CYP27A1

cytochrome P450 family 27 subfamily A member 1, the group of Cytochrome P450 family 27

Basic information

Region (hg38): 2:218781748-218815293

Previous symbols: [ "CYP27" ]

Links

ENSG00000135929 ∙ NCBI:1593 ∙ OMIM:606530 ∙ HGNC:2605 ∙ Uniprot:Q02318 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• cerebrotendinous xanthomatosis (Definitive), mode of inheritance: AR
• cerebrotendinous xanthomatosis (Strong), mode of inheritance: AR
• cerebrotendinous xanthomatosis (Strong), mode of inheritance: AR
• cerebrotendinous xanthomatosis (Supportive), mode of inheritance: AR
• cerebrotendinous xanthomatosis (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Cerebrotendinous xanthomatosis	AR	Biochemical; Cardiovascular	The condition manifests with progressive neurologic dysfunction, as well as cardiovascular and ophthalmologic dysfunction, and medical treatment (eg, with chenodeoxycholic acid and HMG-CoA reductase inhibitors) can be beneficial	Biochemical; Cardiovascular; Gastrointestinal; Neurologic; Ophthalmologic	5636664; 5676919; 5355255; 4825231; 7315872; 7298854; 6504105; 3106810; 3128689; 1708392; 7847220; 7964884; 10430841; 11804206; 12555943; 11939886; 16278884; 18227423; 20301583; 20402754; 20450308; 20558929; 21553098; 22018287; 22336472; 23375591

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CYP27A1 gene.

• Cholestanol storage disease (858 variants)
• not provided (195 variants)
• Cardiovascular phenotype (139 variants)
• not specified (32 variants)
• Inborn genetic diseases (27 variants)
• CYP27A1-related condition (17 variants)
• Intellectual disability (5 variants)
• Premature coronary artery atherosclerosis (1 variants)
• Regression of motor development with severe dystonia and corresponding basal ganglia lesions (1 variants)
• See cases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CYP27A1 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			6	218	1	225
missense	6	14	304	8	1	333
nonsense	19	25	2			46
start loss			1			1
frameshift	28	31	3			62
inframe indel			6			6
splice donor/acceptor (+/-2bp)	16	18	1		1	36
splice region	1		21	37	1	60
non coding			5	75	12	92
Total	69	88	328	301	15

Highest pathogenic variant AF is 0.000289

Variants in CYP27A1

This is a list of pathogenic ClinVar variants found in the CYP27A1 region.

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

Position	Type	Phenotype	Significance	ClinVar
2-218781813-T-C		Cholestanol storage disease	Uncertain significance (Jun 14, 2016)
2-218781824-A-AC		Cholestanol storage disease	Benign (Oct 18, 2020)
2-218781848-C-T		Cholestanol storage disease	Uncertain significance (Jun 14, 2016)
2-218781978-C-A		Cholestanol storage disease	Conflicting classifications of pathogenicity (Oct 14, 2018)
2-218782001-C-T		Cholestanol storage disease	Uncertain significance (Jun 14, 2016)
2-218782021-C-T		Cholestanol storage disease	Uncertain significance (Jun 14, 2016)
2-218782177-C-T		not specified • Cholestanol storage disease	Conflicting classifications of pathogenicity (Feb 07, 2020)
2-218782183-A-G		Cholestanol storage disease	Uncertain significance (May 25, 2018)
2-218782184-T-C		Cholestanol storage disease • not specified • CYP27A1-related disorder	Conflicting classifications of pathogenicity (Jan 23, 2023)
2-218782184-T-TGGCTGCGCTG		Cholestanol storage disease	Pathogenic/Likely pathogenic (Dec 02, 2023)
2-218782186-G-GC		Cholestanol storage disease	Pathogenic (Sep 09, 2022)
2-218782191-G-A		Cardiovascular phenotype • Cholestanol storage disease	Likely benign (Jul 30, 2023)
2-218782191-G-T		Cholestanol storage disease	Likely benign (Jan 16, 2023)
2-218782191-GC-AA		Cholestanol storage disease	Uncertain significance (Sep 06, 2022)
2-218782196-G-A		Cholestanol storage disease	Uncertain significance (Aug 10, 2022)
2-218782197-C-T		Cholestanol storage disease	Likely benign (Oct 21, 2022)
2-218782201-GC-G		Cholestanol storage disease	Likely pathogenic (Jun 12, 2023)
2-218782202-C-T		not specified • Cholestanol storage disease • Cardiovascular phenotype • CYP27A1-related disorder	Uncertain significance (Apr 03, 2023)
2-218782203-G-A		Cholestanol storage disease	Likely benign (May 20, 2021)
2-218782203-G-C		Cholestanol storage disease	Likely benign (Nov 20, 2023)
2-218782204-A-AG		Cholestanol storage disease	Pathogenic (Oct 12, 2023)
2-218782207-C-T		Cholestanol storage disease	Likely benign (Dec 07, 2021)
2-218782208-T-C		Cholestanol storage disease	Uncertain significance (Dec 21, 2023)
2-218782211-G-A		Cholestanol storage disease	Uncertain significance (Jul 01, 2022)
2-218782214-G-A		Cholestanol storage disease	Pathogenic/Likely pathogenic (Oct 10, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CYP27A1	protein_coding	protein_coding	ENST00000258415	9	33545

