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OAS1 2'-5'-oligoadenylate synthetase 1 [ Homo sapiens (human) ]

Gene ID: 4938, updated on 2-Nov-2024

Summary

Official Symbol
OAS1provided by HGNC
Official Full Name
2'-5'-oligoadenylate synthetase 1provided by HGNC
Primary source
HGNC:HGNC:8086
See related
Ensembl:ENSG00000089127 MIM:164350; AllianceGenome:HGNC:8086
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
OIAS; IFI-4; OIASI; IMD100; E18/E16
Summary
This interferon-induced gene encodes a protein that synthesizes 2',5'-oligoadenylates (2-5As). This protein plays a key role in innate cellular antiviral response, and has been implicated in other cellular processes like cell growth and apoptosis. Alternative splicing results in multiple transcript variants with different enzymatic activities. Polymorphisms in this gene have been associated with susceptibility to viral infection, including SARS-CoV-2, and diabetes mellitus, type 1. This gene is located in a cluster of related genes on chromosome 12. [provided by RefSeq, May 2022]
Annotation information
Note: This gene has been reviewed for its involvement in coronavirus biology, and is involved in immune response or antiviral activity.
Expression
Ubiquitous expression in spleen (RPKM 18.0), colon (RPKM 15.8) and 24 other tissues See more
Orthologs
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Genomic context

See OAS1 in Genome Data Viewer
Location:
12q24.13
Exon count:
7
Annotation release Status Assembly Chr Location
RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 12 NC_000012.12 (112906962..112933219)
RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 12 NC_060936.1 (112883649..112909905)
RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 12 NC_000012.11 (113344767..113371024)

Chromosome 12 - NC_000012.12Genomic Context describing neighboring genes Neighboring gene protein tyrosine phosphatase non-receptor type 11 Neighboring gene uncharacterized LOC124903024 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:112954684-112955184 Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr12:113015949-113016468 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:113018366-113018890 Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr12:113039985-113040713 Neighboring gene H3K27ac hESC enhancer GRCh37_chr12:113055106-113055606 Neighboring gene rabphilin 3A Neighboring gene NANOG hESC enhancer GRCh37_chr12:113079622-113080142 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:113147969-113148469 Neighboring gene microRNA 1302-1 Neighboring gene NANOG-H3K4me1 hESC enhancer GRCh37_chr12:113185662-113186162 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:113229645-113230186 Neighboring gene ReSE screen-validated silencer GRCh37_chr12:113306366-113306564 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 7051 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 7052 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_24142 Neighboring gene Neanderthal introgressed variant-containing enhancers experimental_24146 and experimental_24152 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_24159 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_24163 Neighboring gene Neanderthal introgressed variant-containing enhancers experimental_24171 and experimental_24176 Neighboring gene Neanderthal introgressed variant-containing enhancers experimental_24215 and experimental_24231 Neighboring gene Neanderthal introgressed variant-containing enhancers experimental_24264 and experimental_24270 Neighboring gene Sharpr-MPRA regulatory region 3381 Neighboring gene Neanderthal introgressed variant-containing enhancers experimental_24293 and experimental_24295 Neighboring gene Neanderthal introgressed variant-containing enhancers experimental_24298, experimental_24301 and experimental_24306 Neighboring gene Neanderthal introgressed variant-containing enhancers experimental_24317/24320 and experimental_24338 Neighboring gene Neanderthal introgressed variant-containing enhancers experimental_24357 and experimental_24368 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_24404 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_24448 Neighboring gene Neanderthal introgressed variant-containing enhancers experimental_24456 and experimental_24461 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_24463 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_24487 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 7053 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_24505 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 4887 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_24515 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_24520 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_24535 Neighboring gene MPRA-validated peak1965 silencer Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:113400746-113401246 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:113401247-113401747 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_24547 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_24553 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 7054 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 7055 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 7056 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 7057 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_24560 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_24566 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_24567 Neighboring gene BRD4-independent group 4 enhancer GRCh37_chr12:113444541-113445740 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_24568 Neighboring gene 2'-5'-oligoadenylate synthetase 3 Neighboring gene 2'-5'-oligoadenylate synthetase 2

Genomic regions, transcripts, and products

Expression

  • Project title: HPA RNA-seq normal tissues 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

GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Phenotypes

Associated conditions

Description Tests
Pulmonary alveolar proteinosis with hypogammaglobulinemia
MedGen: C4747984 OMIM: 618042 GeneReviews: Not available
not available

EBI GWAS Catalog

Description
New susceptibility loci in MYL2, C12orf51 and OAS1 associated with 1-h plasma glucose as predisposing risk factors for type 2 diabetes in the Korean population.
EBI GWAS Catalog
Preliminary evidence of genetic determinants of adiponectin response to fenofibrate in the Genetics of Lipid Lowering Drugs and Diet Network.
EBI GWAS Catalog

HIV-1 interactions

Protein interactions

Protein Gene Interaction Pubs
Envelope surface glycoprotein gp120 env HIV-1 gp120 downregulates the expression of 2'-5'-oligoadenylate synthetase 1 (OAS1) in human B cells PubMed
Nef nef Production of infectious triple deletion vpr/vpu/nef HIV-1 mutant is suppressed, indicating that Nef may antagonize restriction activity of OAS1 against production of infectious wild-type HIV-1 PubMed
Tat tat HIV-1 and the viral protein Tat modulate the expression of 2',5'-oligoadenylate synthetase 1, 40/46kDa (OAS1) in immature dendritic cells and monocyte-derived macrophages PubMed
tat HIV-1 Tat interacts with interferon-inducible enzymes 2-5A synthetase and dsRNA-dependent protein kinase to influence the rate of translation and protein synthesis in vitro PubMed
Vpr vpr Production of infectious triple deletion vpr/vpu/nef HIV-1 mutant is suppressed, indicating that Vpr may antagonize restriction activity of OAS1 against production of infectious wild-type HIV-1 PubMed
Vpu vpu Production of infectious triple deletion vpr/vpu/nef HIV-1 mutant is suppressed, indicating that Vpu may antagonize restriction activity of OAS1 against production of infectious wild-type HIV-1 PubMed

Go to the HIV-1, Human Interaction Database

Pathways from PubChem

Interactions

Products Interactant Other Gene Complex Source Pubs Description

General gene information

Markers

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables 2'-5'-oligoadenylate synthetase activity IBA
Inferred from Biological aspect of Ancestor
more info
 
enables 2'-5'-oligoadenylate synthetase activity IDA
Inferred from Direct Assay
more info
PubMed 
enables ATP binding TAS
Traceable Author Statement
more info
PubMed 
enables double-stranded RNA binding IBA
Inferred from Biological aspect of Ancestor
more info
 
enables double-stranded RNA binding IDA
Inferred from Direct Assay
more info
PubMed 
enables metal ion binding IEA
Inferred from Electronic Annotation
more info
 
enables protein binding IPI
Inferred from Physical Interaction
more info
PubMed 
Process Evidence Code Pubs
involved_in antiviral innate immune response IBA
Inferred from Biological aspect of Ancestor
more info
 
involved_in antiviral innate immune response IDA
Inferred from Direct Assay
more info
PubMed 
involved_in antiviral innate immune response IEP
Inferred from Expression Pattern
more info
PubMed 
involved_in cellular response to interferon-alpha IDA
Inferred from Direct Assay
more info
PubMed 
involved_in cellular response to interferon-beta IDA
Inferred from Direct Assay
more info
PubMed 
involved_in cellular response to virus IEP
Inferred from Expression Pattern
more info
PubMed 
involved_in defense response to bacterium IMP
Inferred from Mutant Phenotype
more info
PubMed 
involved_in defense response to virus IDA
Inferred from Direct Assay
more info
PubMed 
involved_in glucose homeostasis IMP
Inferred from Mutant Phenotype
more info
PubMed 
involved_in glucose metabolic process IMP
Inferred from Mutant Phenotype
more info
PubMed 
involved_in interleukin-27-mediated signaling pathway IBA
Inferred from Biological aspect of Ancestor
more info
 
involved_in interleukin-27-mediated signaling pathway IEP
Inferred from Expression Pattern
more info
PubMed 
involved_in negative regulation of IP-10 production IMP
Inferred from Mutant Phenotype
more info
PubMed 
involved_in negative regulation of chemokine (C-X-C motif) ligand 2 production IMP
Inferred from Mutant Phenotype
more info
PubMed 
involved_in negative regulation of type I interferon-mediated signaling pathway IMP
Inferred from Mutant Phenotype
more info
PubMed 
involved_in negative regulation of viral genome replication IBA
Inferred from Biological aspect of Ancestor
more info
 
