Spring newsletter 2026

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VGNC Updates

HGNC gene group news

We now have over 2100 HGNC Gene groups. Recent additions include:

We have continued to review gene symbols with a view to long term stabilisation, prioritizing those with known variants that have been linked to human phenotypes as listed in ClinGen. There is now a total number of 3610 protein coding genes with the stable tag.

We recently reviewed the CLC chloride channel and transporter family for stabilisation, which are a set of paralogs named with a CLCN root symbol. The CLCN symbols are highly published and functionally informative and so they could be assigned the stable tag.

However, during this process we noticed a name mismatch between our resource and UniProt for some of the genes in this set. After reviewing the literature, we retained the “chloride voltage-gated channel #” name format for CLCNKA, CLCNKB, CLCN1 and CLCN2 but updated the names of CLCN3, CLCN4, CLCN5, CLCN6 and CLCN7 to reflect that these family members encode proteins that act as two-way ion pumps known as “Cl-/H+ antiporters” rather than as passive chloride channels. For example, the name of CLCN3 was updated as “Cl-/H+ antiporter 3”. PMID:38027030 discusses how variants in CLCN encoded exchangers (a synonym for antiporters) have been linked to neurological phenotypes in patients.

The symbol RET with the associated name “ret proto-oncogene” has been stabilised. A review by Romei, Ciampi and Elisei states that “the ‘rearranged during transfection’ (RET) proto-oncogene was identified in 1985 and, very soon thereafter, a rearrangement named RET/PTC was discovered in papillary thyroid carcinoma (PTC)” PMID:26868437. DNA damage can cause the RET gene to become fused with other genes, resulting in its encoded receptor tyrosine kinase becoming continuously activated which then drives cancer growth.

The RET symbol has been extremely heavily published on (>13000 PubMed hits, 6433 hits for a search for “RET and oncogene”) and associated with cancer and so was a prime candidate for symbol stabilisation as it is used in so many clinical papers. We considered adjusting the gene name, but as “ret proto-oncogene” is so highly used in the literature we decided to keep it rather than adding extra information into its name. Alias names including “RET receptor tyrosine kinase” and “rearranged during transfection” are still associated with the gene record.

We have been able to update the nomenclature of 17 protein coding genes with placeholder symbols since our last newsletter.

The gene symbol of HGNC:26346 was updated from C16orf92 to FIMP1 “fertilization-influencing membrane protein 1” based on the usage of the alias “FIMP” in several papers(PMID:32295885, 36050562,40138310). FIMP was not ideal nomenclature, as it brings up multiple false hits in PubMed (notably Federation of Italian Pediatricians). However, we were able to approve FIMP1 for this gene which is a better search term.

The gene symbols of HGNC:1313 and HGNC:26110 were updated from FAM118A and FAM118B to SIRAL2 “SIR2 antiphage like 2” and SIRAL1 “SIR2 antiphage like 1” respectively. Both encoded proteins share a domain called the “Sir2-like” domain or “SIR2_2” in InterPro. Two separate publications reported that these genes encode non-canonical sirtuin proteins PMID:40705877 and PMID:41249820. These proteins are more similar to bacterial antiphage sirtuins than to human SIRTs (which are named using the root symbol SIRT). Their coexpression in cells strongly depletes cellular NAD levels, validating a previously unrecognized eukaryotic NAD-processing system (PMID:41249820).

Bonhomme et al assigned FAM118B the alias symbol “SIRal” (SIR antiphage-like) and FAM118A the alias symbol “SIRal2”. They stated that the FAM118B encoded protein plays a pivotal role in the animal Toll-like receptor pathway of innate immunity and protects against bacterial and viral infections (PMID:40705877).

Baretic et al also stated that FAM118A and FAM118B encode sirtuins with similarities to bacterial antiphage sirtuins (PMID:41249820). They showed that both FAM118 proteins form head-to-tail filaments both in vitro and in living human cells. Although the FAM118B and FAM118A proteins were shown to have individually very weak NAD-processing activity in vitro, their interaction resulted in markedly increased activity. The FAM118A and FAM118B proteins were shown to have much greater NAD processing enzyme activity when their strands are mixed together. The active form of these enzymes may correspond to a mixed FAM118B:FAM118A filament or to a higher-order structure composed of homotypic FAM118B-only and FAM118A-only filaments (PMID:41249820).

