LPIN2

lipin 2, the group of Lipins

Basic information

Region (hg38): 18:2885296-3013144

Links

ENSG00000101577

∙ NCBI:9663 ∙ OMIM:605519 ∙ HGNC:14450 ∙ Uniprot:Q92539 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

Majeed syndrome (Supportive), mode of inheritance: AR
Majeed syndrome (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Majeed syndrome	AR	Allergy/Immunology/Infectious; Hematologic	Individuals may manifest with Chronic recurrent multifocal osteomyelitis (CRMO), for which treatment with NSAIDs/corticosteroids may be beneficial; Individuals may require surveillance and blood transfusion treatment for anemia	Allergy/Immunology/Infectious; Dermatologic; Hematologic	11381255; 17011878; 17330256; 18055821; 20301735; 22559933; 22570351

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the LPIN2 gene.

Majeed_syndrome (670 variants)
not_provided (144 variants)
Inborn_genetic_diseases (89 variants)
Autoinflammatory_syndrome (78 variants)
not_specified (47 variants)
LPIN2-related_disorder (22 variants)
Psoriasis (1 variants)
See_cases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the LPIN2 gene is commonly pathogenic or not. These statistics are base on transcript: NM_001375808.2. 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	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous			11 clinvar	187 clinvar	2 clinvar	200
missense	1 clinvar	2 clinvar	308 clinvar	17 clinvar	2 clinvar	330
nonsense	7 clinvar	4 clinvar	2 clinvar			13
start loss						0
frameshift	11 clinvar	3 clinvar	1 clinvar			15
splice donor/acceptor (+/-2bp)	1 clinvar	12 clinvar	1 clinvar	1 clinvar		15
Total	20	21	323	205	4

Highest pathogenic variant AF is 0.0000225821

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
LPIN2	protein_coding	protein_coding	ENST00000261596	19	96322

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0000503	1.00	125686	0	62	125748	0.000247

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.983	431	492	0.875	0.0000283	5883
Missense in Polyphen		139	223.79	0.62113		2696
Synonymous	-1.14	215	195	1.10	0.0000133	1700
Loss of Function	4.33	17	50.0	0.340	0.00000287	579

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000482	0.000481
Ashkenazi Jewish	0.00139	0.00139
East Asian	0.000163	0.000163
Finnish	0.0000469	0.0000462
European (Non-Finnish)	0.000229	0.000229
Middle Eastern	0.000163	0.000163
South Asian	0.000131	0.000131
Other	0.000489	0.000489

dbNSFP

Source: dbNSFP

Function: FUNCTION: Plays important roles in controlling the metabolism of fatty acids at different levels. Acts as a magnesium-dependent phosphatidate phosphatase enzyme which catalyzes the conversion of phosphatidic acid to diacylglycerol during triglyceride, phosphatidylcholine and phosphatidylethanolamine biosynthesis in the reticulum endoplasmic membrane. Acts also as a nuclear transcriptional coactivator for PPARGC1A to modulate lipid metabolism (By similarity). {ECO:0000250}.;
Disease: DISEASE: Majeed syndrome (MJDS) [MIM:609628]: An autosomal recessive syndrome characterized by chronic recurrent multifocal osteomyelitis that is of early onset with a lifelong course, congenital dyserythropoietic anemia that presents as hypochromic, microcytic anemia during the first year of life and ranges from mild to transfusion-dependent, and transient inflammatory dermatosis, often manifesting as Sweet syndrome (neutrophilic skin infiltration). {ECO:0000269|PubMed:15994876}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Pathway: Glycerolipid metabolism - Homo sapiens (human);Glycerophospholipid metabolism - Homo sapiens (human);Adipogenesis;Metabolism of lipids;Metabolism;Synthesis of PC;Synthesis of PE;Triglyceride biosynthesis;Triglyceride metabolism;Depolymerisation of the Nuclear Lamina;Nuclear Envelope Breakdown;Mitotic Prophase;Glycerophospholipid biosynthesis;Phospholipid metabolism;M Phase;Cell Cycle;Cell Cycle, Mitotic (Consensus)

Recessive Scores

pRec: 0.155

Intolerance Scores

loftool: 0.319
rvis_EVS: -0.79
rvis_percentile_EVS: 12.57

Haploinsufficiency Scores

pHI: 0.340
hipred: N
hipred_score: 0.414
ghis: 0.512

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: N
essential_gene_gene_trap: N
gene_indispensability_pred: N
gene_indispensability_score: 0.261

Gene Damage Prediction

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

Mouse Genome Informatics

Gene name: Lpin2
Phenotype: reproductive system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); hematopoietic 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); liver/biliary system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); embryo phenotype; immune system phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); growth/size/body region phenotype; homeostasis/metabolism phenotype;

Gene ontology

Biological process: lipid metabolic process;phosphatidylethanolamine biosynthetic process;phosphatidylcholine biosynthetic process;fatty acid catabolic process;dephosphorylation;triglyceride biosynthetic process;cellular response to insulin stimulus;positive regulation of transcription by RNA polymerase II
Cellular component: nucleus;endoplasmic reticulum membrane;cytosol
Molecular function: transcription coactivator activity;phosphatidate phosphatase activity