APOA5

apolipoprotein A5, the group of Apolipoproteins

Basic information

Region (hg38): 11:116789366-116792420

Links

ENSG00000110243 ∙ NCBI:116519 ∙ OMIM:606368 ∙ HGNC:17288 ∙ Uniprot:Q6Q788 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• hyperlipoproteinemia type V (Strong), mode of inheritance: AD
• hyperlipoproteinemia type V (Strong), mode of inheritance: Semidominant
• hyperlipoproteinemia type V (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Hyperlipoproteinemia, type V	AD/AR	Cardiovascular	Individuals may have severe hypertriglyceridemia, and interventions related to factors that contribute to cardiovascular sequelae (including through diet and exercise control) may be beneficial, though individuals may develop refractory hypertriglyceridemia	Cardiovascular; Gastrointestinal	16143024; 16200213; 19410254; 19447388; 21993410; 22239554
Variants in additional genes may contribute to phenotypic manifestations

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the APOA5 gene.

• Cardiovascular phenotype (102 variants)
• not provided (94 variants)
• not specified (20 variants)
• Inborn genetic diseases (10 variants)
• Hypertriglyceridemia 1 (6 variants)
• Familial type 5 hyperlipoproteinemia (6 variants)
• Hypertriglyceridemia 1;Familial type 5 hyperlipoproteinemia (2 variants)
• Familial type 5 hyperlipoproteinemia;Hypertriglyceridemia 1 (2 variants)
• Hyperlipoproteinemia, type I (1 variants)
• Hypertriglyceridemia (1 variants)
• APOA5-related condition (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the APOA5 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	42	2	45
missense			84	8	2	94
nonsense	1	5	1			7
start loss						0
frameshift	2	3	2			7
inframe indel			3			3
splice donor/acceptor (+/-2bp)						0
splice region			5	1		6
non coding			1	6	9	16
Total	3	8	92	56	13

Highest pathogenic variant AF is 0.0000526

Variants in APOA5

This is a list of pathogenic ClinVar variants found in the APOA5 region.

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

Position	Type	Phenotype	Significance	ClinVar
11-116789838-C-CCT			Benign (Mar 25, 2019)
11-116789956-G-A			Likely benign (Dec 08, 2020)
11-116789970-G-A		Hypertriglyceridemia 1	Benign (Aug 30, 2018)
11-116790097-G-A			Benign (Sep 17, 2018)
11-116790111-C-T		not specified	Uncertain significance (Aug 07, 2023)
11-116790116-G-A		not specified	Benign (Aug 07, 2023)
11-116790134-G-A			Likely benign (Nov 30, 2023)
11-116790148-T-G		Familial type 5 hyperlipoproteinemia;Hypertriglyceridemia 1	Uncertain significance (Aug 30, 2021)
11-116790163-G-A		Cardiovascular phenotype	Uncertain significance (Nov 26, 2023)
11-116790185-C-T		Cardiovascular phenotype	Uncertain significance (Jan 16, 2024)
11-116790190-G-T		not specified	Uncertain significance (May 04, 2022)
11-116790194-A-G		Cardiovascular phenotype	Likely benign (Jan 26, 2022)
11-116790201-C-G			Uncertain significance (Mar 01, 2023)
11-116790201-C-T		not specified	Uncertain significance (May 04, 2022)
11-116790204-G-A			Uncertain significance (Jan 25, 2023)
11-116790205-C-T		Cardiovascular phenotype	Uncertain significance (Aug 22, 2021)
11-116790227-G-T		Cardiovascular phenotype	Likely benign (Jul 13, 2023)
11-116790233-G-C		Cardiovascular phenotype	Uncertain significance (Dec 27, 2023)
11-116790235-CTGTT-C		Familial type 5 hyperlipoproteinemia • Cardiovascular phenotype • Hypertriglyceridemia 1	Pathogenic/Likely pathogenic (Dec 19, 2023)
11-116790250-C-G			Uncertain significance (Jun 22, 2022)
11-116790254-G-A		Cardiovascular phenotype	Benign (Dec 22, 2023)
11-116790256-C-T			Uncertain significance (Apr 13, 2022)
11-116790261-G-A		Cardiovascular phenotype	Uncertain significance (Sep 28, 2023)
11-116790267-T-A		Cardiovascular phenotype	Benign/Likely benign (Oct 27, 2022)
11-116790275-T-G			Likely benign (Jan 13, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
APOA5	protein_coding	protein_coding	ENST00000542499	3	3054

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
5.58e-10	0.0656	125654	0	86	125740	0.000342

