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IGH immunoglobulin heavy locus [ Homo sapiens (human) ]

Gene ID: 3492, updated on 2-Nov-2024

Summary

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Official Symbol
IGHprovided by HGNC
Official Full Name
immunoglobulin heavy locusprovided by HGNC
Primary source
HGNC:HGNC:5477
See related
MIM:146910; MIM:147010; MIM:147070; AllianceGenome:HGNC:5477
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
IGD1; IGH@; IGHJ; IGHV; IGHD@; IGHJ@; IGHV@; IGH.1@; IGHDY1
Summary
Immunoglobulins recognize foreign antigens and initiate immune responses such as phagocytosis and the complement system. Each immunoglobulin molecule consists of two identical heavy chains and two identical light chains. This region represents the germline organization of the heavy chain locus. The locus includes V (variable), D (diversity), J (joining), and C (constant) segments. During B cell development, a recombination event at the DNA level joins a single D segment with a J segment; this partially rearranged D-J gene is then joined to a V segment. The rearranged V-D-J is then transcribed with the IGHM constant region; this transcript encodes a mu heavy chain. Later in development B cells generate V-D-J-Cmu-Cdelta pre-messenger RNA, which is alternatively spliced to encode either a mu or a delta heavy chain. Mature B cells in the lymph nodes undergo switch recombination, so that the V-D-J gene is brought in proximity to one of the IGHG, IGHA, or IGHE genes and each cell expresses either the gamma, alpha, or epsilon heavy chain. Recombination of many different V segments with several J segments provides a wide range of antigen recognition. Additional diversity is attained by junctional diversity, resulting from the random addition of nucleotides by terminal deoxynucleotidyltransferase, and by somatic hypermutation, which occurs during B cell maturation in the spleen and lymph nodes. Due to polymorphism, the numbers of functional V, J, and D genes differ among individuals and some V, D, J, and C segments may be pseudogenes. [provided by RefSeq, Dec 2017]
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Genomic context

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See IGH in Genome Data Viewer
Location:
14q32.33
Annotation release Status Assembly Chr Location
RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 14 NC_000014.9 (105586437..106879844, complement)
RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 14 NC_060938.1 (99839469..101155136, complement)
RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 14 NC_000014.8 (106052774..107288051, complement)

