LZTFL1

LZTFL1
Identifiers
Aliases	LZTFL1 , BBS17, leucine zipper transcription factor like 1
External IDs	OMIM: 606568; MGI: 1934860; HomoloGene: 41368; GeneCards: LZTFL1; OMA:LZTFL1 - orthologs
Gene location (Human) Chr. Chromosome 3 (human) [1] Band 3p21.31 Start 45,823,316 bp [1] End 45,916,042 bp [1]
Gene location (Mouse) Chr. Chromosome 9 (mouse) [2] Band 9 F4|9 74.36 cM Start 123,523,481 bp [2] End 123,546,762 bp [2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in bronchial epithelial cell sperm Brodmann area 23 caput epididymis endothelial cell Epithelium of choroid plexus middle temporal gyrus left testis right testis tendon of biceps brachii Top expressed in spermatid spermatocyte tail of embryo genital tubercle seminiferous tubule zygote secondary oocyte olfactory epithelium thymus parotid gland More reference expression data BioGPS n/a
Gene ontology Molecular function protein binding identical protein binding protein-containing complex binding Cellular component cytoplasm cytosol Biological process negative regulation of protein localization to cilium negative regulation of protein localization to ciliary membrane Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 54585 93730 Ensembl ENSG00000163818 ENSMUSG00000025245 UniProt Q9NQ48 Q9JHQ5 RefSeq (mRNA) NM_001276378 NM_001276379 NM_020347 NM_001386451 NM_001386452 NM_033322 RefSeq (protein) NP_001263307 NP_001263308 NP_065080 NP_201579 Location (UCSC) Chr 3: 45.82 – 45.92 Mb Chr 9: 123.52 – 123.55 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Leucine zipper transcription factor like 1 also known as LZTFL1 is a ubiquitously expressed protein which localizes to the cytoplasm and in humans is encoded by the LZTFL1 gene. ^[5]

Function

This protein regulates protein trafficking to the ciliary membrane through interaction with the Bardet-Biedl syndrome (BBS) complex of proteins. ^[6]

Clinical significance

Mutations in the LZTFL1 gene are associated with Bardet-Biedl syndrome, ^[7] and the gene also acts as a tumor suppressor ^[8] through regulation of epithelial-mesenchymal transition. ^[9]

Identified as the gene on chromosome 3 at location 3p21.31 responsible for mediating an associated with genetic susceptibility to SARS-CoV-2 infection ^[10] and COVID-19 respiratory failure. ^{[11] [12]} The DNA segment conferring the risk is inherited from Neanderthals. ^[13]

References

1. GRCh38: Ensembl release 89: ENSG00000163818 – Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000025245 – Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. "LZTFL1 leucine zipper transcription factor like 1 [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2021-08-17.
6. Seo S, Zhang Q, Bugge K, Breslow DK, Searby CC, Nachury MV, et al. (November 2011). "A novel protein LZTFL1 regulates ciliary trafficking of the BBSome and Smoothened". PLOS Genetics. 7 (11) e1002358. doi: 10.1371/journal.pgen.1002358 . PMC   3207910 . PMID   22072986.
7. Marion V, Stutzmann F, Gérard M, De Melo C, Schaefer E, Claussmann A, et al. (May 2012). "Exome sequencing identifies mutations in LZTFL1, a BBSome and smoothened trafficking regulator, in a family with Bardet--Biedl syndrome with situs inversus and insertional polydactyly". Journal of Medical Genetics. 49 (5): 317–321. doi:10.1136/jmedgenet-2012-100737. PMID   22510444. S2CID   33467850.
8. Kiss H, Kedra D, Kiss C, Kost-Alimova M, Yang Y, Klein G, et al. (April 2001). "The LZTFL1 gene is a part of a transcriptional map covering 250 kb within the common eliminated region 1 (C3CER1) in 3p21.3". Genomics. 73 (1): 10–19. doi:10.1006/geno.2000.6498. PMID   11352561.
9. Wei Q, Zhou W, Wang W, Gao B, Wang L, Cao J, et al. (April 2010). "Tumor-suppressive functions of leucine zipper transcription factor-like 1". Cancer Research. 70 (7): 2942–2950. doi:10.1158/0008-5472.CAN-09-3826. PMC   2848875 . PMID   20233871.
10. Niemi ME, Karjalainen J, Liao RG, Neale BM, Daly M, Ganna A, et al. (July 2021). "Mapping the human genetic architecture of COVID-19". Nature. 600 (7889): 472–477. Bibcode:2021Natur.600..472C. doi:10.1038/s41586-021-03767-x. PMC   8674144 . PMID   34237774. S2CID   235776838.
11. Ellinghaus D, Degenhardt F, Bujanda L, Buti M, Albillos A, Invernizzi P, et al. (October 2020). "Genomewide Association Study of Severe Covid-19 with Respiratory Failure". The New England Journal of Medicine. 383 (16): 1522–1534. doi:10.1056/NEJMoa2020283. PMC   7315890 . PMID   32558485.
12. Downes DJ, Cross AR, Hua P, Roberts N, Schwessinger R, Cutler AJ, et al. (2021-11-04). "Identification of LZTFL1 as a candidate effector gene at a COVID-19 risk locus". Nature Genetics. 53 (11): 1606–1615. doi:10.1038/s41588-021-00955-3. PMC   7611960 . PMID   34737427.
13. Zeberg H, Pääbo S (November 2020). "The major genetic risk factor for severe COVID-19 is inherited from Neanderthals". Nature. 587 (7835): 610–612. Bibcode:2020Natur.587..610Z. doi: 10.1038/s41586-020-2818-3 . hdl: 21.11116/0000-0007-0F26-F . PMID   32998156. S2CID   222148977.