ACE2

Chr X

angiotensin converting enzyme 2

NCBI Gene: 59272 ENSG00000130234 UniProt: Q9BYF1 OMIM: 300335

This enzyme cleaves angiotensin peptides to regulate cardiovascular homeostasis and also traffics the neutral amino acid transporter SLC6A19 to intestinal epithelial cell membranes. Mutations cause X-linked intellectual disability, seizures, and failure to thrive, typically presenting in infancy or early childhood. The gene is highly constrained against loss-of-function variants and shows X-linked inheritance.

OMIM ResearchSummary from RefSeq, UniProt

Essential counter-regulatory carboxypeptidase of the renin-angiotensin hormone system that is a critical regulator of blood volume, systemic vascular resistance, and thus cardiovascular homeostasis (PubMed:27217402). Converts angiotensin I to angiotensin 1-9, a nine-amino acid peptide with anti-hypertrophic effects in cardiomyocytes, and angiotensin II to angiotensin 1-7, which then acts as a beneficial vasodilator and anti-proliferation agent, counterbalancing the actions of the vasoconstrictor angiotensin II (PubMed:10924499, PubMed:10969042, PubMed:11815627, PubMed:14504186, PubMed:19021774). Also removes the C-terminal residue from three other vasoactive peptides, neurotensin, kinetensin, and des-Arg bradykinin, but is not active on bradykinin (PubMed:10969042, PubMed:11815627). Also cleaves other biological peptides, such as apelins (apelin-13, [Pyr1]apelin-13, apelin-17, apelin-36), casomorphins (beta-casomorphin-7, neocasomorphin) and dynorphin A with high efficiency (PubMed:11815627, PubMed:27217402, PubMed:28293165). In addition, ACE2 C-terminus is homologous to collectrin and is responsible for the trafficking of the neutral amino acid transporter SL6A19 to the plasma membrane of gut epithelial cells via direct interaction, regulating its expression on the cell surface and its catalytic activity (PubMed:18424768, PubMed:19185582)

OMIM 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

1431

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.25

LOEUF· LoF intol.

—

Mechanism

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — X-linked: males carry a single copy

LoF Constraint?

0.25LOEUF

pLI 0.998

Z-score 4.66

OE 0.10 (0.04–0.25)

Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?

1.25Z-score

OE missense 0.79 (0.71–0.88)

223 obs / 281.8 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.10 (0.04–0.25)

0≤0.351.4

Missense OE?0.79 (0.71–0.88)

0≤0.61.4

Synonymous OE?0.83

0≤1.21.6

LoF obs/exp: 3 / 31.0Missense obs/exp: 223 / 281.8Syn Z: 1.33

Background carrier burden — how many people carry a rare variant somewhere in ACE2?

gnomAD v4 · ~732k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 87

562 rare PASS variants

Rare truncating (LoF)

1 in 2,200

34 rare PASS variants

Rare synonymous (reference)

1 in 390

211 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for ACE2. 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)	~561k	1 in 130	1 in 5,900
South Asian	~36k	1 in 110	≈ 1 in 17,000
Remaining (unassigned)	~31k	1 in 83	≈ 1 in 10,000
European (Finnish)	~27k	1 in 240	1 in 1,600
Admixed American	~23k	1 in 130	none seen
African / African American	~21k	1 in 110	none seen
East Asian	~20k	1 in 160	1 in 2,100
Ashkenazi Jewish	~13k	1 in 790	≈ 1 in 13,000
Middle Eastern	~2,758	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 18 coding exons well covered in gnomAD exomes and genomes.? see exons ↓