Chromosome 14 - NC_000014.9Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC105370698 Neighboring gene ATP synthase membrane subunit c locus 1 pseudogene 1 Neighboring gene ETS transcription factor ELK2B, pseudogene Neighboring gene microRNA 8071-1 Neighboring gene microRNA 8071-2 Neighboring gene immunoglobulin heavy constant alpha 2 (A2m marker) Neighboring gene immunoglobulin heavy constant epsilon Neighboring gene immunoglobulin heavy constant gamma 4 (G4m marker) Neighboring gene uncharacterized LOC105378184 Neighboring gene immunoglobulin heavy constant gamma 2 (G2m marker) Neighboring gene ETS transcription factor ELK2A, pseudogene Neighboring gene immunoglobulin heavy constant gamma P (non-functional) Neighboring gene MPRA-validated peak2261 silencer Neighboring gene ATP6V1G1P1-IGHD intergenic CAGE-defined B cell enhancer Neighboring gene ATPase H+ transporting V1 subunit G1 pseudogene 1 Neighboring gene immunoglobulin heavy constant epsilon P1 (pseudogene) Neighboring gene immunoglobulin heavy constant alpha 1 Neighboring gene immunoglobulin heavy constant gamma 1 (G1m marker) Neighboring gene immunoglobulin heavy constant gamma 3 (G3m marker) Neighboring gene immunoglobulin heavy diversity 7-27 Neighboring gene microRNA 4537 Neighboring gene microRNA 4538 Neighboring gene microRNA 4539 Neighboring gene microRNA 4507 Neighboring gene immunoglobulin heavy diversity 6-25 Neighboring gene immunoglobulin heavy diversity 1-26 Neighboring gene immunoglobulin heavy diversity 3-22 Neighboring gene immunoglobulin heavy diversity 4-23 (non-functional) Neighboring gene immunoglobulin heavy diversity 5-24 (non-functional) Neighboring gene immunoglobulin heavy diversity 2-21 Neighboring gene immunoglobulin heavy diversity 5-18 Neighboring gene immunoglobulin heavy diversity 6-19 Neighboring gene immunoglobulin heavy diversity 1-20 Neighboring gene immunoglobulin heavy diversity 3-16 Neighboring gene immunoglobulin heavy diversity 4-17 Neighboring gene immunoglobulin heavy diversity 2-15 Neighboring gene immunoglobulin heavy diversity 1-14 (non-functional) Neighboring gene immunoglobulin heavy diversity 6-13 Neighboring gene immunoglobulin heavy joining 3P (pseudogene) Neighboring gene immunoglobulin heavy joining 1P (pseudogene) Neighboring gene P300/CBP strongly-dependent group 1 enhancer GRCh37_chr14:106445918-106447117 Neighboring gene immunoglobulin heavy joining 2P (pseudogene) Neighboring gene immunoglobulin heavy diversity 5-12 Neighboring gene immunoglobulin heavy diversity 4-11 (non-functional) Neighboring gene immunoglobulin heavy diversity 3-10 Neighboring gene immunoglobulin heavy variable (II)-1-1 (pseudogene) Neighboring gene immunoglobulin heavy constant delta Neighboring gene immunoglobulin heavy joining 5 Neighboring gene immunoglobulin heavy joining 6 Neighboring gene immunoglobulin heavy joining 1 Neighboring gene immunoglobulin heavy joining 2 Neighboring gene immunoglobulin heavy joining 3 Neighboring gene immunoglobulin heavy joining 4 Neighboring gene immunoglobulin heavy diversity 3-9 Neighboring gene immunoglobulin heavy diversity 2-8 Neighboring gene immunoglobulin heavy constant mu Neighboring