DHCR7

7-dehydrocholesterol reductase

Basic information

Region (hg38): 11:71428192-71452868

Previous symbols: [ "SLOS" ]

Links

ENSG00000172893 ∙ NCBI:1717 ∙ OMIM:602858 ∙ HGNC:2860 ∙ Uniprot:Q9UBM7 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Smith-Lemli-Opitz syndrome (Definitive), mode of inheritance: AR
• Smith-Lemli-Opitz syndrome (Definitive), mode of inheritance: AR
• Smith-Lemli-Opitz syndrome (Strong), mode of inheritance: AR
• Smith-Lemli-Opitz syndrome (Supportive), mode of inheritance: AR
• Smith-Lemli-Opitz syndrome (Definitive), mode of inheritance: AR
• Smith-Lemli-Opitz syndrome (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Smith-Lemli-Opitz syndrome	AR	Biochemical	Though the data are not definitive, anecdotal reports suggest that cholesterol supplementation and medical treatment (eg, with statins) may be clinically beneficial; Awareness of the potential for multiple malformations (some of which may be occult) may be beneficial to allow prompt recognition and management	Biochemical; Cardiovascular; Craniofacial; Endocrine; Genitourinary; Musculoskeletal; Neurologic; Renal	14119520; 3812577; 8209913; 7632194; 7684480; 8831138; 8863875; 9024557; 9024564; 9024565; 9024566; 9130950; 9653161; 9683618; 11562938; 9634533; 9683613; 11161831; 10946022; 10951458; 11223857; 11167696; 12366604; 12407710; 15192627; 16761297; 17497248; 20301322; 18285838; 19430384; 20635399; 19365639; 20014133; 23042628; 23072947; 23162303; 23293579; 23319240; 23321614; 23426833; 23532938; 23538569; 23595802; 23688395; 23790112

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the DHCR7 gene.

• Smith-Lemli-Opitz syndrome (708 variants)
• not provided (219 variants)
• Inborn genetic diseases (141 variants)
• not specified (70 variants)
• DHCR7-related condition (13 variants)
• Microcephaly (2 variants)
• See cases (2 variants)
• Global developmental delay (1 variants)
• Abnormal brain morphology (1 variants)
• 2-3 toe syndactyly;Primary microcephaly;Small for gestational age;Elevated circulating 7-dehydrocholesterol concentration (1 variants)
• Elevated circulating 7-dehydrocholesterol concentration;Primary microcephaly;Small for gestational age;2-3 toe syndactyly (1 variants)
• Hepatoblastoma (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the DHCR7 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			2	191	7	200
missense	18	66	137	4		225
nonsense	14	27	2			43
start loss	1	2	1		1	5
frameshift	12	20	1			33
inframe indel	2	1	3			6
splice donor/acceptor (+/-2bp)		17				17
splice region	1	2	4	23	1	31
non coding		6	32	63	23	124
Total	47	139	178	258	31

Highest pathogenic variant AF is 0.0000722

Variants in DHCR7

This is a list of pathogenic ClinVar variants found in the DHCR7 region.

