LIPA

lipase A, lysosomal acid type, the group of Lipases

Basic information

Region (hg38): 10:89213569-89414557

Links

ENSG00000107798 ∙ NCBI:3988 ∙ OMIM:613497 ∙ HGNC:6617 ∙ Uniprot:P38571 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• lysosomal acid lipase deficiency (Definitive), mode of inheritance: AR
• lysosomal acid lipase deficiency (Definitive), mode of inheritance: AR
• lysosomal acid lipase deficiency (Strong), mode of inheritance: AR
• lysosomal acid lipase deficiency (Strong), mode of inheritance: AR
• lysosomal acid lipase deficiency (Definitive), mode of inheritance: AR
• Wolman disease (Supportive), mode of inheritance: AR
• cholesteryl ester storage disease (Supportive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Cholesterol ester storage disease; Wolman disease	AR	Biochemical; Cardiovascular	Enzyme replacement therapy has been shown to be beneficial in terms of clinical parameters including liver function testing, LDL levels, and hepatic fat content; Treatment with HMG-CoA reductase inhibitors may be effective for management of atherosclerotic risk in milder forms of the condition; Enzyme replacement therapy (eg, with sebelipase alfa) has been described; HSCT has been described	Biochemical; Cardiovascular; Gastrointestinal	14008104; 5642714; 5477680; 859064; 2347551; 1528002; 8254026; 8146180; 8617513; 18174560; 18776925; 19214773; 19308038; 21291321; 21963785; 22227072; 23007684; 23035117; 23348766; 23999269; 24072694; 24122380; 26352813

ClinVar

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

• Wolman_disease (485 variants)
• Cardiovascular_phenotype (195 variants)
• Lysosomal_acid_lipase_deficiency (183 variants)
• not_provided (91 variants)
• Cholesteryl_ester_storage_disease (60 variants)
• LIPA-related_disorder (36 variants)
• not_specified (20 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the LIPA gene is commonly pathogenic or not. These statistics are base on transcript: NM_000000235.4. 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		2	3	183	1	189
missense	5	52	199	16		272
nonsense	18	15				33
start loss			1			1
frameshift	24	21	1			46
splice donor/acceptor (+/-2bp)	8	13	2			23
Total	55	103	206	199	1

Highest pathogenic variant AF is 0.0011113163

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
LIPA	protein_coding	protein_coding	ENST00000336233	9	200989

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
		125712	0	36	125748	0.000143

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.228	205	214	0.956	0.0000106	2658
Missense in Polyphen		82	83.618	0.98065		1064
Synonymous	-1.38	96	80.3	1.20	0.00000448	732
Loss of Function	1.57	13	20.7	0.628	0.00000107	231

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000337	0.000337
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000545	0.0000544
Finnish	0.0000924	0.0000924
European (Non-Finnish)	0.000229	0.000229
Middle Eastern	0.0000545	0.0000544
South Asian	0.0000327	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Crucial for the intracellular hydrolysis of cholesteryl esters and triglycerides that have been internalized via receptor- mediated endocytosis of lipoprotein particles. Important in mediating the effect of LDL (low density lipoprotein) uptake on suppression of hydroxymethylglutaryl-CoA reductase and activation of endogenous cellular cholesteryl ester formation.
• Disease: DISEASE: Wolman disease (WOD) [MIM:278000]: A severe manifestation of LIPA deficiency, leading to the accumulation of cholesteryl esters and triglycerides in most tissues of the body. WD occurs in infancy and is nearly always fatal before the age of 1 year. {ECO:0000269|PubMed:8146180}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Cholesteryl ester storage disease (CESD) [MIM:278000]: A mild manifestation of LIPA deficiency, leading to the accumulation of cholesteryl esters and triglycerides in most tissues of the body. It is characterized by late-onset. {ECO:0000269|PubMed:8146180, ECO:0000269|PubMed:9633819}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Lysosome - Homo sapiens (human);Steroid biosynthesis - Homo sapiens (human);Cholesterol metabolism - Homo sapiens (human);27-Hydroxylase Deficiency;Simvastatin Action Pathway;Pravastatin Action Pathway;Bile Acid Biosynthesis;Atorvastatin Action Pathway;Congenital Bile Acid Synthesis Defect Type II;Cerebrotendinous Xanthomatosis (CTX);Zellweger Syndrome;Hyper-IgD syndrome;Cholesteryl ester storage disease;Familial Hypercholanemia (FHCA);Congenital Bile Acid Synthesis Defect Type III;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;Phase I biotransformations, non P450;LDL clearance;Plasma lipoprotein clearance;Transport of small molecules;Glycerophospholipid metabolism;Plasma lipoprotein assembly, remodeling, and clearance (Consensus)

Recessive Scores

• pRec: 0.166

Intolerance Scores

• loftool: 0.934
• rvis_EVS: 0.15
• rvis_percentile_EVS: 64.51

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.377

Gene Damage Prediction

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

Gene ontology

• Biological process: cell morphogenesis;cytokine production;inflammatory response;cell population proliferation;lipid catabolic process;sterol metabolic process;lung development;low-density lipoprotein particle clearance;cellular lipid metabolic process;tissue remodeling;homeostasis of number of cells within a tissue
• Cellular component: fibrillar center;lysosome;lysosomal lumen;intracellular membrane-bounded organelle
• Molecular function: sterol esterase activity;lipase activity