gene immunoglobulin heavy diversity 1-7 Neighboring gene immunoglobulin heavy diversity 6-6 Neighboring gene immunoglobulin heavy diversity 5-5 Neighboring gene immunoglobulin heavy diversity 3-3 Neighboring gene immunoglobulin heavy diversity 4-4 Neighboring gene immunoglobulin heavy diversity 1-1 Neighboring gene immunoglobulin heavy diversity 2-2 Neighboring gene immunoglobulin heavy variable (III)-2-1 (pseudogene) Neighboring gene family with sequence similarity 30 member A Neighboring gene immunoglobulin heavy variable 6-1 Neighboring gene immunoglobulin heavy variable (III)-5-1 (pseudogene) Neighboring gene immunoglobulin heavy variable (III)-5-2 (pseudogene) Neighboring gene immunoglobulin heavy variable 1-2 Neighboring gene immunoglobulin heavy variable 7-4-1 Neighboring gene ribosomal protein S8 pseudogene 1 Neighboring gene immunoglobulin heavy variable 1-3 Neighboring gene ADAM metallopeptidase domain 6 (pseudogene) Neighboring gene immunoglobulin heavy variable 4-4 Neighboring gene immunoglobulin heavy variable (III)-11-1 (pseudogene) Neighboring gene immunoglobulin heavy variable 2-5 Neighboring gene immunoglobulin heavy variable 3-64D Neighboring gene immunoglobulin heavy variable (III)-13-1 (pseudogene) Neighboring gene immunoglobulin heavy variable 5-10-1 Neighboring gene immunoglobulin heavy variable 3-6 (pseudogene) Neighboring gene immunoglobulin heavy variable 3-7 Neighboring gene immunoglobulin heavy variable (III)-16-1 (pseudogene) Neighboring gene immunoglobulin heavy variable (II)-15-1 (pseudogene) Neighboring gene immunoglobulin heavy variable 3-11 Neighboring gene uncharacterized LOC105370700 Neighboring gene immunoglobulin heavy variable 1-12 (pseudogene) Neighboring gene CDK7 strongly-dependent group 2 enhancer GRCh37_chr14:106657005-106658204 Neighboring gene immunoglobulin heavy variable 3-13 Neighboring gene BRD4-independent group 4 enhancer GRCh37_chr14:106662526-106663725 Neighboring gene immunoglobulin heavy variable 1-14 (pseudogene) Neighboring gene immunoglobulin heavy variable 3-15 Neighboring gene immunoglobulin heavy variable (II)-20-1 (pseudogene) Neighboring gene solute carrier family 20 member 1 pseudogene 2 Neighboring gene immunoglobulin heavy variable 3-16 (non-functional) Neighboring gene immunoglobulin heavy variable 1-17 (pseudogene) Neighboring gene immunoglobulin heavy variable 1-18 Neighboring gene ReSE screen-validated silencer GRCh37_chr14:106714469-106714636 Neighboring gene immunoglobulin heavy variable (III)-22-2 (pseudogene) Neighboring gene immunoglobulin heavy variable 3-19 (pseudogene) Neighboring gene immunoglobulin heavy variable (II)-22-1 (pseudogene) Neighboring gene immunoglobulin heavy variable 3-20 Neighboring gene immunoglobulin heavy variable (III)-25-1 (pseudogene) Neighboring gene immunoglobulin heavy variable 3-21 Neighboring gene immunoglobulin heavy variable (III)-26-1 (pseudogene) Neighboring gene immunoglobulin heavy variable 3-22 (pseudogene) Neighboring gene immunoglobulin heavy variable (II)-26-2 (pseudogene) Neighboring gene long intergenic non-protein coding RNA 226 Neighboring gene immunoglobulin heavy variable 3-23 Neighboring gene