CYP17A1

cytochrome P450 family 17 subfamily A member 1, the group of Cytochrome P450 family 17

Basic information

Region (hg38): 10:102830531-102837472

Previous symbols: [ "CYP17" ]

Links

ENSG00000148795 ∙ NCBI:1586 ∙ OMIM:609300 ∙ HGNC:2593 ∙ Uniprot:P05093 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• congenital adrenal hyperplasia due to 17-alpha-hydroxylase deficiency (Supportive), mode of inheritance: AR
• 46,XY disorder of sex development due to isolated 17,20-lyase deficiency (Supportive), mode of inheritance: AR
• congenital adrenal hyperplasia due to 17-alpha-hydroxylase deficiency (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Adrenal hyperplasia, congenital, due to 17-alpha-hydroxylase deficiency	AR	Endocrine; Genitourinary; Oncologic	Individuals may not necessarily manifest with adrenal crisis, but mineralocorticoid excess may result in severe hypokalaemic hypertension, and awareness may allow preventive measures and treatment (eg, including glucocorticoids and mineralcorticoid antagonists); Treatment of genitourinary anomalies, as well as related hypogonadotrophic hypogonadism (eg, with hormone replacement therapy, as well as surgery in some individuals), can be beneficial; Due to risk of malignancy, gonadectomy may be indicated in genotypic males	Endocrine;Genitourinary; Oncologic	4288776; 6039879; 4303304; 5456802; 999330; 6976525; 2843762; 2026124; 1648117; 2808364; 7629254; 8855840; 9360545; 9326943; 9177409; 11549685; 14671162; 16121340; 18559916; 20170344; 21823532; 22452398; 21550081; 22954317

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CYP17A1 gene.

• not provided (58 variants)
• Deficiency of steroid 17-alpha-monooxygenase (30 variants)
• 17-alpha-hydroxylase/17,20-lyase deficiency, combined complete (8 variants)
• Congenital adrenal hyperplasia (4 variants)
• CYP17A1-related disorder (3 variants)
• 17,20-lyase deficiency, isolated (1 variants)
• 17-alpha-hydroxylase/17,20-lyase deficiency, combined partial (1 variants)
• Breast cancer, susceptibility to (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CYP17A1 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous		1		188	2	191
missense	16	27	49	2		94
nonsense	20	4				24
start loss		3				3
frameshift	20	15				35
inframe indel	2	3				5
splice donor/acceptor (+/-2bp)	5	7				12
splice region		1		20		21
non coding		1	7	76	21	105
Total	63	61	56	266	23

Highest pathogenic variant AF is 0.0000460

Variants in CYP17A1

This is a list of pathogenic ClinVar variants found in the CYP17A1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
10-102830536-G-GA		Congenital adrenal hyperplasia	Uncertain significance (Jun 14, 2016)
10-102830572-G-A		Deficiency of steroid 17-alpha-monooxygenase	Uncertain significance (Jan 12, 2018)
10-102830635-G-T		Deficiency of steroid 17-alpha-monooxygenase	Uncertain significance (Jan 13, 2018)
10-102830637-G-T		Deficiency of steroid 17-alpha-monooxygenase	Uncertain significance (Jan 13, 2018)
10-102830705-G-A			Conflicting classifications of pathogenicity (Dec 05, 2023)
10-102830705-G-C			Likely benign (Mar 19, 2022)
10-102830708-G-A			Likely benign (Mar 22, 2023)
10-102830708-G-T		Inborn genetic diseases	Uncertain significance (Mar 20, 2023)
10-102830714-C-G			Uncertain significance (Aug 17, 2023)
10-102830714-C-T			Likely benign (Sep 28, 2019)
10-102830716-C-T			Uncertain significance (May 01, 2021)
10-102830720-C-T			Likely benign (Jan 25, 2024)
10-102830726-T-C			Likely benign (Apr 06, 2023)
10-102830737-C-A			Uncertain significance (Sep 24, 2021)
10-102830741-G-A		Deficiency of steroid 17-alpha-monooxygenase	Conflicting classifications of pathogenicity (Oct 30, 2023)
10-102830742-C-T		Deficiency of steroid 17-alpha-monooxygenase	Likely pathogenic (May 09, 2023)
10-102830743-G-A		Deficiency of steroid 17-alpha-monooxygenase	Pathogenic/Likely pathogenic (Dec 18, 2023)
10-102830746-C-T		Inborn genetic diseases	Uncertain significance (Apr 28, 2022)
10-102830750-G-T			Likely benign (Oct 31, 2021)
10-102830761-TGAAAGAGTC-T		Deficiency of steroid 17-alpha-monooxygenase • 17-alpha-hydroxylase/17,20-lyase deficiency, combined complete	Pathogenic (Mar 23, 2024)
10-102830771-G-A		Deficiency of steroid 17-alpha-monooxygenase	Likely benign (Dec 14, 2023)
10-102830776-G-A			Likely benign (Oct 08, 2021)
10-102830780-G-C			Likely benign (Feb 15, 2021)
10-102830786-C-T			Likely benign (Oct 24, 2021)
10-102830789-G-A			Likely benign (Dec 20, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CYP17A1	protein_coding	protein_coding	ENST00000369887	8	7003

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.000263	0.985	125709	0	39	125748	0.000155

