Autumn newsletter 2025
Newsletters ·
Farewell to Susan
The HGNC is sad to say farewell to one of our curators, the wonderful Susan Tweedie. We are, though, happy that she has started her well-earned retirement and know that she has much travelling and many parkruns ahead of her!
Before retiring, Susan was working on a collaboration with Elsevier/SciBite to expand our gene group resource. This work resulted in the addition of many new enzyme gene groups. A recent example is the Carbon-carbon lyases which forms the top of a gene group hierarchy with seven subgroups, including Aldehyde lyases, Decarboxylases and Oxo-acid lyases, see the image below. An example of a standalone enzyme gene group that Susan also recently curated is the Thioester hydrolases, which encode enzymes that hydrolyse thioester bonds.
We are extremely grateful for Susan’s recent work on gene groups and for all of her work for both HGNC and VGNC over the years. We miss her already!
Spotlight on publications
The HGNC has been involved in a number of publications in the past few months, see the Publications section at the end of this newsletter for a full list.
We would like to highlight the article Invisible infrastructure at risk: funding crises threaten global bioscience research, a collaboration between the HGNC, authors from PomBase and FlyBase, and [Elspeth - how do we describe the others?] other database specialists and researchers. This article is a call to action to prevent the irreversible loss of biomedical resources, including the HGNC.
Updating the symbols of ten cytokines and their receptors: report of the IUIS Cytokine Nomenclature Sub-Committee introduces the new Cytokine Nomenclature Sub-Committee which was established by the International Union of Immunological Societies (IUIS) in December 2025 and replaces the former Interleukin Nomenclature Sub-Committee. Elspeth is happy to be a member of this new sub-committee. The publication also describes the following gene nomenclature updates:
C17orf99 -> IL40, interleukin 40 IL1F10 -> IL38, interleukin 38 IL1RL1 -> IL33R, interleukin 33 receptor IL1RL2 -> IL36R, interleukin 36 receptor
There is growing interest in finding and defining genes encoding the ‘dark proteome’ that are translated and ultimately determining to what extent such translated products have a function with cells. The HGNC was involved in two recent publications on this subject:
An expanded reference catalog of translated open reading frames for biomedical research presents a catalog of translated ‘non-canonical’ ORFs detected by Ribo-seq, based on GENCODE v45. Note these are not manually annotated by Ensembl/GENCODE but exist as a starting reference for future biomedical research.
Expanding the human proteome with microproteins and peptideins introduces the concept of ‘peptideins’. These are defined as protein-like molecules that can be confidently assessed as existing in the cell, but for which no functional insights are available to allow them to be classed as proteins.
Update on genes with the ‘stable’ tag and placeholder symbols
We continue our aim of adding a stable tag to the gene reports of clinically relevant genes - we now have 3647 Symbol Reports that display this tag. Recent examples where genes had the stable tag added with no required changes to their nomenclature are: CRLF1, GALT, GFPT1 and GFPT2.
The following are examples where the stable tag was added following a required change to the gene symbol or gene name:
The gene symbol NUCLEOLIN was updated from NCL because NCL is also used as a symbol for the unrelated phenotype “neuronal ceroid lipofuscinosis”. In addition, NCL is a poor search term that returns many other unrelated hits in literature search engines, referring to other concepts such as ‘nidopallium caudolaterale’ and ‘native chemical ligation’. NCL had the corresponding gene name ‘nucleolin’, which has been made the unique gene symbol with the updated corresponding name ‘nucleolin multifunctional protein’. Over 100 researchers were contacted about this change and there was not a single objection.
The gene name of TRIM44 was updated from ‘tripartite motif containing 44’ to ‘TRIM family member 44’ because the encoded protein does not contain all of the motifs typical of other family members. To explain this, we have added the following comment to the TRIM44 Symbol Report: This gene has been named as a member of the tripartite motif family due to homology, but its encoded protein lacks a RING domain and a SPRY domain and hence is unlikely to be able to function as an E3 ubiquitin ligase.
The names of two genes were updated to remove the term ‘like’ which could have suggested that the genes did not have the function referenced in the gene names: the DNM1L gene name was updated from ‘dynamin 1 like’ to ‘dynamin 1L’ and the CKAP2L gene name was updated from ‘cytoskeleton associated protein 2 like’ to ‘cytoskeleton associated protein 2L’.
