APLN
protein-codingapelin, the group of Neuropeptides
Gene summary
This gene encodes a peptide that functions as an endogenous ligand for the G-protein coupled apelin receptor. The encoded preproprotein is proteolytically processed into biologically active C-terminal peptide fragments. These peptide fragments activate different tissue specific signaling pathways that regulate diverse biological functions including fluid homeostasis, cardiovascular function and insulin secretion. This protein also functions as a coreceptor for the human immunodeficiency virus 1. [provided by RefSeq, Feb 2016]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~9.7 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to APLN variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_017413.5. 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 | 12 | 1 | 13 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 12 | 1 | 0 | 13 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_059109.3 | 2 | MANE Select | |
| Ensembl | ENSP00000391800.2 | 2 | MANE Select | |
| Ensembl | ENSP00000535599.1 | 2 | Standard | |
| Ensembl | ENSP00000812590.1 | 2 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| apln | Danio rerio | Structure: lymph vessel endothelium Quality: decreased amount abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Apelin signaling pathway - Homo sapiens (human)
- Signaling by GPCR
- Signal Transduction
- Peptide ligand-binding receptors
- Class A/1 (Rhodopsin-like receptors)
Biological Process
- angiogenesis
- regulation of the force of heart contraction
- immune response
- signal transduction
- G protein-coupled receptor signaling pathway
Molecular Function
- signaling receptor binding
- hormone activity
- apelin receptor binding
- protein homodimerization activity
Cellular Component
- extracellular region
- extracellular space
- perinuclear region of cytoplasm
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000307484
- Coding exons
- 2
- Length
- 9694
- Individuals with no LoFs
- 0
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 0
- Defined
- 0
- p
- 0.00
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.239 | 31 | 27.5 | 1.13 | 0.00000249 | 467 |
| Missense (PolyPhen) | 17 | 13.259 | 1.2821 | 189 | ||
| Synonymous | -0.400 | 13 | 11.3 | 1.15 | 9.04e-7 | 168 |
| Loss of Function | 1.16 | 0 | 1.57 | 0.00 | 1.00e-7 | 32 |
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 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0 | 0.0 | absent |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Endogenous ligand for the apelin receptor (APLNR) (PubMed:10525157). Drives internalization of the apelin receptor (By similarity). Apelin-36 dissociates more hardly than (pyroglu)apelin-13 from APLNR (By similarity). Hormone involved in the regulation of cardiac precursor cell movements during gastrulation and heart morphogenesis (By similarity). Has an inhibitory effect on cytokine production in response to T-cell receptor/CD3 cross-linking; the oral intake of apelin in the colostrum and the milk might therefore modulate immune responses in neonates (By similarity). Plays a role in early coronary blood vessels formation (By similarity). Mediates myocardial contractility in an ERK1/2-dependent manner (By similarity). May also have a role in the central control of body fluid homeostasis by influencing vasopressin release and drinking behavior (By similarity). {ECO:0000250|UniProtKB:Q4TTN8, ECO:0000250|UniProtKB:Q9R0R3, ECO:0000250|UniProtKB:Q9R0R4, ECO:0000269|PubMed:10525157}.;
Recessive Scores
- pRec
- 0.0288
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.00261
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |