TFR2

Chr 7

transferrin receptor 2

NCBI Gene: 7036 ENSG00000106327 UniProt: Q9UP52

Mediates cellular uptake of transferrin-bound iron in a non-iron dependent manner. May be involved in iron metabolism, hepatocyte function and erythrocyte differentiation

GeneReviews Research

Mediates cellular uptake of transferrin-bound iron in a non-iron dependent manner. May be involved in iron metabolism, hepatocyte function and erythrocyte differentiation

GeneReviews ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtHemochromatosis 3

Clinical highlights

Gene–disease validity (ClinGen)

Definitive · hemochromatosis type 3 · AR · ClinGen 2025

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

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.77

LOEUF

LOF

Mechanism· G2P

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GeneReview available — TFR2

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

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?

0.77LOEUF

pLI 0.000

Z-score 2.72

OE 0.53 (0.38–0.77)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

1.14Z-score

OE missense 0.85 (0.78–0.93)

401 obs / 470.9 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.53 (0.38–0.77)

0≤0.351.4

Missense OE?0.85 (0.78–0.93)

0≤0.61.4

Synonymous OE?0.89

0≤1.21.6

LoF obs/exp: 21 / 39.4Missense obs/exp: 401 / 470.9Syn Z: 1.18

Background carrier burden — how many people carry a rare variant somewhere in TFR2?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 44

1,055 rare PASS variants

Rare truncating (LoF)

1 in 890

154 rare PASS variants

Rare synonymous (reference)

1 in 110

450 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for TFR2. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 51	1 in 870
South Asian	~43k	1 in 62	1 in 1,800
Remaining (unassigned)	~30k	1 in 35	1 in 1,100
European (Finnish)	~27k	1 in 120	1 in 3,500
Admixed American	~22k	1 in 63	1 in 400
African / African American	~21k	1 in 40	1 in 1,200
East Asian	~20k	1 in 49	1 in 750
Ashkenazi Jewish	~13k	1 in 200	≈ 1 in 6,300
Middle Eastern	~2,884	1 in 49	≈ 1 in 1,400

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 18 coding exons well covered in gnomAD exomes and genomes.? see exons ↓