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.861	200	237	0.843	0.0000168	2370
Missense in Polyphen		64	79.33	0.80676		812
Synonymous	1.65	81	102	0.792	0.00000764	734
Loss of Function	-0.102	14	13.6	1.03	6.90e-7	130

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000886	0.000865
Ashkenazi Jewish	0.0000994	0.0000992
East Asian	0.000274	0.000272
Finnish	0.000186	0.000185
European (Non-Finnish)	0.000365	0.000360
Middle Eastern	0.000274	0.000272
South Asian	0.000327	0.000327
Other	0.000491	0.000489

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Minor apolipoprotein mainly associated with HDL and to a lesser extent with VLDL. May also be associated with chylomicrons. Important determinant of plasma triglyceride (TG) levels by both being a potent stimulator of apo-CII lipoprotein lipase (LPL) TG hydrolysis and a inhibitor of the hepatic VLDL-TG production rate (without affecting the VLDL-apoB production rate) (By similarity). Activates poorly lecithin:cholesterol acyltransferase (LCAT) and does not enhance efflux of cholesterol from macrophages. {ECO:0000250, ECO:0000269|PubMed:11588264, ECO:0000269|PubMed:12899628, ECO:0000269|PubMed:15528295}.
• Disease: DISEASE: Hypertriglyceridemia, familial (FHTR) [MIM:145750]: A common inherited disorder in which the concentration of very low density lipoprotein (VLDL) is elevated in the plasma. This leads to increased risk of heart disease, obesity, and pancreatitis. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.; DISEASE: Hyperlipoproteinemia 5 (HLPP5) [MIM:144650]: Characterized by increased amounts of chylomicrons and very low density lipoprotein (VLDL) and decreased low density lipoprotein (LDL) and high density lipoprotein (HDL) in the plasma after a fast. Numerous conditions cause this phenotype, including insulin- dependent diabetes mellitus, contraceptive steroids, alcohol abuse, and glycogen storage disease type 1A (GSD1A). {ECO:0000269|PubMed:16200213}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: PPAR signaling pathway - Homo sapiens (human);Statin Pathway, Pharmacodynamics;Regulation of lipid metabolism by Peroxisome proliferator-activated receptor alpha (PPARalpha);PPAR Alpha Pathway;Nuclear Receptors Meta-Pathway;PPAR signaling pathway;Plasma lipoprotein assembly, remodeling, and clearance;Statin Pathway;Chylomicron remodeling;Post-translational protein phosphorylation;Post-translational protein modification;Metabolism of proteins;Transport of small molecules;Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs);Plasma lipoprotein assembly, remodeling, and clearance;Plasma lipoprotein remodeling (Consensus)

Recessive Scores

• pRec: 0.357

Intolerance Scores

• loftool: 0.927
• rvis_EVS: 0.42
• rvis_percentile_EVS: 77.06

Haploinsufficiency Scores

• pHI: 0.274
• hipred: N
• hipred_score: 0.238
• ghis: 0.408

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.304

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Apoa5
• Phenotype: homeostasis/metabolism phenotype; normal phenotype

Gene ontology

• Biological process: triglyceride metabolic process;cholesterol biosynthetic process;lipid transport;positive regulation of cholesterol esterification;positive regulation of triglyceride catabolic process;positive regulation of very-low-density lipoprotein particle remodeling;regulation of lipid metabolic process;triglyceride catabolic process;regulation of intestinal cholesterol absorption;regulation of cholesterol transport;cholesterol efflux;phospholipid efflux;very-low-density lipoprotein particle remodeling;high-density lipoprotein particle assembly;lipoprotein metabolic process;tissue regeneration;cholesterol homeostasis;post-translational protein modification;reverse cholesterol transport;cellular protein metabolic process;positive regulation of fatty acid biosynthetic process;phosphatidylcholine metabolic process;positive regulation of lipid biosynthetic process;positive regulation of receptor-mediated endocytosis;positive regulation of lipid catabolic process;positive regulation of lipoprotein lipase activity;acylglycerol homeostasis;triglyceride homeostasis
• Cellular component: extracellular region;extracellular space;endoplasmic reticulum lumen;very-low-density lipoprotein particle;low-density lipoprotein particle;high-density lipoprotein particle;chylomicron
• Molecular function: phospholipid binding;enzyme activator activity;heparin binding;lipid binding;cholesterol binding;cholesterol transporter activity;enzyme binding;phosphatidylcholine binding;lipase binding;low-density lipoprotein particle receptor binding;phosphatidylcholine-sterol O-acyltransferase activator activity;lipase activator activity;lipoprotein lipase activator activity;lipoprotein particle receptor binding