ANGPTL4

angiopoietin like 4, the group of Angiopoietin like family|Fibrinogen C domain containing

Basic information

Region (hg38): 19:8363288-8374370

Links

ENSG00000167772 ∙ NCBI:51129 ∙ OMIM:605910 ∙ HGNC:16039 ∙ Uniprot:Q9BY76 ∙ 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 ANGPTL4 gene.

• Inborn genetic diseases (15 variants)
• not provided (8 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ANGPTL4 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	1	2
missense			14	3	1	18
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region					3	3
non coding						0
Total	0	0	14	4	2

Variants in ANGPTL4

This is a list of pathogenic ClinVar variants found in the ANGPTL4 region.

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

Position	Type	Phenotype	Significance	ClinVar
19-8364346-G-A		not specified	Uncertain significance (Oct 06, 2021)
19-8364410-C-A		not specified	Uncertain significance (Dec 28, 2022)
19-8364439-G-A		Plasma triglyceride level quantitative trait locus	association (May 08, 2009)
19-8364441-G-A			Likely benign (May 15, 2018)
19-8364507-C-T		ANGPTL4-related disorder	Benign (Mar 29, 2019)
19-8364522-C-G		ANGPTL4-related disorder	Likely benign (Jul 01, 2019)
19-8364532-C-T		not specified	Uncertain significance (Oct 11, 2023)
19-8366033-A-G		not specified	Uncertain significance (Jan 26, 2022)
19-8366196-TC-T			Benign (May 20, 2018)
19-8366269-C-T		not specified	Uncertain significance (Oct 02, 2023)
19-8366293-C-T		not specified	Uncertain significance (Oct 03, 2022)
19-8366310-C-T		not specified	Uncertain significance (Nov 18, 2022)
19-8369213-C-T			Benign (Jun 12, 2018)
19-8369216-C-T			Benign (May 20, 2018)
19-8369219-G-T		not specified	Uncertain significance (May 27, 2022)
19-8369300-C-T		not specified	Uncertain significance (Aug 05, 2023)
19-8369301-G-A		ANGPTL4-related disorder	Benign (Nov 26, 2019)
19-8369320-A-T		Plasma triglyceride level quantitative trait locus	association (Jan 01, 2009)
19-8371103-T-G		not specified	Uncertain significance (Oct 29, 2021)
19-8371109-C-T		not specified	Uncertain significance (Feb 23, 2023)
19-8371237-C-G		ANGPTL4-related disorder	Likely benign (Apr 09, 2019)
19-8371298-G-A		not specified	Uncertain significance (Jan 04, 2024)
19-8371316-G-A			Benign (Jun 21, 2018)
19-8371354-G-A		not specified	Uncertain significance (Dec 28, 2022)
19-8371360-C-A		not specified	Uncertain significance (Jan 10, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ANGPTL4	protein_coding	protein_coding	ENST00000301455	7	11085

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
2.31e-11	0.134	125636	0	112	125748	0.000445

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.439	227	246	0.921	0.0000151	2610
Missense in Polyphen		98	99.459	0.98533		1127
Synonymous	0.601	98	106	0.926	0.00000628	809
Loss of Function	0.570	18	20.8	0.865	0.00000118	185

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000360	0.000359
Ashkenazi Jewish	0.00120	0.00119
East Asian	0.0000544	0.0000544
Finnish	0.000428	0.000416
European (Non-Finnish)	0.000640	0.000633
Middle Eastern	0.0000544	0.0000544
South Asian	0.000165	0.000163
Other	0.000491	0.000489

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Protein with hypoxia-induced expression in endothelial cells. May act as a regulator of angiogenesis and modulate tumorigenesis. Inhibits proliferation, migration, and tubule formation of endothelial cells and reduces vascular leakage. May exert a protective function on endothelial cells through an endocrine action. It is directly involved in regulating glucose homeostasis, lipid metabolism, and insulin sensitivity. In response to hypoxia, the unprocessed form of the protein accumulates in the subendothelial extracellular matrix (ECM). The matrix-associated and immobilized unprocessed form limits the formation of actin stress fibers and focal contacts in the adhering endothelial cells and inhibits their adhesion. It also decreases motility of endothelial cells and inhibits the sprouting and tube formation (By similarity). {ECO:0000250, ECO:0000269|PubMed:12015030, ECO:0000269|PubMed:14583458}.
• Pathway: Cholesterol metabolism - Homo sapiens (human);PPAR signaling pathway - Homo sapiens (human);Transcriptional regulation of white adipocyte differentiation;Regulation of lipid metabolism by Peroxisome proliferator-activated receptor alpha (PPARalpha);Glucocorticoid Receptor Pathway;Nuclear Receptors Meta-Pathway;PPAR signaling pathway;Transport of small molecules;Assembly of active LPL and LIPC lipase complexes;Plasma lipoprotein assembly, remodeling, and clearance;Plasma lipoprotein remodeling (Consensus)

Intolerance Scores

• loftool: 0.837
• rvis_EVS: 0.11
• rvis_percentile_EVS: 61.91

Haploinsufficiency Scores

• pHI: 0.0674
• hipred: N
• hipred_score: 0.170
• ghis: 0.420

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.382

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Angptl4
• Phenotype: adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); growth/size/body region phenotype; immune system phenotype; homeostasis/metabolism 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); vision/eye 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); digestive/alimentary phenotype

Zebrafish Information Network

• Gene name: angptl4
• Affected structure: endothelial cell
• Phenotype tag: abnormal
• Phenotype quality: increased occurrence

Gene ontology

• Biological process: angiogenesis;response to hypoxia;regulation of lipid metabolic process;cell differentiation;negative regulation of apoptotic process;positive regulation of angiogenesis;negative regulation of lipoprotein lipase activity;protein homooligomerization;triglyceride homeostasis;negative regulation of endothelial cell apoptotic process
• Cellular component: extracellular region;extracellular space;blood microparticle
• Molecular function: enzyme inhibitor activity;protein binding;identical protein binding