LIPI

protein-coding

lipase I, the group of Lipases

Gene summary

The protein encoded by this gene is a phospholipase that hydrolyzes phosphatidic acid to produce lysophosphatidic acid. Defects in this gene are a cause of susceptibility to familial hypertrigliceridemia. This gene is also expressed at high levels in Ewing family tumor cells. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2014]

MANE transcript

NM_001302998.2

Inheritance

ClinVar variants

U:106B:32

Top phenotype

Hypertriglyceridemia, familial

gnomAD constraint

pLI —, LoF o/e 1.25

Max pathogenic AF

—

Genomic locus

chr21:14,108,813-14,210,955

External References & Databases

Ensembl (ENSG00000188992)

Transcript & Mutation Effects

hg38 • Region Span ~102.1 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

hypertriglyceridemiaLIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0005347

Submitter: Genomics England PanelApp

Clinical Genomic Database (CGD)

Hypertriglyceridemia, familialAD

Manifestation: Cardiovascular

Intervention: Cardiovascular

Rationale: Surveillance and treatment for cholesterol and cardiovascular perturbations may decrease morbidity and mortality

Refs: 12719377

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to LIPI variants in ClinVar

4 Conditions Cataloged

not providedTotal: 118

not specifiedTotal: 83

LIPI-related disorderTotal: 4

Hypertriglyceridemia 1Total: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001302998.2. 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			3 clinvar	18 clinvar	2 clinvar	23
missense			100 clinvar	8 clinvar	4 clinvar	112
nonsense			1 clinvar			1
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	106	26	6	138

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 20 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001302998.2	RefSeq	NP_001289927.1	10	MANE Select
ENST00000681601.1	Ensembl	ENSP00000505323.1	10	MANE Select
NM_001302999.2	RefSeq	NP_001289928.1	9	Standard
NM_001303000.2	RefSeq	NP_001289929.1	10	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Metabolism of lipids
Metabolism
Glycerophospholipid biosynthesis
Phospholipid metabolism
Synthesis of PA

Biological Process

phosphatidic acid biosynthetic process
lipid catabolic process

Molecular Function

phospholipase activity
heparin binding
carboxylic ester hydrolase activity

Cellular Component

extracellular region
plasma membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000344577
Coding exons: 10
Length: 102033
Individuals with no LoFs: 125692
Homozygous LoFs: 0
Heterozygous LoFs: 47
Defined: 125739
p: 0.000187

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.365	261	245	1.07	0.0000112	3179
Missense (PolyPhen)		100	92.14	1.0853		1184
Synonymous	-0.516	93	86.9	1.07	0.00000413	862
Loss of Function	-1.06	26	20.8	1.25	8.66e-7	297

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00037	0.00037	rare
Latino/Admixed American	0.00017	0.00014	rare
Ashkenazi Jewish	0.000099	0.000099	rare
East Asian	0.00038	0.00038	rare
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.00016	0.00016	rare
South Asian	0.00020	0.00020	rare
Other	0.00050	0.00049	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Hydrolyzes specifically phosphatidic acid (PA) to produce 2-acyl lysophosphatidic acid (LPA; a potent bioactive lipid mediator) and fatty acid. Does not hydrolyze other phospholipids, like phosphatidylserine (PS), phosphatidylcholine (PC) and phosphatidylethanolamine (PE) or triacylglycerol (TG). {ECO:0000269|PubMed:12963729}.;

Intolerance Scores

LoFtool: 0.241
RVIS EVS: 1.2
RVIS percentile EVS: 92.95

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.124

Gene Damage Prediction

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