ACE angiotensin I converting enzyme [Homo sapiens (human)] - Gene

Summary

Official Symbol: ACEprovided by HGNC
Official Full Name: angiotensin I converting enzymeprovided by HGNC
Primary source: HGNC:HGNC:2707
See related: Ensembl:ENSG00000159640 MIM:106180; AllianceGenome:HGNC:2707
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: DCP; ACE1; DCP1; CD143
Summary: This gene encodes an enzyme involved in blood pressure regulation and electrolyte balance. It catalyzes the conversion of angiotensin I into a physiologically active peptide angiotensin II. Angiotensin II is a potent vasopressor and aldosterone-stimulating peptide that controls blood pressure and fluid-electrolyte balance. This angiotensin converting enzyme (ACE) also inactivates the vasodilator protein, bradykinin. Accordingly, the encoded enzyme increases blood pressure and is a drug target of ACE inhibitors, which are often prescribed to reduce blood pressure. This enzyme additionally plays a role in fertility through its ability to cleave and release GPI-anchored membrane proteins in spermatozoa. Many studies have associated the presence or absence of a 287 bp Alu repeat element in this gene with the levels of circulating enzyme. This polymorphism, as well as mutations in this gene, have been implicated in a wide variety of diseases including cardiovascular pathophysiologies, psoriasis, renal disease, stroke, and Alzheimer's disease. Regulation of the homologous ACE2 gene may be involved in progression of disease caused by several human coronaviruses, including SARS-CoV and SARS-CoV-2. Alternative splicing results in multiple transcript variants encoding both somatic (sACE) and male-specific testicular (tACE) isoforms. [provided by RefSeq, Sep 2020]
Annotation information: Note: This gene has been reviewed for its involvement in coronavirus biology, and is relevant for disease process.
Expression: Biased expression in small intestine (RPKM 118.5), duodenum (RPKM 76.7) and 7 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 17q23.3

Exon count:: 26

Annotation release	Status	Assembly	Chr	Location
110	current	GRCh38.p14 (GCF_000001405.40)	17	NC_000017.11 (63477061..63498373)
110	current	T2T-CHM13v2.0 (GCF_009914755.1)	17	NC_060941.1 (64347269..64368872)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	17	NC_000017.10 (61554422..61575734)

Chromosome 17 - NC_000017.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

A Pilot Study on the Prediction of Non-Contact Muscle Injuries Based on ACTN3 R577X and ACE I/D Polymorphisms in Professional Soccer Athletes.
Title: A Pilot Study on the Prediction of Non-Contact Muscle Injuries Based on <i>ACTN3</i> R577X and <i>ACE</i> I/D Polymorphisms in Professional Soccer Athletes.
Associations between ACE Genotypes, +8.5 Gz Tolerance, and Body Composition in F-15 Pilot Candidates.
Title: Associations between ACE Genotypes, +8.5 Gz Tolerance, and Body Composition in F-15 Pilot Candidates.
Performance of Serum Angiotensin-Converting Enzyme in Diagnosing Sarcoidosis and Predicting the Active Status of Sarcoidosis: A Meta-Analysis.
Title: Performance of Serum Angiotensin-Converting Enzyme in Diagnosing Sarcoidosis and Predicting the Active Status of Sarcoidosis: A Meta-Analysis.
Moderate exercise reveals the influence of ACTN3 R577X and ACE I/D polymorphisms on physical performance in non-athlete active subjects.
Title: Moderate exercise reveals the influence of ACTN3 R577X and ACE I/D polymorphisms on physical performance in non-athlete active subjects.
Global distribution of ACE1 (rs4646994) and ACE2 (rs2285666) polymorphisms associated with COVID-19: A systematic review and meta-analysis.
Title: Global distribution of ACE1 (rs4646994) and ACE2 (rs2285666) polymorphisms associated with COVID-19: A systematic review and meta-analysis.
Increased frequency of angiotensin converting enzyme D allele in Chinese Han patients with idiopathic pulmonary fibrosis: A systematic review and meta-analysis.
Title: Increased frequency of angiotensin converting enzyme D allele in Chinese Han patients with idiopathic pulmonary fibrosis: A systematic review and meta-analysis.
Correlation between serum angiotensin-converting enzyme (ACE) levels and intervertebral disc degeneration.
Title: Correlation between serum angiotensin-converting enzyme (ACE) levels and intervertebral disc degeneration.
Angiotensin-converting enzyme gene insertion/deletion polymorphism and hypertension disease.
Title: Angiotensin-converting enzyme gene insertion/deletion polymorphism and hypertension disease.
Tryptophan degradation enzymes and Angiotensin (1-7) expression in human placenta.
Title: Tryptophan degradation enzymes and Angiotensin (1-7) expression in human placenta.
Dysregulation of ACE-1 in Normal Aging and the Early Stages of Alzheimer's Disease.
Title: Dysregulation of ACE-1 in Normal Aging and the Early Stages of Alzheimer's Disease.

