ACE

angiotensin I converting enzyme, the group of CD molecules

Basic information

Region (hg38): 17:63477061-63498380

Previous symbols: [ "DCP1" ]

Links

ENSG00000159640 ∙ NCBI:1636 ∙ OMIM:106180 ∙ HGNC:2707 ∙ Uniprot:P12821 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• intracerebral hemorrhage (Limited), mode of inheritance: Unknown
• renal tubular dysgenesis of genetic origin (Limited), mode of inheritance: AR
• renal tubular dysgenesis of genetic origin (Supportive), mode of inheritance: AR
• renal tubular dysgenesis of genetic origin (Strong), mode of inheritance: AR
• renal tubular dysgenesis of genetic origin (Moderate), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Renal tubular dysgenesis	AR	Endocrine; Renal	Individuals have been described with severe, early-onset renal and related sequelae, and vasopressin has been described as successfully treating refractory hypotension and anuria; Treatment of low aldosterone (with fludrocortisone) has been described as beneficial	Endocrine; Renal	2989970; 1976655; 1328889; 1386652; 8131299; 7909524; 8208911; 8314010; 8675669; 7593601; 9120002; 11076943; 11551873; 11956052; 12666117; 15381116; 15531537; 15277638; 16116425; 22095942; 25899979

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ACE gene.

• not provided (13 variants)
• Renal tubular dysgenesis (6 variants)
• ACE-related disorder (2 variants)
• Hereditary angioedema with normal C1Inh (1 variants)
• Renal tubular dysgenesis of genetic origin (1 variants)
• Renal tubular dysgenesis of genetic origin;Microvascular complications of diabetes, susceptibility to, 3;Hemorrhage, intracerebral, susceptibility to (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ACE gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			13	87	12	112
missense		2	190	22	10	224
nonsense	10	3	1			14
start loss		2	1			3
frameshift	9	6	1			16
inframe indel		3	1	1		5
splice donor/acceptor (+/-2bp)	1	4				5
splice region		1	12	8	5	26
non coding			18	36	43	97
Total	20	20	225	146	65

Highest pathogenic variant AF is 0.0000724

Variants in ACE

This is a list of pathogenic ClinVar variants found in the ACE region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
17-63477096-T-C		Renal tubular dysgenesis of genetic origin	Pathogenic/Likely pathogenic (Apr 05, 2021)
17-63477096-T-G		Renal tubular dysgenesis of genetic origin	Uncertain significance (-)
17-63477097-G-T		Renal tubular dysgenesis of genetic origin	Likely pathogenic (-)
17-63477099-G-A			Uncertain significance (Jul 20, 2022)
17-63477099-G-T		Renal tubular dysgenesis	Benign (Dec 30, 2023)
17-63477105-CCTCGGGCCGCCGGGGGCCGG-C		Renal tubular dysgenesis	Pathogenic/Likely pathogenic (Feb 28, 2018)
17-63477108-CGGGCCGCCGG-C		Renal tubular dysgenesis of genetic origin	Pathogenic (Sep 27, 2024)
17-63477109-G-C			Likely benign (Oct 07, 2022)
17-63477114-G-T		Inborn genetic diseases	Uncertain significance (May 11, 2022)
17-63477116-C-T		Renal tubular dysgenesis • Microvascular complications of diabetes, susceptibility to, 3;Renal tubular dysgenesis of genetic origin;Hemorrhage, intracerebral, susceptibility to	Uncertain significance (May 03, 2022)
17-63477119-G-A		Renal tubular dysgenesis	Uncertain significance (Jan 12, 2018)
17-63477124-G-C			Likely benign (Jan 18, 2023)
17-63477126-GGCTGCT-G		Microvascular complications of diabetes, susceptibility to, 3;Hemorrhage, intracerebral, susceptibility to;Renal tubular dysgenesis of genetic origin	Pathogenic/Likely pathogenic (Mar 30, 2022)
17-63477128-CTGCTGCTGCCGCTGCCGCTGCTGT-C		Renal tubular dysgenesis • Hemorrhage, intracerebral, susceptibility to;Renal tubular dysgenesis of genetic origin;Microvascular complications of diabetes, susceptibility to, 3 • ACE-related disorder	Conflicting classifications of pathogenicity (Nov 11, 2023)
17-63477132-TGCTGCC-T		Renal tubular dysgenesis of genetic origin;Microvascular complications of diabetes, susceptibility to, 3;Hemorrhage, intracerebral, susceptibility to	Uncertain significance (Nov 28, 2022)
17-63477132-T-TGCTGCC		Renal tubular dysgenesis	Benign/Likely benign (Jan 29, 2024)
17-63477139-G-C		Renal tubular dysgenesis • ACE-related disorder	Conflicting classifications of pathogenicity (Jan 18, 2024)
17-63477144-C-G		Inborn genetic diseases	Uncertain significance (Oct 20, 2023)
17-63477146-CTGCTGT-C			Likely pathogenic (Mar 01, 2020)
17-63477151-G-A		ACE-related disorder	Likely benign (Jul 28, 2021)
17-63477152-TTGCTGCTGCCG-T		ACE-related disorder	Pathogenic/Likely pathogenic (Oct 23, 2023)
17-63477161-C-G			Uncertain significance (Mar 31, 2022)
17-63477168-A-T		Inborn genetic diseases	Uncertain significance (Jun 24, 2022)
17-63477172-C-T			Likely benign (Oct 19, 2022)
17-63477174-C-T			Uncertain significance (Nov 17, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ACE	protein_coding	protein_coding	ENST00000290866	25	44784