immunoglobulin heavy variable (II)-28-1 (pseudogene) Neighboring gene immunoglobulin heavy variable 1-24 Neighboring gene immunoglobulin heavy variable (II)-30-21 (pseudogene) Neighboring gene HOMER2 pseudogene 2 Neighboring gene immunoglobulin heavy variable (II)-30-1 (pseudogene) Neighboring gene immunoglobulin heavy variable 3-25 (pseudogene) Neighboring gene immunoglobulin heavy variable 2-26 Neighboring gene immunoglobulin heavy variable 3-30-2 (pseudogene) Neighboring gene immunoglobulin heavy variable (II)-33-1 (pseudogene) Neighboring gene immunoglobulin heavy variable 4-30-2 Neighboring gene immunoglobulin heavy variable 7-27 (pseudogene) Neighboring gene immunoglobulin heavy variable 4-28 Neighboring gene uncharacterized LOC124903400 Neighboring gene immunoglobulin heavy variable 3-33-2 (pseudogene) Neighboring gene immunoglobulin heavy variable 3-29 (pseudogene) Neighboring gene immunoglobulin heavy variable 3-30 Neighboring gene golgin A4 pseudogene 2 Neighboring gene immunoglobulin heavy variable 7-34-1 (pseudogene) Neighboring gene immunoglobulin heavy variable (III)-38-1 (pseudogene) Neighboring gene immunoglobulin heavy variable 3-32 (pseudogene) Neighboring gene golgin A4 pseudogene 1 Neighboring gene immunoglobulin heavy variable 3-33 Neighboring gene immunoglobulin heavy variable 4-34 Neighboring gene immunoglobulin heavy variable (II)-40-1 (pseudogene) Neighboring gene immunoglobulin heavy variable 3-35 (non-functional) Neighboring gene immunoglobulin heavy variable 3-36 (pseudogene) Neighboring gene immunoglobulin heavy variable 3-37 (pseudogene) Neighboring gene immunoglobulin heavy variable 3-38 (non-functional) Neighboring gene immunoglobulin heavy variable (II)-43-1 (pseudogene) Neighboring gene immunoglobulin heavy variable 4-39 Neighboring gene immunoglobulin heavy variable 7-40 (pseudogene) Neighboring gene immunoglobulin heavy variable (IV)-44-1 (pseudogene) Neighboring gene immunoglobulin heavy variable (II)-44-2 (pseudogene) Neighboring gene immunoglobulin heavy variable 3-41 (pseudogene) Neighboring gene immunoglobulin heavy variable (III)-44 (pseudogene) Neighboring gene HOMER2 pseudogene 1 Neighboring gene immunoglobulin heavy variable (III)-47-1 (pseudogene) Neighboring gene immunoglobulin heavy variable (II)-46-1 (pseudogene) Neighboring gene long intergenic non-protein coding RNA 221 Neighboring gene immunoglobulin heavy variable 3-42 (pseudogene) Neighboring gene immunoglobulin heavy variable 3-43 Neighboring gene immunoglobulin heavy variable 1-45 Neighboring gene immunoglobulin heavy variable (II)-49-1 (pseudogene) Neighboring gene immunoglobulin heavy variable 1-46 Neighboring gene immunoglobulin heavy variable 3-47 (pseudogene) Neighboring gene immunoglobulin heavy variable (II)-51-2 (pseudogene) Neighboring gene immunoglobulin heavy variable 3-48 Neighboring gene immunoglobulin heavy variable (II)-53-1 (pseudogene) Neighboring gene immunoglobulin heavy variable IGHV8-51-1 (non-functional) Neighboring gene immunoglobulin heavy variable 3-49 Neighboring gene immunoglobulin heavy variable 3-50 (pseudogene) Neighboring gene immunoglobulin heavy variable 5-51 Neighboring gene