TFRC

Chr 3AR

transferrin receptor

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

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.

Summary from RefSeq, OMIM, UniProt
Research Assistant →

Primary Disease Associations & Inheritance

Immunodeficiency 46MIM #616740
AR
11
Active trials
235
Pubs (1 yr)
13
P/LP submissions
0%
P/LP missense
0.58
LOEUF
DN
Mechanism· predicted
Clinical SummaryTFRC
🧬
Gene-Disease Validity (ClinGen)
TFRC-related combined immunodeficiency · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
13 unique Pathogenic / Likely Pathogenic· 272 VUS of 500 total submissions
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Clinical Trials
11 active or recruiting trials — potential therapeutic options may be available
📖
GeneReview available — TFRC
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.58LOEUF
pLI 0.000
Z-score 3.58
OE 0.37 (0.240.58)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
0.60Z-score
OE missense 0.92 (0.841.00)
380 obs / 414.7 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.37 (0.240.58)
00.351.4
Missense OE0.92 (0.841.00)
00.61.4
Synonymous OE1.00
01.21.6
LoF obs/exp: 14 / 37.7Missense obs/exp: 380 / 414.7Syn Z: -0.00
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
limitedTFRC-related combined immunodeficiencyOTHERAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.6357th %ile
GOF
0.5856th %ile
LOF
0.3065th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

500 submitted variants in ClinVar

Classification Summary

Pathogenic13
VUS272
Likely Benign155
Benign37
Conflicting5
13
Pathogenic
272
VUS
155
Likely Benign
37
Benign
5
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
13
0
13
Likely Pathogenic
0
0
0
0
0
VUS
5
238
24
5
272
Likely Benign
0
1
81
73
155
Benign
0
0
36
1
37
Conflicting
5
Total523915479482

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

View in 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.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

Chronic Myeloid Leukemia, BCR/ABL-Positive

Follow-up Study on Chronic Myeloid Leukemia Patients Achieving Treatment-free Remission

RECRUITING
NCT05439889National Taiwan University HospitalStarted 2022-08-11
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
VEXAS Syndrome

Multicenter, Interdisciplinary National VEXAS Registry With Accompanying Biomaterial Collection

RECRUITING
NCT06377462Technische Universität DresdenStarted 2024-03-13
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
Malnutrition PregnancyMalnutrition in ChildrenMalnutrition (Calorie)

Early Life Malnutrition, Environmental Enteric Dysfunction and Microbiome Trajectories

RECRUITING
NCT07195006University of ZimbabweStarted 2025-01-27
Malnutrition in pregnancy as exposurePoor WASH living conditions as exposure
Chronic Myeloid Leukemia, Chronic PhaseAdult CMLLeukemia, Myeloid

Asciminib as Initial Therapy for Patients With Chronic Myeloid Leukemia in Chronic Phase

RECRUITING
NCT05143840Phase PHASE2Augusta UniversityStarted 2022-04-22
Single Agent AsciminibLow TKIElective Free Treatment
Sickle Cell Disease

A Study Evaluating Gene Therapy With BB305 Lentiviral Vector in Sickle Cell Disease

ACTIVE NOT RECRUITING
NCT04293185Phase PHASE3Genetix Biotherapeutics Inc.Started 2020-02-14
bb1111
Anemia, Iron DeficiencyIron Overload

Heme and Non-heme Iron Intakes, Gut Microbiota, and Influence on Host Iron Absorption

RECRUITING
NCT06146608Cornell UniversityStarted 2023-01-15
Micronutrient Status

Micronutrient Dose Response Study in Bangladesh

ACTIVE NOT RECRUITING
NCT06081114Phase NAJohns Hopkins Bloomberg School of Public HealthStarted 2023-10-22
Micronutrient Supplement
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]
Weight GainAnemia, Iron DeficiencyBirth Weight

Egg Intervention During Pregnancy in Indonesia

ACTIVE NOT RECRUITING
NCT04694235Phase NASEAMEO Regional Centre for Food and NutritionStarted 2021-02-12
Egg intervention
Clinical Literature
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