APLNR

protein-coding

apelin receptor

Gene summary

This gene encodes a member of the G protein-coupled receptor gene family. The encoded protein is related to the angiotensin receptor, but is actually an apelin receptor that inhibits adenylate cyclase activity and plays a counter-regulatory role against the pressure action of angiotensin II by exerting hypertensive effect. It functions in the cardiovascular and central nervous systems, in glucose metabolism, in embryonic and tumor angiogenesis and as a human immunodeficiency virus (HIV-1) coreceptor. Two transcript variants resulting from alternative splicing have been identified. [provided by RefSeq, Jul 2009]

Previous symbols:

AGTRL1

MANE transcript

NM_005161.6

Inheritance

—

ClinVar variants

U:62B:4

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.11

Max pathogenic AF

—

Genomic locus

chr11:57,233,577-57,237,250

External References & Databases

Ensembl (ENSG00000134817)

Transcript & Mutation Effects

hg38 • Region Span ~3.7 kb

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GenCC 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 APLNR variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 62

not providedTotal: 4

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_005161.6. 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				2 clinvar		2
missense			62 clinvar	1 clinvar	1 clinvar	64
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	62	3	1	66

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 3 of 3 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_005161.6	RefSeq	NP_005152.1	1	MANE Select
ENST00000606794.2	Ensembl	ENSP00000475344.1	1	MANE Select
ENST00000257254.3	Ensembl	ENSP00000257254.3	1	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
aplnra	Danio rerio	Structure: thoracic duct Quality: has fewer parts of type abnormal

Gene / Model

Organism

Observed Phenotype

aplnra

Danio rerio

Structure: thoracic duct

Quality: has fewer parts of type

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Apelin signaling pathway - Homo sapiens (human)
Neuroactive ligand-receptor interaction - Homo sapiens (human)
GPCRs, Class A Rhodopsin-like
Signaling by GPCR
Signal Transduction

Biological Process

angiogenesis
vasculogenesis
G protein-coupled receptor signaling pathway
gastrulation
heart development

Molecular Function

G protein-coupled receptor activity
signaling receptor activity

Cellular Component

plasma membrane
integral component of plasma membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000606794
Coding exons: 1
Length: 3659
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	0.802	216	252	0.858	0.0000163	2487
Missense (PolyPhen)		76	99.308	0.7653		967
Synonymous	-2.27	137	107	1.28	0.00000717	788
Loss of Function	2.56	1	9.50	0.105	4.04e-7	108

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: dbNSFP

Function: FUNCTION: Receptor for apelin receptor early endogenous ligand (APELA) and apelin (APLN) hormones coupled to G proteins that inhibit adenylate cyclase activity (PubMed:11090199, PubMed:25639753, PubMed:28137936). Plays a key role in early development such as gastrulation, blood vessels formation and heart morphogenesis by acting as a receptor for APELA hormone (By similarity). May promote angioblast migration toward the embryonic midline, i.e. the position of the future vessel formation, during vasculogenesis (By similarity). Promotes sinus venosus (SV)- derived endothelial cells migration into the developing heart to promote coronary blood vessel development (By similarity). Plays also a role in various processes in adults such as regulation of blood vessel formation, blood pressure, heart contractility and heart failure (PubMed:25639753, PubMed:28137936). {ECO:0000250|UniProtKB:P79960, ECO:0000250|UniProtKB:Q7SZP9, ECO:0000250|UniProtKB:Q9WV08, ECO:0000269|PubMed:11090199, ECO:0000269|PubMed:25639753, ECO:0000269|PubMed:28137936}.;

Recessive Scores

pRec: 0.191

Intolerance Scores

RVIS EVS: -0.62
RVIS percentile EVS: 17.31

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.146

Gene Damage Prediction

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