CYP17A1
Cytochrome P450 Family 17 Subfamily A Member 1
Gene Information Card
| Symbol | CYP17A1 |
|---|---|
| Full Name | Cytochrome P450 Family 17 Subfamily A Member 1 |
| Gene Type | Protein coding |
| Chromosomal Location | 10q24.32 |
| NCBI Gene ID | 1586 ncbi.nlm.nih.gov/gene/1586 |
| Ensembl ID | ENSG00000148795 |
| UniProt ID | P05093 |
| OMIM ID | 609300 |
| HGNC ID | 2593 |
| Aliases | CYP17, P450C17, CPT17, S17AH |
Description
CYP17A1 encodes cytochrome P450 17A1 (P450c17), a key enzyme in steroidogenesis with both 17α-hydroxylase and 17,20-lyase activities. It catalyzes the conversion of pregnenolone and progesterone to 17α-hydroxypregnenolone and 17α-hydroxyprogesterone, respectively, and subsequently to dehydroepiandrosterone (DHEA) and androstenedione, precursors of sex steroids. The enzyme is expressed primarily in adrenal glands and gonads. Mutations in CYP17A1 cause 17α-hydroxylase/17,20-lyase deficiency, a form of congenital adrenal hyperplasia characterized by hypertension, hypokalemia, and sexual development disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| 17α-Hydroxylase/17,20-Lyase Deficiency | Loss-of-function mutations impair both hydroxylase and lyase activities, reducing cortisol and sex steroid synthesis with mineralocorticoid excess. | OMIM #202110; ClinVar |
| Isolated 17,20-Lyase Deficiency | Specific mutations (e.g., R347H, R358Q) selectively disrupt lyase activity while preserving hydroxylase function. | OMIM #614279; NCBI |
| Adrenocortical Carcinoma | Somatic alterations and altered expression of CYP17A1 contribute to steroidogenic dysregulation in adrenal tumors. | COSMIC; PMID: 25963121 |
| Polycystic Ovary Syndrome (PCOS) | Polymorphisms in CYP17A1 (e.g., -34T>C) are associated with altered androgen biosynthesis and PCOS risk. | NCBI Gene; PMID: 15690347 |
| Hypertension | CYP17A1 variants (e.g., rs11191548) linked to blood pressure regulation and essential hypertension. | ClinVar; PMID: 21909115 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Adrenal Gland | 42.3 | High |
| Testis | 18.7 | Medium |
| Ovary | 12.1 | Medium |
| Placenta | 3.2 | Low |
| Liver | 0.5 | Not detected |
| Kidney | 0.3 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| NCI-H295R (adrenocortical) | 58.4 | High expression; model for steroidogenesis |
| LNCaP (prostate) | 0.8 | Low/absent |
| KGN (ovarian granulosa) | 22.1 | Moderate expression |
| HEK293 | 0.2 | Not detected |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.985_987delTAC (p.Tyr329del) | Deletion | Rare | Loss of 17α-hydroxylase and lyase activities; causes 17OHD |
| c.287G>A (p.Arg96Gln) | Missense | Rare | Partial loss of hydroxylase activity; mild phenotype |
| c.1040G>A (p.Arg347His) | Missense | Rare | Selective loss of 17,20-lyase activity; isolated lyase deficiency |
| c.1073G>A (p.Arg358Gln) | Missense | Rare | Selective loss of 17,20-lyase activity |
| c.1303C>T (p.Arg435Cys) | Missense | Rare | Complete loss of both activities; severe 17OHD |
| c.1A>G (p.Met1Val) | Start loss | Rare | No protein expression; null allele |
Mutation functional classification
Loss of Function (LOF)
Most CYP17A1 mutations cause complete or partial loss of 17α-hydroxylase and/or 17,20-lyase activities, leading to 17α-hydroxylase/17,20-lyase deficiency. Examples: p.Tyr329del, p.Arg435Cys, p.Met1Val.
Gain of Function (GOF)
No well-characterized gain-of-function mutations reported in CYP17A1. Overexpression in adrenocortical carcinoma may contribute to androgen excess.
Dominant Negative (DN)
No dominant-negative mutations described; CYP17A1 deficiency is autosomal recessive.
View complete mutation data：
Gene Ontology (GO)
Pathways
• hsa00140 – Steroid hormone biosynthesis (KEGG)
• hsa04923 – Regulation of lipolysis in adipocytes (KEGG)
• R-HSA-196108 – Pregnenolone biosynthesis (Reactome)
• R-HSA-193048 – Androgen biosynthesis (Reactome)
• R-HSA-196071 – Metabolism of steroids (Reactome)
Protein Summary
CYP17A1 encodes cytochrome P450 17A1 (P450c17), a 508-amino acid microsomal protein localized to the endoplasmic reticulum. It contains a heme-binding domain and a conserved P450 cysteine ligand. The enzyme catalyzes two sequential reactions: 17α-hydroxylation of pregnenolone and progesterone, and subsequent 17,20-lyase cleavage to produce DHEA and androstenedione. P450c17 activity is regulated by cytochrome b5 and serine phosphorylation, which enhance lyase activity. The protein is essential for glucocorticoid and sex steroid synthesis; its deficiency leads to congenital adrenal hyperplasia with hypertension, hypokalemia, and ambiguous genitalia.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| CYP17A1 Knockout HEK293 Cell Line | EDJ-KQ17810 | Human | 1586 | Details Get a Quote |
| CYP17A1 Knockout HeLa Cell Line | EDJ-KQ53060 | Human | 1586 | Details Get a Quote |
| CYP17A1 Knockout A-549 Cell Line | EDJ-KQ61526 | Human | 1586 | Details Get a Quote |
| CYP17A1 Knockout HCT 116 Cell Line | EDJ-KQ70018 | Human | 1586 | Details Get a Quote |
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