immunoglobulin heavy variable (II)-60-1 (pseudogene) Neighboring gene uncharacterized LOC102724977 Neighboring gene immunoglobulin heavy variable 3-52 (pseudogene) Neighboring gene immunoglobulin heavy variable 3-53 Neighboring gene immunoglobulin heavy variable (II)-62-1 (pseudogene) Neighboring gene immunoglobulin heavy variable 3-54 (pseudogene) Neighboring gene immunoglobulin heavy variable 4-55 (pseudogene) Neighboring gene immunoglobulin heavy variable (III)-67-2 (pseudogene) Neighboring gene immunoglobulin heavy variable 7-56 (pseudogene) Neighboring gene immunoglobulin heavy variable (II)-65-1 (pseudogene) Neighboring gene immunoglobulin heavy variable 3-57 (pseudogene) Neighboring gene immunoglobulin heavy variable (III)-67-3 (pseudogene) Neighboring gene RNA, 5S ribosomal pseudogene 389 Neighboring gene immunoglobulin heavy variable (III)-67-4 (pseudogene) Neighboring gene immunoglobulin heavy variable 1-58 Neighboring gene immunoglobulin heavy variable 4-59 Neighboring gene immunoglobulin heavy variable (II)-67-1 (pseudogene) Neighboring gene immunoglobulin heavy variable 3-60 (pseudogene) Neighboring gene immunoglobulin heavy variable 4-61 Neighboring gene immunoglobulin heavy variable 3-62 (pseudogene) Neighboring gene immunoglobulin heavy variable 3-63 (pseudogene) Neighboring gene golgin A4 pseudogene 3 Neighboring gene immunoglobulin heavy variable 3-64 Neighboring gene solute carrier family 20 member 1 pseudogene 1 Neighboring gene immunoglobulin heavy variable 3-65 (pseudogene) Neighboring gene immunoglobulin heavy variable 3-66 Neighboring gene immunoglobulin heavy variable 1-67 (pseudogene) Neighboring gene immunoglobulin heavy variable 3-69-1 (pseudogene) Neighboring gene immunoglobulin heavy variable 1-69-2 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 9151 Neighboring gene immunoglobulin heavy variable 1-68 (pseudogene) Neighboring gene immunoglobulin heavy variable 2-70D Neighboring gene immunoglobulin heavy variable 1-69 Neighboring gene immunoglobulin heavy variable 1-69D Neighboring gene immunoglobulin heavy variable (III)-76-1 (pseudogene) Neighboring gene immunoglobulin heavy variable (II)-74-1 (pseudogene) Neighboring gene uncharacterized LOC124903399 Neighboring gene immunoglobulin heavy variable 2-70 Neighboring gene immunoglobulin heavy variable 3-71 (pseudogene) Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 6254 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 9152 Neighboring gene immunoglobulin heavy variable 3-72 Neighboring gene immunoglobulin heavy variable (II)-78-1 (pseudogene) Neighboring gene immunoglobulin heavy variable 3-73 Neighboring gene immunoglobulin heavy variable 3-74 Neighboring gene immunoglobulin heavy variable (III)-82 (pseudogene) Neighboring gene immunoglobulin heavy variable 3-75 (pseudogene) Neighboring gene immunoglobulin heavy variable 3-76 (pseudogene) Neighboring gene immunoglobulin heavy variable 5-78 (pseudogene) Neighboring gene immunoglobulin heavy variable 3-79 (pseudogene) Neighboring gene immunoglobulin heavy variable 4-80 (pseudogene) Neighboring gene immunoglobulin heavy variable 7-81 (non-functional) Neighboring gene microRNA 5195