We are also working hard to update placeholder symbols with more informative nomenclature. We have already mentioned the update of C17orf99 to IL40 as part of our work with the IUIS Cytokine Nomenclature Sub-Committee.
Other recent examples of updates to placeholder symbols are:
C17orf50 was updated to PGBDF, for ‘plakoglobin binding and degradation factor’, based on the publication Identification and characterization of a novel Plakoglobin-binding protein highly expressed in the testes.
C12orf54 was updated to LYLDT1 for ‘lysosomal-lipid droplet tether 1’ based on discussion with the authors of C12ORF54 mediates lipid droplet delivery to lysosomes with mutation causing childhood-onset metabolic dysfunction-associated steatotic liver disease.
C16orf87 was updated to HDIP1 for ‘HDAC and MIER1 interacting protein 1’ based on discussion with several different groups who have recently published on this gene.
C2orf74 was updated to DEMA1 for ‘DPM1 ER membrane anchor 1’ based on discussions between the HGNC, Mouse Genome Nomenclature Committee and researchers who have published on this gene.
C2orf49 was updated to TSLIG2 for ‘tRNA splicing ligase complex subunit 2’ and the FAM98 family members FAM98A, FAM98B and FAM98C were updated to [TSLIG3A](https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:24520, TSLIG3B and TSLIG3C for tRNA splicing ligase complex subunit 3A, 3B and 3C to reflect their published function. All genes encoding subunits of the tRNA splicing ligase complex can be viewed on our gene group page.
FAM72A was updated to [RUMY1] for ‘regulator of UNG2 and MKLN1 interacting yippee protein 1’ following agreement from researchers working on the function of this gene. The FAM72B, FAM72C and FAM72D paralogous were renamed as RUMY2, RUMY3 and RUMY4 with the corresponding gene name format ‘RUMY family member’.
Gene Symbols in the News
We begin with two genes that have recently been associated with neurodevelopmental disorders. De novo variants of MAP2K4 were discovered in nine patients that had a neurodevelopmental disorder with associated epilepsy, while six children were identified with a gain-of-function variant of BMPR2 that caused a phenotype with varying levels of developmental delay, autism and seizures.
In other genetic disease news, fourteen patients were identified with variants of the IDUA gene that were causative for their retinitis pigmentosa. This gene has previously been identified as causative for mucopolysaccharidosis type 1 which is a multisystem disorder that can include ophthalmologic symptoms. This is an example of different gene variants causing milder genetic disease.
In positive news, clinical studies on patients treated with a single of WAS gene therapy to treat Wiskott–Aldrich syndrome found that patients experienced sustained clinical benefit with a reduction in rates of infections and bleeding.
The SRSF1 gene has been associated with a decreased rate of ageing. Increasing expression in human fibroblasts results in a shifted molecular profile consistent with younger cells. Inducing expression of mouse Srsf1 in livers of mice resulted in an extended lifespan.
As usual, we like to find news about one of our VGNC species and this time we bring you a story of feline brothers, Gary and Shaggy. These siblings both have the first identified case of Marfan syndrome in cats cats. They both carry two variant copies of the FBN1 gene. In humans, just one FBN1 variant can cause Marfan syndrome; individuals with two variant copies have a more severe version of the disease. Fortunately for Gary and Shaggy, their variants did not result in complete loss of gene function, hence they have reached adulthood without a severe form of the disease.
Meeting News
Ruth attended ncRNA2026: From Molecular Mechanisms to Clinical Impact (Leuven, Belgium) from 24th-26th June during one of the many heatwaves of the summer of 2026. She presented a poster entitled ‘Standardized gene naming for human non-coding RNA genes’.
Bryony and Ruth attended RAREsummit26 (Hinxton, UK) on 7th October where they presented a poster about our recent survey of genetic counsellors.
Elspeth attended the first annual Global Biodata Coalition Conference (Cambridge, UK) from 7th-8th October. She also went to ASHG 2026 (Montreal, Canada) from 20th-24th October 2026 where she presented a poster entitled ‘One Person’s Trash Is Another’s Treasure: Naming in the “Junk” DNA’ which presented gave an overview of ncRNA nomenclature, highlighted naming of unitary pseudogenes and introduced the concept of peptideins.
