APLNR

Chr 11

apelin receptor

Also known as: AGTRL1, APJ, APJR, HG11

NCBI Gene: 187 ENSG00000134817 UniProt: P35414

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]

Research

ResearchGenerating clinical summary…

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.50

LOEUF

Multiple*

Mechanism· predicted

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.50LOEUF

pLI 0.789

Z-score 2.56

OE 0.11 (0.04–0.50)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

0.80Z-score

OE missense 0.86 (0.77–0.96)

216 obs / 251.8 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.11 (0.04–0.50)

0≤0.351.4

Missense OE?0.86 (0.77–0.96)

0≤0.61.4

Synonymous OE?1.28

0≤1.21.6

LoF obs/exp: 1 / 9.5Missense obs/exp: 216 / 251.8Syn Z: -2.27

Background carrier burden — how many people carry a rare variant somewhere in APLNR?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 97

508 rare PASS variants

Rare truncating (LoF)

1 in 5,100

44 rare PASS variants

Rare synonymous (reference)

1 in 120

250 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for APLNR. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 100	1 in 5,000
South Asian	~43k	1 in 85	1 in 2,200
Remaining (unassigned)	~30k	1 in 80	≈ 1 in 15,000
European (Finnish)	~27k	1 in 230	none seen
Admixed American	~22k	1 in 95	1 in 2,500
African / African American	~21k	1 in 98	none seen
East Asian	~20k	1 in 100	≈ 1 in 20,000
Ashkenazi Jewish	~13k	1 in 570	≈ 1 in 13,000
Middle Eastern	~2,884	1 in 140	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 1 coding exons well covered in gnomAD exomes and genomes.? see exons ↓