HLA-B

Chr 6Multi

major histocompatibility complex, class I, B

Also known as: AS, B-4901, HLAB

NCBI Gene: 3106ENSG00000234745UniProt: P01889

HLA-B belongs to the HLA class I heavy chain paralogues. This class I molecule is a heterodimer consisting of a heavy chain and a light chain (beta-2 microglobulin). The heavy chain is anchored in the membrane. Class I molecules play a central role in the immune system by presenting peptides derived from the endoplasmic reticulum lumen. They are expressed in nearly all cells. The heavy chain is approximately 45 kDa and its gene contains 8 exons. Exon 1 encodes the leader peptide, exon 2 and 3 encode the alpha1 and alpha2 domains, which both bind the peptide, exon 4 encodes the alpha3 domain, exon 5 encodes the transmembrane region and exons 6 and 7 encode the cytoplasmic tail. Polymorphisms within exon 2 and exon 3 are responsible for the peptide binding specificity of each class one molecule. Typing for these polymorphisms is routinely done for bone marrow and kidney transplantation. Hundreds of HLA-B alleles have been described. [provided by RefSeq, Jul 2008]

Primary Disease Associations & Inheritance

{Ankylosing spondylitis, susceptibility to, 1}MIM #106300
Multi
{Severe cutaneous adverse reaction, susceptibility to}MIM #608579
{Stevens-Johnson syndrome, susceptibility to}MIM #608579
{Toxic epidermal necrolysis, susceptibility to}MIM #608579
UniProtSpondyloarthropathy 1
45
ClinVar variants
8
Pathogenic / LP
0.00
pLI score
12
Active trials
Clinical Summary— HLA-B
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
8 Pathogenic / Likely Pathogenic· 5 VUS of 45 total submissions
💊
Clinical Trials
12 active or recruiting trials — potential therapeutic options may be available

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.
0.91LOEUF
pLI 0.000
Z-score 1.85
OE 0.54 (0.33–0.91)
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.
-0.01Z-score
OE missense 1.00 (0.89–1.13)
196 obs / 195.6 exp
Tolerant

Tolerant to missense variation

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.0.54 (0.33–0.91)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.00 (0.89–1.13)
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.0.98
0≤1.21.6
LoF obs/exp: 10 / 18.6Missense obs/exp: 196 / 195.6Syn Z: 0.13

ClinVar Variant Classifications

45 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic5
Likely Pathogenic3
VUS5
Likely Benign21
Benign10
Conflicting1
5
Pathogenic
3
Likely Pathogenic
5
VUS
21
Likely Benign
10
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
5
0
5
Likely Pathogenic
0
0
3
0
3
VUS
0
1
4
0
5
Likely Benign
3
6
0
12
21
Benign
5
4
0
1
10
Conflicting
—1
Total811121345

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

HLA-B · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

{Ankylosing spondylitis, susceptibility to, 1}

MIM #106300

Molecular basis of disorder known

Multifactorial

{Severe cutaneous adverse reaction, susceptibility to}

MIM #608579

Molecular basis of disorder known

{Stevens-Johnson syndrome, susceptibility to}

MIM #608579

Molecular basis of disorder known

{Toxic epidermal necrolysis, susceptibility to}

MIM #608579

Molecular basis of disorder known

📖
GeneReview available — HLA-B
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Autoimmunity-associated T cell receptors recognize HLA-B*27-bound peptides.
Yang X et al.·Nature
2022
Understanding the Pathogenesis of Spondyloarthritis.
Sharip A et al.·Biomolecules
2020Review
Mucosal signatures of pathogenic T cells in HLA-B*27+ anterior uveitis and axial spondyloarthritis.
Paley MA et al.·JCI Insight
2024
Autoimmune Hepatitis: Pathophysiology.
Yuming Z et al.·Clin Liver Dis
2024Review
STAMBPL1/TRIM21 Balances AXL Stability Impacting Mesenchymal Phenotype and Immune Response in KIRC.
Huang S et al.·Adv Sci (Weinh)
2025
HLA-B*51 and Behçet Disease.
Gul A et al.·Ocul Immunol Inflamm
2012Review
Ankylosing Spondylitis: HLA-B*27-Positive Versus HLA-B*27-Negative Disease.
Akkoç N et al.·Curr Rheumatol Rep
2017Review
Whole-exome sequencing association study reveals genetic effects on tumor microenvironment components in nasopharyngeal carcinoma.
Zeng Y et al.·J Clin Invest
2025
Polymorphisms of HLA-B: influences on assembly and immunity.
Olson E et al.·Curr Opin Immunol
2020Review
Spondyloarthritis and the Human Leukocyte Antigen (HLA)-B(*)27 Connection.
Kavadichanda CG et al.·Front Immunol
2021Review
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
End-Stage Renal DiseaseEnd Stage Renal Disease on DialysisEnd Stage Renal Disease With Renal Transplant