Submit: New GeneRIF Correction See all GeneRIFs (1631)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Disorder of cardiovascular system MedGen: C0007222 GeneReviews: Not available	Compare labs
Intracerebral hemorrhage MedGen: C3281105 OMIM: 614519 GeneReviews: Not available	Compare labs
Microvascular complications of diabetes, susceptibility to, 3 MedGen: C2675470 OMIM: 612624 GeneReviews: Not available	Compare labs
Renal tubular dysgenesis of genetic origin MedGen: CN305377 OMIM: 267430 GeneReviews: Not available	Compare labs

EBI GWAS Catalog

Description
A genome-wide assessment of variability in human serum metabolism. EBI GWAS Catalog EBI GWAS CatalogPubMed
A genome-wide association study identifies new loci for ACE activity: potential implications for response to ACE inhibitor. EBI GWAS Catalog EBI GWAS CatalogPubMed
An atlas of genetic influences on human blood metabolites. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genetic determinants influencing human serum metabolome among African Americans. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-Wide Association Study of CSF Levels of 59 Alzheimer's Disease Candidate Proteins: Significant Associations with Proteins Involved in Amyloid Processing and Inflammation. EBI GWAS Catalog EBI GWAS CatalogPubMed
Human metabolic individuality in biomedical and pharmaceutical research. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Protein interactions

Protein	Gene	Interaction	Pubs
Envelope surface glycoprotein gp160, precursor	env	HIV-1 gp160-derived peptide p18 presented by H-2Dd class I major histocompatibility complex molecules is processed by angiotensin-1 converting enzyme (ACE) prior to T cell stimulation by the peptide p18	PubMed

Go to the HIV-1, Human Interaction Database

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

SHGC-57821 (e-PCR)
- UniSTS:19461

SHGC-175 (e-PCR)
- UniSTS:25620

ACE (e-PCR)
- UniSTS:504596

GDB:186915 (e-PCR)
- UniSTS:155520

PMC310924P2 (e-PCR)
- UniSTS:272813

PMC310924P3 (e-PCR)
- UniSTS:272814

G59596 (e-PCR)
- UniSTS:136900

RH17589 (e-PCR)
- UniSTS:50661

GDB:631883 (e-PCR)
- UniSTS:158438

GDB:631894 (e-PCR)
- UniSTS:158439

Homology

Homologs of the ACE gene: The ACE gene is conserved in chimpanzee, Rhesus monkey, dog, cow, mouse, rat, chicken, zebrafish, mosquito, and frog.
Orthologs from Annotation Pipeline: 358 organisms have orthologs with human gene ACE
Orthologs

