ACE2

protein-coding

angiotensin converting enzyme 2

Gene summary

The protein encoded by this gene belongs to the angiotensin-converting enzyme family of dipeptidyl carboxydipeptidases and has considerable homology to human angiotensin 1 converting enzyme. This secreted protein catalyzes the cleavage of angiotensin I into angiotensin 1-9, and angiotensin II into the vasodilator angiotensin 1-7. ACE2 is known to be expressed in various human organs, and its organ- and cell-specific expression suggests that it may play a role in the regulation of cardiovascular and renal function, as well as fertility. In addition, the encoded protein is a functional receptor for the spike glycoprotein of the human coronavirus HCoV-NL63 and the human severe acute respiratory syndrome coronaviruses, SARS-CoV and SARS-CoV-2, the latter is the causative agent of coronavirus disease-2019 (COVID-19). Multiple splice variants have been found for this gene and the dACE2 (or MIRb-ACE2) splice variant has been found to be interferon inducible. [provided by RefSeq, Nov 2020]

MANE transcript

NM_001371415.1

Inheritance

—

ClinVar variants

U:132B:5

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.1

Max pathogenic AF

—

Genomic locus

chrX:15,494,566-15,607,236

External References & Databases

Ensembl (ENSG00000130234)

Transcript & Mutation Effects

hg38 • Region Span ~112.7 kb

Loading mutation effect viewer...

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 ACE2 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 16

not providedTotal: 9

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001371415.1. 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			19 clinvar	2 clinvar	1 clinvar	22
missense			77 clinvar	2 clinvar		79
nonsense			14 clinvar			14
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)			21 clinvar			21
Total	0	0	132	4	1	137

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 34 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001371415.1	RefSeq	NP_001358344.1	18	MANE Select
ENST00000252519.8	Ensembl	ENSP00000252519.3	18	MANE Select
NM_001386259.1	RefSeq	NP_001373188.1	18	Standard
NM_001386260.1	RefSeq	NP_001373189.1	15	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Agents Acting on the Renin-Angiotensin System Pathway, Pharmacodynamics
Renin-angiotensin system - Homo sapiens (human)
Protein digestion and absorption - Homo sapiens (human)
ACE Inhibitor Pathway, Pharmacodynamics
ACE Inhibitor Pathway

Biological Process

regulation of cytokine production
angiotensin maturation
angiotensin-mediated drinking behavior
regulation of systemic arterial blood pressure by renin-angiotensin
tryptophan transport

Molecular Function

virus receptor activity
endopeptidase activity
carboxypeptidase activity
metallocarboxypeptidase activity
protein binding

Cellular Component

extracellular region
extracellular space
cytoplasm
plasma membrane
cell surface

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000427411
Coding exons: 18
Length: 41116
Individuals with no LoFs: 125627
Homozygous LoFs: 2
Heterozygous LoFs: 6
Defined: 125635
p: 0.0000318

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.25	223	282	0.791	0.0000198	5358
Missense (PolyPhen)		72	101.38	0.71019		1960
Synonymous	1.33	84	101	0.832	0.00000736	1445
Loss of Function	4.66	3	31.0	0.0968	0.00000225	532

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0.00016	0.000099	rare
East Asian	0.00016	0.00011	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000052	0.000035	rare
South Asian	0.000065	0.000033	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Carboxypeptidase which converts angiotensin I to angiotensin 1-9, a peptide of unknown function, and angiotensin II to angiotensin 1-7, a vasodilator. Also able to hydrolyze apelin- 13 and dynorphin-13 with high efficiency. May be an important regulator of heart function. {ECO:0000269|PubMed:10924499, ECO:0000269|PubMed:10969042, ECO:0000269|PubMed:14647384, ECO:0000269|PubMed:24227843}.; FUNCTION: (Microbial infection) Acts as a receptor for Human coronavirus NL63/HCoV-NL63. {ECO:0000269|PubMed:15897467}.;

Recessive Scores

pRec: 0.284

Intolerance Scores

LoFtool: 0.0718
RVIS EVS: 0.89
RVIS percentile EVS: 89.14

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Indispensability pred.: N
Indispensability score: 0.0433

Gene Damage Prediction

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