Winter newsletter 2025
Newsletters ·
Spotlight on lncRNAs
One of the current key aims for the HGNC is naming long non-coding RNA (lncRNA) genes and in this newsletter we would like to highlight some of the lncRNA genes that we have approved recently. LncRNA genes are the only class of genes, aside from protein-coding genes, where research groups may suggest a symbol based on a function or important characteristic. We welcome gene symbol requests from lncRNA researchers, ideally ahead of initial publication. We also search the scientific literature for papers on lncRNA genes; where published symbols do not fulfil our guidelines we contact authors to discuss suitable alternatives. A recent example of this is the lncRNA symbol DAGAR PMID: 39273443, which returned over 350 unrelated results in PubMed; the addition of one extra letter in the symbol to give the approved symbol DAGARR has provided a unique search term and is still able to accompany the published name “differentiation and growth arrest related lncRNA”. In some cases, we are able to approve the published symbol but may approve a gene name that is different in format to that published, for example for LNCR-SMAL we approved the name “lncRNA senescence and mitophagy associated regulator of PRKN” instead of “Senescence-Mitophagy Associated LncRNA” to fit with the beginning of the gene symbol and to provide more functional information. For similar reasons, we approved the gene name “lncRNA regulator of PLAAT3 mediated phospholipid metabolism” instead of “a regulator of phospholipid metabolism” for the LNCROPM lncRNA. Other lncRNA gene symbols that we have approved recently based on publications include LNC-WAL, LALTOP, SYNAGE and CYKILR.
In addition to naming lncRNA genes based on publications, we have a systematic naming protocol, please see PMID: 35880706 for full details. We have recently been focusing on adding to our set of lncRNA genes that are named as antisense to protein coding genes, which is part of this systematic naming. We have named 230 new antisense lncRNA genes within the last three months; examples are IFITM3-AS1, TEPSIN-AS1 and ENHO-AS1.
Update on genes with the ‘stable’ tag and placeholder symbols
Continuing with a non-coding RNA theme, we have reviewed the first set of non-coding genes that have been included in the Matched Annotation from NCBI and EMBL-EBI (MANE) project and were able to add stable tags to the following well-published genes included in this dataset: RNU12, BACE1-AS, MIAT, IFNG-AS1, ATXN8OS, NR2F1-AS1 and GAS5. All of these are lncRNA genes, except for RNU12, which encodes a small nuclear RNA and has been identified as causing CDAGS syndrome. For some of the genes in the initial ncRNA MANE dataset we had already added a stable tag, such as RNU4-2 and XIST.
We have recently added stable tags to the following protein-coding gene symbols without any changes to the gene nomenclature: DLAT, DLD, ATP6AP2, BRWD3, AIPL1, DBT, ADK, BACE1 and CHM. For the following genes, the gene names were updated to provide functional information, but in all cases the gene symbols were unchanged: CPAP “centrosome assembly and centriole elongation protein”; MBOAT7 “membrane bound acylglycerophosphatidylinositol O-acyltransferase MBOAT7”; CCDC93 “CCC complex scaffolding subunit CCDC93”; CCDC22 “CCC complex scaffolding subunit CCDC22”; AIP “AHR interacting HSP90 co-chaperone”.
Two genes which previously had less informative symbols, TMEM199 (transmembrane protein 199) and CCDC115 (coiled-coil domain containing 115) were on our list of key symbols to stabilise, as both are associated with human phenotypes. These genes were both reported to encode V-ATPase assembly factors and were identified as the human orthologs of the S.cerevisiae genes Vph2 (also known as Vma12) and Vma22. We already had a gene encoding a V-ATPase assembly factor named in line with its yeast ortholog as VMA21 vacuolar ATPase assembly factor VMA21, so after discussion with authors who had published on these two genes we updated their nomenclature to VMA12 “vacuolar ATPase assembly factor VMA12” and VMA22 “vacuolar ATPase assembly factor VMA22” respectively.