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables bradykinin receptor binding	IPI Inferred from Physical Interaction more info	PubMed
enables calmodulin binding	IEA Inferred from Electronic Annotation more info
enables carboxypeptidase activity	IEA Inferred from Electronic Annotation more info
enables chloride ion binding	IDA Inferred from Direct Assay more info	PubMed
enables endopeptidase activity	IDA Inferred from Direct Assay more info	PubMed
enables exopeptidase activity	IDA Inferred from Direct Assay more info	PubMed
enables heterocyclic compound binding	IEA Inferred from Electronic Annotation more info
enables metallodipeptidase activity	EXP Inferred from Experiment more info	PubMed
enables metallodipeptidase activity	IDA Inferred from Direct Assay more info	PubMed
enables metalloendopeptidase activity	IDA Inferred from Direct Assay more info	PubMed
enables metallopeptidase activity	IBA Inferred from Biological aspect of Ancestor more info	PubMed
enables metallopeptidase activity	IDA Inferred from Direct Assay more info	PubMed
enables metallopeptidase activity	ISS Inferred from Sequence or Structural Similarity more info
enables metallopeptidase activity	TAS Traceable Author Statement more info	PubMed
enables mitogen-activated protein kinase binding	IPI Inferred from Physical Interaction more info	PubMed
enables mitogen-activated protein kinase kinase binding	IPI Inferred from Physical Interaction more info	PubMed
enables peptidase activity	IDA Inferred from Direct Assay more info	PubMed
enables peptidyl-dipeptidase activity	IBA Inferred from Biological aspect of Ancestor more info	PubMed
enables peptidyl-dipeptidase activity	IDA Inferred from Direct Assay more info	PubMed
enables peptidyl-dipeptidase activity	ISS Inferred from Sequence or Structural Similarity more info	PubMed
enables peptidyl-dipeptidase activity	TAS Traceable Author Statement more info	PubMed
enables tripeptidyl-peptidase activity	IDA Inferred from Direct Assay more info	PubMed
enables zinc ion binding	IDA Inferred from Direct Assay more info	PubMed

