SQLE

protein-coding

squalene epoxidase

Gene summary

Enables FAD binding activity and squalene monooxygenase activity. Involved in cholesterol biosynthetic process; lipid droplet formation; and regulation of cell population proliferation. Located in membrane. Is active in endoplasmic reticulum membrane. [provided by Alliance of Genome Resources, Jun 2026]

MANE transcript

NM_003129.4

Inheritance

—

ClinVar variants

P:1U:61B:6

Top phenotype

Hypercholesterolemia, familial, 1

gnomAD constraint

pLI —, LoF o/e 0.12

Max pathogenic AF

—

Genomic locus

chr8:124,998,497-125,022,283

External References & Databases

Ensembl (ENSG00000104549)

Transcript & Mutation Effects

hg38 • Region Span ~23.8 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to SQLE variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 58

not providedTotal: 2

Hypercholesterolemia, familial, 1Total: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_003129.4. 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	2 clinvar		4
missense			55 clinvar	4 clinvar		59
nonsense						0
start loss						0
frameshift	1 clinvar		1 clinvar			2
splice donor/acceptor (+/-2bp)			3 clinvar			3
Total	1	0	61	6	0	68

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 25 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_003129.4	RefSeq	NP_003120.2	11	MANE Select
ENST00000265896.10	Ensembl	ENSP00000265896.5	11	MANE Select
ENST00000518931.1	Ensembl	ENSP00000429916.1	5	Standard
ENST00000521232.1	Ensembl	ENSP00000428239.1	3	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Steroid biosynthesis - Homo sapiens (human)
Bisphosphonate Pathway, Pharmacodynamics
Statin Pathway, Pharmacodynamics
Simvastatin Action Pathway
Pravastatin Action Pathway

Biological Process

cholesterol biosynthetic process
cellular aromatic compound metabolic process
cholesterol metabolic process
response to organic substance
sterol biosynthetic process

Molecular Function

squalene monooxygenase activity
flavin adenine dinucleotide binding

Cellular Component

endoplasmic reticulum
endoplasmic reticulum membrane
integral component of membrane
organelle membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000265896
Coding exons: 11
Length: 23787
Individuals with no LoFs: 124599
Homozygous LoFs: 0
Heterozygous LoFs: 5
Defined: 124604
p: 0.0000201

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.14	227	281	0.808	0.0000134	3685
Missense (PolyPhen)		61	95.994	0.63546		1247
Synonymous	0.144	104	106	0.982	0.00000548	1136
Loss of Function	4.04	3	24.7	0.122	0.00000126	330

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.000019	0.000018	rare
South Asian	0.000034	0.000033	rare
Other	0.00035	0.00033	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Catalyzes the first oxygenation step in sterol biosynthesis and is suggested to be one of the rate-limiting enzymes in this pathway.;

Recessive Scores

pRec: 0.329

Intolerance Scores

LoFtool: 0.303
RVIS EVS: -0.09
RVIS percentile EVS: 46.99

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.979

Gene Damage Prediction

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