CYP11A1

cytochrome P450 family 11 subfamily A member 1, the group of Cytochrome P450 family 11

Basic information

Region (hg38): 15:74337759-74367646

Previous symbols: [ "CYP11A" ]

Links

ENSG00000140459 ∙ NCBI:1583 ∙ OMIM:118485 ∙ HGNC:2590 ∙ Uniprot:P05108 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Congenital adrenal insufficiency with 46, XY sex reversal OR 46,XY disorder of sex development-adrenal insufficiency due to CYP11A1 deficiency (Strong), mode of inheritance: AR
• Congenital adrenal insufficiency with 46, XY sex reversal OR 46,XY disorder of sex development-adrenal insufficiency due to CYP11A1 deficiency (Supportive), mode of inheritance: AD
• inherited isolated adrenal insufficiency due to partial CYP11A1 deficiency (Supportive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Adrenal insufficiency, congenital, with 46,XY sex reversal, partial or complete	AD/AR	Endocrine; Oncologic; Genitourinary	Presentation of classic enzymatic deficiency involves adrenal failure and salt wasting in infancy, which can be treatable; Nonclassic forms may present later with some retained adrenal function and abnormal sexual development; Surgical interventions may decrease the risk of gonadal tumors	Endocrine; Oncologic; Genitourinary	11502818; 12161514; 15507506; 16705068; 18182448; 21159840

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CYP11A1 gene.

• not_provided (280 variants)
• Congenital_adrenal_insufficiency_with_46,_XY_sex_reversal_OR_46,XY_disorder_of_sex_development-adrenal_insufficiency_due_to_CYP11A1_deficiency (120 variants)
• Inborn_genetic_diseases (38 variants)
• not_specified (12 variants)
• CYP11A1-related_disorder (11 variants)
• Classic_congenital_adrenal_hyperplasia_due_to_21-hydroxylase_deficiency (5 variants)
• Congenital_Adrenal_Insufficiency (2 variants)
• Wilson_disease (2 variants)
• Congenital_adrenal_hyperplasia (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CYP11A1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000000781.3. 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				132	2	134
missense	4	12	105	7		128
nonsense	12	2	1			15
start loss						0
frameshift	10	7				17
splice donor/acceptor (+/-2bp)	1	4				5
Total	27	25	106	139	2

Highest pathogenic variant AF is 0.0000532989

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CYP11A1	protein_coding	protein_coding	ENST00000268053	9	29982

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
5.49e-7	0.967	125709	0	39	125748	0.000155

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.769	277	315	0.878	0.0000199	3431
Missense in Polyphen		94	120.64	0.77917		1323
Synonymous	0.635	118	127	0.928	0.00000797	1036
Loss of Function	2.01	14	24.8	0.564	0.00000151	253

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000275	0.000275
Ashkenazi Jewish	0.0000992	0.0000992
East Asian	0.000272	0.000272
Finnish	0.00	0.00
European (Non-Finnish)	0.000211	0.000202
Middle Eastern	0.000272	0.000272
South Asian	0.0000980	0.0000980
Other	0.000326	0.000326

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Catalyzes the side-chain cleavage reaction of cholesterol to pregnenolone, the precursor of most steroid hormones. {ECO:0000269|PubMed:21636783}.
• Disease: DISEASE: Adrenal insufficiency, congenital, with 46,XY sex reversal (AICSR) [MIM:613743]: A rare disorder that can present as acute adrenal insufficiency in infancy or childhood. ACTH and plasma renin activity are elevated and adrenal steroids are inappropriately low or absent; the 46,XY patients have female external genitalia, sometimes with clitoromegaly. The phenotypic spectrum ranges from prematurity, complete underandrogenization, and severe early-onset adrenal failure to term birth with clitoromegaly and later-onset adrenal failure. Patients with congenital adrenal insufficiency do not manifest the massive adrenal enlargement typical of congenital lipoid adrenal hyperplasia. {ECO:0000269|PubMed:11502818, ECO:0000269|PubMed:12161514, ECO:0000269|PubMed:16705068, ECO:0000269|PubMed:18182448, ECO:0000269|PubMed:19116240}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Cortisol synthesis and secretion - Homo sapiens (human);Aldosterone synthesis and secretion - Homo sapiens (human);Cushing,s syndrome - Homo sapiens (human);Steroid hormone biosynthesis - Homo sapiens (human);Ovarian steroidogenesis - Homo sapiens (human);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;17-alpha-hydroxylase deficiency (CYP17);11-beta-hydroxylase deficiency (CYP11B1);Corticotropin-releasing hormone signaling pathway;Glucocorticoid and Mineralcorticoid Metabolism;WikiPathways Academy- draw-compartment;Oxidation by Cytochrome P450;Metapathway biotransformation Phase I and II;Prostaglandin Synthesis and Regulation;Phase I - Functionalization of compounds;Metabolism of lipids;Endogenous sterols;Cytochrome P450 - arranged by substrate type;Biological oxidations;Metabolism;Pregnenolone biosynthesis;Metabolism of steroid hormones;Metabolism of steroids;C21-steroid hormone biosynthesis and metabolism;pregnenolone biosynthesis;superpathway of steroid hormone biosynthesis;Steroid hormones (Consensus)

Recessive Scores

• pRec: 0.140

Intolerance Scores

• loftool: 0.589
• rvis_EVS: 0.02
• rvis_percentile_EVS: 55.61

Haploinsufficiency Scores

• pHI: 0.308
• hipred: N
• hipred_score: 0.261
• ghis: 0.392

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.990

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Cyp11a1
• Phenotype: nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); vision/eye phenotype; immune system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); liver/biliary system phenotype; normal 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; hematopoietic system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); endocrine/exocrine gland phenotype; muscle phenotype; cellular phenotype; homeostasis/metabolism phenotype; growth/size/body region phenotype

Zebrafish Information Network

• Gene name: cyp11a2
• Affected structure: head
• Phenotype tag: abnormal
• Phenotype quality: decreased size

Gene ontology

• Biological process: C21-steroid hormone biosynthetic process;glucocorticoid biosynthetic process;cholesterol metabolic process;sterol metabolic process;cortisol metabolic process;vitamin D metabolic process;oxidation-reduction process;cellular response to peptide hormone stimulus
• Cellular component: mitochondrion;mitochondrial inner membrane;mitochondrial matrix
• Molecular function: iron ion binding;protein binding;cholesterol monooxygenase (side-chain-cleaving) activity;heme binding