HLA-G

Chr 6AD

major histocompatibility complex, class I, G

Also known as: MHC-G

NCBI Gene: 3135ENSG00000204632UniProt: P17693

HLA-G 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-G is expressed on fetal derived placental cells. 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 domain, which both bind the peptide, exon 4 encodes the alpha3 domain, exon 5 encodes the transmembrane region, and exon 6 encodes the cytoplasmic tail. [provided by RefSeq, Jul 2008]

Primary Disease Associations & Inheritance

{Asthma, susceptibility to}MIM #600807
AD
14
ClinVar variants
6
Pathogenic / LP
0.00
pLI score
11
Active trials
Clinical Summary— HLA-G
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
6 Pathogenic / Likely Pathogenic· 2 VUS of 14 total submissions
💊
Clinical Trials
11 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.
1.46LOEUF
pLI 0.000
Z-score 0.11
OE 0.97 (0.67–1.46)
Tolerant

Highly tolerant — LoF variants common in population

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.
0.23Z-score
OE missense 0.95 (0.85–1.07)
198 obs / 207.3 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.0.97 (0.67–1.46)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.95 (0.85–1.07)
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.1.07
0≤1.21.6
LoF obs/exp: 17 / 17.5Missense obs/exp: 198 / 207.3Syn Z: -0.52

ClinVar Variant Classifications

14 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic5
Likely Pathogenic1
VUS2
Likely Benign3
Benign3
5
Pathogenic
1
Likely Pathogenic
2
VUS
3
Likely Benign
3
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
5
0
5
Likely Pathogenic
0
0
1
0
1
VUS
0
0
2
0
2
Likely Benign
0
0
0
3
3
Benign
0
0
0
3
3
Total008614

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

View in ClinVar →

Protein Context — Lollipop Plot

HLA-G · 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

{Asthma, susceptibility to}

MIM #600807

Disorder mapped to chromosomal region

Autosomal dominant
📖
GeneReview available — HLA-G
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Soluble HLA revisited.
Tabayoyong WB et al.·Leuk Res
2007Review
HLA-G molecule.
Kamishikiryo J et al.·Curr Pharm Des
2009
Human uterine lymphocytes.
King A et al.·Hum Reprod Update
1998Review
Immunology of implantation.
Loke YW et al.·Baillieres Best Pract Res Clin Obstet Gynaecol
2000Review
Editorial: The Biological and Clinical Aspects of HLA-G.
LeMaoult J et al.·Front Immunol
2021
Harnessing the potential of HLA-G in cancer therapy: advances, challenges, and prospects.
Wang S et al.·J Transl Med
2024Review
Future of Muse Cells.
Young W·Adv Exp Med Biol
2018Review
HLA-G transgenic mice.
Mellor A et al.·J Reprod Immunol
1999
Role of HLA-G in tumors and upon COVID-19 infection.
Seliger B·Hum Immunol
2024Review
HLA-G/ILTs Targeted Solid Cancer Immunotherapy: Opportunities and Challenges.
Lin A 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
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
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
Acute Myeloid LeukemiaMinimal Residual DiseaseNatural Killer Cell

Infusion of Alloreactive nk Cells for Mrd-positive Aml Patients

RECRUITING
NCT06885476Phase NAIRCCS Azienda Ospedaliero-Universitaria di BolognaStarted 2021-01-22
Infusion of alloreactive NK cells
Glioma

Clinical Study for the Safety and Therapeutic Efficacy of the AI-QMMM Designed TamavaqTM Personalised Vaccine in Patients With Newly Diagnosed Glioma.

RECRUITING
NCT07077616Phase EARLY_PHASE1Biogenea Pharmaceuticals Ltd.Started 2025-07-01
Biological: personalized vaccine Based on genetic and transcriptional sequencing information, personalized peptide vaccines would be designed and produced;
Obstructive Sleep Apnea-Hypopnea SyndromeAnxiety DisordersDepressive Disorders

EGR2 and NLRP3 Pathways in Obstructive Sleep Apnea-Related Cognitive and Mood Disorders

RECRUITING
NCT07120711Xinhua Hospital, Shanghai Jiao Tong University School of MedicineStarted 2025-07-01
EGR2/NLRP3 pathway activityfatty tissue
X-linked Severe Combined Immunodeficiency (XSCID)

Lentiviral Gene Transfer for Treatment of Children Older Than Two Years of Age With X-Linked Severe Combined Immunodeficiency (XSCID)

RECRUITING
NCT01306019Phase PHASE1, PHASE2National Institute of Allergy and Infectious Diseases (NIAID)Started 2012-09-25
Ex vivo culture and transduction of the patient's autologous CD34+ HSC with lentivirus vector VSV-G pseudotyped CL20- 4i-EF1alpha-hgammac-OPT vectorBusulfanPalifermin
Heart Transplant Rejection

Trifecta-Heart cfDNA-MMDx Study

RECRUITING
NCT04707872University of AlbertaStarted 2021-06-01
MMDx diagnostic testProsperaHLA antibody
Neoplasms

Study to Evaluate Safety and Antitumor Activity of Lete-Cel (GSK3377794) in HLA-A2+ Participants With NY-ESO-1 Positive Previously Treated Advanced (Metastatic or Unresectable) Synovial Sarcoma or Myxoid/Round Cell Liposarcoma

ACTIVE NOT RECRUITING
NCT06703346Phase PHASE2USWM CT, LLCStarted 2019-12-31
Letetresgene autoleucel (Lete-Cel (GSK3377794))CyclophosphamideFludarabine
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
Autoimmune Hepatitis

A Study on Factors of Biochemical Response in Autoimmune Hepatitis

NOT YET RECRUITING
NCT06356506Beijing Friendship HospitalStarted 2024-05-01
Neoplasms

Study to Evaluate Safety and Antitumor Activity of Lete-Cel (GSK3377794) in HLA-A2+ Participants With NY-ESO-1 Positive Previously Untreated Advanced (Metastatic or Unresectable) Synovial Sarcoma and Myxoid/Round Cell Liposarcoma

ACTIVE NOT RECRUITING
NCT05993299Phase PHASE2AdaptimmuneStarted 2019-12-31
Letetresgene autoleucelCyclophosphamideFludarabine

External Resources

Links to major genomics databases and tools