ANGPTL8

angiopoietin like 8, the group of Angiopoietin like family

Basic information

Region (hg38): 19:11237502-11241943

Previous symbols: [ "C19orf80" ]

Links

ENSG00000130173 ∙ NCBI:55908 ∙ OMIM:616223 ∙ HGNC:24933 ∙ Uniprot:Q6UXH0 ∙ 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 ANGPTL8 gene.

• not_specified (3 variants)
• Inborn_genetic_diseases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ANGPTL8 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000018687.7. 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						0
missense			3			3
nonsense				1		1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	3	1	0

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ANGPTL8	protein_coding	protein_coding	ENST00000252453	4	4442

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
6.88e-12	0.00504	124502	0	21	124523	0.0000843

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.04	88	120	0.733	0.00000784	1213
Missense in Polyphen		17	28.265	0.60146		353
Synonymous	1.50	38	51.7	0.734	0.00000312	433
Loss of Function	-1.66	14	8.70	1.61	4.42e-7	88

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.000376	0.000334
Finnish	0.00	0.00
European (Non-Finnish)	0.0000195	0.0000177
Middle Eastern	0.000376	0.000334
South Asian	0.000400	0.000360
Other	0.000367	0.000331

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Hormone that acts as a blood lipid regulator by regulating serum triglyceride levels (PubMed:22569073, PubMed:22809513, PubMed:23150577). May be involved in the metabolic transition between fasting and refeeding: required to direct fatty acids to adipose tissue for storage in the fed state (By similarity). {ECO:0000250|UniProtKB:Q8R1L8, ECO:0000269|PubMed:22569073, ECO:0000269|PubMed:22809513, ECO:0000269|PubMed:23150577}.
• Disease: DISEASE: Diabetes mellitus, insulin-dependent (IDDM) [MIM:222100]: A multifactorial disorder of glucose homeostasis that is characterized by susceptibility to ketoacidosis in the absence of insulin therapy. Clinical features are polydipsia, polyphagia and polyuria which result from hyperglycemia-induced osmotic diuresis and secondary thirst. These derangements result in long-term complications that affect the eyes, kidneys, nerves, and blood vessels. {ECO:0000305|PubMed:24078058}. Note=The gene represented in this entry may be involved in disease pathogenesis. Increased protein levels are observed in the serum of patients. This result should however be reinvestigated in light of recent advances that suggest that this protein is not promoting pancreatic beta cell proliferation. {ECO:0000305|PubMed:24078058}.; DISEASE: Diabetes mellitus, non-insulin-dependent (NIDDM) [MIM:125853]: A multifactorial disorder of glucose homeostasis caused by a lack of sensitivity to the body's own insulin. Affected individuals usually have an obese body habitus and manifestations of a metabolic syndrome characterized by diabetes, insulin resistance, hypertension and hypertriglyceridemia. The disease results in long-term complications that affect the eyes, kidneys, nerves, and blood vessels. {ECO:0000305|PubMed:24852694, ECO:0000305|PubMed:24963292, ECO:0000305|PubMed:25024395, ECO:0000305|PubMed:25303484}. Note=The gene represented in this entry may be involved in disease pathogenesis. Increased protein levels are observed in the serum of patients and are associated with insulin resistance (PubMed:25024395, PubMed:25303484, PubMed:24963292, PubMed:24852694). According to another report, protein levels are decreased in the serum of patients (PubMed:25050901). Discrepancies between increased and decreased levels of proteins levels in NIDDM patients may be explained by the use of different kits developed on the market that either use antibodies recognizing the N-terminal or the C-terminal part of the protein (PubMed:25099942). These results should however be reinvestigated in light of recent advances that suggest that this protein is not promoting pancreatic beta cell proliferation. {ECO:0000305|PubMed:24852694, ECO:0000305|PubMed:24963292, ECO:0000305|PubMed:25024395, ECO:0000305|PubMed:25050901, ECO:0000305|PubMed:25099942, ECO:0000305|PubMed:25303484}.
• Pathway: Cholesterol metabolism - Homo sapiens (human);Angiopoietin Like Protein 8 Regulatory 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

• rvis_EVS: 0.66
• rvis_percentile_EVS: 84.35

Haploinsufficiency Scores

• hipred: N
• hipred_score: 0.123
• ghis: 0.396

Essentials

• essential_gene_gene_trap: N

Mouse Genome Informatics

• Gene name: Angptl8
• Phenotype: growth/size/body region phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); homeostasis/metabolism phenotype

Gene ontology

• Biological process: regulation of signaling receptor activity;positive regulation of protein processing;regulation of lipid metabolic process;cellular lipid metabolic process;type B pancreatic cell proliferation;fat cell differentiation;cell maturation;regulation of lipoprotein metabolic process;regulation of lipoprotein lipase activity;triglyceride homeostasis
• Cellular component: extracellular region
• Molecular function: hormone activity;protein binding