CRISPR-Edited HLA Donor Kidney Transplant to Reduce Rejection Risk

RECRUITING
NCT07053462Phase PHASE1, PHASE2AMERICAN ORGAN TRANSPLANT AND CANCER RESEARCH INSTITUTE LLCStarted 2025-06-01
Ex Vivo CRISPR-Cas9 Gene Editing of Donor KidneyKidney Transplantation with Standard Care
Humoral Primary Immunodeficiencies (PIDs)Secondary Form of Humoral ImmunodeficienciesCombined Immunodeficiency (CID)

Study of Populations at Risk of Developing Chronic Hepatitis Linked to Chronic Enteric Virus Infection in Patients With Primary Immunodeficiency and Secondary Humoral Deficiency

RECRUITING
NCT06659588Assistance Publique - Hôpitaux de ParisStarted 2024-10-10
Plasma, urine and stool collection
Cutaneous Squamous Cell Carcinoma (CSCC)

Next-gen Flow Cytometry to Find Immune Profiles, Treatment Response, and Toxicity Markers in Skin Cancer Patients Treated With Cemiplimab.

RECRUITING
NCT07064330Instituto de Investigación Biomédica de SalamancaStarted 2025-07-17
Cemiplimab
EndometriosisImmunityMicrobiota

Innate Immunity, MIcrobiota and Inovative Treatments in Endometriosis

NOT YET RECRUITING
NCT07078435Phase NAUniversity Hospital, GrenobleStarted 2025-09-09
surgery (any volume) and / or pharmaceuticals treatment initiated or planned or only dynamic observation, in accordance with current clinical guidelinesBlood testStool samples
Influenza

Human Infection Study of H3N2 Influenza in Healthy Adults

ACTIVE NOT RECRUITING
NCT06972810Phase NAUniversity of MelbourneStarted 2025-05-05
A/Texas/71/2017, clade 3C3a H3N2 influenza virus
Liver DiseasesLiver CancerLiver Cirrhosis

CRISPR-Edited HLA Donor Liver Transplant to Reduce Rejection

RECRUITING
NCT07053488Phase PHASE1, PHASE2AMERICAN ORGAN TRANSPLANT AND CANCER RESEARCH INSTITUTE LLCStarted 2025-06-01
Ex Vivo CRISPR-Cas9 Gene Editing of Donor Liver
NY-ESO-1 Expressing Solid Tumors in HLA-A2 Positive PatientsSynovial SarcomaMelanoma

Study of TBI-1301 (NY-ESO-1 Specific TCR Gene Transduced Autologous T Lymphocytes) in Patients With Solid Tumors

ACTIVE NOT RECRUITING
NCT02869217Phase PHASE1University Health Network, TorontoStarted 2016-09
CyclophosphamideTBI-1301Fludarabine
AutophagyGalectinsHIV Infections

Study of Autophagy and the Effects of GALIG Gene Products in HIV-1 Infected Patients Who Are Under Antiretroviral Therapy Since Primary-infection, Chronic Phase, or Never Treated.

RECRUITING
NCT04160455Centre Hospitalier Régional d'OrléansStarted 2019-11-07
expression of a panel
B-cell Acute Lymphoblastic Leukemia

Allogeneic Second-generation CD19-CAR T Cells for Pediatric Relapsed/Refractory B-ALL

RECRUITING
NCT06080191Phase PHASE1Bambino Gesù Hospital and Research InstituteStarted 2024-04-28
CD19-CAR_Lenti_ALLO
Non Hodgkin's Lymphoma

Allogenic CD19-targeting CAR-γδT Cell Therapy in R/R NHL

RECRUITING
NCT05554939Phase PHASE1, PHASE2Chinese PLA General HospitalStarted 2022-12-11
Allogenic CD19 CAR-γδT cellFludarabineCyclophosphamide
Diabetic Foot Ulcer (DFU)Venous Leg Ulcer (VLU)

Safety and Preliminary Efficacy of TrophiPatch, an Adipose-Derived Stromal Cell Patch for Chronic Leg Ulcers

RECRUITING
NCT07048054Phase PHASE1, PHASE2Nicolò BrembillaStarted 2025-07
TrophiPatch: allogeneic adipose-derived stromal cell patch
Kidney Transplant

Alloreactive Memory B Lymphocytes and Anti-HLA Sensitization

RECRUITING
NCT07011238University Hospital, RouenStarted 2023-04-17
Patients meeting HLA immunization criteria

External Resources

Links to major genomics databases and tools