HLA-E

Chr 6

major histocompatibility complex, class I, E

Also known as: HLA-6.2, QA1

HLA-E 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. HLA-E binds a restricted subset of peptides derived from the leader peptides of other class I molecules. The heavy chain is approximately 45 kDa and its gene contains 8 exons. Exon one encodes the leader peptide, exons 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. [provided by RefSeq, Jul 2008]

ResearchGenerating clinical summary…

Clinical highlights

Interpreting a novel variant
This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.
10
Active trials
198
Pubs (1 yr)
P/LP submissions
P/LP missense
0.61
LOEUF
DN
Mechanism· predicted
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint?
0.61LOEUF
pLI 0.037
Z-score 2.80
OE 0.31 (0.170.61)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?
1.98Z-score
OE missense 0.62 (0.540.71)
132 obs / 213.3 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?
LoF OE?0.31 (0.170.61)
00.351.4
Missense OE?0.62 (0.540.71)
00.61.4
Synonymous OE?0.79
01.21.6
LoF obs/exp: 6 / 19.3Missense obs/exp: 132 / 213.3Syn Z: 1.58

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

HLA-E · protein map & ClinVar variants

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

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
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
Solid Tumor, AdultColorectal CancerNon-Small Cell Lung

A Study to Evaluate the Safety and Efficacy of A2B395, an Allogeneic Logic-gated CAR T, in Participants With Solid Tumors That Express EGFR and Have Lost HLA-A*02 Expression

RECRUITING
NCT06682793Phase PHASE1, PHASE2A2 Biotherapeutics Inc.Started 2025-05-22
A2B395xT CDx with HLA-LOH assay
Kidney Cancer

HERV-E TCR Transduced Autologous T Cells in People With Metastatic Clear Cell Renal Cell Carcinoma

ACTIVE NOT RECRUITING
NCT03354390Phase PHASE1National Heart, Lung, and Blood Institute (NHLBI)Started 2018-07-20
cell infusion
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
Epilepsy

Precision Medicine in the Treatment of Epilepsy

RECRUITING
NCT05450822Gitte Moos KnudsenStarted 2022-02-18
LevetiracetamLevetiracetam TabletsLamotrigine tablet
Hepatitis C Virus Infection

Characterization of Immune Genotypes and Antibody Profiles to Foster the discoVERY of diagnosticbioMARKERS of Liver Cancer Development

RECRUITING
NCT06718530Centro di Riferimento Oncologico - AvianoStarted 2024-05-13
Sickle Cell Disease

Efficacy Safety Study of Gene Therapy for Sickle Cell DiseaseSCD Using Autologous CD34+ Cells Transduced ex Vivo, Carrying a Corrected Globin Gene and a Silencing RNA.

RECRUITING
NCT07432867Phase PHASE1, PHASE2Assistance Publique - Hôpitaux de ParisStarted 2026-02-25
DREAM01 drug productanti-inflammatory therapy
GATA2ImmunodeficiencyMDS

Allogeneic Hematopoietic Stem Cell Transplant for GATA2 Mutations

RECRUITING
NCT01861106Phase PHASE2National Cancer Institute (NCI)Started 2013-07-24
Allogeneic HSCTBusulfan Test doseFludarabine (Fludara, Berlex Laboratories)
HivHIV I Infection

Multi Interventional Approaches to Mitigate HIV Reservoirs for the Sustained HIV Remission Without Antiretrovirals

RECRUITING
NCT06805656Phase PHASE2Federal University of São PauloStarted 2026-07-15
MaravirocDolutegravirDendritic Cell Vaccine