Process	Evidence Code	Pubs
involved_in aging	IEA Inferred from Electronic Annotation more info
involved_in amyloid-beta metabolic process	IDA Inferred from Direct Assay more info	PubMed
involved_in angiogenesis involved in coronary vascular morphogenesis	IEA Inferred from Electronic Annotation more info
involved_in angiotensin maturation	IC Inferred by Curator more info	PubMed
involved_in angiotensin maturation	IDA Inferred from Direct Assay more info	PubMed
involved_in angiotensin maturation	TAS Traceable Author Statement more info
involved_in animal organ regeneration	IEA Inferred from Electronic Annotation more info
involved_in antigen processing and presentation of peptide antigen via MHC class I	TAS Traceable Author Statement more info	PubMed
involved_in arachidonic acid secretion	IDA Inferred from Direct Assay more info	PubMed
involved_in blood vessel diameter maintenance	IC Inferred by Curator more info	PubMed
involved_in blood vessel remodeling	IC Inferred by Curator more info	PubMed
involved_in bradykinin catabolic process	IDA Inferred from Direct Assay more info	PubMed
involved_in brain development	IEA Inferred from Electronic Annotation more info
involved_in cell proliferation in bone marrow	ISS Inferred from Sequence or Structural Similarity more info
involved_in cellular response to aldosterone	IEA Inferred from Electronic Annotation more info
involved_in cellular response to glucose stimulus	IEA Inferred from Electronic Annotation more info
involved_in eating behavior	IEA Inferred from Electronic Annotation more info
involved_in embryo development ending in birth or egg hatching	IEA Inferred from Electronic Annotation more info
involved_in female pregnancy	IEA Inferred from Electronic Annotation more info
involved_in heart contraction	ISS Inferred from Sequence or Structural Similarity more info
involved_in hematopoietic stem cell differentiation	IC Inferred by Curator more info	PubMed
involved_in hormone catabolic process	IDA Inferred from Direct Assay more info	PubMed
involved_in hormone catabolic process	ISS Inferred from Sequence or Structural Similarity more info	PubMed
involved_in hormone metabolic process	IDA Inferred from Direct Assay more info	PubMed
involved_in kidney development	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in kidney development	ISS Inferred from Sequence or Structural Similarity more info
involved_in lung alveolus development	IEA Inferred from Electronic Annotation more info
involved_in male gonad development	IEA Inferred from Electronic Annotation more info
involved_in mononuclear cell proliferation	IC Inferred by Curator more info	PubMed
involved_in negative regulation of calcium ion import	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of gap junction assembly	ISS Inferred from Sequence or Structural Similarity more info
involved_in negative regulation of gene expression	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of glucose import	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of protein binding	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of renal sodium excretion	IEA Inferred from Electronic Annotation more info
involved_in neutrophil mediated immunity	ISS Inferred from Sequence or Structural Similarity more info
involved_in peptide catabolic process	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of apoptotic process	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of inflammatory response	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of neurogenesis	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of peptidyl-cysteine S-nitrosylation	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of peptidyl-tyrosine autophosphorylation	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of protein binding	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of protein tyrosine kinase activity	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of systemic arterial blood pressure	IBA Inferred from Biological aspect of Ancestor more info	PubMed
involved_in positive regulation of vasoconstriction	IEA Inferred from Electronic Annotation more info
involved_in post-transcriptional regulation of gene expression	IEA Inferred from Electronic Annotation more info
involved_in proteolysis	TAS Traceable Author Statement more info	PubMed
involved_in regulation of angiotensin metabolic process	IDA Inferred from Direct Assay more info	PubMed
involved_in regulation of blood pressure	ISS Inferred from Sequence or Structural Similarity more info	PubMed
involved_in regulation of hematopoietic stem cell proliferation	IC Inferred by Curator more info	PubMed
involved_in regulation of hematopoietic stem cell proliferation	ISS Inferred from Sequence or Structural Similarity more info
involved_in regulation of renal output by angiotensin	IC Inferred by Curator more info	PubMed
involved_in regulation of smooth muscle cell migration	ISS Inferred from Sequence or Structural Similarity more info
involved_in regulation of synaptic plasticity	ISS Inferred from Sequence or Structural Similarity more info
involved_in regulation of systemic arterial blood pressure by renin-angiotensin	IBA Inferred from Biological aspect of Ancestor more info	PubMed
involved_in regulation of systemic arterial blood pressure by renin-angiotensin	IC Inferred by Curator more info	PubMed
involved_in regulation of systemic arterial blood pressure by renin-angiotensin	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of vasoconstriction	IC Inferred by Curator more info	PubMed
involved_in response to dexamethasone	IEA Inferred from Electronic Annotation more info
involved_in response to hypoxia	IEA Inferred from Electronic Annotation more info
involved_in response to laminar fluid shear stress	IEA Inferred from Electronic Annotation more info
involved_in response to lipopolysaccharide	IEA Inferred from Electronic Annotation more info
involved_in response to nutrient levels	IEA Inferred from Electronic Annotation more info
involved_in response to thyroid hormone	IEA Inferred from Electronic Annotation more info
involved_in response to xenobiotic stimulus	IEA Inferred from Electronic Annotation more info
involved_in sensory perception of pain	IEA Inferred from Electronic Annotation more info
involved_in spermatogenesis	ISS Inferred from Sequence or Structural Similarity more info
involved_in substance P catabolic process	IDA Inferred from Direct Assay more info	PubMed
involved_in vasoconstriction	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
located_in basal plasma membrane	IEA Inferred from Electronic Annotation more info
located_in brush border membrane	IEA Inferred from Electronic Annotation more info
located_in endosome	IDA Inferred from Direct Assay more info	PubMed
located_in external side of plasma membrane	IDA Inferred from Direct Assay more info	PubMed
located_in extracellular exosome	HDA more info	PubMed
located_in extracellular exosome	IDA Inferred from Direct Assay more info	PubMed
located_in extracellular region	TAS Traceable Author Statement more info
located_in extracellular space	HDA more info	PubMed
located_in extracellular space	IDA Inferred from Direct Assay more info	PubMed
located_in lysosome	IDA Inferred from Direct Assay more info	PubMed
is_active_in plasma membrane	IBA Inferred from Biological aspect of Ancestor more info	PubMed
located_in plasma membrane	IDA Inferred from Direct Assay more info	PubMed
located_in plasma membrane	TAS Traceable Author Statement more info
located_in sperm midpiece	IEA Inferred from Electronic Annotation more info

General protein information

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Preferred Names: angiotensin-converting enzyme

Names: CD143 antigen; angiotensin I converting enzyme (peptidyl-dipeptidase A) 1; carboxycathepsin; dipeptidyl carboxypeptidase 1; dipeptidyl carboxypeptidase I; kininase II; peptidase P

NP_000780.1

EC 3.4.15.1

NP_001171528.1

EC 3.4.15.1

NP_001369629.1

EC 3.4.15.1

NP_001369630.1

EC 3.4.15.1

NP_001369631.1

EC 3.4.15.1

NP_690043.1

EC 3.4.15.1

XP_006721800.3

EC 3.4.15.1

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_011648.1 RefSeqGene

Range

4989..26301

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_000789.4 → NP_000780.1 angiotensin-converting enzyme isoform 1 precursor

See identical proteins and their annotated locations for NP_000780.1

Status: REVIEWED

Description

Transcript Variant: This variant (1), also known as the endothelial or somatic form, represents the longest transcript and encodes the longest isoform (1).

