LZTFL1

LZTFL1
Identifiers
Aliases	LZTFL1, BBS17, leucine zipper transcription factor like 1
External IDs	OMIM: 606568; MGI: 1934860; GeneCards: LZTFL1
Gene location (Human)
Chr.	Chromosome 3 (human)
End	45,916,042 bp
Gene location (Mouse)
Chr.	Chromosome 9 (mouse)
End	123,546,762 bp
RNA expression pattern
	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
	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
Databases	NCBI: entry; OMA: entry
	54585
	93730
	ENSG00000163818
	ENSMUSG00000025245
	Q9NQ48
	Q9JHQ5
	NM_001276378; NM_001276379; NM_020347; NM_001386451; NM_001386452
	NM_033322
	NP_001263307; NP_001263308; NP_065080
	NP_201579
	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 2 3 GRCh38: Ensembl release 89: ENSG00000163818 – Ensembl, May 2017
1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000025245 – Ensembl, May 2017
↑ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
↑ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
↑ "LZTFL1 leucine zipper transcription factor like 1 [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2021-08-17.
↑ Seo S, Zhang Q, Bugge K, Breslow DK, Searby CC, Nachury MV, Sheffield VC (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.
↑ Marion V, Stutzmann F, Gérard M, De Melo C, Schaefer E, Claussmann A, Hellé S, Delague V, Souied E, Barrey C, Verloes A, Stoetzel C, Dollfus H (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.
↑ Kiss H, Kedra D, Kiss C, Kost-Alimova M, Yang Y, Klein G, Imreh S, Dumanski JP (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.
↑ Wei Q, Zhou W, Wang W, Gao B, Wang L, Cao J, Liu ZP (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.
↑ Niemi ME, Karjalainen J, Liao RG, Neale BM, Daly M, Ganna A, Pathak GA, Andrews SJ, Kanai M, Veerapen K, Fernandez-Cadenas I, Schulte EC, Striano P, Marttila M, Minica C, Marouli E, Karim MA, Wendt FR, Savage J, Sloofman L, Butler-Laporte G, Kim HN, Kanoni S, Okada Y, Byun J, Han Y, Uddin MJ, Smith GD, Willer CJ, Buxbaum JD (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.
↑ Ellinghaus D, Degenhardt F, Bujanda L, Buti M, Albillos A, Invernizzi P, Fernández J, Prati D, Baselli G, Asselta R, Grimsrud MM, Milani C, Aziz F, Kässens J, May S, Wendorff M, Wienbrandt L, Uellendahl-Werth F, Zheng T, Yi X, de Pablo R, Chercoles AG, Palom A, Garcia-Fernandez AE, Rodriguez-Frias F, Zanella A, Bandera A, Protti A, Aghemo A, Lleo A, Biondi A, Caballero-Garralda A, Gori A, Tanck A, Carreras Nolla A, Latiano A, Fracanzani AL, Peschuck A, Julià A, Pesenti A, Voza A, Jiménez D, Mateos B, Nafria Jimenez B, Quereda C, Paccapelo C, Gassner C, Angelini C, Cea C, Solier A, Pestaña D, Muñiz-Diaz E, Sandoval E, Paraboschi EM, Navas E, García Sánchez F, Ceriotti F, Martinelli-Boneschi F, Peyvandi F, Blasi F, Téllez L, Blanco-Grau A, Hemmrich-Stanisak G, Grasselli G, Costantino G, Cardamone G, Foti G, Aneli S, Kurihara H, ElAbd H, My I, Galván-Femenia I, Martín J, Erdmann J, Ferrusquía-Acosta J, Garcia-Etxebarria K, Izquierdo-Sanchez L, Bettini LR, Sumoy L, Terranova L, Moreira L, Santoro L, Scudeller L, Mesonero F, Roade L, Rühlemann MC, Schaefer M, Carrabba M, Riveiro-Barciela M, Figuera Basso ME, Valsecchi MG, Hernandez-Tejero M, Acosta-Herrera M, D'Angiò M, Baldini M, Cazzaniga M, Schulzky M, Cecconi M, Wittig M, Ciccarelli M, Rodríguez-Gandía M, Bocciolone M, Miozzo M, Montano N, Braun N, Sacchi N, Martínez N, Özer O, Palmieri O, Faverio P, Preatoni P, Bonfanti P, Omodei P, Tentorio P, Castro P, Rodrigues PM, Blandino Ortiz A, de Cid R, Ferrer R, Gualtierotti R, Nieto R, Goerg S, Badalamenti S, Marsal S, Matullo G, Pelusi S, Juzenas S, Aliberti S, Monzani V, Moreno V, Wesse T, Lenz TL, Pumarola T, Rimoldi V, Bosari S, Albrecht W, Peter W, Romero-Gómez M, D'Amato M, Duga S, Banales JM, Hov JR, Folseraas T, Valenti L, Franke A, Karlsen TH (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.
↑ Downes DJ, Cross AR, Hua P, Roberts N, Schwessinger R, Cutler AJ, Munis AM, Brown J, Mielczarek O, de Andrea CE, Melero I (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.
↑ 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.

