DHCR24

24-dehydrocholesterol reductase

Basic information

Region (hg38): 1:54849626-54887195

Previous symbols: [ "DCE" ]

Links

ENSG00000116133 ∙ NCBI:1718 ∙ OMIM:606418 ∙ HGNC:2859 ∙ Uniprot:Q15392 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

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

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Desmosterolosis	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Biochemical; Craniofacial; Musculoskeletal; Neurologic	9450875; 11519011; 12457401; 21559050; 21671375

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the DHCR24 gene.

• not provided (169 variants)
• Desmosterolosis (104 variants)
• Inborn genetic diseases (20 variants)
• not specified (7 variants)
• Non-immune hydrops fetalis (2 variants)
• - (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the DHCR24 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			5	51	3	59
missense		5	68		1	74
nonsense	1	1	1			3
start loss						0
frameshift			3			3
inframe indel						0
splice donor/acceptor (+/-2bp)		1	1			2
splice region			2	2		4
non coding			41	39	37	117
Total	1	7	119	90	41

Highest pathogenic variant AF is 0.00000657

Variants in DHCR24

This is a list of pathogenic ClinVar variants found in the DHCR24 region.

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

Position	Type	Phenotype	Significance	ClinVar
1-54849678-T-C		Desmosterolosis	Benign (Jan 13, 2018)
1-54849679-G-A		Desmosterolosis	Likely benign (Jan 13, 2018)
1-54849719-T-C		Desmosterolosis	Uncertain significance (Jan 13, 2018)
1-54849730-G-A		Desmosterolosis	Uncertain significance (Jan 13, 2018)
1-54849765-A-G		Desmosterolosis	Uncertain significance (Jan 13, 2018)
1-54849791-C-A		Desmosterolosis	Likely benign (Jan 13, 2018)
1-54849839-T-G		Desmosterolosis	Uncertain significance (Jan 13, 2018)
1-54849938-C-G		Desmosterolosis	Benign (Jan 12, 2018)
1-54849988-T-A		Desmosterolosis	Uncertain significance (Jan 12, 2018)
1-54850033-C-T		Desmosterolosis	Likely benign (Jan 13, 2018)
1-54850114-G-A		Desmosterolosis	Uncertain significance (Jan 13, 2018)
1-54850149-C-T		Desmosterolosis	Likely benign (Jan 13, 2018)
1-54850152-C-T		Desmosterolosis	Likely benign (Jan 12, 2018)
1-54850153-G-A		Desmosterolosis	Uncertain significance (Jan 13, 2018)
1-54850195-C-T		Desmosterolosis	Uncertain significance (Jan 13, 2018)
1-54850268-G-T		Desmosterolosis	Benign (Jan 12, 2018)
1-54850352-C-T		Desmosterolosis	Uncertain significance (Jan 13, 2018)
1-54850357-A-G		Desmosterolosis	Uncertain significance (Jan 13, 2018)
1-54850409-A-C		Desmosterolosis	Benign (Jan 12, 2018)
1-54850418-T-A		Desmosterolosis	Uncertain significance (Jan 13, 2018)
1-54850556-A-G		Desmosterolosis	Benign (Jan 13, 2018)
1-54850649-A-G		Desmosterolosis	Benign (Jan 12, 2018)
1-54850698-C-T		Desmosterolosis	Uncertain significance (Jan 12, 2018)
1-54850744-C-T		Desmosterolosis	Conflicting classifications of pathogenicity (Feb 01, 2023)
1-54850745-G-A		Desmosterolosis	Benign (Jan 13, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
DHCR24	protein_coding	protein_coding	ENST00000371269	9	37586

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0310	0.969	125709	0	39	125748	0.000155

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.50	232	306	0.758	0.0000191	3377
Missense in Polyphen		58	95.924	0.60464		1003
Synonymous	0.653	120	129	0.927	0.00000839	1008
Loss of Function	3.46	8	27.6	0.290	0.00000158	283

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000124	0.000123
Ashkenazi Jewish	0.00228	0.00228
East Asian	0.0000544	0.0000544
Finnish	0.000139	0.0000924
European (Non-Finnish)	0.0000624	0.0000615
Middle Eastern	0.0000544	0.0000544
South Asian	0.00	0.00
Other	0.000659	0.000652

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Catalyzes the reduction of the Delta-24 double bond of sterol intermediates. Protects cells from oxidative stress by reducing caspase 3 activity during apoptosis induced by oxidative stress. Also protects against amyloid-beta peptide-induced apoptosis. {ECO:0000269|PubMed:11007892, ECO:0000269|PubMed:11519011, ECO:0000269|PubMed:22010141}.
• Pathway: Steroid biosynthesis - Homo sapiens (human);Simvastatin Action Pathway;Pravastatin Action Pathway;Atorvastatin Action Pathway;Hyper-IgD syndrome;Cholesteryl ester storage disease;Lysosomal Acid Lipase Deficiency (Wolman Disease);Alendronate Action Pathway;Rosuvastatin Action Pathway;Lovastatin Action Pathway;Mevalonic aciduria;Wolman disease;Risedronate Action Pathway;Cerivastatin Action Pathway;Pamidronate Action Pathway;Fluvastatin Action Pathway;Smith-Lemli-Opitz Syndrome (SLOS);Chondrodysplasia Punctata II, X Linked Dominant (CDPX2);CHILD Syndrome;Desmosterolosis;Hypercholesterolemia;Steroid Biosynthesis;Zoledronate Action Pathway;Ibandronate Action Pathway;Tryptophan metabolism;Metabolism of lipids;Metabolism;cholesterol biosynthesis III (via desmosterol);cholesterol biosynthesis II (via 24,25-dihydrolanosterol);superpathway of cholesterol biosynthesis;Metabolism of steroids;cholesterol biosynthesis I;Cholesterol biosynthesis via desmosterol;Cholesterol biosynthesis via lathosterol;Cholesterol biosynthesis (Consensus)

Recessive Scores

• pRec: 0.237

Intolerance Scores

• loftool: 0.0320
• rvis_EVS: -0.82
• rvis_percentile_EVS: 11.77

Haploinsufficiency Scores

• pHI: 0.192
• hipred: Y
• hipred_score: 0.853
• ghis: 0.532

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.984

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Dhcr24
• Phenotype: endocrine/exocrine gland phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); growth/size/body region 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); homeostasis/metabolism phenotype; reproductive system 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); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan)

Gene ontology

• Biological process: cholesterol biosynthetic process;apoptotic process;response to oxidative stress;cell cycle arrest;steroid metabolic process;tissue development;cholesterol biosynthetic process via desmosterol;cholesterol biosynthetic process via lathosterol;negative regulation of apoptotic process;negative regulation of cysteine-type endopeptidase activity involved in apoptotic process;skin development;oxidation-reduction process;regulation of neuron death
• Cellular component: Golgi membrane;nucleus;cytoplasm;endoplasmic reticulum;endoplasmic reticulum membrane;membrane;integral component of membrane
• Molecular function: delta24(24-1) sterol reductase activity;oxidoreductase activity, acting on the CH-CH group of donors, NAD or NADP as acceptor;enzyme binding;peptide antigen binding;delta24-sterol reductase activity;FAD binding