LPIN1

lipin 1, the group of MicroRNA protein coding host genes|Lipins

Basic information

Region (hg38): 2:11677595-11827409

Links

ENSG00000134324 ∙ NCBI:23175 ∙ OMIM:605518 ∙ HGNC:13345 ∙ Uniprot:Q14693 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• myoglobinuria, acute recurrent, autosomal recessive (Strong), mode of inheritance: AR
• myoglobinuria, acute recurrent, autosomal recessive (Strong), mode of inheritance: AR
• hereditary recurrent myoglobinuria (Supportive), mode of inheritance: AD
• myoglobinuria, acute recurrent, autosomal recessive (Definitive), mode of inheritance: AR
• myoglobinuria, acute recurrent, autosomal recessive (Strong), mode of inheritance: AR
• myoglobinuria, acute recurrent, autosomal recessive (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Myoglobinuria, acute, recurrent, autosomal recessive	AR	Musculoskeletal; Pharmacogenomic; Renal	Attacks are typically trigerred by illnesses rather than exercise, and avoidance of fasting and prompt treatment of febrile illness may prevent severe sequelae such as renal failure; Anesthesia precautions can be beneficial in order to decrease the risk of malignant hyperthermia	Musculoskeletal; Renal	6851679; 1544519; 18817903

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the LPIN1 gene.

• not provided (20 variants)
• Myoglobinuria, acute recurrent, autosomal recessive (4 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the LPIN1 gene is commonly pathogenic or not.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			1	112	6	119
missense		1	192	4	2	199
nonsense	8	2				10
start loss						0
frameshift	12	2	1			15
inframe indel			1	1		2
splice donor/acceptor (+/-2bp)	1	5	3			9
splice region			9	14	2	25
non coding			45	105	61	211
Total	21	10	243	222	69

Highest pathogenic variant AF is 0.0000591

Variants in LPIN1

This is a list of pathogenic ClinVar variants found in the LPIN1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
2-11677669-C-T		LPIN1-related disorder	Likely benign (Aug 17, 2020)
2-11677686-G-C		not specified • Myoglobinuria, acute recurrent, autosomal recessive	Benign (Aug 19, 2021)
2-11677692-G-A		Myoglobinuria, acute recurrent, autosomal recessive • LPIN1-related disorder	Likely benign (Oct 10, 2023)
2-11677733-G-T		Myoglobinuria, acute recurrent, autosomal recessive	Uncertain significance (Apr 04, 2024)
2-11677857-G-T			Likely benign (Sep 18, 2018)
2-11677893-G-A			Benign (Jun 26, 2018)
2-11677899-T-C			Likely benign (Sep 05, 2018)
2-11677926-G-C			Likely benign (Aug 03, 2018)
2-11678003-G-A			Benign (Jun 26, 2018)
2-11713457-G-T			Benign (Jun 29, 2018)
2-11713459-C-G			Benign (Jul 27, 2018)
2-11713471-A-G			Likely benign (Mar 15, 2019)
2-11713593-G-GT			Likely benign (Nov 21, 2019)
2-11713596-T-C			Benign (Jun 14, 2018)
2-11713629-G-A			Benign (Jun 14, 2018)
2-11713648-T-C			Benign (Jun 16, 2018)
2-11713717-C-T			Likely benign (Sep 11, 2018)
2-11713787-G-A		not specified • Hyperchloremia • LPIN1-related disorder	Benign (Jun 14, 2018)
2-11713837-C-T			Benign (Jul 26, 2018)
2-11713838-G-A		Myoglobinuria, acute recurrent, autosomal recessive	Benign (Aug 19, 2021)
2-11713862-A-T			Benign (Jun 16, 2018)
2-11713886-G-A			Benign (Jun 14, 2018)
2-11713973-T-C			Benign (Jun 16, 2018)
2-11741072-A-C			Benign (Jun 14, 2018)
2-11741294-C-T			Likely benign (Apr 04, 2020)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
LPIN1	protein_coding	protein_coding	ENST00000449576	22	149815

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
6.45e-13	1.00	125688	0	60	125748	0.000239

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.869	499	557	0.896	0.0000314	6397
Missense in Polyphen		169	211.94	0.79738		2406
Synonymous	0.153	230	233	0.987	0.0000153	1883
Loss of Function	3.19	29	54.4	0.533	0.00000292	601

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000721	0.000658
Ashkenazi Jewish	0.00	0.00
East Asian	0.000163	0.000163
Finnish	0.0000465	0.0000462
European (Non-Finnish)	0.000266	0.000264
Middle Eastern	0.000163	0.000163
South Asian	0.000294	0.000294
Other	0.000164	0.000163

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/PPARA to modulate lipid metabolism gene expression (By similarity). Is involved in adipocyte differentiation. May also be involved in mitochondrial fission by converting phosphatidic acid to diacylglycerol (By similarity). {ECO:0000250}.
• Disease: DISEASE: Myoglobinuria, acute recurrent, autosomal recessive (ARARM) [MIM:268200]: Recurrent myoglobinuria is characterized by recurrent attacks of rhabdomyolysis (necrosis or disintegration of skeletal muscle) associated with muscle pain and weakness and followed by excretion of myoglobin in the urine. Renal failure may occasionally occur. {ECO:0000269|PubMed:18817903}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: mTOR signaling pathway - Homo sapiens (human);Glycerolipid metabolism - Homo sapiens (human);Glycerophospholipid metabolism - Homo sapiens (human);Sterol Regulatory Element-Binding Proteins (SREBP) signalling;Adipogenesis;Transcription factor regulation in 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: 0.174

Intolerance Scores

• loftool: 0.359
• rvis_EVS: -1.19
• rvis_percentile_EVS: 5.86

Haploinsufficiency Scores

• pHI: 0.108
• hipred: Y
• hipred_score: 0.706
• ghis: 0.544

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.889

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Lpin1
• Phenotype: liver/biliary system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); embryo 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); 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); 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); skeleton phenotype; homeostasis/metabolism phenotype; endocrine/exocrine gland phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); growth/size/body region phenotype; muscle phenotype

Gene ontology

• Biological process: triglyceride mobilization;phosphatidylethanolamine biosynthetic process;phosphatidylcholine biosynthetic process;mitotic nuclear envelope disassembly;fatty acid catabolic process;dephosphorylation;triglyceride biosynthetic process;animal organ regeneration;cellular response to insulin stimulus;positive regulation of transcription by RNA polymerase II;positive regulation of cold-induced thermogenesis
• Cellular component: nucleus;nuclear envelope;nucleoplasm;cytoplasm;mitochondrial outer membrane;endoplasmic reticulum membrane;cytosol;nuclear membrane
• Molecular function: molecular_function;transcription coactivator activity;phosphatidate phosphatase activity