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.03e-37	0.000143	125471	0	277	125748	0.00110

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.693	797	744	1.07	0.0000490	8524
Missense in Polyphen		312	300.94	1.0368		3489
Synonymous	-3.33	399	323	1.24	0.0000231	2494
Loss of Function	0.978	62	70.9	0.875	0.00000368	735

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00190	0.00190
Ashkenazi Jewish	0.00	0.00
East Asian	0.000871	0.000870
Finnish	0.00292	0.00282
European (Non-Finnish)	0.00103	0.00101
Middle Eastern	0.000871	0.000870
South Asian	0.000786	0.000784
Other	0.00147	0.00147

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Converts angiotensin I to angiotensin II by release of the terminal His-Leu, this results in an increase of the vasoconstrictor activity of angiotensin. Also able to inactivate bradykinin, a potent vasodilator. Has also a glycosidase activity which releases GPI-anchored proteins from the membrane by cleaving the mannose linkage in the GPI moiety.
• Disease: DISEASE: Ischemic stroke (ISCHSTR) [MIM:601367]: A stroke is an acute neurologic event leading to death of neural tissue of the brain and resulting in loss of motor, sensory and/or cognitive function. Ischemic strokes, resulting from vascular occlusion, is considered to be a highly complex disease consisting of a group of heterogeneous disorders with multiple genetic and environmental risk factors. {ECO:0000269|PubMed:15534175}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.; DISEASE: Renal tubular dysgenesis (RTD) [MIM:267430]: Autosomal recessive severe disorder of renal tubular development characterized by persistent fetal anuria and perinatal death, probably due to pulmonary hypoplasia from early-onset oligohydramnios (the Potter phenotype). {ECO:0000269|PubMed:16116425}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Microvascular complications of diabetes 3 (MVCD3) [MIM:612624]: Pathological conditions that develop in numerous tissues and organs as a consequence of diabetes mellitus. They include diabetic retinopathy, diabetic nephropathy leading to end- stage renal disease, and diabetic neuropathy. Diabetic retinopathy remains the major cause of new-onset blindness among diabetic adults. It is characterized by vascular permeability and increased tissue ischemia and angiogenesis. {ECO:0000269|PubMed:10099885}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.; DISEASE: Intracerebral hemorrhage (ICH) [MIM:614519]: A pathological condition characterized by bleeding into one or both cerebral hemispheres including the basal ganglia and the cerebral cortex. It is often associated with hypertension and craniocerebral trauma. Intracerebral bleeding is a common cause of stroke. {ECO:0000269|PubMed:15277638}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.
• Pathway: Agents Acting on the Renin-Angiotensin System Pathway, Pharmacodynamics;Renin-angiotensin system - Homo sapiens (human);Hypertrophic cardiomyopathy (HCM) - Homo sapiens (human);Chagas disease (American trypanosomiasis) - Homo sapiens (human);Renin secretion - Homo sapiens (human);ACE Inhibitor Pathway, Pharmacodynamics;Temocapril Action Pathway;Quinapril Metabolism Pathway;Ramipril Metabolism Pathway;Fosinopril Metabolism Pathway;Moexipril Metabolism Pathway;Cilazapril Metabolism Pathway;Enalapril Metabolism Pathway;Benazepril Metabolism Pathway;Spirapril Metabolism Pathway;Trandolapril Metabolism Pathway;Olmesartan Action Pathway;Losartan Action Pathway;Irbesartan Action Pathway;Forasartan Action Pathway;Valsartan Action Pathway;Telmisartan Action Pathway;Angiotensin Metabolism;Spirapril Action Pathway;Trandolapril Action Pathway;Ramipril Action Pathway;Rescinnamine Action Pathway;Perindopril Action Pathway;Quinapril Action Pathway;Lisinopril Action Pathway;Moexipril Action Pathway;Candesartan Action Pathway;Eprosartan Action Pathway;Fosinopril Action Pathway;Enalapril Action Pathway;Benazepril Action Pathway;Cilazapril Action Pathway;Captopril Action Pathway;Temocapril Metabolism Pathway;ACE Inhibitor Pathway;Peptide hormone metabolism;Metabolism of proteins;Metabolism of Angiotensinogen to Angiotensins (Consensus)