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Bibliography

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Related articles in PubMed

  1. Immunoglobulin heavy chain (IGH@) translocations negatively impact treatment-free survival for chronic lymphocytic leukemia patients who have an isolated deletion 13q abnormality. Gerrie AS, et al. Cancer Genet, 2012 Oct. PMID 22939229
  2. Switching on cytotoxicity by a single mutation at the heavy chain variable region of an anti-ganglioside antibody. Fernández-Marrero Y, et al. Mol Immunol, 2011 Apr. PMID 21306777
  3. Enhancer complexes located downstream of both human immunoglobulin Calpha genes. Mills FC, et al. J Exp Med, 1997 Sep 15. PMID 9294139, Free PMC Article
  4. Searching for surrogates for IGHV mutations in chronic lymphocytic leukemia. Hamblin TJ. Leuk Res, 2011 Nov. PMID 21840049
  5. IGHV gene mutational status and 17p deletion are independent molecular predictors in a comprehensive clinical-biological prognostic model for overall survival prediction in chronic lymphocytic leukemia. Bulian P, et al. J Transl Med, 2012 Jan 30. PMID 22289136, Free PMC Article

See all (145) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. IGH repertoire analysis at scale: deciphering the complexity of B cell infiltration and migration in esophageal squamous cell carcinoma.
    Title: IGH repertoire analysis at scale: deciphering the complexity of B cell infiltration and migration in esophageal squamous cell carcinoma.
  2. IGH cytogenetic abnormalities can be detected in multiple myeloma by imaging flow cytometry.
    Title: IGH cytogenetic abnormalities can be detected in multiple myeloma by imaging flow cytometry.
  3. Unique repetitive nucleic acid structures mirror switch regions in the human IgH locus.
    Title: Unique repetitive nucleic acid structures mirror switch regions in the human IgH locus.
  4. Insights into IGH clonal evolution in BCP-ALL: frequency, mechanisms, associations, and diagnostic implications.
    Title: Insights into IGH clonal evolution in BCP-ALL: frequency, mechanisms, associations, and diagnostic implications.
  5. Igh and Igk loci use different folding principles for V gene recombination due to distinct chromosomal architectures of pro-B and pre-B cells.
    Title: Igh and Igk loci use different folding principles for V gene recombination due to distinct chromosomal architectures of pro-B and pre-B cells.
  6. Analysis of IGH allele content in a sample group of rheumatoid arthritis patients demonstrates unrevealed population heterogeneity.
    Title: Analysis of IGH allele content in a sample group of rheumatoid arthritis patients demonstrates unrevealed population heterogeneity.
  7. Immunoglobulin gene sequence analysis in chronic lymphocytic leukemia: the 2022 update of the recommendations by ERIC, the European Research Initiative on CLL.
    Title: Immunoglobulin gene sequence analysis in chronic lymphocytic leukemia: the 2022 update of the recommendations by ERIC, the European Research Initiative on CLL.
  8. Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma With Secondary Acquisition of t(11;14)(q13;q32)/CCND1-IGH: A Rare Variant Of Richter Transformation to Mantle Cell Lymphoma.
    Title: Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma With Secondary Acquisition of t(11;14)(q13;q32)/CCND1-IGH: A Rare Variant Of Richter Transformation to Mantle Cell Lymphoma.
  9. Oncogenic role of the SOX9-DHCR24-cholesterol biosynthesis axis in IGH-BCL2+ diffuse large B-cell lymphomas.
    Title: Oncogenic role of the SOX9-DHCR24-cholesterol biosynthesis axis in IGH-BCL2+ diffuse large B-cell lymphomas.
  10. Population-specific diversity of the immunoglobulin constant heavy G chain (IGHG) genes.
    Title: Population-specific diversity of the immunoglobulin constant heavy G chain (IGHG) genes.
Submit: New GeneRIF Correction See all GeneRIFs (107)

Phenotypes

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Review eQTL and phenotype association data in this region using PheGenI

EBI GWAS Catalog

Description
Genetic variants in the immunoglobulin heavy chain locus are associated with the IgG index in multiple sclerosis.
EBI GWAS Catalog
Identification of novel susceptibility Loci for kawasaki disease in a Han chinese population by a genome-wide association study.
EBI GWAS Catalog
Meta-analysis of 74,046 individuals identifies 11 new susceptibility loci for Alzheimer's disease.
EBI GWAS Catalog

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Other Names

  • D (diversity) region of heavy chains
  • J (joining) region of heavy chains
  • immunglobulin heavy chain variable region
  • immunoglobulin heavy diversity cluster
  • immunoglobulin heavy diversity group
  • immunoglobulin heavy diversity locus
  • immunoglobulin heavy joining cluster
  • immunoglobulin heavy joining group
  • immunoglobulin heavy polypeptide, joining region
  • immunoglobulin heavy variable cluster
  • immunoglobulin heavy variable group

Clone Names

  • FLJ41981, FLJ43089, FLJ44381, MGC70893, MGC72071, MGC88774, DKFZp686C15213, DKFZp686K04218, DKFZp686L19235, DKFZp686M08189

General protein information

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Names
immunoglobulin heavy locus
D (diversity) region of heavy chains
J (joining) region of heavy chains
immunglobulin heavy chain variable region
immunoglobulin heavy diversity cluster
immunoglobulin heavy diversity group
immunoglobulin heavy diversity locus
immunoglobulin heavy joining cluster
immunoglobulin heavy joining group
immunoglobulin heavy polypeptide, joining region
immunoglobulin heavy variable cluster
immunoglobulin heavy variable group

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

  1. NG_001019.6 

    Range
    501..1293908
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

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_000014.9 Reference GRCh38.p14 Primary Assembly

    Range
    105586437..106879844 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Reference GRCh38.p14 ALT_REF_LOCI_1

Genomic

  1. NT_187600.1 Reference GRCh38.p14 ALT_REF_LOCI_1

    Range
    54793..1351393 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060938.1 Alternate T2T-CHM13v2.0

    Range
    99839469..101155136 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)
Nucleotide Protein
Heading Accession and Version

Gene LinkOut

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Other Literature Sources
Chemical Information
Molecular Biology Databases
Research Materials