Publications
Wood V, Bruford EA, Marygold SJ, O’Donnell VB, Röper K, Davies JA, Orengo C, Nurse P, Hall N. Invisible Infrastructure at Risk: Funding Crises Threaten Global Bioscience Research. Genetics. 2026 Oct 7:iyag274. DOI: 10.1093/genetics/iyag274. PMID: 42842927
Boraschi D, Dong C, Lanz-Mendoza H, Marques-Neto LM, Rezaei N, Bruford E. Updating the symbols of ten cytokines and their receptors: report of the IUIS Cytokine Nomenclature Sub-Committee. Nat Immunol. 2026 Sep 22. DOI: 10.1038/s41590-026-02654-9. PMID: 42773267
Cree IA, Arends MJ, Khoury JD, Denton ERE, Gill AJ, Lazar AJ, Frayling IM, Pfister SM, Rubin MA, Leite KRM, Dalgleish R, Bruford EA, Plon SE, Hamosh A, Walsh MF, Goldman-Lévy G, Wijesinghe H, Foulkes WD, Lokuhetty D. The WHO Classification of Genetic Tumour Syndromes: Considerations for Genetics. Clin Genet. 2026 Jun 16. DOI: 10.1111/cge.70195. PMID: 42304730
Deutsch EW, Kok LW, Mudge JM, Valls CF, Jungreis I, Ruiz-Orera J, Sun Z, Kusebauch U, Fierro-Monti I, Abelin JG, Alba MM, Aspden JL, Bandyopadhyay S, Banerjee K, Baranov PV, Bazzini AA, Bourassa F, Bruford EA, Calviello L, Carr SA, Carvunis AR, Chothani S, Clauwaert J, Dean K, Faridi P, Frankish A, Goodale A, Green T, Hubner N, Ingolia NT, Kellis M, Magrane M, Martin MJ, Martinez TF, Menschaert G, Ohler U, Orchard S, Potter A, Rackham OJL, Rees MG, Root DE, Roth JA, Roucou X, Sialana FJ, Slavoff SA, Świrski MI, Tierney JAS, Trifiro FA, Valen E, Vasylieva V, Wacholder A, Wang S, Wang L, Weissman JS, Wu W, Xie Z, Choudhary JS, Bassani-Sternberg M, Vizcaíno JA, Ternette N, Brunet MA, Moritz RL, Prensner JR, van Heesch S. Expanding the human proteome with microproteins and peptideins. Nature. 2026 Jun;654(8119):813-825. DOI: 10.1038/s41586-026-10459-x. Epub 2026 May 6. PMCID: PMC13275300. PMID: 42092140
Dalgleish R, Freeman PJ, Wagstaff JF, Bruford EA, Fokkema IFAC Why Non-ASCII Unicode Characters Should Not Be Used in the Human Genome Variation Society Nomenclature. J Mol Diagn. 2026 May;28(5):448-449. DOI: 10.1016/j.jmoldx.2026.01.009. PMCID: PMC13197907. PMID: 42034449
Katsafadou AI, Falnes PØ, Bruford E, Braschi B, Hanson QM, Hall MD, Thompson DC, Nebert DW, Vasiliou V. Update of the Methyltransferase Gene Family: Classification, Evolution and Biological Functions. Hum Genomics. 2026 Mar 25. DOI: 10.1186/s40246-026-00949-4. PMCID: PMC13137591. PMID: 41882796
Chothani S, Ruiz-Orera J, Tierney JAS, Swirski MI, Tjeldnes H, Kok LW, Clauwaert J, Deutsch EW, Alba MM, Aspden JL, Baranov PV, Bazzini AA, Bruford EA, Brunet MA, Cardon T, Carvunis AR, Casola C, Choudhary JS, Dean K, Faridi P, Fierro-Monti I, Fournier I, Frankish A, Gerstein M, Hubner N, Jiang Y, Kellis M, Martinez TF, Menschaert G, Ni P, Orchard S, Roucou X, Rozowsky J, Salzet M, Siragusa M, Slavoff S, Ternette N, Vizcaino JA, Wacholder A, Wu W, Xie Z, Yang YT, Moritz RL, Valen E, Mudge J, van Heesch S, Prensner JR, Rackham OJL. An expanded reference catalog of translated open reading frames for biomedical research. Nucleic Acids Res. 2026 Mar 19;54(6):gkag234. DOI: 10.1093/nar/gkag234. PMCID: PMC13010147. PMID: 41873765