APOA4

apolipoprotein A4, the group of Apolipoproteins

Basic information

Region (hg38): 11:116820700-116823304

Links

ENSG00000110244 ∙ NCBI:337 ∙ OMIM:107690 ∙ HGNC:602 ∙ Uniprot:P06727 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the APOA4 gene.

• not_provided (102 variants)
• not_specified (49 variants)
• APOA4-related_disorder (9 variants)
• Tubulointerstitial_kidney_disease,_autosomal_dominant_6 (2 variants)
• APOLIPOPROTEIN_A-IV_RARE_VARIANT,_APOA4*0 (1 variants)
• APOLIPOPROTEIN_A-IV_RARE_VARIANT,_APOA4*3 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the APOA4 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000000482.4. 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				20	7	27
missense	2		90	12	4	108
nonsense			2			2
start loss						0
frameshift			1			1
splice donor/acceptor (+/-2bp)			1			1
Total	2	0	94	32	11

Highest pathogenic variant AF is 0.00000205254

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
APOA4	protein_coding	protein_coding	ENST00000357780	3	2604

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00000545	0.685	125699	0	49	125748	0.000195

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-1.21	286	234	1.22	0.0000166	2581
Missense in Polyphen		59	50.834	1.1606		686
Synonymous	-0.729	116	106	1.09	0.00000788	786
Loss of Function	1.04	10	14.3	0.702	8.01e-7	146

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000497	0.000485
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000544	0.0000544
Finnish	0.000508	0.000508
European (Non-Finnish)	0.000222	0.000220
Middle Eastern	0.0000544	0.0000544
South Asian	0.0000327	0.0000327
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: May have a role in chylomicrons and VLDL secretion and catabolism. Required for efficient activation of lipoprotein lipase by ApoC-II; potent activator of LCAT. Apoa-IV is a major component of HDL and chylomicrons.
• Pathway: Fat digestion and absorption - Homo sapiens (human);Vitamin digestion and absorption - Homo sapiens (human);Cholesterol metabolism - Homo sapiens (human);Statin Pathway, Pharmacodynamics;Plasma lipoprotein assembly, remodeling, and clearance;Statin Pathway;Signaling by GPCR;Signal Transduction;Metabolism of fat-soluble vitamins;Chylomicron assembly;Plasma lipoprotein assembly;Chylomicron remodeling;Metabolism;Transport of small molecules;Metabolism of vitamins and cofactors;Plasma lipoprotein assembly, remodeling, and clearance;Retinoid metabolism and transport;G alpha (i) signalling events;Plasma lipoprotein remodeling;Visual phototransduction;GPCR downstream signalling (Consensus)

Recessive Scores

• pRec: 0.0969

Intolerance Scores

• loftool: 0.722
• rvis_EVS: 0.36
• rvis_percentile_EVS: 74.66

Haploinsufficiency Scores

• pHI: 0.0950
• hipred: N
• hipred_score: 0.146
• ghis: 0.437

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.834

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Apoa4
• 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); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); immune system phenotype; digestive/alimentary 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); homeostasis/metabolism phenotype

Gene ontology

• Biological process: retinoid metabolic process;innate immune response in mucosa;cholesterol biosynthetic process;lipid transport;response to lipid hydroperoxide;leukocyte cell-cell adhesion;cholesterol metabolic process;positive regulation of cholesterol esterification;positive regulation of triglyceride catabolic process;lipid catabolic process;removal of superoxide radicals;triglyceride catabolic process;regulation of intestinal cholesterol absorption;regulation of cholesterol transport;cholesterol efflux;phospholipid efflux;chylomicron remodeling;very-low-density lipoprotein particle remodeling;high-density lipoprotein particle remodeling;chylomicron assembly;high-density lipoprotein particle assembly;negative regulation of plasma lipoprotein oxidation;response to stilbenoid;lipoprotein metabolic process;cholesterol homeostasis;hydrogen peroxide catabolic process;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 lipoprotein lipase activity;lipid homeostasis;protein-lipid complex assembly;triglyceride homeostasis
• Cellular component: extracellular region;extracellular space;early endosome;endoplasmic reticulum lumen;cytosol;cell surface;very-low-density lipoprotein particle;high-density lipoprotein particle;chylomicron;collagen-containing extracellular matrix;extracellular exosome;blood microparticle
• Molecular function: lipid transporter activity;copper ion binding;protein binding;phospholipid binding;lipid binding;cholesterol binding;antioxidant activity;cholesterol transporter activity;phosphatidylcholine binding;identical protein binding;protein homodimerization activity;phosphatidylcholine-sterol O-acyltransferase activator activity