HLA-DOA major histocompatibility complex, class II, DO alpha [Homo sapiens (human)] - Gene

Summary

Official Symbol: HLA-DOAprovided by HGNC
Official Full Name: major histocompatibility complex, class II, DO alphaprovided by HGNC
Primary source: HGNC:HGNC:4936
See related: Ensembl:ENSG00000204252 MIM:142930; AllianceGenome:HGNC:4936
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: HLADZ; HLA-DNA; HLA-DZA
Summary: HLA-DOA belongs to the HLA class II alpha chain paralogues. HLA-DOA forms a heterodimer with HLA-DOB. The heterodimer, HLA-DO, is found in lysosomes in B cells and regulates HLA-DM-mediated peptide loading on MHC class II molecules. In comparison with classical HLA class II molecules, this gene exhibits very little sequence variation, especially at the protein level. [provided by RefSeq, Jul 2008]
Expression: Broad expression in lymph node (RPKM 26.6), spleen (RPKM 26.2) and 20 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 6p21.32

Exon count:: 5

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	6	NC_000006.12 (33004182..33009591, complement)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	6	NC_060930.1 (32825532..32830941, complement)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	6	NC_000006.11 (32971959..32977368, complement)

Chromosome 6 - NC_000006.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

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

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Contribution of a Non-classical HLA Gene, HLA-DOA, to the Risk of Rheumatoid Arthritis
Title: Contribution of a Non-classical HLA Gene, HLA-DOA, to the Risk of Rheumatoid Arthritis.
pH-susceptibility of HLA-DO tunes DO/DM ratios to regulate HLA-DM catalytic activity.
Title: pH-susceptibility of HLA-DO tunes DO/DM ratios to regulate HLA-DM catalytic activity.
significant association was found between white wine liking and rs9276975:C>T polymorphism in the HLA-DOA gene.
Title: Genome-wide association analysis on five isolated populations identifies variants of the HLA-DOA gene associated with white wine liking.
TAP2, HLA-DOA, HLA-DOB, and tapasin loci are novel candidate regions for susceptibility to HCV infection and viral clearance in the Chinese population
Title: Association of polymorphisms in HLA antigen presentation-related genes with the outcomes of HCV infection.
HLA-DO regulates surface presentation of human leukocyte antigen class II-restricted antigens on B cell malignancies.
Title: Human leukocyte antigen-DO regulates surface presentation of human leukocyte antigen class II-restricted antigens on B cell malignancies.
HLA-DOA, HLA-DRA, and HLA-DQA1 associated with spontaneous autoimmunity
Title: Genome-wide study reveals an important role of spontaneous autoimmunity, cardiomyocyte differentiation defect and anti-angiogenic activities in gender-specific gene expression in Keshan disease.
results show that HLA-DO inhibits HLA-DM function by acting as a substrate mimic, and the findings also limit the possible functional roles for HLA-DO in antigen presentation
Title: HLA-DO acts as a substrate mimic to inhibit HLA-DM by a competitive mechanism.
analysis of the HLA-DO/HLA-DM complex by FRET and mutagenesis
Title: Mapping the HLA-DO/HLA-DM complex by FRET and mutagenesis.
Observational study of gene-disease association, gene-environment interaction, and pharmacogenomic / toxicogenomic. (HuGE Navigator)
Title: Variation at the NFATC2 locus increases the risk of thiazolidinedione-induced edema in the Diabetes REduction Assessment with ramipril and rosiglitazone Medication (DREAM) study.
HLA-DOA polymorphisms are associated with Diabetes Mellitus, Type 1.
Title: Exploring the diabetogenicity of the HLA-B18-DR3 CEH: independent association with T1D genetic risk close to HLA-DOA.

Submit: New GeneRIF Correction See all GeneRIFs (17)

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

EBI GWAS Catalog

Description
Association of granulomatosis with polyangiitis (Wegener's) with HLA-DPB1*04 and SEMA6A gene variants: evidence from genome-wide analysis. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association study identifies three new susceptibility loci for adult asthma in the Japanese population. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association study of chronic periodontitis in a general German population. EBI GWAS Catalog EBI GWAS CatalogPubMed
New gene functions in megakaryopoiesis and platelet formation. 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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Replication interactions

Interaction	Pubs
Knockdown of major histocompatibility complex, class II, DO alpha (HLA-DOA) by siRNA inhibits HIV-1 replication in HeLa P4/R5 cells	PubMed

