CYP27B1

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

Basic information

Region (hg38): 12:57762333-57768986

Previous symbols: [ "VDD1", "PDDR" ]

Links

ENSG00000111012 ∙ NCBI:1594 ∙ OMIM:609506 ∙ HGNC:2606 ∙ Uniprot:O15528 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• vitamin D-dependent rickets, type 1A (Strong), mode of inheritance: AR
• vitamin D-dependent rickets, type 1 (Supportive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Vitamin D-dependent rickets, type 1A	AR	Endocrine	Medical treatment with forms of vitamin D can be effective for prevention and treatment of manifestations, such as skeletal anomalies and seizures	Endocrine	6265615; 9486994

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CYP27B1 gene.

• not provided (207 variants)
• Vitamin D-dependent rickets, type 1 (44 variants)
• Vitamin D-dependent rickets, type 1A (40 variants)
• Inborn genetic diseases (16 variants)
• Vitamin D-dependent rickets (1 variants)
• not specified (1 variants)
• CYP27B1-related condition (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CYP27B1 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	54		60
missense	4	17	73	2	1	97
nonsense	6					6
start loss						0
frameshift	19	1				20
inframe indel	1		2			3
splice donor/acceptor (+/-2bp)	2	2				4
splice region			7	9		16
non coding			16	20	4	40
Total	32	20	97	76	5

Highest pathogenic variant AF is 0.0000328

Variants in CYP27B1

This is a list of pathogenic ClinVar variants found in the CYP27B1 region.

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

Position	Type	Phenotype	Significance	ClinVar
12-57762378-A-T		Vitamin D-dependent rickets, type 1	Uncertain significance (Jan 12, 2018)
12-57762420-G-C		Vitamin D-dependent rickets, type 1	Uncertain significance (Jan 13, 2018)
12-57762507-C-T		Vitamin D-dependent rickets, type 1	Uncertain significance (Jan 13, 2018)
12-57762670-G-T		Vitamin D-dependent rickets, type 1	Uncertain significance (Jan 13, 2018)
12-57762696-C-T		Vitamin D-dependent rickets, type 1	Uncertain significance (Jan 12, 2018)
12-57762713-C-CTTA		Vitamin D-dependent rickets	Uncertain significance (Jun 14, 2016)
12-57762716-A-G		Vitamin D-dependent rickets, type 1	Uncertain significance (Jan 13, 2018)
12-57762727-C-T		Vitamin D-dependent rickets, type 1	Likely benign (Apr 27, 2017)
12-57762797-A-G		Vitamin D-dependent rickets, type 1	Uncertain significance (Jan 13, 2018)
12-57762813-A-G		Vitamin D-dependent rickets, type 1	Uncertain significance (Jan 12, 2018)
12-57762841-A-G		Vitamin D-dependent rickets, type 1	Uncertain significance (Jan 13, 2018)
12-57762847-C-T		Vitamin D-dependent rickets, type 1	Uncertain significance (Jan 12, 2018)
12-57762927-C-G		Vitamin D-dependent rickets, type 1	Uncertain significance (Mar 23, 2018)
12-57762999-C-T		Vitamin D-dependent rickets, type 1	Uncertain significance (Jan 13, 2018)
12-57763065-C-T		Vitamin D-dependent rickets, type 1	Likely benign (Jan 12, 2018)
12-57763066-C-T		Vitamin D-dependent rickets, type 1	Uncertain significance (Jan 12, 2018)
12-57763148-G-A			Likely benign (Nov 13, 2023)
12-57763152-A-C			Uncertain significance (Feb 18, 2022)
12-57763157-C-T			Likely benign (Jan 06, 2024)
12-57763164-T-C		Vitamin D-dependent rickets, type 1	Conflicting classifications of pathogenicity (Jan 28, 2024)
12-57763166-G-T			Likely benign (Jun 25, 2023)
12-57763170-C-T			Uncertain significance (Sep 13, 2022)
12-57763178-A-C			Likely benign (Dec 14, 2023)
12-57763190-A-T			Likely benign (Oct 06, 2023)
12-57763194-C-G		Inborn genetic diseases	Conflicting classifications of pathogenicity (Jan 23, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CYP27B1	protein_coding	protein_coding	ENST00000228606	9	6653