The gene symbols of HGNC:28210,HGNC:21357,HGNC:16121,HGNC:16122,HGNC:25972,HGNC:25148,HGNC:32554 and HGNC:24797 have been updated from uninformative FAM83 root symbols to SACK1A through to SACK1H with the associated names of “scaffolding CK1 anchoring protein #” reflecting that all contain a “Scaffolding anchor of CK1 domain”. This domain was previously known as the “DUF1669 domain” with DUF standing for “domain of unknown function” - we were able to work with Professor Gopal Sapkota and curators at InterPro so that it could be assigned a more functionally informative name that the nomenclature could also then be based on. A review by Bozatzi and Sapkota PMID:29871876 discusses this set of genes in more detail.

Gene Symbols in the News

We begin this issue of ‘Gene Symbols in the News’ with two gene therapy stories. In the first, a 3-year-old boy with a severe form of AADC deficiency was treated with a one-off gene therapy that delivered a functional copy of the DDC gene directly to his brain. Before the gene therapy, the child was unable to stand or walk without support, but two years after therapy he is now able to walk and run. The second story is about the use of gene therapy to improve the success of vein grafts in heart surgery. The new gene therapy treats the grafted vessels with the TIMP3 gene to prevent thickening and blockage of the graft over time.

In cancer news, researchers have found that leukemias with BRD9::NUTM1 fusions were more sensitive to chemotherapy than leukemias with other common gene rearrangements. This finding means that infants with this form of leukemia could be treated with lower doses of chemotherapy. Scientists at The Institute of Cancer Research, London have found PSA testing identified men with more dangerous prostate cancers in men with cancer-associated BRCA1 or BRCA2 gene variants compared to men who do not carry these variants. As a result, the researchers are recommending that men with risk-associated BRCA1 or BRCA2 gene variants should be offered regular PSA testing from the age of 40.

A recent study has found that the human orthologs of dog genes linked to specific behavioural traits are associated with human cognitive and psychiatric traits. The study analysed DNA from 1,300 golden retrievers and used questionnaires completed by the dog owners to find associations between genes and behaviour. One of the genes identified was PTPN1, which was associated with aggression in the golden retrievers, while human PTPN1 has been associated with both intelligence and depression. The dog ROMO1 gene was associated with trainability in golden retrievers while human ROMO1 has been associated with intelligence and emotional sensitivity.

Meeting News

Elspeth attended [PAG33](https://intlpag.org/PAG33/program/archives/pag-33-archives (the 33rd Plant and Animal Conference) in San Diego, USA from January 9th-24th, where she presented a poster entitled ‘Gene naming branches out: standardized gene naming in Populus trichocarpa’ about our plant nomenclature project. She also took part in the EMBL-EBI-hosted workshop where she gave a talk entitled ‘Standardized Gene Naming in Humans and Beyond’ about the HGNC and VGNC.

Ruth will attend the ncRNA2026: From Molecular Mechanisms to Clinical Impact meeting in Leuven, Belgium in June where she looks forward to meeting members of the ncRNA community.

Publications

Publications:

Cree IA, Arends MJ, Khoury JD, Denton ER, Gill AJ, Lazar AJ, Frayling IM, Pfister SM, Rubin MA, Leite KR, Dalgleish R, Bruford EA, Plon S, Hamosh A, Walsh MF, Goldman-Lévy G, Wijesinghe H, Foulkes WD, Lokuhetty D. The WHO Classification of Genetic Tumour Syndromes: Considerations for histopathology. Histopathology. 2026 Mar 19. DOI: 10.1111/his.70139. PMID: 41852243

Braschi B, Seal RL, Bruford EA. Naming the alpha-2-macroglobulin gene family across vertebrates. Hum Genomics. 2026 Jan 13. DOI: 10.1186/s40246-026-00909-y. PMID: 41527088

RNAcentral Consortium (inc. Bruford, E.A. and Seal, R.L.). RNAcentral in 2026: genes and literature integration. Nucleic Acids Res. 2026 Jan 6;54(D1):D303-D313. DOI: 10.1093/nar/gkaf1329. PMCID: PMC12807676. PMID: 41404707

Seal RL, Braschi B, Gray K, McClay J, Tweedie S, Bruford EA. Genenames.org: the HGNC and PGNC resources in 2026. Nucleic Acids Res. 2025 Nov 25:gkaf1229. DOI: 10.1093/nar/gkaf1229. PMID: 41287213

Gyimesi G, Tweedie S, Bruford E, Hediger MA. The SLC-ome of membrane transport: From molecular discovery to physiology and clinical applications. Physiol Rev. 2025 Sep 30. DOI: 10.1152/physrev.00001.2024. PMID: 41026912 The WHO Classification of Genetic Tumour Syndromes: Considerations for histopathology