CYP19A1

cytochrome P450 family 19 subfamily A member 1, the group of Cytochrome P450 family 19|MicroRNA protein coding host genes

Basic information

Region (hg38): 15:51208057-51338601

Previous symbols: [ "CYP19" ]

Links

ENSG00000137869 ∙ NCBI:1588 ∙ OMIM:107910 ∙ HGNC:2594 ∙ Uniprot:P11511 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• aromatase excess syndrome (Moderate), mode of inheritance: AD
• aromatase deficiency (Definitive), mode of inheritance: AR
• aromatase excess syndrome (Limited), mode of inheritance: AD
• aromatase deficiency (Strong), mode of inheritance: AR
• aromatase deficiency (Supportive), mode of inheritance: AR
• aromatase excess syndrome (Supportive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Aromatase excess syndrome; Aromatase deficiency	AD/AR	Endocrine	In Aromatase excess syndrome, medical treatment (eg, with aromatase inhibitors) can be beneficial; In Androgen deficiency, females may present with virilization resulting in manifestations such as pseudohermaphroditism, while males may present later with manifestations such as delayed skeletal maturation and epiphyseal closure, skeletal pain, eunuchoid habitus and increased adiposity, and estrogen therapy reverses symptoms	Endocrine	1825497; 8265607; 9543166; 12736278; 15811932; 17452968; 21521281; 21470988

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CYP19A1 gene.

• not_provided (384 variants)
• Aromatase_deficiency (118 variants)
• Aromatase_excess_syndrome (15 variants)
• Inborn_genetic_diseases (14 variants)
• not_specified (8 variants)
• CYP19A1-related_disorder (5 variants)
• Premature_ovarian_failure (1 variants)
• Differences_in_sex_development (1 variants)
• ADRENAL_HYPERPLASIA,_CONGENITAL,_DUE_TO_21-HYDROXYLASE_DEFICIENCY (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CYP19A1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000000103.4. Only rare variants are included in the table.

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.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			8	196	6	210
missense	4	5	73	7	1	90
nonsense	15	5				20
start loss						0
frameshift	24	4				28
splice donor/acceptor (+/-2bp)	2	10				12
Total	45	24	81	203	7

Highest pathogenic variant AF is 0.000014986194

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CYP19A1	protein_coding	protein_coding	ENST00000396402	9	130554

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
		125723	0	25	125748	0.0000994

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.535	263	289	0.911	0.0000160	3360
Missense in Polyphen		99	122.42	0.80872		1454
Synonymous	-0.654	109	101	1.08	0.00000581	928
Loss of Function	1.99	11	20.8	0.530	0.00000110	258

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000904	0.0000904
Ashkenazi Jewish	0.00	0.00
East Asian	0.000326	0.000326
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.0000616	0.0000615
Middle Eastern	0.000326	0.000326
South Asian	0.000261	0.000261
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Catalyzes the formation of aromatic C18 estrogens from C19 androgens.
• Disease: DISEASE: Aromatase excess syndrome (AEXS) [MIM:139300]: An autosomal dominant disorder characterized by increased extraglandular aromatization of steroids that presents with heterosexual precocity in males and isosexual precocity in females. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Aromatase deficiency (AROD) [MIM:613546]: A rare disease in which fetal androgens are not converted into estrogens due to placental aromatase deficiency. Thus, pregnant women exhibit a hirsutism, which spontaneously resolves after post-partum. At birth, female babies present with pseudohermaphroditism due to virilization of extern genital organs. In adult females, manifestations include delay of puberty, breast hypoplasia and primary amenorrhoea with multicystic ovaries. {ECO:0000269|PubMed:24705274, ECO:0000269|PubMed:8265607, ECO:0000269|PubMed:8530621, ECO:0000269|PubMed:9211678}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Steroid hormone biosynthesis - Homo sapiens (human);Ovarian steroidogenesis - Homo sapiens (human);Aromatase Inhibitor Pathway (Multiple Tissues), Pharmacodynamics;Estrogen Metabolism Pathway;Aromatase Inhibitor Pathway (Breast Cell), Pharmacodynamics;17-Beta Hydroxysteroid Dehydrogenase III Deficiency;Androgen and Estrogen Metabolism;Aromatase deficiency;Integrated Breast Cancer Pathway;Follicle Stimulating Hormone (FSH) signaling pathway;Ovarian Infertility Genes;Oxidation by Cytochrome P450;Tryptophan metabolism;Metapathway biotransformation Phase I and II;Phase I - Functionalization of compounds;Metabolism of lipids;Endogenous sterols;Tyrosine metabolism;Androgen and estrogen biosynthesis and metabolism;Cytochrome P450 - arranged by substrate type;Leukotriene metabolism;Biological oxidations;Metabolism;Estrogen biosynthesis;Metabolism of steroid hormones;Metabolism of steroids;Linoleate metabolism;C21-steroid hormone biosynthesis and metabolism;Xenobiotics metabolism;Tryptophan degradation;estradiol biosynthesis II;estradiol biosynthesis I;Arachidonic acid metabolism;superpathway of steroid hormone biosynthesis;Steroid hormones (Consensus)

Recessive Scores

• pRec: 0.854

Intolerance Scores

• loftool: 0.495
• rvis_EVS: -0.56
• rvis_percentile_EVS: 19.73

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.767

Gene Damage Prediction

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

Zebrafish Information Network

• Gene name: cyp19a1a
• Affected structure: germ line cell
• Phenotype tag: abnormal
• Phenotype quality: increased occurrence

Gene ontology

• Biological process: negative regulation of chronic inflammatory response;steroid biosynthetic process;estrogen biosynthetic process;androgen catabolic process;female gonad development;negative regulation of macrophage chemotaxis;sterol metabolic process;electron transport chain;female genitalia development;mammary gland development;uterus development;prostate gland growth;testosterone biosynthetic process;positive regulation of estradiol secretion
• Cellular component: endoplasmic reticulum;endoplasmic reticulum membrane;membrane
• Molecular function: iron ion binding;steroid hydroxylase activity;electron transfer activity;oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen;oxygen binding;heme binding;aromatase activity