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.92e-7	0.881	125655	0	93	125748	0.000370

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.0655	278	281	0.989	0.0000150	3190
Missense in Polyphen		105	118.45	0.88642		1388
Synonymous	-1.67	144	121	1.19	0.00000623	1137
Loss of Function	1.62	14	22.3	0.629	9.95e-7	245

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00125	0.00113
Ashkenazi Jewish	0.00	0.00
East Asian	0.000544	0.000544
Finnish	0.000231	0.000231
European (Non-Finnish)	0.000282	0.000281
Middle Eastern	0.000544	0.000544
South Asian	0.000327	0.000327
Other	0.000821	0.000815

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Catalyzes the conversion of 25-hydroxyvitamin D3 (25(OH)D3) to 1-alpha,25-dihydroxyvitamin D3 (1alpha,25(OH)(2)D3), and of 24,25-dihydroxyvitamin D3 (24,25(OH)(2)D3) to 1- alpha,24,25-trihydroxyvitamin D3 (1alpha,24,25(OH)(3)D3). Is also active with 25-hydroxy-24-oxo-vitamin D3. Plays an important role in normal bone growth, calcium metabolism, and tissue differentiation. {ECO:0000269|PubMed:10518789}.
• Pathway: Steroid biosynthesis - Homo sapiens (human);Tuberculosis - Homo sapiens (human);Vitamin D Metabolism;Vitamin D Receptor Pathway;Nuclear Receptors in Lipid Metabolism and Toxicity;Oxidation by Cytochrome P450;Metapathway biotransformation Phase I and II;Phase I - Functionalization of compounds;Metabolism of lipids;Vitamins;Cytochrome P450 - arranged by substrate type;Biological oxidations;Metabolism;Metabolism of steroids;Vitamin D3 (cholecalciferol) metabolism;Vitamin D (calciferol) metabolism;vitamin D₃ biosynthesis;Steroid hormones (Consensus)

Recessive Scores

• pRec: 0.399

Intolerance Scores

• loftool: 0.456
• rvis_EVS: -0.4
• rvis_percentile_EVS: 26.53

Haploinsufficiency Scores

• pHI: 0.0977
• hipred: N
• hipred_score: 0.364
• ghis: 0.449

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.286

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Cyp27b1
• Phenotype: renal/urinary system phenotype; skeleton phenotype; immune system phenotype; limbs/digits/tail phenotype; reproductive 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); hematopoietic system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); cellular phenotype; homeostasis/metabolism phenotype; craniofacial phenotype; muscle phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); endocrine/exocrine gland phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); growth/size/body region phenotype

Zebrafish Information Network

• Gene name: cyp27b1
• Affected structure: ventral wall of dorsal aorta
• Phenotype tag: abnormal
• Phenotype quality: has fewer parts of type

Gene ontology

• Biological process: vitamin metabolic process;calcium ion transport;negative regulation of cell population proliferation;negative regulation of calcidiol 1-monooxygenase activity;positive regulation of vitamin D 24-hydroxylase activity;bone mineralization;negative regulation of cell growth;regulation of bone mineralization;response to lipopolysaccharide;response to vitamin D;response to interferon-gamma;calcitriol biosynthetic process from calciol;vitamin D metabolic process;vitamin D catabolic process;response to estrogen;positive regulation of keratinocyte differentiation;decidualization;calcium ion homeostasis;oxidation-reduction process;G1 to G0 transition;positive regulation of vitamin D receptor signaling pathway
• Cellular component: cytoplasm;mitochondrion;mitochondrial outer membrane
• Molecular function: calcidiol 1-monooxygenase activity;iron ion binding;heme binding