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.24	219	277	0.791	0.0000162	3337
Missense in Polyphen		80	107.32	0.74545		1292
Synonymous	-0.0109	114	114	1.00	0.00000701	1002
Loss of Function	2.16	9	19.2	0.468	9.92e-7	226

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000181	0.000181
Ashkenazi Jewish	0.000107	0.0000992
East Asian	0.000544	0.000544
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.000144	0.000141
Middle Eastern	0.000544	0.000544
South Asian	0.000231	0.000229
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Conversion of pregnenolone and progesterone to their 17- alpha-hydroxylated products and subsequently to dehydroepiandrosterone (DHEA) and androstenedione. Catalyzes both the 17-alpha-hydroxylation and the 17,20-lyase reaction. Involved in sexual development during fetal life and at puberty. {ECO:0000269|PubMed:22266943}.
• Disease: DISEASE: Adrenal hyperplasia 5 (AH5) [MIM:202110]: A form of congenital adrenal hyperplasia, a common recessive disease due to defective synthesis of cortisol. Congenital adrenal hyperplasia is characterized by androgen excess leading to ambiguous genitalia in affected females, rapid somatic growth during childhood in both sexes with premature closure of the epiphyses and short adult stature. Four clinical types: 'salt wasting' (SW, the most severe type), 'simple virilizing' (SV, less severely affected patients), with normal aldosterone biosynthesis, 'non-classic form' or late- onset (NC or LOAH) and 'cryptic' (asymptomatic). {ECO:0000269|PubMed:10720067, ECO:0000269|PubMed:11549685, ECO:0000269|PubMed:11836339, ECO:0000269|PubMed:12466376, ECO:0000269|PubMed:14671162, ECO:0000269|PubMed:1515452, ECO:0000269|PubMed:1714904, ECO:0000269|PubMed:1740503, ECO:0000269|PubMed:19793597, ECO:0000269|PubMed:24140098, ECO:0000269|PubMed:24498484, ECO:0000269|PubMed:25650406, ECO:0000269|PubMed:2808364, ECO:0000269|PubMed:8027220, ECO:0000269|PubMed:8245018, ECO:0000269|PubMed:8345056, ECO:0000269|PubMed:8396144, ECO:0000269|PubMed:8550762, ECO:0000269|Ref.20}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Cortisol synthesis and secretion - Homo sapiens (human);Cushing,s syndrome - Homo sapiens (human);Steroid hormone biosynthesis - Homo sapiens (human);Prolactin signaling pathway - Homo sapiens (human);Ovarian steroidogenesis - Homo sapiens (human);17-Beta Hydroxysteroid Dehydrogenase III Deficiency;Steroidogenesis;Apparent mineralocorticoid excess syndrome;3-Beta-Hydroxysteroid Dehydrogenase Deficiency;21-hydroxylase deficiency (CYP21);Corticosterone methyl oxidase I deficiency (CMO I);Corticosterone methyl oxidase II deficiency - CMO II;Adrenal Hyperplasia Type 5 or Congenital Adrenal Hyperplasia due to 17 Alpha-hydroxylase Deficiency;Adrenal Hyperplasia Type 3 or Congenital Adrenal Hyperplasia due to 21-hydroxylase Deficiency;Congenital Lipoid Adrenal Hyperplasia (CLAH) or Lipoid CAH;Androgen and Estrogen Metabolism;17-alpha-hydroxylase deficiency (CYP17);Aromatase deficiency;11-beta-hydroxylase deficiency (CYP11B1);Androgen Receptor Network in Prostate Cancer;Glucocorticoid and Mineralcorticoid Metabolism;Oxidation by Cytochrome P450;Steroid Biosynthesis;Metapathway biotransformation Phase I and II;Phase I - Functionalization of compounds;Metabolism of lipids;Endogenous sterols;Cytochrome P450 - arranged by substrate type;Biological oxidations;Metabolism;Androgen biosynthesis;Metabolism of steroid hormones;Metabolism of steroids;C21-steroid hormone biosynthesis and metabolism;Glucocorticoid biosynthesis;androgen biosynthesis;glucocorticoid biosynthesis;superpathway of steroid hormone biosynthesis;Steroid hormones (Consensus)

Recessive Scores

• pRec: 0.806

Intolerance Scores

• loftool: 0.455
• rvis_EVS: -0.69
• rvis_percentile_EVS: 14.97

Haploinsufficiency Scores

• pHI: 0.0363
• hipred: N
• hipred_score: 0.309
• ghis: 0.482

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.897

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Cyp17a1
• Phenotype: skeleton phenotype; renal/urinary system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); reproductive system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); homeostasis/metabolism phenotype; cellular phenotype; growth/size/body region phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan)

Gene ontology

• Biological process: steroid biosynthetic process;androgen biosynthetic process;glucocorticoid biosynthetic process;sex differentiation;steroid metabolic process;sterol metabolic process;hormone biosynthetic process;progesterone metabolic process;oxidation-reduction process
• Cellular component: endoplasmic reticulum;endoplasmic reticulum membrane;axon;neuronal cell body
• Molecular function: steroid 17-alpha-monooxygenase activity;iron ion binding;oxygen binding;heme binding;17-alpha-hydroxyprogesterone aldolase activity