TFRC

Chr 3AR

transferrin receptor

Also known as: CD71, IMD46, T9, TFR, TFR1, TR, TRFR, p90

NCBI Gene: 7037 ENSG00000072274 UniProt: P02786 OMIM: 190010

The transferrin receptor mediates cellular iron uptake through receptor-mediated endocytosis and is essential for erythropoiesis and neurologic development. Mutations cause immunodeficiency 46, inherited in an autosomal recessive pattern. The gene is highly constrained against loss-of-function variants (LOEUF 0.581), reflecting its critical role in iron homeostasis and immune cell proliferation.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a cell surface receptor necessary for cellular iron uptake by the process of receptor-mediated endocytosis. This receptor is required for erythropoiesis and neurologic development. Multiple alternatively spliced variants have been identified. [provided by RefSeq, Sep 2015]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Immunodeficiency 46MIM #616740

Clinical highlights

Gene-disease validity (ClinGen)

TFRC-related combined immunodeficiency · ARDefinitivesufficient evidence for diagnostic panels

Active trials

354

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.58

LOEUF

Mechanism· predicted

📖

GeneReview available — TFRC

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.58LOEUF

pLI 0.000

Z-score 3.58

OE 0.37 (0.24–0.58)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

0.60Z-score

OE missense 0.92 (0.84–1.00)

380 obs / 414.7 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.37 (0.24–0.58)

0≤0.351.4

Missense OE?0.92 (0.84–1.00)

0≤0.61.4

Synonymous OE?1.00

0≤1.21.6

LoF obs/exp: 14 / 37.7Missense obs/exp: 380 / 414.7Syn Z: -0.00

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

TFRC · 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

📖

GeneReview available — TFRC

Authoritative clinical overview · NCBI Bookshelf · Recommended first read

Open GeneReview ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

Chronic Myeloid Leukemia, Chronic PhaseWithdrawal;Drug

Efficacy and Safety of TKIs' Withdrawal After a Two-step Dose Reduction in Patients with Chronic Myeloid Leukemia

ACTIVE NOT RECRUITING

NCT04147533Phase PHASE2Masaryk UniversityStarted 2020-06-16

Imatinib withdrawalDasatinibNilotinib

Anemia

How Precision Diets, Through Gut Bacteria, Affect Anemia in Nepalese Adolescent

NOT YET RECRUITING

NCT07661602Phase PHASE3Southern Medical University, ChinaStarted 2026-07

Iron folic acid supplementGoat liver supplementationNutrition education on anemia prevention and control

Micronutrient Status

Micronutrient Dose Response Study in Bangladesh

ACTIVE NOT RECRUITING

NCT06081114Phase NAJohns Hopkins Bloomberg School of Public HealthStarted 2023-10-22

Micronutrient Supplement

Philadelphia Chromosome-Positive Chronic Myeloid Leukemia

A Study to Investigate Tolerability and Efficacy of Asciminib (Oral) Versus Nilotinib (Oral) in Adult Participants (≥18 Years of Age) With Newly Diagnosed Philadelphia Chromosome Positive Chronic Myelogenous Leukemia in Chronic Phase (Ph+ CML-CP)

ACTIVE NOT RECRUITING

NCT05456191Phase PHASE3Novartis PharmaceuticalsStarted 2022-11-21

AsciminibNilotinib

Acute Coronary Syndromes (ACS)Iron DeficienciesElderly (People Aged 65 or More)

Effect of Intravenous Iron on Quality of Life in Older Patients With Acute Coronary Syndrome

RECRUITING

NCT07476859Phase PHASE4Fundación para la Investigación del Hospital Clínico de ValenciaStarted 2026-03-05

Ferric Carboxymaltose Injection [Ferinject]

Transfusion-dependent Beta-Thalassemia

Gene-Modified Stem Cell Therapy for Subjects With Transfusion-dependent Beta-thalassemia

RECRUITING

NCT07680803Phase PHASE2Fondazione TelethonStarted 2026-07-06