LIPC

lipase C, hepatic type, the group of Lipases

Basic information

Region (hg38): 15:58410569-58569844

Links

ENSG00000166035 ∙ NCBI:3990 ∙ OMIM:151670 ∙ HGNC:6619 ∙ Uniprot:P11150 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• hyperlipidemia due to hepatic triglyceride lipase deficiency (Strong), mode of inheritance: AR
• hyperlipidemia due to hepatic triglyceride lipase deficiency (Limited), mode of inheritance: AR
• hyperlipidemia due to hepatic triglyceride lipase deficiency (Limited), mode of inheritance: Unknown

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Hepatic lipase deficiency	AR	Cardiovascular	Surveillance and treatment for cholesterol and cardiovascular perturbations may decrease morbidity and mortality	Cardiovascular	1883393; 1671786; 12777476; 19428034

ClinVar

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

• not_provided (177 variants)
• not_specified (64 variants)
• Hyperlipidemia_due_to_hepatic_triglyceride_lipase_deficiency (58 variants)
• Type_2_diabetes_mellitus (16 variants)
• High_density_lipoprotein_cholesterol_level_quantitative_trait_locus_12 (10 variants)
• LIPC-related_disorder (7 variants)
• Abnormal_circulating_lipid_concentration (2 variants)
• HIGH_DENSITY_LIPOPROTEIN_CHOLESTEROL_LEVEL_QUANTITATIVE_TRAIT_LOCUS_6 (1 variants)
• Type_1_diabetes_mellitus_2 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the LIPC gene is commonly pathogenic or not. These statistics are base on transcript: NM_000000236.3. 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			8	45	2	55
missense	1	2	140	11		154
nonsense		1	1			2
start loss						0
frameshift			4			4
splice donor/acceptor (+/-2bp)	1		2	1		4
Total	2	3	155	57	2

Highest pathogenic variant AF is 0.000120804

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
LIPC	protein_coding	protein_coding	ENST00000356113	9	158384

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
3.28e-7	0.936	125607	0	141	125748	0.000561

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.919	335	291	1.15	0.0000193	3261
Missense in Polyphen		121	105.63	1.1455		1237
Synonymous	-1.80	148	123	1.21	0.00000939	969
Loss of Function	1.82	14	23.5	0.595	0.00000136	249

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00158	0.00152
Ashkenazi Jewish	0.000198	0.000198
East Asian	0.000444	0.000435
Finnish	0.00	0.00
European (Non-Finnish)	0.000765	0.000765
Middle Eastern	0.000444	0.000435
South Asian	0.000165	0.000163
Other	0.00134	0.00130

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Hepatic lipase has the capacity to catalyze hydrolysis of phospholipids, mono-, di-, and triglycerides, and acyl-CoA thioesters. It is an important enzyme in HDL metabolism. Hepatic lipase binds heparin.
• Disease: DISEASE: Hepatic lipase deficiency (HL deficiency) [MIM:614025]: A disorder characterized by elevated levels of beta-migrating very low density lipoproteins, and abnormally triglyceride-rich low and high density lipoproteins. {ECO:0000269|PubMed:10660332, ECO:0000269|PubMed:1301939}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Glycerolipid metabolism - Homo sapiens (human);Cholesterol metabolism - Homo sapiens (human);Statin Pathway, Pharmacodynamics;Familial lipoprotein lipase deficiency;Glycerolipid Metabolism;Glycerol Kinase Deficiency;D-glyceric acidura;Fatty Acid Beta Oxidation;Triacylglyceride Synthesis;Statin Pathway;Chylomicron clearance;Plasma lipoprotein clearance;Transport of small molecules;Glycerophospholipid metabolism;Assembly of active LPL and LIPC lipase complexes;retinol biosynthesis;triacylglycerol degradation;Plasma lipoprotein assembly, remodeling, and clearance;Plasma lipoprotein remodeling (Consensus)

Recessive Scores

• pRec: 0.361

Intolerance Scores

• loftool: 0.189
• rvis_EVS: -0.71
• rvis_percentile_EVS: 14.78

Haploinsufficiency Scores

• pHI: 0.510
• hipred: N
• hipred_score: 0.350
• ghis: 0.454

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.457

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Lipc
• Phenotype: homeostasis/metabolism phenotype; endocrine/exocrine gland phenotype; reproductive system phenotype

Gene ontology

• Biological process: fatty acid biosynthetic process;cholesterol metabolic process;triglyceride catabolic process;very-low-density lipoprotein particle remodeling;intermediate-density lipoprotein particle remodeling;low-density lipoprotein particle remodeling;high-density lipoprotein particle remodeling;chylomicron remnant clearance;phosphatidylcholine catabolic process;cholesterol homeostasis;reverse cholesterol transport;regulation of lipoprotein lipase activity;triglyceride homeostasis
• Cellular component: extracellular region;extracellular space;endoplasmic reticulum lumen;high-density lipoprotein particle
• Molecular function: phospholipase activity;triglyceride lipase activity;heparin binding;low-density lipoprotein particle binding;apolipoprotein binding