ACE
angiotensin I converting enzyme, the group of CD molecules
Basic information
Region (hg38): 17:63477060-63498380
Previous symbols: [ "DCP1" ]
Links
Phenotypes
GenCC
Source:
- 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:
| 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
- not provided (326 variants)
- Renal tubular dysgenesis (194 variants)
- Inborn genetic diseases (46 variants)
- Intracerebral hemorrhage;Microvascular complications of diabetes, susceptibility to, 3;Renal tubular dysgenesis of genetic origin (33 variants)
- not specified (13 variants)
- ACE-related condition (11 variants)
- Microvascular complications of diabetes, susceptibility to, 3;Renal tubular dysgenesis of genetic origin;Intracerebral hemorrhage (8 variants)
- Renal tubular dysgenesis of genetic origin;Microvascular complications of diabetes, susceptibility to, 3;Intracerebral hemorrhage (5 variants)
- Renal tubular dysgenesis of genetic origin;Intracerebral hemorrhage;Microvascular complications of diabetes, susceptibility to, 3 (5 variants)
- Microvascular complications of diabetes, susceptibility to, 3;Intracerebral hemorrhage;Renal tubular dysgenesis of genetic origin (5 variants)
- Renal tubular dysgenesis of genetic origin (5 variants)
- Microcephaly (2 variants)
- Hereditary angioedema with normal C1Inh (2 variants)
- Intracerebral hemorrhage;Renal tubular dysgenesis of genetic origin;Microvascular complications of diabetes, susceptibility to, 3 (2 variants)
- Risk of requirement of invasive mechanical ventilation in patients with severe COVID-19 (1 variants)
- Intracerebral hemorrhage (1 variants)
- Congenital anomaly of kidney and urinary tract (1 variants)
- Myocardial infarction, susceptibility to (1 variants)
- ACE-Related Disorders (1 variants)
- captopril response - Efficacy (1 variants)
- Renal dysplasia, cystic, susceptibility to;Anhydramnios (1 variants)
- Abnormality of prenatal development or birth (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 | 18 | 64 | 13 | 95 | ||
| missense | 169 | 20 | 10 | 200 | ||
| nonsense | 12 | |||||
| start loss | 3 | |||||
| frameshift | 15 | |||||
| inframe indel | 5 | |||||
| splice donor/acceptor (+/-2bp) | 4 | |||||
| splice region ? | 1 | 12 | 5 | 5 | 23 | |
| non coding ? | 18 | 21 | 42 | 81 | ||
| Total | 19 | 16 | 209 | 106 | 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) | ||
| 17-63477109-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 • Hemorrhage, intracerebral, susceptibility to;Microvascular complications of diabetes, susceptibility to, 3;Renal tubular dysgenesis of genetic origin | 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 | Hemorrhage, intracerebral, susceptibility to;Renal tubular dysgenesis of genetic origin;Microvascular complications of diabetes, susceptibility to, 3 | Pathogenic/Likely pathogenic (Mar 30, 2022) | ||
| 17-63477128-CTGCTGCTGCCGCTGCCGCTGCTGT-C | Microvascular complications of diabetes, susceptibility to, 3;Renal tubular dysgenesis of genetic origin;Hemorrhage, intracerebral, susceptibility to • Renal tubular dysgenesis | Conflicting classifications of pathogenicity (Nov 11, 2023) | ||
| 17-63477132-TGCTGCC-T | Microvascular complications of diabetes, susceptibility to, 3;Hemorrhage, intracerebral, susceptibility to;Renal tubular dysgenesis of genetic origin | 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 | 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) | |||
| 17-63477176-C-T | Likely benign (Oct 07, 2022) |
GnomAD
Source:
| 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:
- 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