Another of our current key aims is reassigning gene nomenclature for genes that currently have “placeholder” symbols. Since our previous newsletter we have renamed C1orf127 as CIROZ for “ciliated left-right organizer protein containing ZP-N domains” based on a pre-publication agreement with the authors of PMID: 39753129; C4orf19 as PGCKA1 for “PDCD10 and GCKIII kinases associated 1” based on agreement with authors prior to publication of PMID: 38517886; C7orf50 as CHLSN for “cholesin” based on a discussion with the authors of PMID:38503280; and C14orf28 as DORIP1 for “dopamine receptor interacting protein 1”, an agreed-upon modified, unique version of the published symbol DRIP1.
Gene Symbols in the News
AIPL1, mentioned above as we recently added a stable tag to this gene, has recently appeared in the news and happily this is a good news story! AIPL1 is the causative gene for an aggressive form of Leber Congenital Amaurosis; gene therapy for AIPL1 injected directly into the back of the eye of four young children with this condition has resulted in improvements to the eyesight for all four children.
Copy number variation of a region of chromosome 9 has previously been identified in patients with schizophrenia. This region contains several different genes, including GLDC, which was suspected to be significant as this gene encodes an enzyme that is involved in the degradation of glycine. In a recent study, mouse models were made both with increased copy number of the equivalent chromosome region and increased copy number of only the mouse ortholog of GLDC. Mice with increased levels of only Gldc showed the same schizophrenia-like behavioural symptoms as those with the increased larger DNA chromosomal region, further implicating the GLDC gene as having as association with schizophrenia in humans.
In separate mouse model news, a group used CRISPR gene editing to generate mice with a Nova1 gene containing sequence that is unique to the human NOVA1 gene. NOVA1 has previously been identified as important for brain development in humans so the effect of a human-specific substitution that affects the encoded protein is of particular interest. The authors found a surprising result - the humanized mice showed differences in the vocalizations that they made compared to mice with the murine version of Nova1. The authors hope that their work may contribute to helping humans with speech problems one day.
Another group used a different model organism in their quest to learn more about a gene variant that causes human disease with incomplete penetrance. They were studying a family with a variant of PIGA that causes phosphatidylinositol glycan class A congenital disorder of glycosylation in some family members but not others; the researchers hypothesised that unaffected individuals carry a variant of a separate gene that prevents them from suffering from this disease - genome sequencing revealed CNTN2 as a candidate for being this modifier gene. The group then used Drosophila melanogaster to study genes that genetically modify the PIGA ortholog in this model organism - knockdown of fly PIG-A results in a smaller eye and seizures in flies, while both of these phenotypes could be rescued by double knockdown of PIG-A and Cont (the CNTN2 fly ortholog), further implicating CNTN2 as a genetic modifier of PIGA in humans.
We now turn to genetic news about one of our VGNC species, a story which has given our developer Kris’s ginger cat Flynn a starring role at the top of this newsletter. It has long been known that the causative gene for orange cat fur must be on the X chromosome due to tortoiseshell and calico cats being female, while orange cats like Flynn are usually male, but the actual gene causing this had not previously been identified. Now, two separate studies have identified the culprit - ARHGAP36 which is on the feline X chromosome. One study observed that the melanocytes of orange cats produce more RNA from the ARHGAP36 gene due to a variant in a non-coding region of this gene, they then identified the same gene variant in all orange, tortoiseshell and calico cats from a cat genomic database. The other study identified the same variant in cat genomes from around the world and confirmed that ARHGAP36 is subject to X inactivation in female cats.
Finally, we bring news about another of our VGNC species, this time chimpanzee. Research has found that forest-dwelling chimpanzees carry variants of GYPA and HBB, two genes that have been associated with different gene variants in humans that offer protection from malaria. This suggests that both species have independent genetic variants of the same genes to adapt to living in regions high in malaria.
Meeting News
Elspeth attended ASHG 2024 in Denver, Colorado, USA in November 5th-9th where she presented a talk entitled “How should we name non-coding elements?” at the featured symposium “How do we describe and ascribe clinical significance to the non-coding genome?” alongside other speakers Andrew Stergachis (University of Washington), Melissa Landrum (ClinVar Database) and Nicola Whiffin (University of Oxford). This is clearly a hot topic as the symposium was very popular and the speakers received many questions.
Ruth attended the annual RNAcentral consortium meeting on 18th November and, following this, is now part of the RNAcentral consortium gene function working group.