Guidelines for human gene nomenclature.

Standardized gene naming is crucial for effective communication about genes, and as genomics becomes increasingly important in healthcare, the need for a consistent language for human genes becomes ever more vital. Here we present the current HUGO Gene Nomenclature Committee (HGNC) guidelines for naming not only protein-coding but also RNA genes and pseudogenes, and outline the changes in approach and ethos that have resulted from the discoveries of the last few decades.National Human Genome Research Institute (NHGRI) grant U24HG003345 (1.5.2018-30.4.-2023) Wellcome Trust grant 208349/Z/17/Z (1.9.2017-31.8.2022

Update on the human and mouse lipocalin (LCN) gene family, including evidence the mouse Mup cluster is result of an evolutionary bloom .

Lipocalins (LCNs) are members of a family of evolutionarily conserved genes present in all kingdoms of life. There are 19 LCN-like genes in the human genome, and 45 Lcn-like genes in the mouse genome, which include 22 major urinary protein (Mup) genes. The Mup genes, plus 29 of 30 Mup-ps pseudogenes, are all located together on chromosome (Chr) 4; evidence points to an evolutionary bloom that resulted in this Mup cluster in mouse, syntenic to the human Chr 9q32 locus at which a single MUPP pseudogene is located. LCNs play important roles in physiological processes by binding and transporting small hydrophobic molecules -such as steroid hormones, odorants, retinoids, and lipids-in plasma and other body fluids. LCNs are extensively used in clinical practice as biochemical markers. LCN-like proteins (18-40 kDa) have the characteristic eight β-strands creating a barrel structure that houses the binding-site; LCNs are synthesized in the liver as well as various secretory tissues. In rodents, MUPs are involved in communication of information in urine-derived scent marks, serving as signatures of individual identity, or as kairomones (to elicit fear behavior). MUPs also participate in regulation of glucose and lipid metabolism via a mechanism not well understood. Although much has been learned about LCNs and MUPs in recent years, more research is necessary to allow better understanding of their physiological functions, as well as their involvement in clinical disorders

Update of the keratin gene family: evolution, tissue-specific expression patterns, and relevance to clinical disorders.

Intermediate filament (IntFil) genes arose during early metazoan evolution, to provide mechanical support for plasma membranes contacting/interacting with other cells and the extracellular matrix. Keratin genes comprise the largest subset of IntFil genes. Whereas the first keratin gene appeared in sponge, and three genes in arthropods, more rapid increases in keratin genes occurred in lungfish and amphibian genomes, concomitant with land animal-sea animal divergence (~ 440 to 410 million years ago). Human, mouse and zebrafish genomes contain 18, 17 and 24 non-keratin IntFil genes, respectively. Human has 27 of 28 type I "acidic" keratin genes clustered at chromosome (Chr) 17q21.2, and all 26 type II "basic" keratin genes clustered at Chr 12q13.13. Mouse has 27 of 28 type I keratin genes clustered on Chr 11, and all 26 type II clustered on Chr 15. Zebrafish has 18 type I keratin genes scattered on five chromosomes, and 3 type II keratin genes on two chromosomes. Types I and II keratin clusters-reflecting evolutionary blooms of keratin genes along one chromosomal segment-are found in all land animal genomes examined, but not fishes; such rapid gene expansions likely reflect sudden requirements for many novel paralogous proteins having divergent functions to enhance species survival following sea-to-land transition. Using data from the Genotype-Tissue Expression (GTEx) project, tissue-specific keratin expression throughout the human body was reconstructed. Clustering of gene expression patterns revealed similarities in tissue-specific expression patterns for previously described "keratin pairs" (i.e., KRT1/KRT10, KRT8/KRT18, KRT5/KRT14, KRT6/KRT16 and KRT6/KRT17 proteins). The ClinVar database currently lists 26 human disease-causing variants within the various domains of keratin proteins

Consensus nomenclature for dyneins and associated assembly factors.

Dyneins are highly complex, multicomponent, microtubule-based molecular motors. These enzymes are responsible for numerous motile behaviors in cytoplasm, mediate retrograde intraflagellar transport (IFT), and power ciliary and flagellar motility. Variants in multiple genes encoding dyneins, outer dynein arm (ODA) docking complex subunits, and cytoplasmic factors involved in axonemal dynein preassembly (DNAAFs) are associated with human ciliopathies and are of clinical interest. Therefore, clear communication within this field is particularly important. Standardizing gene nomenclature, and basing it on orthology where possible, facilitates discussion and genetic comparison across species. Here, we discuss how the human gene nomenclature for dyneins, ODA docking complex subunits, and DNAAFs has been updated to be more functionally informative and consistent with that of the unicellular green alga Chlamydomonas reinhardtii, a key model organism for studying dyneins and ciliary function. We also detail additional nomenclature updates for vertebrate-specific genes that encode dynein chains and other proteins involved in dynein complex assembly

A guide to naming human non-coding RNA genes.

Research on non-coding RNA (ncRNA) is a rapidly expanding field. Providing an official gene symbol and name to ncRNA genes brings order to otherwise potential chaos as it allows unambiguous communication about each gene. The HUGO Gene Nomenclature Committee (HGNC, www.genenames.org) is the only group with the authority to approve symbols for human genes. The HGNC works with specialist advisors for different classes of ncRNA to ensure that ncRNA nomenclature is accurate and informative, where possible. Here, we review each major class of ncRNA that is currently annotated in the human genome and describe how each class is assigned a standardised nomenclature

Selenoprotein gene nomenclature

The human genome contains 25 genes coding for selenocysteine-containing proteins (selenoproteins). These proteins are involved in a variety of functions, most notably redox homeostasis. Selenoprotein enzymes with known functions are designated according to these functions: TXNRD1, TXNRD2, and TXNRD3 (thioredoxin reductases), GPX1, GPX2, GPX3, GPX4 and GPX6 (glutathione peroxidases), DIO1, DIO2, and DIO3 (iodothyronine deiodinases), MSRB1 (methionine-R-sulfoxide reductase 1) and SEPHS2 (selenophosphate synthetase 2). Selenoproteins without known functions have traditionally been denoted by SEL or SEP symbols. However, these symbols are sometimes ambiguous and conflict with the approved nomenclature for several other genes. Therefore, there is a need to implement a rational and coherent nomenclature system for selenoprotein-encoding genes. Our solution is to use the root symbol SELENO followed by a letter. This nomenclature applies to SELENOF (selenoprotein F, the 15 kDa selenoprotein, SEP15), SELENOH (selenoprotein H, SELH, C11orf31), SELENOI (selenoprotein I, SELI, EPT1), SELENOK (selenoprotein K, SELK), SELENOM (selenoprotein M, SELM), SELENON (selenoprotein N, SEPN1, SELN), SELENOO (selenoprotein O, SELO), SELENOP (selenoprotein P, SeP, SEPP1, SELP), SELENOS (selenoprotein S, SELS, SEPS1, VIMP), SELENOT (selenoprotein T, SELT), SELENOV (selenoprotein V, SELV) and SELENOW (selenoprotein W, SELW, SEPW1). This system, approved by the HUGO Gene Nomenclature Committee, also resolves conflicting, missing and ambiguous designations for selenoprotein genes and is applicable to selenoproteins across vertebrates