involved_in negative regulation of viral genome replication IDA
Inferred from Direct Assay
more info
PubMed 
involved_in positive regulation of cellular respiration IDA
Inferred from Direct Assay
more info
PubMed 
involved_in positive regulation of interferon-beta production IMP
Inferred from Mutant Phenotype
more info
PubMed 
involved_in positive regulation of monocyte chemotactic protein-1 production IMP
Inferred from Mutant Phenotype
more info
PubMed 
involved_in positive regulation of tumor necrosis factor production IMP
Inferred from Mutant Phenotype
more info
PubMed 
involved_in protein complex oligomerization IDA
Inferred from Direct Assay
more info
PubMed 
involved_in regulation of ribonuclease activity IDA
Inferred from Direct Assay
more info
PubMed 
involved_in response to virus IDA
Inferred from Direct Assay
more info
PubMed 
involved_in surfactant homeostasis IMP
Inferred from Mutant Phenotype
more info
PubMed 
involved_in toll-like receptor 3 signaling pathway IMP
Inferred from Mutant Phenotype
more info
PubMed 
involved_in toll-like receptor 4 signaling pathway IMP
Inferred from Mutant Phenotype
more info
PubMed 
involved_in type I interferon-mediated signaling pathway IBA
Inferred from Biological aspect of Ancestor
more info
 
involved_in type I interferon-mediated signaling pathway IMP
Inferred from Mutant Phenotype
more info
PubMed 
Component Evidence Code Pubs
colocalizes_with cytoplasm IDA
Inferred from Direct Assay
more info
PubMed 
located_in cytoplasm IDA
Inferred from Direct Assay
more info
PubMed 
is_active_in cytosol IBA
Inferred from Biological aspect of Ancestor
more info
 
located_in cytosol IDA
Inferred from Direct Assay
more info
PubMed 
located_in cytosol TAS
Traceable Author Statement
more info
 
located_in endoplasmic reticulum IEA
Inferred from Electronic Annotation
more info
 
located_in extracellular region IEA
Inferred from Electronic Annotation
more info
 
is_active_in membrane IBA
Inferred from Biological aspect of Ancestor
more info
 
located_in mitochondrion IDA
Inferred from Direct Assay
more info
PubMed 
located_in mitochondrion IEA
Inferred from Electronic Annotation
more info
 
is_active_in nucleoplasm IBA
Inferred from Biological aspect of Ancestor
more info
 
located_in nucleoplasm IDA
Inferred from Direct Assay
more info
 
is_active_in nucleus IDA
Inferred from Direct Assay
more info
PubMed 
located_in nucleus IDA
Inferred from Direct Assay
more info
PubMed 
located_in ribosome IDA
Inferred from Direct Assay
more info
PubMed 

General protein information

Preferred Names
2'-5'-oligoadenylate synthase 1
Names
(2-5')oligo(A) synthase 1
2',5'-oligo A synthetase 1
2'-5'-oligoadenylate synthase 1 isoform p42
2'-5'-oligoadenylate synthetase 1, 40/46kDa
2'-5'-oligoisoadenylate synthetase 1
2-5A synthase 1
2-5A synthetase 1
E16 (2'-5') oligo A synthetase
NP_001027581.1
NP_001307080.1
NP_001392949.1
NP_001392950.1
NP_001392951.1
NP_001392952.1
NP_001392953.1
NP_001392954.1
NP_001392955.1
NP_001392956.1
NP_001392958.1
NP_001392959.1
NP_001399157.1
NP_002525.2
NP_058132.2

NCBI Reference Sequences (RefSeq)

NEW Try the new Transcript table

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

  1. NG_011530.2 RefSeqGene

    Range
    5029..17970
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_001032409.3NP_001027581.1  2'-5'-oligoadenylate synthase 1 isoform 3