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

Position	Type	Phenotype	Significance	ClinVar
11-71434585-G-A		Smith-Lemli-Opitz syndrome	Uncertain significance (Jan 13, 2018)
11-71434596-A-G		Smith-Lemli-Opitz syndrome	Uncertain significance (Jan 13, 2018)
11-71434610-C-T		Smith-Lemli-Opitz syndrome	Uncertain significance (Jan 13, 2018)
11-71434614-T-A		Smith-Lemli-Opitz syndrome	Uncertain significance (Jan 13, 2018)
11-71434620-G-A		Smith-Lemli-Opitz syndrome	Uncertain significance (Jan 13, 2018)
11-71434641-T-C		Smith-Lemli-Opitz syndrome	Benign (Jan 12, 2018)
11-71434652-G-T		Smith-Lemli-Opitz syndrome	Uncertain significance (Jan 13, 2018)
11-71434675-C-T		Smith-Lemli-Opitz syndrome	Uncertain significance (Jan 12, 2018)
11-71434694-A-G		Smith-Lemli-Opitz syndrome	Uncertain significance (Jan 13, 2018)
11-71434731-C-T		Smith-Lemli-Opitz syndrome	Uncertain significance (Jan 12, 2018)
11-71434732-G-A		Smith-Lemli-Opitz syndrome	Benign (Jan 13, 2018)
11-71434810-C-T		Smith-Lemli-Opitz syndrome	Likely benign (Apr 27, 2017)
11-71434895-G-A		Smith-Lemli-Opitz syndrome	Benign (Jan 12, 2018)
11-71434924-T-C		Smith-Lemli-Opitz syndrome	Likely benign (Jan 13, 2018)
11-71434937-C-T		Smith-Lemli-Opitz syndrome	Uncertain significance (Jan 13, 2018)
11-71434951-C-T		Smith-Lemli-Opitz syndrome	Uncertain significance (Jan 13, 2018)
11-71434958-G-A		Smith-Lemli-Opitz syndrome	Uncertain significance (Jan 12, 2018)
11-71435017-G-A		Smith-Lemli-Opitz syndrome	Likely benign (Apr 27, 2017)
11-71435051-G-A		Smith-Lemli-Opitz syndrome	Uncertain significance (Jan 12, 2018)
11-71435114-C-T		Smith-Lemli-Opitz syndrome	Uncertain significance (Jan 13, 2018)
11-71435149-G-A		Smith-Lemli-Opitz syndrome	Conflicting classifications of pathogenicity (Jul 01, 2023)
11-71435183-G-A		Smith-Lemli-Opitz syndrome	Uncertain significance (Jan 12, 2018)
11-71435202-AAGCAAGGAACAG-A		Smith-Lemli-Opitz syndrome	Benign/Likely benign (Jun 16, 2018)
11-71435256-C-T		Smith-Lemli-Opitz syndrome	Conflicting classifications of pathogenicity (Jul 01, 2023)
11-71435274-G-C		Smith-Lemli-Opitz syndrome	Uncertain significance (Jan 12, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
DHCR7	protein_coding	protein_coding	ENST00000355527	7	24676

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
3.95e-13	0.0471	124575	0	1173	125748	0.00468

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.452	322	300	1.07	0.0000214	3082
Missense in Polyphen		134	119.84	1.1182		1281
Synonymous	-1.88	159	132	1.21	0.00000999	947
Loss of Function	0.308	20	21.5	0.928	9.42e-7	221

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00460	0.00432
Ashkenazi Jewish	0.0128	0.0122
East Asian	0.000273	0.000272
Finnish	0.00252	0.00199
European (Non-Finnish)	0.00800	0.00743
Middle Eastern	0.000273	0.000272
South Asian	0.000459	0.000457
Other	0.00636	0.00604

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Production of cholesterol by reduction of C7-C8 double bond of 7-dehydrocholesterol (7-DHC).
• Pathway: Steroid biosynthesis - Homo sapiens (human);Vitamin D Metabolism;Cholesterol Biosynthesis;Activation of gene expression by SREBF (SREBP);Metabolism of lipids;Regulation of cholesterol biosynthesis by SREBP (SREBF);Squalene and cholesterol biosynthesis;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;Steroids metabolism;Cholesterol biosynthesis via lathosterol;Cholesterol biosynthesis;Activation of gene expression by SREBF (SREBP) (Consensus)

Recessive Scores

• pRec: 0.322

Intolerance Scores

• loftool: 0.0387
• rvis_EVS: -0.86
• rvis_percentile_EVS: 10.89

Haploinsufficiency Scores

• pHI: 0.101
• hipred: N
• hipred_score: 0.399
• ghis: 0.518

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.997

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Dhcr7
• Phenotype: homeostasis/metabolism phenotype; craniofacial phenotype; muscle phenotype; growth/size/body region phenotype; liver/biliary system phenotype; renal/urinary system phenotype; digestive/alimentary 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); limbs/digits/tail 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); 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); respiratory system phenotype

Gene ontology

• Biological process: blood vessel development;cholesterol biosynthetic process;post-embryonic development;sterol biosynthetic process;brassinosteroid biosynthetic process;cell differentiation;lung development;cholesterol biosynthetic process via desmosterol;cholesterol biosynthetic process via lathosterol;multicellular organism growth;regulation of cell population proliferation;regulation of cholesterol biosynthetic process;oxidation-reduction process
• Cellular component: nuclear outer membrane;endoplasmic reticulum;endoplasmic reticulum membrane;cytosol;membrane;integral component of endoplasmic reticulum membrane
• Molecular function: sterol delta7 reductase activity;7-dehydrocholesterol reductase activity;NADP binding