HLA-DOA

protein-coding

major histocompatibility complex, class II, DO alpha, the group of Histocompatibility complex|C1-set domain containing

Gene 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]

Previous symbols:

HLA-DZA
HLA-DNA

MANE transcript

NM_002119.4

Inheritance

—

ClinVar variants

U:2B:2

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 1.27

Max pathogenic AF

—

Genomic locus

chr6:33,004,182-33,009,591

External References & Databases

Ensembl (ENSG00000204252)

Transcript & Mutation Effects

hg38 • Region Span ~5.4 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to HLA-DOA variants in ClinVar

1 Conditions Cataloged

not providedTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_002119.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			1 clinvar		2 clinvar	3
missense			1 clinvar			1
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	2	0	2	4

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 7 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_002119.4	RefSeq	NP_002110.1	5	MANE Select
ENST00000229829.7	Ensembl	ENSP00000229829.3	5	MANE Select
ENST00000374813.1	Ensembl	ENSP00000363946.1	3	Standard
ENST00000892664.1	Ensembl	ENSP00000562723.1	4	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Antigen processing and presentation - Homo sapiens (human)
Cell adhesion molecules (CAMs) - Homo sapiens (human)
Type I diabetes mellitus - Homo sapiens (human)
Allograft rejection - Homo sapiens (human)
Graft-versus-host disease - Homo sapiens (human)

Biological Process

negative regulation of antigen processing and presentation of peptide antigen via MHC class II
immune response
antigen processing and presentation of exogenous peptide antigen via MHC class II
regulation of T cell differentiation

Molecular Function

protein binding
MHC class II protein complex binding
MHC class II receptor activity

Cellular Component

lysosomal membrane
plasma membrane
endosome membrane
integral component of membrane
MHC class II protein complex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000229829
Coding exons: 5
Length: 5435
Individuals with no LoFs: 123451
Homozygous LoFs: 1
Heterozygous LoFs: 116
Defined: 123568
p: 0.000474

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.470	141	158	0.895	0.00000966	1603
Missense (PolyPhen)		65	65.363	0.99445		685
Synonymous	1.08	57	68.4	0.834	0.00000449	526
Loss of Function	-0.812	13	10.2	1.27	4.36e-7	108

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.00055	0.00055	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.0046	0.0045	notable
Finnish	0	0.0	absent
European (Non-Finnish)	0.000082	0.000081	rare
South Asian	0.00017	0.00016	rare
Other	0.00017	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Important modulator in the HLA class II restricted antigen presentation pathway by interaction with the HLA-DM molecule in B-cells. Modifies peptide exchange activity of HLA-DM.;

Recessive Scores

pRec: 0.0932

Intolerance Scores

LoFtool: 0.763
RVIS EVS: 0.66
RVIS percentile EVS: 84.44

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.458

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium