
, fertility, and modes of inheritance can vary. Some mutations are dominant, some are recessive.
Interactions
Steroidogenic factor 1 has been shown to interactProtein-protein interaction
Protein–protein interactions occur when two or more proteins bind together, often to carry out their biological function. Many of the most important molecular processes in the cell such as DNA replication are carried out by large molecular machines that are built from a large number of protein...
with:
- Beta-cateninBeta-cateninBeta-catenin is a protein that in humans is encoded by the CTNNB1 gene. In Drosophila, the homologous protein is called armadillo...
- DAX1DAX1DAX1 is a nuclear receptor protein that in humans is encoded by the NR0B1 gene...
- NRIP1NRIP1Nuclear receptor-interacting protein 1 is a protein that in humans is encoded by the NRIP1 gene.RIP140 has an important role in regulating lipid and glucose metabolism, and regulates gene expression in metabolic tissues including heart, skeletal muscle, and liver.Knockout mice that completely lack...
- SOX9SOX9Transcription factor SOX-9 is a protein that in humans is encoded by the SOX9 gene.- Function :SOX-9 recognizes the sequence CCTTGAG along with other members of the HMG-box class DNA-binding proteins...
- TRERF1TRERF1Transcriptional-regulating factor 1 is a protein that in humans is encoded by the TRERF1 gene.-Interactions:TRERF1 has been shown to interact with Steroidogenic factor 1, EP300 and CREB-binding protein.-Further reading:...
.