Five genetically AnWj-negative individuals entered the study, including members of an Arab-Israeli family and the woman first identified as AnWj-negative in the 1970s, who donated a sample in 2015. Each carried homozygous deletions in MAL, with both copies of the gene disrupted.

Those deletions removed full-length Mal protein from the red cell surface. Insert a normal MAL gene into cultured cells and those cells react with anti-AnWj antibodies. Insert the altered form and they do not. Mal proved both necessary and sufficient for AnWj expression.

Takeaway: the genetic evidence meets the molecular threshold the ISBT requires before a new blood group system can be ratified.

Why was the case so hard to crack?

Inherited AnWj-negative blood is vanishingly rare. Researchers had documented only a handful of cases, leaving almost no genetic material to compare.

The Mal protein offered few outward hints. It is a small, membrane-embedded protein tied to membrane organization and cellular transport, not to red cell biology. Nothing flagged it as the carrier of a long-mysterious antigen.

A further complication: most AnWj-negative people are negative because of acquired suppression during hematological disorders or cancers, not inherited deletions. Sorting the inherited cases from the acquired ones required careful clinical matching.

How will the new system help patients in practice?

Nicole Thornton, Head of IBGRL Red Cell Reference at NHS Blood and Transplant, said: "Now genotyping tests can be designed to identify genetically AnWj-negative patients and donors. Such tests can be added to the existing genotyping platforms."

For inherited AnWj-negative patients, those platforms turn an emergency donor search into a routine genetic lookup. For acquired AnWj-negative patients, the test clarifies whether antibodies are disease-driven: in a 2026 case, a 75-year-old man with severe anemia and an anti-AnWj autoantibody had a normal MAL gene, and his antibody traced to his underlying disease rather than any inherited deletion.

Ash Toye, Professor of Cell Biology at the University of Bristol, said: "It's really exciting we were able use our ability to manipulate gene expression in the developing blood cells to help confirm the identity of the AnWj blood group. This development will help identify these rare donors and help patients in the future."

Takeaway: gene expression manipulation converted a statistical association into causal evidence that serology alone could not deliver.

What comes next in the blood group catalog?

The ISBT 2026 terminology report ratified four systems, including MAL at ISBT 047. By September 2026 the society had formally added JAMA, making it the 49th blood group system, evidence that the catalog of human blood antigens continues to expand.

For transfusion specialists that pace matters. ABO and Rh explain most daily compatibility decisions, but more than 360 antigens across the recognized systems shape the harder cases. Each new entry converts an unexplained serological curiosity into a defined, testable target.

Takeaway: every additional system narrows the search space when a rare patient needs blood.