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
5.29e-19	0.00315	125591	0	157	125748	0.000624

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.310	319	304	1.05	0.0000186	3416
Missense in Polyphen		102	94.918	1.0746		1011
Synonymous	0.294	126	130	0.967	0.00000808	1087
Loss of Function	-0.0185	28	27.9	1.00	0.00000167	275

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00123	0.00123
Ashkenazi Jewish	0.00109	0.00109
East Asian	0.000707	0.000707
Finnish	0.000185	0.000185
European (Non-Finnish)	0.000484	0.000484
Middle Eastern	0.000707	0.000707
South Asian	0.00134	0.00134
Other	0.000489	0.000489

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Catalyzes the first step in the oxidation of the side chain of sterol intermediates; the 27-hydroxylation of 5-beta- cholestane-3-alpha,7-alpha,12-alpha-triol. Has also a vitamin D3- 25-hydroxylase activity. {ECO:0000250|UniProtKB:P17177}.
• Disease: DISEASE: Cerebrotendinous xanthomatosis (CTX) [MIM:213700]: Rare sterol storage disorder characterized clinically by progressive neurologic dysfunction, premature atherosclerosis, and cataracts. {ECO:0000269|PubMed:12000359, ECO:0000269|PubMed:2019602, ECO:0000269|PubMed:7915755, ECO:0000269|PubMed:9186905, ECO:0000269|PubMed:9790667}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Cholesterol metabolism - Homo sapiens (human);Primary bile acid biosynthesis - Homo sapiens (human);PPAR signaling pathway - Homo sapiens (human);27-Hydroxylase Deficiency;Bile Acid Biosynthesis;Congenital Bile Acid Synthesis Defect Type II;Cerebrotendinous Xanthomatosis (CTX);Zellweger Syndrome;Familial Hypercholanemia (FHCA);Congenital Bile Acid Synthesis Defect Type III;Vitamin D Metabolism;PPAR signaling pathway;Oxidation by Cytochrome P450;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;Synthesis of bile acids and bile salts via 7alpha-hydroxycholesterol;Synthesis of bile acids and bile salts via 24-hydroxycholesterol;Synthesis of bile acids and bile salts via 27-hydroxycholesterol;Synthesis of bile acids and bile salts;Bile acid and bile salt metabolism;Metabolism of steroids;Bile acid biosynthesis;C21-steroid hormone biosynthesis and metabolism;Vitamin D3 (cholecalciferol) metabolism;bile acid biosynthesis, neutral pathway (Consensus)

Recessive Scores

• pRec: 0.449

Intolerance Scores

• loftool: 0.705
• rvis_EVS: -0.31
• rvis_percentile_EVS: 32.23

Haploinsufficiency Scores

• pHI: 0.420
• hipred: N
• hipred_score: 0.146
• ghis: 0.440

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.900

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Cyp27a1
• 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); hematopoietic system phenotype; liver/biliary system phenotype; renal/urinary system 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); digestive/alimentary phenotype; endocrine/exocrine gland phenotype; homeostasis/metabolism phenotype

Gene ontology

• Biological process: bile acid biosynthetic process;sterol metabolic process;oxidation-reduction process
• Cellular component: mitochondrion;mitochondrial matrix;mitochondrial membrane
• Molecular function: iron ion binding;steroid hydroxylase activity;oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen;heme binding