    See identical proteins and their annotated locations for NP_001027581.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (3) uses an alternate splice site in the 3' coding region, which results in a frameshift, compared to variant 1. It encodes isoform 3 (also known as p48), which has a longer, distinct C-terminus, compared to isoform 1.
    Source sequence(s)
    AJ629455, AY730628, BF055326, CB112445
    Consensus CDS
    CCDS31905.1
    UniProtKB/TrEMBL
    S4R3A5
    Related
    ENSP00000388001.2, ENST00000445409.7
    Conserved Domains (2) summary
    cd05400
    Location:29211
    NT_2-5OAS_ClassI-CCAase; Nucleotidyltransferase (NT) domain of 2'5'-oligoadenylate (2-5A)synthetase (2-5OAS) and class I CCA-adding enzyme
    pfam10421
    Location:163343
    OAS1_C; 2'-5'-oligoadenylate synthetase 1, domain 2, C-terminus
  2. NM_001320151.2NP_001307080.1  2'-5'-oligoadenylate synthase 1 isoform 4

    Status: REVIEWED

    Description
    Transcript Variant: This variant (4) represents the allele encoded by the GRCh38 reference genome, and differs in the 3' coding region and 3' UTR compared to variant 1. It encodes isoform 4 (also known as p44b), which has a shorter, distinct C-terminus, compared to isoform 1.
    Source sequence(s)
    AA085948, AC004551, AJ629455, CB112445
    Consensus CDS
    CCDS81742.1
    UniProtKB/TrEMBL
    A0A7P0T854
    Related
    ENSP00000448790.1, ENST00000551241.6
    Conserved Domains (2) summary
    cd05400
    Location:29211
    NT_2-5OAS_ClassI-CCAase; Nucleotidyltransferase (NT) domain of 2'5'-oligoadenylate (2-5A)synthetase (2-5OAS) and class I CCA-adding enzyme
    pfam10421
    Location:163343
    OAS1_C; 2'-5'-oligoadenylate synthetase 1, domain 2, C-terminus
  3. NM_001406020.1NP_001392949.1  2'-5'-oligoadenylate synthase 1 isoform 5

    Status: REVIEWED

    Source sequence(s)
    AC004551
  4. NM_001406021.1NP_001392950.1  2'-5'-oligoadenylate synthase 1 isoform 6

    Status: REVIEWED

    Source sequence(s)
    AC004551
    Consensus CDS
    CCDS91755.1
    UniProtKB/TrEMBL
    A0A7P0Z4N8
    Related
    ENSP00000506580.1, ENST00000681700.1
  5. NM_001406022.1NP_001392951.1  2'-5'-oligoadenylate synthase 1 isoform 7

    Status: REVIEWED

    Source sequence(s)
    AC004551
    Consensus CDS
    CCDS91752.1
    UniProtKB/TrEMBL
    H0YIB8
    Related
    ENSP00000449053.2, ENST00000553152.2
  6. NM_001406023.1NP_001392952.1  2'-5'-oligoadenylate synthase 1 isoform 8

    Status: REVIEWED

    Source sequence(s)
    AC004551
  7. NM_001406024.1NP_001392953.1  2'-5'-oligoadenylate synthase 1 isoform 9

    Status: REVIEWED

    Source sequence(s)
    AC004551
    UniProtKB/TrEMBL
    A0A6Q8PHR1
    Related
    ENSP00000502804.1, ENST00000675868.2
  8. NM_001406025.1NP_001392954.1  2'-5'-oligoadenylate synthase 1 isoform 10

    Status: REVIEWED

    Source sequence(s)
    AC004551
  9. NM_001406026.1NP_001392955.1  2'-5'-oligoadenylate synthase 1 isoform 11

    Status: REVIEWED

    Source sequence(s)
    AC004551
    UniProtKB/TrEMBL
    A0A7P0T9Q4
    Related
    ENSP00000505786.1, ENST00000679971.1
  10. NM_001406027.1NP_001392956.1  2'-5'-oligoadenylate synthase 1 isoform 12

    Status: REVIEWED

    Source sequence(s)
    AC004551
    UniProtKB/TrEMBL
    A0A7P0T8F9
    Related
    ENSP00000505165.1, ENST00000680455.1
  11. NM_001406029.1NP_001392958.1  2'-5'-oligoadenylate synthase 1 isoform 13

    Status: REVIEWED

    Source sequence(s)
    AC004551
  12. NM_001406030.1NP_001392959.1  2'-5'-oligoadenylate synthase 1 isoform 14