Source sequence(s)

AB208971, AC113554, AK296566

Consensus CDS

CCDS11637.1

UniProtKB/Swiss-Prot

P12821, Q7M4L4

UniProtKB/TrEMBL

B4DKH4

Related

ENSP00000290866.4, ENST00000290866.10

Conserved Domains (1) summary

pfam01401
Location:643 → 1221

Peptidase_M2; Angiotensin-converting enzyme
NM_001178057.2 → NP_001171528.1 angiotensin-converting enzyme isoform 3 precursor

See identical proteins and their annotated locations for NP_001171528.1

Status: REVIEWED

Description

Transcript Variant: This variant (3) lacks multiple 5' exons and an in-frame exon in the 3' region, but has an alternate 5' exon, compared to variant 1. The resulting isoform (3) is shorter, and has a distinct N-terminus and lacks an internal segment, compared to isoform 1.

Source sequence(s)

AB208971, AC113554, AK301988, BM908222, M26657

Consensus CDS

CCDS54155.1

UniProtKB/Swiss-Prot

P12821

Related

ENSP00000392247.3, ENST00000413513.7

Conserved Domains (1) summary

pfam01401
Location:69 → 606

Peptidase_M2; Angiotensin-converting enzyme
NM_001382700.1 → NP_001369629.1 angiotensin-converting enzyme isoform 4

Status: REVIEWED

Source sequence(s)

AC113554

Conserved Domains (2) summary

pfam01401
Location:454 → 1032

Peptidase_M2; Angiotensin-converting enzyme

cl14813
Location:184 → 434

GluZincin; Gluzincin Peptidase family (thermolysin-like proteinases, TLPs) which includes peptidases M1, M2, M3, M4, M13, M32 and M36 (fungalysins)
NM_001382701.1 → NP_001369630.1 angiotensin-converting enzyme isoform 5

Status: REVIEWED

Source sequence(s)

AC113554

Conserved Domains (2) summary

pfam01401
Location:359 → 937

Peptidase_M2; Angiotensin-converting enzyme

cl14813
Location:1 → 339

GluZincin; Gluzincin Peptidase family (thermolysin-like proteinases, TLPs) which includes peptidases M1, M2, M3, M4, M13, M32 and M36 (fungalysins)
NM_001382702.1 → NP_001369631.1 angiotensin-converting enzyme isoform 6

Status: REVIEWED

Source sequence(s)

AC113554

Conserved Domains (1) summary

pfam01401
Location:1 → 426

Peptidase_M2; Angiotensin-converting enzyme
NM_152830.3 → NP_690043.1 angiotensin-converting enzyme isoform 2 precursor

See identical proteins and their annotated locations for NP_690043.1

Status: REVIEWED

Description

Transcript Variant: This variant (2), also known as the testicular form, lacks multiple 5' exons, but has an alternate 5' exon, compared to variant 1. The resulting isoform (2) is shorter and has a distinct N-terminus, compared to isoform 1.

Source sequence(s)

AB208971, AC113554, BM908222, M26657

Consensus CDS

CCDS45755.1

UniProtKB/Swiss-Prot

P12821

Related

ENSP00000290863.6, ENST00000290863.10

Conserved Domains (1) summary

pfam01401
Location:69 → 647

Peptidase_M2; Angiotensin-converting enzyme

RNA

NR_168483.1 RNA Sequence

Status: REVIEWED

Source sequence(s)

AC113554

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 110 details...

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000017.11 Reference GRCh38.p14 Primary Assembly

Range

63477061..63498373

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_006721737.4 → XP_006721800.3 angiotensin-converting enzyme isoform X1

UniProtKB/TrEMBL

D3DU13

Alternate T2T-CHM13v2.0

Genomic

NC_060941.1 Alternate T2T-CHM13v2.0

Range

64347269..64368872

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Suppressed Reference Sequence(s)

The following Reference Sequences have been suppressed. Explain

NM_152831.1: Suppressed sequence

Description

NM_152831.1: This RefSeq was permanently suppressed because it is a nonsense-mediated mRNA decay (NMD) candidate.