Recessive Scores

• pRec: 0.719

Intolerance Scores

• loftool: 0.822
• rvis_EVS: -0.57
• rvis_percentile_EVS: 18.91

Haploinsufficiency Scores

• pHI: 0.781
• hipred: N
• hipred_score: 0.158
• ghis: 0.458

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.725

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Ace
• Phenotype: growth/size/body region phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); endocrine/exocrine gland phenotype; homeostasis/metabolism phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); reproductive system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); hematopoietic system phenotype; neoplasm; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); immune system phenotype; renal/urinary system phenotype

Gene ontology

• Biological process: kidney development;blood vessel remodeling;angiotensin maturation;regulation of renal output by angiotensin;neutrophil mediated immunity;antigen processing and presentation of peptide antigen via MHC class I;regulation of systemic arterial blood pressure by renin-angiotensin;positive regulation of systemic arterial blood pressure;proteolysis;spermatogenesis;regulation of blood pressure;posttranscriptional regulation of gene expression;negative regulation of gene expression;regulation of smooth muscle cell migration;regulation of vasoconstriction;negative regulation of protein binding;positive regulation of protein binding;mononuclear cell proliferation;hormone catabolic process;peptide catabolic process;positive regulation of blood pressure;amyloid-beta metabolic process;arachidonic acid secretion;heart contraction;regulation of angiotensin metabolic process;hematopoietic stem cell differentiation;positive regulation of protein tyrosine kinase activity;cell proliferation in bone marrow;regulation of blood vessel diameter;positive regulation of peptidyl-tyrosine autophosphorylation;regulation of hematopoietic stem cell proliferation;negative regulation of gap junction assembly;positive regulation of peptidyl-cysteine S-nitrosylation
• Cellular component: extracellular region;extracellular space;lysosome;endosome;plasma membrane;external side of plasma membrane;integral component of membrane;extracellular exosome
• Molecular function: endopeptidase activity;carboxypeptidase activity;drug binding;metallopeptidase activity;exopeptidase activity;dipeptidyl-peptidase activity;tripeptidyl-peptidase activity;peptidyl-dipeptidase activity;zinc ion binding;chloride ion binding;mitogen-activated protein kinase kinase binding;bradykinin receptor binding;mitogen-activated protein kinase binding;metallodipeptidase activity