[refGRCh38Ensembl-1] 1 2 3 GRCh38: Ensembl release 89: ENSG00000163818 – Ensembl, May 2017

[refGRCm38Ensembl-2] 1 2 3 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, Sheffield VC (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, Hellé S, Delague V, Souied E, Barrey C, Verloes A, Stoetzel C, Dollfus H (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, Imreh S, Dumanski JP (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, Liu ZP (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, Pathak GA, Andrews SJ, Kanai M, Veerapen K, Fernandez-Cadenas I, Schulte EC, Striano P, Marttila M, Minica C, Marouli E, Karim MA, Wendt FR, Savage J, Sloofman L, Butler-Laporte G, Kim HN, Kanoni S, Okada Y, Byun J, Han Y, Uddin MJ, Smith GD, Willer CJ, Buxbaum JD (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, Fernández J, Prati D, Baselli G, Asselta R, Grimsrud MM, Milani C, Aziz F, Kässens J, May S, Wendorff M, Wienbrandt L, Uellendahl-Werth F, Zheng T, Yi X, de Pablo R, Chercoles AG, Palom A, Garcia-Fernandez AE, Rodriguez-Frias F, Zanella A, Bandera A, Protti A, Aghemo A, Lleo A, Biondi A, Caballero-Garralda A, Gori A, Tanck A, Carreras Nolla A, Latiano A, Fracanzani AL, Peschuck A, Julià A, Pesenti A, Voza A, Jiménez D, Mateos B, Nafria Jimenez B, Quereda C, Paccapelo C, Gassner C, Angelini C, Cea C, Solier A, Pestaña D, Muñiz-Diaz E, Sandoval E, Paraboschi EM, Navas E, García Sánchez F, Ceriotti F, Martinelli-Boneschi F, Peyvandi F, Blasi F, Téllez L, Blanco-Grau A, Hemmrich-Stanisak G, Grasselli G, Costantino G, Cardamone G, Foti G, Aneli S, Kurihara H, ElAbd H, My I, Galván-Femenia I, Martín J, Erdmann J, Ferrusquía-Acosta J, Garcia-Etxebarria K, Izquierdo-Sanchez L, Bettini LR, Sumoy L, Terranova L, Moreira L, Santoro L, Scudeller L, Mesonero F, Roade L, Rühlemann MC, Schaefer M, Carrabba M, Riveiro-Barciela M, Figuera Basso ME, Valsecchi MG, Hernandez-Tejero M, Acosta-Herrera M, D'Angiò M, Baldini M, Cazzaniga M, Schulzky M, Cecconi M, Wittig M, Ciccarelli M, Rodríguez-Gandía M, Bocciolone M, Miozzo M, Montano N, Braun N, Sacchi N, Martínez N, Özer O, Palmieri O, Faverio P, Preatoni P, Bonfanti P, Omodei P, Tentorio P, Castro P, Rodrigues PM, Blandino Ortiz A, de Cid R, Ferrer R, Gualtierotti R, Nieto R, Goerg S, Badalamenti S, Marsal S, Matullo G, Pelusi S, Juzenas S, Aliberti S, Monzani V, Moreno V, Wesse T, Lenz TL, Pumarola T, Rimoldi V, Bosari S, Albrecht W, Peter W, Romero-Gómez M, D'Amato M, Duga S, Banales JM, Hov JR, Folseraas T, Valenti L, Franke A, Karlsen TH (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, Munis AM, Brown J, Mielczarek O, de Andrea CE, Melero I (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.

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