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

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 (8 variants)
• not provided (5 variants)
• Congenital generalized lipodystrophy (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.

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			9	19	1	29
missense	2	1	44	3		50
nonsense	2	1				3
start loss						0
frameshift	4	3				7
inframe indel			1	1		2
splice donor/acceptor (+/-2bp)	1	4				5
splice region			2	5	1	8
non coding			25	11	10	46
Total	9	9	79	34	11

Highest pathogenic variant AF is 0.000407

Variants in AGPAT2

This is a list of pathogenic ClinVar variants found in the AGPAT2 region.

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

Position	Type	Phenotype	Significance	ClinVar
9-136673180-G-A		Congenital generalized lipodystrophy type 1	Uncertain significance (Jan 13, 2018)
9-136673217-G-A		Congenital generalized lipodystrophy type 1	Benign (Jan 13, 2018)
9-136673235-G-A		Congenital generalized lipodystrophy type 1	Benign (Jan 12, 2018)
9-136673238-T-G		Congenital generalized lipodystrophy type 1	Uncertain significance (Jan 12, 2018)
9-136673240-C-T		Congenital generalized lipodystrophy type 1	Uncertain significance (Jan 13, 2018)
9-136673242-G-A		Congenital generalized lipodystrophy type 1	Likely benign (Jan 12, 2018)
9-136673264-G-A		Congenital generalized lipodystrophy type 1	Uncertain significance (Jan 13, 2018)
9-136673310-G-C		Congenital generalized lipodystrophy type 1	Benign (Jan 12, 2018)
9-136673334-C-T		Congenital generalized lipodystrophy type 1	Uncertain significance (Jan 12, 2018)
9-136673341-G-A		Congenital generalized lipodystrophy type 1	Uncertain significance (Apr 27, 2017)
9-136673370-G-A		Congenital generalized lipodystrophy type 1	Uncertain significance (Jan 13, 2018)
9-136673398-G-A		Congenital generalized lipodystrophy type 1	Uncertain significance (Jan 13, 2018)
9-136673475-G-A		Congenital generalized lipodystrophy type 1	Uncertain significance (Jan 12, 2018)
9-136673513-C-T		Congenital generalized lipodystrophy type 1	Benign (Jan 12, 2018)
9-136673516-G-A		Congenital generalized lipodystrophy type 1	Likely benign (Jan 13, 2018)
9-136673520-G-A		Congenital generalized lipodystrophy type 1	Uncertain significance (Jan 13, 2018)
9-136673522-G-A		Congenital generalized lipodystrophy type 1	Likely benign (Jan 13, 2018)
9-136673535-C-T		Congenital generalized lipodystrophy type 1	Uncertain significance (Jan 13, 2018)
9-136673534-T-TCGAGCC		Congenital generalized lipodystrophy	Benign/Likely benign (Jun 18, 2021)
9-136673541-C-T		Congenital generalized lipodystrophy type 1	Uncertain significance (Jan 13, 2018)
9-136673551-C-G		Congenital generalized lipodystrophy type 1	Uncertain significance (Jan 13, 2018)
9-136673588-G-T		Congenital generalized lipodystrophy type 1	Uncertain significance (Jan 13, 2018)
9-136673595-G-A		Congenital generalized lipodystrophy type 1	Benign (Jul 14, 2021)
9-136673650-G-A		Congenital generalized lipodystrophy type 1	Likely benign (Jan 13, 2018)
9-136673673-G-C		Congenital generalized lipodystrophy type 1	Benign/Likely benign (Aug 24, 2021)

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
1.24e-7	0.207	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

Haploinsufficiency Scores

• pHI: 0.102
• hipred: N
• hipred_score: 0.346
• ghis: 0.422

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

Mouse Genome Informatics

• Gene name: Agpat2
• Phenotype: homeostasis/metabolism phenotype; craniofacial phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); endocrine/exocrine gland phenotype; 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; skeleton phenotype; renal/urinary system phenotype; immune system phenotype; limbs/digits/tail phenotype; digestive/alimentary 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; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); liver/biliary system phenotype

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