CYP2R1

cytochrome P450 family 2 subfamily R member 1, the group of Cytochrome P450 family 2

Basic information

Region (hg38): 11:14877440-14892231

Links

ENSG00000186104 ∙ NCBI:120227 ∙ OMIM:608713 ∙ HGNC:20580 ∙ Uniprot:Q6VVX0 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

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

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Vitamin D hydroxylation deficient rickets, type 1B	AR	Endocrine	Medical treatment (eg, with supraphysiological levels of vitamin D3 or D2) has been reported to result in improvement or resolution of biochemical and clinical/radiographic anomalies	Endocrine	8201479; 15128933; 22855339

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CYP2R1 gene.

• not provided (11 variants)
• Vitamin D hydroxylation-deficient rickets, type 1B (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CYP2R1 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				40	1	41
missense		1	64	2		67
nonsense	7	2	1			10
start loss						0
frameshift	4					4
inframe indel			1			1
splice donor/acceptor (+/-2bp)	1					1
splice region				1		1
non coding				16	1	17
Total	12	3	66	58	2

Highest pathogenic variant AF is 0.000545

Variants in CYP2R1

This is a list of pathogenic ClinVar variants found in the CYP2R1 region.

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

Position	Type	Phenotype	Significance	ClinVar
11-14878128-T-C			Likely benign (Nov 04, 2023)
11-14878130-T-A			Uncertain significance (Jul 11, 2022)
11-14878146-G-A			Likely benign (Jun 10, 2023)
11-14878149-G-A			Likely benign (Nov 21, 2023)
11-14878150-G-C		not specified	Uncertain significance (Mar 20, 2024)
11-14878176-C-T			Likely benign (Nov 08, 2022)
11-14878192-G-T			Uncertain significance (Apr 17, 2022)
11-14878201-T-A			Uncertain significance (Mar 23, 2023)
11-14878204-T-C		not specified	Uncertain significance (Dec 22, 2023)
11-14878230-A-C			Likely benign (Aug 19, 2022)
11-14878231-A-G		not specified	Uncertain significance (Jun 18, 2021)
11-14878234-A-C		Low serum calcitriol	Uncertain significance (-)
11-14878264-C-T		Vitamin D hydroxylation-deficient rickets, type 1B	Uncertain significance (Feb 08, 2022)
11-14878265-G-A			Uncertain significance (Dec 21, 2023)
11-14878277-C-T			Uncertain significance (Oct 17, 2022)
11-14878280-C-G		Vitamin D hydroxylation-deficient rickets, type 1B	Uncertain significance (Jul 13, 2022)
11-14878287-A-G			Likely benign (Jun 15, 2022)
11-14878316-T-C			Likely benign (Aug 30, 2023)
11-14879094-C-G			Likely benign (Oct 05, 2022)
11-14879097-C-T		Vitamin D hydroxylation-deficient rickets, type 1B	Likely benign (Nov 04, 2023)
11-14879098-G-A			Benign (Jun 17, 2021)
11-14879122-A-G			Uncertain significance (Jul 27, 2023)
11-14879141-T-C		not specified	Uncertain significance (May 31, 2023)
11-14879146-G-C			Uncertain significance (Nov 03, 2023)
11-14879153-A-G		not specified	Uncertain significance (Dec 21, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CYP2R1	protein_coding	protein_coding	ENST00000334636	5	14246

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
3.79e-10	0.327	125604	0	144	125748	0.000573

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.481	247	269	0.918	0.0000129	3284
Missense in Polyphen		83	116.68	0.71134		1441
Synonymous	-0.468	106	100	1.06	0.00000466	969
Loss of Function	0.899	17	21.5	0.791	0.00000134	249

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00229	0.00227
Ashkenazi Jewish	0.00	0.00
East Asian	0.000608	0.000598
Finnish	0.0000926	0.0000924
European (Non-Finnish)	0.000455	0.000422
Middle Eastern	0.000608	0.000598
South Asian	0.000396	0.000392
Other	0.000673	0.000489

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Has a D-25-hydroxylase activity on both forms of vitamin D, vitamin D(2) and D(3). {ECO:0000269|PubMed:12867411, ECO:0000269|PubMed:15465040, ECO:0000269|PubMed:18511070}.
• Disease: DISEASE: Rickets vitamin D-dependent 1B (VDDR1B) [MIM:600081]: An autosomal recessive disorder caused by a selective deficiency of the active form of vitamin D (1,25-dihydroxyvitamin D3) and resulting in defective bone mineralization and clinical features of rickets. The patients sera have low calcium concentrations, low phosphate concentrations, elevated alkaline phosphatase activity and low levels of 25-hydroxyvitamin D. {ECO:0000269|PubMed:15128933, ECO:0000269|PubMed:25942481}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Steroid biosynthesis - Homo sapiens (human);Vitamin D Metabolism;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 D (calciferol) metabolism;bile acid biosynthesis, neutral pathway;vitamin D₃ biosynthesis;Steroid hormones (Consensus)

Recessive Scores

• pRec: 0.189

Intolerance Scores

• loftool: 0.669
• rvis_EVS: -0.09
• rvis_percentile_EVS: 46.92

Haploinsufficiency Scores

• pHI: 0.126
• hipred: N
• hipred_score: 0.197
• ghis: 0.521

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.186

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Cyp2r1
• Phenotype: liver/biliary system phenotype; homeostasis/metabolism phenotype

Zebrafish Information Network

• Gene name: cyp2r1
• Affected structure: subcutaneous fat
• Phenotype tag: abnormal
• Phenotype quality: increased amount

Gene ontology

• Biological process: organic acid metabolic process;vitamin metabolic process;xenobiotic metabolic process;response to cesium ion;response to ionizing radiation;calcitriol biosynthetic process from calciol;vitamin D metabolic process;exogenous drug catabolic process;oxidation-reduction process
• Cellular component: cytoplasm;endoplasmic reticulum membrane;organelle membrane;intracellular membrane-bounded organelle
• Molecular function: iron ion binding;steroid hydroxylase 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;heme binding;vitamin D3 25-hydroxylase activity