ANGPTL8
protein-codingangiopoietin like 8, the group of Angiopoietin like family
Gene summary
Predicted to enable hormone activity. Involved in regulation of lipid metabolic process and triglyceride homeostasis. Acts upstream of or within positive regulation of protein processing and regulation of lipoprotein metabolic process. Located in extracellular region. [provided by Alliance of Genome Resources, Jul 2025]
Previous symbols:
- C19orf80
MANE transcript
NM_018687.7
Inheritance
AD
ClinVar variants
U:4B:1
Top phenotype
Inborn genetic diseases
gnomAD constraint
pLI —, LoF o/e 1.61
Max pathogenic AF
—
Genomic locus
chr19:11,237,502-11,241,943
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~4.4 kbLoading mutation effect viewer...
GenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
coronary artery disorderLIMITED
Inheritance Pattern: AD
Disease ID:MONDO:0005010
Submitter: PanelApp Australia
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to ANGPTL8 variants in ClinVar
not specifiedTotal: 3
Inborn genetic diseasesTotal: 1
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_018687.7. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 0 | |||||
| missense | 4 | 4 | ||||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 4 | 1 | 0 | 5 |
Loading ClinVar variants...
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
Showing 4 of 10 transcripts
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_061157.3 | 4 | MANE Select | |
| Ensembl | ENSP00000252453.7 | 4 | MANE Select | |
| Ensembl | ENSP00000465378.1 | 3 | Standard | |
| Ensembl | ENSP00000464941.1 | 3 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- 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
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
Molecular Function
- hormone activity
- protein binding
Cellular Component
- extracellular region
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000252453
- Coding exons
- 4
- Length
- 4442
- Individuals with no LoFs
- 124502
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 21
- Defined
- 124523
- p
- 0.0000843
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.04 | 88 | 120 | 0.733 | 0.00000784 | 1213 |
| Missense (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 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00038 | 0.00033 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000019 | 0.000018 | rare |
| South Asian | 0.00040 | 0.00036 | rare |
| Other | 0.00037 | 0.00033 | rare |
dbNSFP Gene Annotations
Source:
- 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}.;
Intolerance Scores
- RVIS EVS
- 0.66
- RVIS percentile EVS
- 84.35
Essentials
- Essential (gene trap)
- N