AGPAT2

1-acylglycerol-3-phosphate O-acyltransferase 2, the group of 1-acylglycerol-3-phosphate O-acyltransferases

Basic information

Region (hg38): 9:136673143-136687457

Previous symbols: [ "BSCL" ]

Links

ENSG00000169692 ∙ NCBI:10555 ∙ OMIM:603100 ∙ HGNC:325 ∙ Uniprot:O15120 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• neonatal diabetes mellitus (Limited), mode of inheritance: AR
• Berardinelli-Seip congenital lipodystrophy (Supportive), mode of inheritance: AR
• congenital generalized lipodystrophy type 1 (Strong), mode of inheritance: AR
• congenital generalized lipodystrophy type 1 (Definitive), mode of inheritance: AR
• lipodystrophy (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Lipodystrophy, congenital generalized, type 1	AR	Cardiovascular; Endocrine; Gastrointestinal	Dietary measures (eg, restriction of fat intake to 20-30% of total dietary energy) and medications (eg, leptin, though availability may be limited) may be beneficial; Surveillance for manifestations, including diabetes and cardiac and hepatic manifestations, may allow early diagnosis and treatment	Cardiovascular; Endocrine; Gastrointestinal; Musculoskeletal	8783769; 11967537; 14602785; 14557463; 15181077; 17671040; 17118991; 19278620; 20301391

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the AGPAT2 gene.

• Congenital_generalized_lipodystrophy_type_1 (143 variants)
• not_provided (107 variants)
• Inborn_genetic_diseases (52 variants)
• not_specified (17 variants)
• Monogenic_diabetes (12 variants)
• AGPAT2-related_disorder (10 variants)
• Congenital_generalized_lipodystrophy (4 variants)
• Prostate_cancer (1 variants)
• Lipodystrophy_-_childhood_onset (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the AGPAT2 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000006412.4. 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			7	38	1	46
missense	4	2	102	16	1	125
nonsense	5	1	3			9
start loss						0
frameshift	6	8	2			16
splice donor/acceptor (+/-2bp)	2	4	5			11
Total	17	15	119	54	2

Highest pathogenic variant AF is 0.000072410265

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
AGPAT2	protein_coding	protein_coding	ENST00000371696	6	14281

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
		125585	0	25	125610	0.0000995

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.722	199	172	1.15	0.0000118	1762
Missense in Polyphen		37	40.555	0.91233		428
Synonymous	-1.51	97	79.8	1.22	0.00000560	588
Loss of Function	0.199	11	11.7	0.937	6.90e-7	115

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000454	0.000453
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000544	0.0000544
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.0000642	0.0000617
Middle Eastern	0.0000544	0.0000544
South Asian	0.000167	0.000163
Other	0.000164	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Converts lysophosphatidic acid (LPA) into phosphatidic acid by incorporating an acyl moiety at the sn-2 position of the glycerol backbone. {ECO:0000269|PubMed:15629135, ECO:0000269|PubMed:21873652, ECO:0000269|PubMed:9242711}.
• Disease: DISEASE: Congenital generalized lipodystrophy 1 (CGL1) [MIM:608594]: An autosomal recessive disorder characterized by a near complete absence of adipose tissue, extreme insulin resistance, hypertriglyceridemia, hepatic steatosis and early onset of diabetes. {ECO:0000269|PubMed:11967537, ECO:0000269|PubMed:15629135}. 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);Fat digestion and absorption - Homo sapiens (human);Phospholipase D signaling pathway - Homo sapiens (human);Adipogenesis;Triacylglyceride Synthesis;Neutrophil degranulation;Metabolism of lipids;Innate Immune System;Immune System;Metabolism;CDP-diacylglycerol biosynthesis;Glycerophospholipid metabolism;triacylglycerol biosynthesis;Glycerophospholipid biosynthesis;Phospholipid metabolism;Synthesis of PA (Consensus)

Recessive Scores

• pRec: 0.160

Intolerance Scores

• loftool: 0.108
• rvis_EVS: 0.2
• rvis_percentile_EVS: 67.3

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.986

Gene Damage Prediction

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

Gene ontology

• Biological process: positive regulation of cytokine production;positive regulation of cytokine-mediated signaling pathway;phospholipid metabolic process;phosphatidic acid biosynthetic process;epidermis development;CDP-diacylglycerol biosynthetic process;response to drug;neutrophil degranulation
• Cellular component: endoplasmic reticulum;endoplasmic reticulum membrane;plasma membrane;integral component of membrane;specific granule membrane
• Molecular function: 1-acylglycerol-3-phosphate O-acyltransferase activity