Autumn newsletter 2023

HGNC members on sabbatical

Undoubtedly any of our readers who are involved in producing online resources for the biomedical community are aware of the difficulties in securing funding for these kind of crucial resources, even for those of us who have been recognised as a Global Core Biodata Resource. And for any of you who aren’t aware of this we can assure you, it’s tough out there. We remain committed to serving the community and ensuring there is standardisation for human and vertebrate gene nomenclature, but due to lack of funding three members of the HGNC will be taking sabbaticals away from the team over the coming months. Bryony will be working with the WormBase team at the EBI, Tamsin will be working with the Ensembl/Havana team also at the EBI, and Ruth will be working with the FlyBase team at the University of Cambridge. We look forward to them bringing their new curatorial experiences back to the HGNC team. Susan will also leave the team at the end of November having completed 9 years at EBI but we are hopeful that she will be able to rejoin us early next year in a new role… watch this space! So please bear with us during these next few months while we keep the ship afloat with a much reduced team; we hope that 2024 will bring much more positive news on the funding front.

Update on genes with the ‘stable’ tag

We currently have 3459 gene symbols marked with the stable tag, which is an increase of 197 since our last newsletter. Within this batch, no symbols or gene names were changed prior to stabilisation. Examples of genes with the stable tag added include the frizzled class receptors FZD1, FZD3, FZD7, FZD8, FZD9 and FZD10, the mucins MUC2, MUC4, MUC5B, MUC6 and MUC7, and the RBFOX family, RBFOX1, RBFOX2 and RBFOX3.

Updates to placeholder symbols

We have made the following updates to genes that previously had placeholder symbols:

C12orf40 was updated to REDIC1 (regulator of DNA class I crossover intermediates 1). The REDIC1 symbol was published in PMID: 37612290, but no full gene name was mentioned in this publication so the HGNC worked with authors to agree upon a suitable name to go with the symbol.

C21orf62 was updated to EPCIP (exosomal polycystin 1 interacting protein). This gene had been published using the symbol “CU062”, taken from the CU062_HUMAN identifier used in the UniProt database. Discussion between the HGNC and two groups working on the gene resulted in agreement on an appropriate symbol that will be published in future.

The following symbols were updated based on Pfam-N (N stands for network) matches between proteins and pre-existing Pfam domains that were not called by the Pfam database previously. The Pfam-N matches are the result of a deep learning method that was trained on Pfam data; see the Xfam blog post “Google Research Team bring Deep Learning to Pfam”. Pfam-N calls are displayed in the “Other Features” section of InterPro reports.

C9orf131 and C2orf16 were updated to SPATA31G1 (SPATA31 subfamily G member 1) and SPATA31H1 (SPATA31 subfamily H member 1) based on a Pfam-N domain match to PF14650 in the encoded proteins, which are found in other SPATA31 family members.

KIAA2026 was updated to BRD10 (bromodomain containing 10) based on a Pfam-N match to the PF00439 bromodomain.

KIAA1522 was updated to NHSL3 based on a Pfam-N match to the PF15273

Finally, C5orf64 was renamed to LINC03122 (long intergenic non-protein coding RNA 3122) based on a change in gene type from protein-coding gene to long non-coding RNA.

New gene groups

We have added many new different gene groups to our resource over the last few months, including:

We would like to highlight an unusual gene group that we created recently based on a user request: Proteins encoded by multiple genes. This group presents all genes on the current human reference assembly for which another gene in the genome encodes an identical protein. For example, ARL17A and ARL17B both encode the Q8IVW1 protein. The gene list was constructed from a set of UniProt accessions that are associated with multiple genes. Note that we have excluded read-through transcripts and genes present on alternate loci. We hope that other members of the scientific community will find this gene group to be a useful reference.

Gene Symbols in the News

Data analysed from the UK Biobank has found rare genetic variants in five genes (EDA2R, WNT10A, HEPH, CEPT1 and EIF3F) that are associated with hereditary male pattern baldness. While common variants have already been identified in EDA2R and WNT10A, identification of variants in the other three genes is a novel finding.

A gene variant has been discovered in the APOL1 gene that protects the carrier from a kidney disease causative mutation within the same gene. The disease-causing variant results in a hole in kidney cells, while the presence of the protective SNP prevents this hole from forming.

Gene-editing therapy may provide long-term management for those with familial hypercholesterolemia, preventing the need for medication. Researchers have used a CRISPR-based gene therapy to switch off the expression of the PCSK9 gene in the liver resulting in reduced LDL cholesterol levels. Further studies are needed to determine the safety and efficacy of this treatment on a larger scale.

The ACBD6 gene has been identified as causing a neurodevelopmental disorder that shows some similarities to Parkinson disease, although onset of symptoms occurs in childhood. Twenty different ACBD6 variants were identified within 28 affected but unrelated families from across the world; in all cases two altered ACBD6 copies were needed to cause disease. Zebrafish and Xenopus models have been created which showed phenotypic similarities to the human disease.