Protein interactions

Protein	Gene	Interaction	Pubs
Envelope surface glycoprotein gp120	env	HIV envelope protein gp120 can specifically inhibit CD4-dependent class II MHC-restricted T cell response to Ag	PubMed
	env	Amino acid residues 42-49 in the V1 region of CD4 are involved in the interaction between HIV-1 gp120 and class II major histocompatibility complex molecules	PubMed
Envelope surface glycoprotein gp160, precursor	env	Processing of HIV-1 gp160 to gp120 and gp41 is necessary for the association of HIV-1 envelope glycoproteins with class II MHC	PubMed
Envelope transmembrane glycoprotein gp41	env	Soluble HIV-1 gp41 enhancement effects on MHC class I and II antigen expression can be inhibited by soluble gp41-binding proteins of 45, 49 and 62 kD from human B cells	PubMed
	env	Soluble HIV-1 gp41 can selectively enhance MHC class I and II expression on human B cells, but does not increase expression of other cell surface antigens such as CD21 and CD54 (ICAM-1)	PubMed
	env	A 43-amino-acid sequence between amino acids 708 and 750 in the HIV-1 gp41(TM) cytoplasmic tail is required for efficient incorporation of HLA class II proteins into virions	PubMed
Nef	nef	Expression of patient-derived HIV-1 nef alleles downregulates MHC-II cell surface expression in activated CD4+ T cells	PubMed
	nef	HIV-1 group N and group O Nef alleles only weakly downregulate CD4, CD28, and class I and II MHC molecules	PubMed
	nef	HIV-1 Nef expression inhibits MHC II presentation of viral antigens in infected antigen-presenting cells	PubMed
	nef	Nef-triggered MHCII endocytosis requires Rab5 activity and lyst function, whereas lysosomal trafficking of internalized MHCII molecules requires Rab7 activity	PubMed
Pr55(Gag)	gag	HIV-1 Gag virus-like particles efficiently activate human monocyte-derived dendritic cells (MDDC) and induce MDDC maturation with an associated increase in the surface expression of CD80, CD86 and MHC classes I and II	PubMed
	gag	Two peptides of the CA domain of HIV-1 Gag, VDRFYKTLRAEQASQ and DRFYKLTRAEQASQ, are presented on MHC II molecules of dendritic cells and have similar sensitivity for antigen-specific T cells	PubMed
	gag	HIV-1 Gag virus-like particle-induced monocyte activation is shown by upregulation of molecules involved in antigen presentation (MHC II, CD80, CD86) and cell adhesion (CD54)	PubMed
Tat	tat	HIV-1 Tat downregulates expression of MHC class II genes in antigen-presenting cells (APC) by inhibiting the transactivator of MHC class II genes, CIITA	PubMed
Vpu	vpu	HIV-1 Vpu interacts with CD74 and modulates MHC II in HIV-1-infected cells	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

WI-18569 (e-PCR)
- UniSTS:19230

CGCb066 (e-PCR)
- UniSTS:240928

D8S2279 (e-PCR)
- UniSTS:473907

G20835 (e-PCR)
- UniSTS:60990

A006I10 (e-PCR)
- UniSTS:60991

RH46819 (e-PCR)
- UniSTS:11143

D11S3114 (e-PCR)
- UniSTS:152207

HLA-DOA_2011 (e-PCR)
- UniSTS:280753

D6S1939 (e-PCR)
- UniSTS:68287

RH66832 (e-PCR)
- UniSTS:30144

D11S2875 (e-PCR)
- UniSTS:152053

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables MHC class II protein complex binding	IBA Inferred from Biological aspect of Ancestor more info
enables MHC class II protein complex binding	IDA Inferred from Direct Assay more info	PubMed
enables MHC class II receptor activity	TAS Traceable Author Statement more info	PubMed
enables peptide antigen binding	IBA Inferred from Biological aspect of Ancestor more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
involved_in adaptive immune response	IEA Inferred from Electronic Annotation more info
involved_in antigen processing and presentation of exogenous peptide antigen via MHC class II	IBA Inferred from Biological aspect of Ancestor more info
involved_in negative regulation of antigen processing and presentation of peptide antigen via MHC class II	IDA Inferred from Direct Assay more info	PubMed
involved_in peptide antigen assembly with MHC class II protein complex	IBA Inferred from Biological aspect of Ancestor more info
involved_in positive regulation of T cell activation	IBA Inferred from Biological aspect of Ancestor more info
involved_in positive regulation of immune response	IBA Inferred from Biological aspect of Ancestor more info
involved_in regulation of T cell differentiation	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
part_of MHC class II protein complex	IBA Inferred from Biological aspect of Ancestor more info
part_of MHC class II protein complex	IDA Inferred from Direct Assay more info	PubMed
is_active_in late endosome membrane	IBA Inferred from Biological aspect of Ancestor more info
is_active_in lysosomal membrane	IBA Inferred from Biological aspect of Ancestor more info
located_in lysosomal membrane	TAS Traceable Author Statement more info
located_in plasma membrane	TAS Traceable Author Statement more info	PubMed

