SC5D

protein-coding

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

Gene summary

This gene encodes an enzyme of cholesterol biosynthesis. The encoded protein catalyzes the conversion of lathosterol into 7-dehydrocholesterol. Mutations in this gene have been associated with lathosterolosis. Alternatively spliced transcript variants encoding the same protein have been described. [provided by RefSeq, Jul 2008]

Previous symbols:

SC5DL

MANE transcript

NM_006918.5

Inheritance

ClinVar variants

P:7U:64B:33

Top phenotype

Lathosterolosis

gnomAD constraint

pLI —, LoF o/e 0.49

Max pathogenic AF

—

Genomic locus

chr11:121,292,681-121,313,410

External References & Databases

Ensembl (ENSG00000109929)

Transcript & Mutation Effects

hg38 • Region Span ~20.7 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

lathosterolosisSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0011816

Submitter: PanelApp Australia

lathosterolosisSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0011816

Submitter: Labcorp Genetics (formerly Invitae)

lathosterolosisSUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0011816

Submitter: Orphanet

lathosterolosisDEFINITIVE

Inheritance Pattern: AR

Disease ID:MONDO:0011816

Submitter: G2P

Clinical Genomic Database (CGD)

LathosterolosisAR

Manifestation: Biochemical; Craniofacial; Gastrointestinal; Musculoskeletal; Neurologic

Intervention: General

Rationale: 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

Comments: Lipid storage has been reported as being aggravated by supplemental cholesterol

Refs: 12189593; 12812989; 17853487; 19123163

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to SC5D variants in ClinVar

5 Conditions Cataloged

not providedTotal: 81

LathosterolosisTotal: 28

Inborn genetic diseasesTotal: 27

SC5D-related disorderTotal: 10

not specifiedTotal: 7

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_006918.5. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			2 clinvar	24 clinvar		26
missense	3 clinvar	2 clinvar	51 clinvar	8 clinvar	1 clinvar	65
nonsense		1 clinvar	4 clinvar			5
start loss						0
frameshift		1 clinvar	4 clinvar			5
splice donor/acceptor (+/-2bp)			3 clinvar			3
Total	3	4	64	32	1	104

Highest pathogenic variant AF is 0.00010295493

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 29 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_006918.5	RefSeq	NP_008849.2	4	MANE Select
ENST00000264027.9	Ensembl	ENSP00000264027.4	4	MANE Select
NM_001024956.3	RefSeq	NP_001020127.1	4	Standard
ENST00000392789.2	Ensembl	ENSP00000376539.2	4	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Steroid biosynthesis - Homo sapiens (human)
Simvastatin Action Pathway
Pravastatin Action Pathway
Atorvastatin Action Pathway
Hyper-IgD syndrome

Biological Process

lipid metabolic process
sterol biosynthetic process
cholesterol biosynthetic process via desmosterol
cholesterol biosynthetic process via lathosterol
regulation of cholesterol biosynthetic process

Molecular Function

C-5 sterol desaturase activity
iron ion binding

Cellular Component

endoplasmic reticulum membrane
integral component of membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000264027
Coding exons: 4
Length: 16242
Individuals with no LoFs: 125708
Homozygous LoFs: 0
Heterozygous LoFs: 37
Defined: 125745
p: 0.000147

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.721	139	165	0.842	0.00000861	1994
Missense (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

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.00017	0.00017	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00016	0.00016	rare
Finnish	0.000092	0.000092	rare
European (Non-Finnish)	0.00021	0.00021	rare
South Asian	0.000065	0.000065	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

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.;

Recessive Scores

pRec: 0.151

Intolerance Scores

RVIS EVS: -0.25
RVIS percentile EVS: 35.75

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N

Gene Damage Prediction

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