LIPE

lipase E, hormone sensitive type, the group of Lipases

Basic information

Region (hg38): 19:42401497-42427388

Links

ENSG00000079435 ∙ NCBI:3991 ∙ OMIM:151750 ∙ HGNC:6621 ∙ Uniprot:Q05469 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• LIPE-related familial partial lipodystrophy (Supportive), mode of inheritance: AR
• LIPE-related familial partial lipodystrophy (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Lipodystrophy, familial partial, type 6	AR	Cardiovascular	Among other manifestations, individuals have been described with dyslipidemia, and awareness may allow surveillance and early management	Cardiovascular; Endocrine	24848981; 27862896
Heterozygous individuals may also demonstrate findings including dyslipidemia and insulin resistance

ClinVar

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

• Inborn_genetic_diseases (157 variants)
• not_provided (60 variants)
• LIPE-related_disorder (26 variants)
• not_specified (15 variants)
• LIPE-related_familial_partial_lipodystrophy (11 variants)
• See_cases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the LIPE gene is commonly pathogenic or not. These statistics are base on transcript: NM_000005357.4. Only rare variants are included in the table.

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.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			1	22	6	29
missense			160	20	10	190
nonsense		2	1			3
start loss						0
frameshift	1	1	2			4
splice donor/acceptor (+/-2bp)						0
Total	1	3	164	42	16

Highest pathogenic variant AF is 0.00047723728

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
LIPE	protein_coding	protein_coding	ENST00000244289	10	25920

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
9.75e-12	0.974	125660	0	88	125748	0.000350

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.952	582	650	0.895	0.0000414	6781
Missense in Polyphen		187	230.17	0.81246		2301
Synonymous	0.119	284	287	0.991	0.0000191	2363
Loss of Function	2.30	24	39.7	0.605	0.00000206	434

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000493	0.000488
Ashkenazi Jewish	0.00	0.00
East Asian	0.000707	0.000707
Finnish	0.000519	0.000508
European (Non-Finnish)	0.000310	0.000299
Middle Eastern	0.000707	0.000707
South Asian	0.000523	0.000523
Other	0.000164	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: In adipose tissue and heart, it primarily hydrolyzes stored triglycerides to free fatty acids, while in steroidogenic tissues, it principally converts cholesteryl esters to free cholesterol for steroid hormone production.
• Disease: DISEASE: Lipodystrophy, familial partial, 6 (FPLD6) [MIM:615980]: A form of lipodystrophy characterized by abnormal subcutaneous fat distribution. Affected individuals have increased visceral fat, impaired lipolysis, dyslipidemia, hepatic steatosis, systemic insulin resistance, and diabetes. Some patients manifest muscular dystrophy. {ECO:0000269|PubMed:24848981}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Aldosterone synthesis and secretion - Homo sapiens (human);Regulation of lipolysis in adipocytes - Homo sapiens (human);AMPK signaling pathway - Homo sapiens (human);Thermogenesis - Homo sapiens (human);cAMP signaling pathway - Homo sapiens (human);Apelin signaling pathway - Homo sapiens (human);Insulin signaling pathway - Homo sapiens (human);AMP-activated Protein Kinase (AMPK) Signaling;Fatty Acid Beta Oxidation;Adipogenesis;Lipid storage and perilipins in skeletal muscle;Triacylglyceride Synthesis;Focal Adhesion-PI3K-Akt-mTOR-signaling pathway;Lipid Metabolism Pathway;Liver steatosis AOP;Insulin Signaling;Metabolism of lipids;Metabolism;Triglyceride catabolism;Triglyceride metabolism;triacylglycerol degradation (Consensus)

Recessive Scores

• pRec: 0.532

Intolerance Scores

• loftool: 0.914
• rvis_EVS: 0.55
• rvis_percentile_EVS: 81.13

Haploinsufficiency Scores

• pHI: 0.192
• hipred: N
• hipred_score: 0.286
• ghis: 0.472

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.714

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Lipe
• Phenotype: muscle phenotype; homeostasis/metabolism phenotype; cellular phenotype; 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); reproductive system 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; digestive/alimentary phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); liver/biliary system 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)

Gene ontology

• Biological process: protein phosphorylation;cholesterol metabolic process;lipid catabolic process;triglyceride catabolic process;long-chain fatty acid catabolic process;diacylglycerol catabolic process
• Cellular component: lipid droplet;cytosol;caveola
• Molecular function: triglyceride lipase activity;protein binding;serine hydrolase activity;protein kinase binding;hormone-sensitive lipase activity