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HFE H63D

A DNA test for a common change in the HFE gene. On its own it rarely causes iron overload, but together with C282Y it can raise iron levels a little.

AI-verified against cited sources. Awaiting expert reviewAlso called H63DLOINC 21696-0

What it is

The HFE gene helps your body control how much iron it absorbs from food. H63D is a common change in HFE that swaps histidine for aspartic acid at position 63 of the HFE protein. You inherit one copy of the gene from each parent. The result is usually not detected, heterozygous (one copy) or homozygous (two copies). Labs usually report it together with C282Y, the other common HFE change. H63D is most common in people of European descent.

Why it matters

H63D often shows up when someone is checked for hereditary hemochromatosis, a condition where the body absorbs too much iron. On its own, H63D is generally not linked to iron overload. What matters more is whether it comes with C282Y. One C282Y copy plus one H63D copy (compound heterozygous) can be linked to somewhat higher iron levels, although iron-related illness was rare in a large study that followed people for about 12 years. The blood tests ferritin and transferrin saturation show your iron levels, and your clinician reads them together with this result.

If it’s high

One or two copies of H63D usually do not cause iron overload. Liver-disease guidelines say people with one or two H63D copies can be reassured that they are generally not at risk of progressive iron overload, although they may have small changes in iron tests, and occasionally a person with two copies develops mild iron overload. If you also carry C282Y, the combination is read differently, so look at the C282Y result as well.

Common causes

  • Inherited from one or both parents
  • Common in people of European descent

What can help

  • Ask your clinician how this result fits with your ferritin and transferrin saturation
  • Ask whether your C282Y result was checked at the same time
  • If your iron tests are raised, ask whether other causes, such as fatty liver disease or alcohol-related liver disease, should be looked at

If this applies to you

HFE H63D means a little more for some people. Open the one that fits you.

Hemochromatosis or iron overload

ACG advises that people with H63D and no C282Y be told they are not at higher risk of iron overload. H63D matters mainly when it comes with one copy of C282Y.

Blood tests for hemochromatosis

What can affect your result

  • Whether C282Y is also present, because the combination is read differently from H63D alone
  • Other liver conditions, such as fatty liver disease, hepatitis C or alcohol-related liver disease, can add to liver damage
  • Iron blood tests that go with this result can shift for other reasons, such as menopause
  • A past bone marrow transplant from a donor can interfere with the DNA test
  • A previous bone marrow transplant from a donor will interfere with the test, because the DNA may come from the donor's cells (Mayo Clinic Laboratories).
  • The gene result does not change with food, supplements or illness. The iron blood tests that go with it can shift for other reasons, such as menopause, fatty liver disease or alcohol-related liver disease.

Your result is fixed at birth and does not change.

When to talk to a clinician

An H63D result alone is not urgent. Talk with your clinician if your ferritin or transferrin saturation is raised, or if you have ongoing tiredness, joint pain or belly pain.

Questions you could ask

  • Should any of my relatives be tested?
  • If my iron tests are raised, what else could explain it?
  • Do my iron tests (ferritin and transferrin saturation) fit with this result?
  • Was my C282Y result checked at the same time?

Questions people ask

Does H63D mean I have hemochromatosis?

Not by itself. H63D alone is generally not linked to iron overload. Whether you have too much iron depends on blood tests such as ferritin and transferrin saturation and, in some cases, imaging. Your clinician puts the gene result together with those tests.

What if I have both H63D and C282Y?

Having one copy of each is called compound heterozygous. Some people with this result have somewhat higher iron levels, especially women after menopause. In a large study that followed people for about 12 years, iron-related illness was rare: 1 of 82 men and none of 95 women. Your clinician reads the result with your iron tests.

Show the science and sources

For clinicians and researchers

The variant is HFE c.187C>G, p.His63Asp (rs1799945, NM_000410). AASLD 2011 states that H63D and S65C are generally not associated with iron loading unless seen with C282Y as a compound heterozygote; that H63D heterozygotes and homozygotes can be reassured they are generally not at risk of progressive iron overload, although they may have minor abnormalities in transferrin saturation or ferritin; that occasional H63D homozygotes develop mild iron overload; and that any of these genotypes can act as a cofactor for liver disease alongside porphyria cutanea tarda, hepatitis C, alcohol-related liver disease or NAFLD. The 2022 EASL guideline requires hepatic iron overload on MRI or liver biopsy to diagnose haemochromatosis in people with high transferrin saturation and raised ferritin but HFE genotypes other than C282Y homozygosity. The ACG 2019 guideline notes that fatty liver and alcohol-related liver disease are more common than hereditary hemochromatosis in patients with raised ferritin who are not C282Y homozygotes or C282Y/H63D compound heterozygotes. In 31,192 northern Europeans, C282Y/H63D compound heterozygotes had higher mean ferritin and transferrin saturation than people with neither variant, but documented iron-overload-related disease was seen in 1 of 82 males and 0 of 95 females; compound heterozygotes make up about 2% of northern Europeans, around four times the rate of C282Y homozygotes (Gurrin 2009). In the HEIRS study, C282Y and H63D genotype frequencies were highest in white participants and H63D genotype frequencies lowest in black participants (Acton 2006). Mayo Clinic Laboratories tests C282Y and H63D together (HFET, droplet digital PCR, interpretive report, CPT 81256, LOINC 34519-9) and does not recommend it for population screening.

LOINC 21696-0 (primary), 34519-9, 21694-5. Specimen: whole-blood.

Sources

  1. HFE gene, MedlinePlus Genetics, National Library of Medicine
  2. Diagnosis and management of hemochromatosis: 2011 practice guideline by the American Association for the Study of Liver Diseases, Hepatology (2011)
  3. EASL Clinical Practice Guidelines on haemochromatosis, Journal of Hepatology (2022)
  4. ACG Clinical Guideline: Hereditary Hemochromatosis, American Journal of Gastroenterology (2019)
  5. HFE C282Y/H63D compound heterozygotes are at low risk of hemochromatosis-related morbidity, Hepatology (2009)
  6. Geographic and racial/ethnic differences in HFE mutation frequencies in the Hemochromatosis and Iron Overload Screening (HEIRS) Study, Ethnicity & Disease (2006)
  7. Hereditary Hemochromatosis, HFE Variant Analysis, Varies (test HFET), Mayo Clinic Laboratories (Extended Catalog, testcatalog.org)
  8. dbSNP record for rs1799945 (HFE c.187C>G, p.His63Asp) (NCBI Variation Services API), NCBI dbSNP
  9. LOINC 21696-0 (NLM Clinical Tables API), National Library of Medicine / Regenstrief Institute

AI-verified against cited sources. Awaiting expert review. Last reviewed 2026-10-03. How we build and check these pages.

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