SC5D

sterol-C5-desaturase, the group of Fatty acid hydroxylase domain containing

Basic information

Region (hg38): 11:121292680-121313410

Previous symbols: [ "SC5DL" ]

Links

ENSG00000109929 ∙ NCBI:6309 ∙ OMIM:602286 ∙ HGNC:10547 ∙ Uniprot:O75845 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

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

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Lathosterolosis	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; Gastrointestinal; Musculoskeletal; Neurologic	12189593; 12812989; 17853487; 19123163
Lipid storage has been reported as being aggravated by supplemental cholesterol

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SC5D gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SC5D 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			1	15		16
missense			35	3	2	40
nonsense			2			2
start loss						0
frameshift			3			3
inframe indel						0
splice donor/acceptor (+/-2bp)			1			1
splice region			2	2		4
non coding			87	16	22	125
Total	0	0	129	34	24

Variants in SC5D

This is a list of pathogenic ClinVar variants found in the SC5D region.

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

Position	Type	Phenotype	Significance	ClinVar
11-121292700-T-G		Lathosterolosis	Uncertain significance (Jun 14, 2016)
11-121292733-C-G		Lathosterolosis	Uncertain significance (Jun 14, 2016)
11-121292736-C-G		Lathosterolosis	Uncertain significance (Jun 14, 2016)
11-121301298-TA-T		not specified	Benign (Apr 02, 2020)
11-121303380-A-G			Uncertain significance (Mar 14, 2022)
11-121303391-C-T			Benign (Jul 26, 2022)
11-121303392-G-C			Uncertain significance (Jul 17, 2023)
11-121303397-G-A			Uncertain significance (-)
11-121303423-C-CTGGATGT			Uncertain significance (Apr 07, 2022)
11-121303432-A-G			Likely benign (Sep 24, 2021)
11-121303438-A-G			Likely benign (May 20, 2023)
11-121303441-GC-G			Uncertain significance (Nov 02, 2022)
11-121303461-G-A		Lathosterolosis	Pathogenic (Oct 01, 2002)
11-121303473-G-A			Uncertain significance (Nov 18, 2022)
11-121303481-A-T		Inborn genetic diseases	Uncertain significance (Apr 19, 2023)
11-121303512-A-C		Lathosterolosis	Pathogenic (Jul 01, 2003)
11-121303526-A-G		Lathosterolosis	Uncertain significance (Jan 13, 2018)
11-121303537-T-C			Likely benign (Mar 27, 2022)
11-121303539-A-G			Uncertain significance (Jun 27, 2022)
11-121303544-G-C			Uncertain significance (Apr 25, 2022)
11-121303549-C-T			Likely benign (Dec 13, 2023)
11-121303550-G-A		Inborn genetic diseases	Uncertain significance (Sep 23, 2023)
11-121303556-G-A		Lathosterolosis	Uncertain significance (Apr 27, 2017)
11-121303564-G-T			Uncertain significance (Mar 04, 2022)
11-121303604-T-A			Benign (Nov 19, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SC5D	protein_coding	protein_coding	ENST00000264027	4	16242

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00259	0.939	125708	0	37	125745	0.000147

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.721	139	165	0.842	0.00000861	1994
Missense in Polyphen		47	61.176	0.76827		787
Synonymous	0.749	51	58.3	0.875	0.00000303	543
Loss of Function	1.66	6	12.3	0.490	6.73e-7	140

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000174	0.000174
Ashkenazi Jewish	0.00	0.00
East Asian	0.000163	0.000163
Finnish	0.0000924	0.0000924
European (Non-Finnish)	0.000211	0.000211
Middle Eastern	0.000163	0.000163
South Asian	0.0000653	0.0000653
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Catalyzes a dehydrogenation to introduce C5-6 double bond into lathosterol.
• Disease: DISEASE: Lathosterolosis (LATHST) [MIM:607330]: Autosomal recessive disorder characterized by a complex phenotype, including multiple congenital anomalies, mental retardation, and liver disease. {ECO:0000269|PubMed:12189593, ECO:0000269|PubMed:12812989}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• 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;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: 0.151

Intolerance Scores

• rvis_EVS: -0.25
• rvis_percentile_EVS: 35.75

Haploinsufficiency Scores

• pHI: 0.128
• hipred: Y
• hipred_score: 0.551
• ghis: 0.481

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Sc5d
• Phenotype: cellular phenotype; homeostasis/metabolism phenotype; craniofacial 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; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); endocrine/exocrine gland phenotype; respiratory system phenotype; liver/biliary system phenotype; skeleton phenotype; renal/urinary system 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; digestive/alimentary 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); 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)

Gene ontology

• Biological process: lipid metabolic process;sterol biosynthetic process;cholesterol biosynthetic process via desmosterol;cholesterol biosynthetic process via lathosterol;regulation of cholesterol biosynthetic process;oxidation-reduction process
• Cellular component: endoplasmic reticulum membrane;integral component of membrane
• Molecular function: C-5 sterol desaturase activity;iron ion binding