    Status: REVIEWED

    Source sequence(s)
    AC004551
  13. NM_001412228.1NP_001399157.1  2'-5'-oligoadenylate synthase 1 isoform 15

    Status: REVIEWED

    Description
    Transcript Variant: This variant (24) uses the same exon combination as variant 4 but represents the allele encoded by the T2T-CHM13v2.0 genome assembly. The encoded isoform (15) has a frameshifted C-terminus compared to isoform 4.
    Source sequence(s)
    CP068266
  14. NM_002534.4NP_002525.2  2'-5'-oligoadenylate synthase 1 isoform 2

    See identical proteins and their annotated locations for NP_002525.2

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) differs in the 3' coding region and 3' UTR compared to variant 1. It encodes isoform 2 (also known as E16, p40, or p42), which has a shorter, distinct C-terminus compared to isoform 1.
    Source sequence(s)
    AC004551, BC061587, BE048946, CB112445
    Consensus CDS
    CCDS44980.1
    UniProtKB/TrEMBL
    A0A7P0T854
    Related
    ENSP00000415721.2, ENST00000452357.7
    Conserved Domains (2) summary
    cd05400
    Location:29211
    NT_2-5OAS_ClassI-CCAase; Nucleotidyltransferase (NT) domain of 2'5'-oligoadenylate (2-5A)synthetase (2-5OAS) and class I CCA-adding enzyme
    pfam10421
    Location:163343
    OAS1_C; 2'-5'-oligoadenylate synthetase 1, domain 2, C-terminus
  15. NM_016816.4NP_058132.2  2'-5'-oligoadenylate synthase 1 isoform 1

    See identical proteins and their annotated locations for NP_058132.2

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) represents the longest transcript. It encodes isoform 1 (also known as E18 and p46). This variant is produced in individuals with a G allele at a polymorphic splice acceptor site in the 3' most intron(PMID:15732009).
    Source sequence(s)
    AJ629455, AK225384, CB112445
    Consensus CDS
    CCDS41838.1
    UniProtKB/Swiss-Prot
    A8K4N8, F8VXY3, P00973, P04820, P29080, P29081, P78485, P78486, Q16700, Q16701, Q1PG42, Q3ZM01, Q53GC5, Q53YA4, Q6A1Z3, Q6IPC6, Q6P7N9, Q96J61
    UniProtKB/TrEMBL
    A0A7P0TBG0
    Related
    ENSP00000202917.5, ENST00000202917.10
    Conserved Domains (2) summary
    cd05400
    Location:29211
    NT_2-5OAS_ClassI-CCAase; Nucleotidyltransferase (NT) domain of 2'5'-oligoadenylate (2-5A)synthetase (2-5OAS) and class I CCA-adding enzyme
    pfam10421
    Location:163343
    OAS1_C; 2'-5'-oligoadenylate synthetase 1, domain 2, C-terminus

RNA

  1. NR_175985.1 RNA Sequence

    Status: REVIEWED

    Source sequence(s)
    AC004551
  2. NR_175986.1 RNA Sequence

    Status: REVIEWED

    Source sequence(s)
    AC004551
    Related
    ENST00000681505.1
  3. NR_175987.1 RNA Sequence

    Status: REVIEWED

    Source sequence(s)
    AC004551
  4. NR_175988.1 RNA Sequence

    Status: REVIEWED

    Source sequence(s)
    AC004551
  5. NR_175989.1 RNA Sequence

    Status: REVIEWED

    Source sequence(s)
    AC004551
  6. NR_175990.1 RNA Sequence

    Status: REVIEWED

    Source sequence(s)
    AC004551
    Related
    ENST00000680934.1
  7. NR_175991.1 RNA Sequence

    Status: REVIEWED

    Source sequence(s)
    AC004551
  8. NR_175992.1 RNA Sequence

    Status: REVIEWED

    Source sequence(s)
    AC004551
    Related
    ENST00000680919.1
  9. NR_175993.1 RNA Sequence

    Status: REVIEWED

    Source sequence(s)
    AC004551

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

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

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000012.12 Reference GRCh38.p14 Primary Assembly

    Range
    112906962..112933219
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060936.1 Alternate T2T-CHM13v2.0

    Range
    112883649..112909905
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)