HFE

Chr 6

homeostatic iron regulator

Also known as: HFE1, HH, HLA-H, MVCD7, TFQTL2

NCBI Gene: 3077 ENSG00000010704 UniProt: Q30201

The protein encoded by this gene is a membrane protein that is similar to MHC class I-type proteins and associates with beta2-microglobulin (beta2M). It is thought that this protein functions to regulate iron absorption by regulating the interaction of the transferrin receptor with transferrin. The iron storage disorder, hereditary haemochromatosis, is a recessive genetic disorder that results from defects in this gene. [provided by RefSeq, May 2022]

Research

ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtHemochromatosis 1

Clinical highlights

Gene-disease validity (ClinGen)

hemochromatosis type 1 · ARDefinitivesufficient evidence for diagnostic panels

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

237

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.19

LOEUF

LOF

Mechanism· G2P

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.19LOEUF

pLI 0.000

Z-score 0.96

OE 0.76 (0.50–1.19)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.63Z-score

OE missense 0.87 (0.77–0.99)

165 obs / 189.5 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.76 (0.50–1.19)

0≤0.351.4

Missense OE?0.87 (0.77–0.99)

0≤0.61.4

Synonymous OE?0.89

0≤1.21.6

LoF obs/exp: 14 / 18.5Missense obs/exp: 165 / 189.5Syn Z: 0.76

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

HFE · protein map & ClinVar variants

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

External Resources

Links to major genomics databases and tools

Franklin by Genoox

AI-powered variant curation and clinical analysis

DECIPHER

Genomic variants and phenotypes in rare disease patients

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

Central Nervous System Lymphoma

Selinexor in Combination With MTX+Ritu to Treat R/R CNSL

RECRUITING

NCT05698147Phase PHASE1, PHASE2Tong Chen, MDStarted 2023-08-03

SelinexorRituximabMethotrexate

Neovascular Age-Related Macular Degeneration

Safety and Efficacy of LX102 Gene Therapy in Patients With Neovascular Age-related Macular Degeneration (nAMD) (VENUS)

ACTIVE NOT RECRUITING

NCT06196840Phase PHASE2Innostellar Biotherapeutics Co.,LtdStarted 2024-01-24

LX102 subretinal injectionAflibercept intravitreal injection

Neovascular Age-related Macular Degeneration

Phase I/II Study of SKG0106 Intravitreal Injection in Patients With Neovascular Age-related Macular Degeneration (nAMD)

RECRUITING

NCT05986864Phase PHASE1, PHASE2Skyline Therapeutics (US) Inc.Started 2024-02-23

SKG0106

Breast NeoplasmsTriple Negative Breast NeoplasmsHR Low-Positive/HER2-Negative Breast Neoplasms

A Clinical Study of Sacituzumab Tirumotecan (Sac-TMT, MK-2870) in People With Breast Cancer (MK-2870-032)

RECRUITING

NCT06966700Phase PHASE3Merck Sharp & Dohme LLCStarted 2025-06-30

Sacituzumab tirumotecanPembrolizumabRescue Medication

Primary Hepatocellular Carcinoma

29-Gene Liver Cancer Subtype and Immunotherapy Effectiveness

NOT YET RECRUITING

NCT07100236Junjie XuStarted 2025-08-01

Observational study of 29 - gene - defined HCC subtypes and immunotherapy responsiveness correlation

Non-Small Cell Lung Cancer

Study of MCLA-129 in the Treatment of Advanced Non-small Cell Lung Cancer with AGA and MET Amplification.

NOT YET RECRUITING

NCT06885840Phase PHASE2Betta Pharmaceuticals Co., Ltd.Started 2025-03-31

MCLA-129

Advanced Solid Tumor

A Phase I/IIa Study of JAB-23E73 in Patients With Advanced Solid Tumors Harboring KRAS Gene Alteration

RECRUITING

NCT06959615Phase PHASE1, PHASE2Jacobio Pharmaceuticals Co., Ltd.Started 2024-11-22

JAB-23E73JAB-23E73

Familial Hypercholesterolemia

Child-Parent Familial Hypercholesterolemia Screening

RECRUITING

NCT04529967Children's Hospital of Fudan UniversityStarted 2025-04-01

no interventions

Intrahepatic Cholangiocarcinoma (Icc)Advanced Cholangiocarcinoma

Efficacy and Safety of TT-00420 (Tinengotinib) Tablets Versus Chemotherapy in Patients With Advanced Intrahepatic Cholangiocarcinoma Harboring FGFR2 Fusions/Rearrangements or Mutations

NOT YET RECRUITING

NCT07328919Phase PHASE3TransThera Sciences (Nanjing), Inc.Started 2026-01

TT-00420 (tinengotinib)Oxaliplatin, fluorouracil, calcium folinate, irinotecan, capecitabine

NSCLC (Advanced Non-small Cell Lung Cancer)

QL1706 Combined With Chemotherapy in the Treatment of Immune-mediated NSCLC

RECRUITING

NCT07330596Phase PHASE2Anhui Provincial Cancer HospitalStarted 2025-10-30

QL1706 combined with ChemotherapyChemotherapy

Non-small Cell Lung Cancer

A Clinical Trial of Calderasib (MK-1084) and Durvalumab in People With Non-Small Cell Lung Cancer (MK-1084-015/KANDLELIT-015)

RECRUITING

NCT07554339Phase PHASE3Merck Sharp & Dohme LLCStarted 2026-06-18