LPIN3

protein-coding

lipin 3, the group of Lipins

Gene summary

The protein encoded by this gene is a member of the lipin family of proteins, and all family members share strong homology in their C-terminal region. This protein is thought to form hetero-oligomers with other lipin family members, while one family member, lipin 1, can also form homo-oligomers. This protein contains conserved motifs for phosphatidate phosphatase 1 (PAP1) activity as well as a domain that interacts with a transcriptional co-activator. Lipin complexes act in the cytoplasm to catalyze the dephosphorylation of phosphatidic acid to produce diacylglycerol, which is the precursor of both triglycerides and phospholipids. Lipin complexes are also thought to regulate gene expression as transcriptional co-activators in the nucleus. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2014]

Previous symbols:

LIPN3L

MANE transcript

NM_022896.3

Inheritance

—

ClinVar variants

U:138B:13

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.63

Max pathogenic AF

—

Genomic locus

chr20:41,340,821-41,360,582

External References & Databases

Ensembl (ENSG00000132793)

Transcript & Mutation Effects

hg38 • Region Span ~19.8 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 LPIN3 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 127

not providedTotal: 12

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_022896.3. 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	6 clinvar		9
missense			126 clinvar	6 clinvar	1 clinvar	133
nonsense			1 clinvar			1
start loss						0
frameshift			2 clinvar			2
splice donor/acceptor (+/-2bp)			6 clinvar			6
Total	0	0	138	12	1	151

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 33 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_022896.3	RefSeq	NP_075047.1	19	MANE Select
ENST00000373257.8	Ensembl	ENSP00000362354.3	19	MANE Select
NM_001301860.2	RefSeq	NP_001288789.1	19	Standard
ENST00000445975.1	Ensembl	ENSP00000398092.1	9	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Glycerolipid metabolism - Homo sapiens (human)
Glycerophospholipid metabolism - Homo sapiens (human)
Adipogenesis
Metabolism of lipids
Metabolism

Biological Process

phosphatidylethanolamine biosynthetic process
phosphatidylcholine biosynthetic process
fatty acid catabolic process
dephosphorylation
triglyceride biosynthetic process

Molecular Function

transcription coactivator activity
phosphatidate phosphatase activity

Cellular Component

nucleus
endoplasmic reticulum membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000373257
Coding exons: 19
Length: 19663
Individuals with no LoFs: 125313
Homozygous LoFs: 1
Heterozygous LoFs: 434
Defined: 125748
p: 0.00173

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.652	466	507	0.919	0.0000302	5477
Missense (PolyPhen)		132	156.34	0.84429		1662
Synonymous	1.03	196	215	0.910	0.0000133	1755
Loss of Function	2.24	27	42.9	0.630	0.00000211	480

Population LoF Frequency

Population	CAF	p-value	Status
African	0.0021	0.0021	notable
Latino/Admixed American	0.0057	0.0056	notable
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00043	0.00044	rare
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.0013	0.0013	notable
South Asian	0.0013	0.0012	notable
Other	0.0020	0.0020	notable

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Regulates fatty acid metabolism. Magnesium-dependent phosphatidate phosphatase enzyme which catalyzes the conversion of phosphatidic acid to diacylglycerol during triglyceride, phosphatidylcholine and phosphatidylethanolamine biosynthesis (By similarity). {ECO:0000250}.;

Recessive Scores

pRec: 0.106

Intolerance Scores

LoFtool: 0.431
RVIS EVS: 0.56
RVIS percentile EVS: 81.72

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.511

Gene Damage Prediction

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