CYP24A1

cytochrome P450 family 24 subfamily A member 1, the group of Cytochrome P450 family 24

Basic information

Region (hg38): 20:54153446-54173986

Previous symbols: [ "CYP24" ]

Links

ENSG00000019186 ∙ NCBI:1591 ∙ OMIM:126065 ∙ HGNC:2602 ∙ Uniprot:Q07973 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• autosomal recessive infantile hypercalcemia (Supportive), mode of inheritance: AR
• hypercalcemia, infantile, 1 (Strong), mode of inheritance: AR
• hypercalcemia, infantile, 1 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Hypercalcemia, infantile 1	AR	Endocrine; Renal	Individuals may present early in life with typical hypercalcemic signs/symptoms (eg, failure to thrive,dehydration, and muscular hypotonia or lethargy), or may present later with nephrolithiasis and nephrocalcinosis, and dietary measures, including avoidance of certain vitamin supplements (eg, vitamin D-containing compounds) to avoid hypercalcemia can be beneficial	Endocrine; Renal	3490596; 21675912; 22047572; 23293122

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CYP24A1 gene.

• not provided (13 variants)
• Hypercalcemia, infantile, 1 (8 variants)
• Ataxia-telangiectasia syndrome (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CYP24A1 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			3	24	5	32
missense	3	4	86	7	4	104
nonsense	5	2				7
start loss						0
frameshift	8	3				11
inframe indel			1			1
splice donor/acceptor (+/-2bp)	2	4	1			7
splice region			3	4	1	8
non coding			32	27	50	109
Total	18	13	123	58	59

Highest pathogenic variant AF is 0.000145

Variants in CYP24A1

This is a list of pathogenic ClinVar variants found in the CYP24A1 region.

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

Position	Type	Phenotype	Significance	ClinVar
20-54153484-T-C		Hypercalcemia, infantile, 1	Uncertain significance (Jan 13, 2018)
20-54153515-C-CAT		Infantile hypercalcemia	Benign (Jun 14, 2016)
20-54153637-G-A		Hypercalcemia, infantile, 1	Uncertain significance (Jan 12, 2018)
20-54153650-T-G		Hypercalcemia, infantile, 1	Uncertain significance (Jan 12, 2018)
20-54153677-G-C		Hypercalcemia, infantile, 1	Uncertain significance (Jan 13, 2018)
20-54153681-G-A		Hypercalcemia, infantile, 1	Uncertain significance (Jan 13, 2018)
20-54153758-G-A		Hypercalcemia, infantile, 1	Uncertain significance (Jan 13, 2018)
20-54153785-A-G		Hypercalcemia, infantile, 1	Uncertain significance (Jan 13, 2018)
20-54153887-A-C		Hypercalcemia, infantile, 1	Benign (Jan 13, 2018)
20-54153900-G-A		Hypercalcemia, infantile, 1	Benign (Jan 13, 2018)
20-54153934-A-C		Hypercalcemia, infantile, 1	Uncertain significance (Jan 12, 2018)
20-54154024-C-T		Hypercalcemia, infantile, 1	Uncertain significance (Jan 13, 2018)
20-54154056-C-T		Hypercalcemia, infantile, 1	Benign (Jan 13, 2018)
20-54154057-G-C		Hypercalcemia, infantile, 1	Benign (Jan 13, 2018)
20-54154058-GAC-G		Infantile hypercalcemia	Uncertain significance (Jun 14, 2016)
20-54154072-G-GAC		Infantile hypercalcemia	Uncertain significance (Jun 14, 2016)
20-54154223-T-A		Hypercalcemia, infantile, 1	Uncertain significance (Jan 12, 2018)
20-54154247-G-A		Hypercalcemia, infantile, 1	Uncertain significance (Jan 13, 2018)
20-54154254-T-C		Infantile hypercalcemia	Uncertain significance (Jun 14, 2016)
20-54154318-C-T		Hypercalcemia, infantile, 1	Uncertain significance (Jan 13, 2018)
20-54154334-G-A		Hypercalcemia, infantile, 1	Benign (Jan 13, 2018)
20-54154397-T-C		Hypercalcemia, infantile, 1	Uncertain significance (Jan 12, 2018)
20-54154455-A-G		Hypercalcemia, infantile, 1	Uncertain significance (Jan 13, 2018)
20-54154528-G-A		Hypercalcemia, infantile, 1	Uncertain significance (Jan 12, 2018)
20-54154555-T-C		Hypercalcemia, infantile, 1	Uncertain significance (Jan 13, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CYP24A1	protein_coding	protein_coding	ENST00000216862	11	20525

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
3.20e-23	0.000142	125628	0	120	125748	0.000477

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-1.10	332	280	1.19	0.0000156	3345
Missense in Polyphen		145	121.48	1.1936		1411
Synonymous	-0.969	123	110	1.12	0.00000608	973
Loss of Function	-0.729	32	27.9	1.15	0.00000138	329

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000926	0.000926
Ashkenazi Jewish	0.00	0.00
East Asian	0.00154	0.00152
Finnish	0.000139	0.000139
European (Non-Finnish)	0.000475	0.000466
Middle Eastern	0.00154	0.00152
South Asian	0.000265	0.000261
Other	0.000826	0.000815

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Has a role in maintaining calcium homeostasis. Catalyzes the adrenodoxin-dependent 24-hydroxylation of calcidiol (25- hydroxyvitamin D(3)) and calcitriol (1-alpha,25-dihydroxyvitamin D(3)). The enzyme can perform up to 6 rounds of hydroxylation of calcitriol leading to calcitroic acid. It also shows 23- hydroxylating activity leading to 1-alpha,25-dihydroxyvitamin D(3)-26,23-lactone as end product. {ECO:0000269|PubMed:15574355}.
• Disease: DISEASE: Hypercalcemia, infantile, 1 (HCINF1) [MIM:143880]: A disorder characterized by abnormally high level of calcium in the blood, failure to thrive, vomiting, dehydration, and nephrocalcinosis. {ECO:0000269|PubMed:21675912}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Steroid biosynthesis - Homo sapiens (human);MicroRNAs in cancer - Homo sapiens (human);Vitamin D Metabolism;Vitamin D Receptor Pathway;Nuclear Receptors in Lipid Metabolism and Toxicity;PI3K-AKT-mTOR - VitD3 Signalling;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;Steroid hormones (Consensus)

Recessive Scores

• pRec: 0.424

Intolerance Scores

• loftool: 0.973
• rvis_EVS: 0.02
• rvis_percentile_EVS: 55.76

Haploinsufficiency Scores

• pHI: 0.0881
• hipred: N
• hipred_score: 0.419

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.219

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Cyp24a1
• Phenotype: homeostasis/metabolism phenotype; growth/size/body region phenotype; renal/urinary system phenotype; skeleton 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)

Gene ontology

• Biological process: osteoblast differentiation;vitamin metabolic process;response to vitamin D;vitamin D metabolic process;vitamin D catabolic process;oxidation-reduction process;vitamin D receptor signaling pathway
• Cellular component: nucleus;nucleoplasm;mitochondrion;mitochondrial outer membrane;plasma membrane
• Molecular function: iron ion binding;25-hydroxycholecalciferol-24-hydroxylase activity;oxidoreductase activity;heme binding;1-alpha,25-dihydroxyvitamin D3 24-hydroxylase activity