General protein information

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Preferred Names: HLA class II histocompatibility antigen, DO alpha chain

Names: HLA-D0-alpha; MHC DN-alpha; MHC DZ alpha; MHC class II antigen DOA; lymphocyte antigen; major histocompatibility complex, class II, DN alpha

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_012007.1 RefSeqGene

Range

5022..10431

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_002119.4 → NP_002110.1 HLA class II histocompatibility antigen, DO alpha chain precursor

See identical proteins and their annotated locations for NP_002110.1

Status: REVIEWED

Source sequence(s)

AL645931, M31525

Consensus CDS

CCDS4763.1

UniProtKB/Swiss-Prot

P06340, Q58HU0, Q58HU1, Q5STC7, Q9TQC6, Q9TQC7, Q9TQC8, Q9TQC9, Q9TQD0, Q9TQD1, Q9TQD2, Q9TQD3

UniProtKB/TrEMBL

A0A1V0E3M6, A0A1V0E3M7, A0A1V0E3N1, A0A1V0E3N3, A0A1V0E3N6, A0A1V0E3N7, A0A1V0E3P0, A0A1V0E3P1, A0A1V0E3P3, A0A1V0E3P6, A0A1V0E3P8, A0A1V0E3P9, A0A1V0E3Q1, A0A1V0E3Q2, A0A1V0E3Q3, A0A1V0E3Q4, A0A1V0E3Q5, A0A1V0E3Q6, A0A1V0E3Q7, A0A1V0E3Q8, A0A1V0E3R0, A0A1V0E3R3, A0A1V0E3R4, A0A1V0E3R6, A0A1V0E3R8, A0A1V0E3S0, A0A1V0E3S4, A0A1V0E3S6, A0A1V0E3S7, A0A1V0E3T1, X5CF87, X5CKB7

Related

ENSP00000229829.3, ENST00000229829.7

Conserved Domains (3) summary

cd05767
Location:112 → 205

IgC_MHC_II_alpha; Class II major histocompatibility complex (MHC) alpha chain immunoglobulin domain

pfam00993
Location:29 → 109

MHC_II_alpha; Class II histocompatibility antigen, alpha domain

pfam16196
Location:202 → 250

C1-set_C; C1-set C-terminal domain

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

NC_000006.12 Reference GRCh38.p14 Primary Assembly

Range

33004182..33009591 complement

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Reference GRCh38.p14 ALT_REF_LOCI_2

Genomic

NT_113891.3 Reference GRCh38.p14 ALT_REF_LOCI_2

Range

4416350..4421759 complement

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Reference GRCh38.p14 ALT_REF_LOCI_3

Genomic

NT_167245.2 Reference GRCh38.p14 ALT_REF_LOCI_3

Range

4247723..4253131 complement

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Reference GRCh38.p14 ALT_REF_LOCI_4

Genomic

NT_167246.2 Reference GRCh38.p14 ALT_REF_LOCI_4

Range

4423531..4428939 complement

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Reference GRCh38.p14 ALT_REF_LOCI_5

Genomic

NT_167247.2 Reference GRCh38.p14 ALT_REF_LOCI_5

Range

4303237..4308646 complement

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Reference GRCh38.p14 ALT_REF_LOCI_6

Genomic

NT_167248.2 Reference GRCh38.p14 ALT_REF_LOCI_6

Range

4198456..4203865 complement

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Reference GRCh38.p14 ALT_REF_LOCI_7

Genomic

NT_167249.2 Reference GRCh38.p14 ALT_REF_LOCI_7

Range

4453377..4458785 complement

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Alternate T2T-CHM13v2.0

Genomic

NC_060930.1 Alternate T2T-CHM13v2.0

Range

32825532..32830941 complement

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Suppressed Reference Sequence(s)

The following Reference Sequences have been suppressed. Explain

NM_015851.1: Suppressed sequence

Description

NM_015851.1: This RefSeq record was removed by NCBI staff. Contact info@ncbi.nlm.nih.gov for further information.