HLA-DQB1

Chr 6ARMultiAD

major histocompatibility complex, class II, DQ beta 1

Also known as: CELIAC1, HLA-DQB, IDDM1

NCBI Gene: 3119 ENSG00000179344 UniProt: P01920

HLA-DQB1 belongs to the HLA class II beta chain paralogs. This class II molecule is a heterodimer consisting of an alpha (DQA) and a beta chain (DQB), both anchored in the membrane. It plays a central role in the immune system by presenting peptides derived from extracellular proteins. Class II molecules are expressed in antigen presenting cells (APC: B lymphocytes, dendritic cells, macrophages). The beta chain is approximately 26-28 kDa and it contains six exons. Exon 1 encodes the leader peptide, exons 2 and 3 encode the two extracellular domains, exon 4 encodes the transmembrane domain and exon 5 encodes the cytoplasmic tail. Within the DQ molecule both the alpha chain and the beta chain contain the polymorphisms specifying the peptide binding specificities, resulting in up to four different molecules. Typing for these polymorphisms is routinely done for bone marrow transplantation. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2011]

Primary Disease Associations & Inheritance

{Celiac disease, susceptibility to}MIM #212750

ARMulti

{Creutzfeldt-Jakob disease, variant, resistance to}MIM #123400

{Multiple sclerosis, susceptibility to, 1}MIM #126200

Multi

ClinVar variants

Pathogenic / LP

0.01

pLI score

Active trials

Clinical Summary— HLA-DQB1

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Population Constraint (gnomAD)

Low constraint (pLI 0.01) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

6 Pathogenic / Likely Pathogenic· 4 VUS of 20 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.

0.94LOEUF

pLI 0.009

Z-score 1.70

OE 0.45 (0.23–0.94)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.

1.31Z-score

OE missense 0.68 (0.57–0.81)

91 obs / 133.7 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.

LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.45 (0.23–0.94)

0≤0.351.4

Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.68 (0.57–0.81)

0≤0.61.4

Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.60

0≤1.21.6

LoF obs/exp: 5 / 11.1Missense obs/exp: 91 / 133.7Syn Z: 2.25