PHF6

PHF6
Available structures
PDB	Ortholog search: PDBe RCSB
List of PDB id codes
	4NN2, 4R7A
Identifiers
Aliases	PHF6, BFLS, BORJ, CENP-31, PHD finger protein 6
External IDs	OMIM: 300414 MGI: 1918248 HomoloGene: 12375 GeneCards: PHF6
Gene location (Human)
Chr.	X chromosome (human)
End	134,428,791 bp
Gene location (Mouse)
Chr.	X chromosome (mouse)
End	52,045,820 bp
RNA expression pattern
	Top expressed in
	corpus epididymis; ; oocyte; ; endothelial cell; ; germinal epithelium; ; secondary oocyte; ; ganglionic eminence; ; pancreatic epithelial cell; ; palpebral conjunctiva; ; Brodmann area 23; ; caput epididymis;
	Top expressed in
	hand; ; superior cervical ganglion; ; medial ganglionic eminence; ; maxillary prominence; ; trigeminal ganglion; ; median eminence; ; secondary oocyte; ; neural tube; ; pineal gland; ; cumulus cell;
	More reference expression data
	More reference expression data
Gene ontology
Molecular function	tubulin binding; enzyme binding; scaffold protein binding; DNA binding; ribonucleoprotein complex binding; histone binding; phosphoprotein binding; histone deacetylase binding; protein binding; metal ion binding; RNA binding; DNA-binding transcription repressor activity, RNA polymerase II-specific; sequence-specific DNA binding;
Cellular component	nucleolus; chromosome, centromeric region; nucleus; kinetochore; nucleoplasm; chromosome;
Biological process	regulation of transcription, DNA-templated; transcription, DNA-templated; negative regulation of transcription by RNA polymerase II; blastocyst hatching;
	Sources:Amigo / QuickGO
Orthologs
	84295
	70998
	ENSG00000156531
	ENSMUSG00000025626
	Q8IWS0
	Q9D4J7
	NM_032458; NM_001015877; NM_032335
	NM_001290546; NM_027642
	NP_001015877; NP_115711; NP_115834
	NP_001277475; NP_081918
	Wikidata
View/Edit Human	View/Edit Mouse

PHD finger protein 6 is a protein that in humans is encoded by the PHF6 gene.^[5]^[6]

This gene is a member of the plant homeodomain (PHD)-like finger (PHF) family. It encodes a protein with two atypical PHD-type zinc finger domains, indicating a potential role in transcriptional regulation, that localizes to the nucleolus.^[6]

Mutations

Mutations affecting the coding region of this gene or the splicing of the transcript have been associated with Börjeson-Forssman-Lehmann syndrome (BFLS), a disorder characterized by mental retardation, epilepsy, hypogonadism, hypometabolism, obesity, swelling of subcutaneous tissue of the face, narrow palpebral fissures, and large ears. Alternate transcriptional splice variants, encoding different isoforms, have been characterized.^[6]

The PHF6 gene in humans is also frequently mutated in human hematological malignancies, including T-cell acute lymphoblastic Leukemia (T-ALL)^[7] and Acute Myeloid Leukemia (AML)^[8] and at least two BFLS patients have developed leukemia or lymphoma.^[9] PHF6 has been shown to be important for the regulation of blood stem and progenitor cells^[10]^[11]^[12]^[13] and loss of PHF6 protein synergizes with over-expression of the TLX3 protein to cause lymphoid neoplasms.^[11]

References

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000156531 - Ensembl, May 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000025626 - 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.
^ Lower KM, Turner G, Kerr BA, Mathews KD, Shaw MA, Gedeon AK, et al. (December 2002). "Mutations in PHF6 are associated with Börjeson-Forssman-Lehmann syndrome". Nature Genetics. 32 (4): 661–5. doi:10.1038/ng1040. PMID 12415272. S2CID 10274037.
^ ^a ^b ^c "Entrez Gene: PHF6 PHD finger protein 6".
^ Van Vlierberghe P, Palomero T, Khiabanian H, Van der Meulen J, Castillo M, Van Roy N, et al. (April 2010). "PHF6 mutations in T-cell acute lymphoblastic leukemia". Nature Genetics. 42 (4): 338–42. doi:10.1038/ng.542. PMC 2847364. PMID 20228800.
^ Van Vlierberghe P, Patel J, Abdel-Wahab O, Lobry C, Hedvat CV, Balbin M, et al. (January 2011). "PHF6 mutations in adult acute myeloid leukemia". Leukemia. 25 (1): 130–4. doi:10.1038/leu.2010.247. PMC 3878659. PMID 21030981.
^ Chao MM, Todd MA, Kontny U, Neas K, Sullivan MJ, Hunter AG, et al. (October 2010). "T-cell acute lymphoblastic leukemia in association with Börjeson-Forssman-Lehmann syndrome due to a mutation in PHF6". Pediatric Blood & Cancer. 55 (4): 722–4. doi:10.1002/pbc.22574. PMC 2933084. PMID 20806366.
^ Wendorff AA, Quinn SA, Rashkovan M, Madubata CJ, Ambesi-Impiombato A, Litzow MR, et al. (March 2019). "Phf6 Loss Enhances HSC Self-Renewal Driving Tumor Initiation and Leukemia Stem Cell Activity in T-ALL". Cancer Discovery. 9 (3): 436–451. doi:10.1158/2159-8290.CD-18-1005. PMC 6425751. PMID 30567843.
^ ^a ^b McRae HM, Garnham AL, Hu Y, Witkowski MT, Corbett MA, Dixon MP, et al. (April 2019). "PHF6 regulates hematopoietic stem and progenitor cells and its loss synergizes with expression of TLX3 to cause leukemia". Blood. 133 (16): 1729–1741. doi:10.1182/blood-2018-07-860726. PMC 6695515. PMID 30755422.
^ Miyagi S, Sroczynska P, Kato Y, Nakajima-Takagi Y, Oshima M, Rizq O, et al. (June 2019). "The chromatin-binding protein Phf6 restricts the self-renewal of hematopoietic stem cells". Blood. 133 (23): 2495–2506. doi:10.1182/blood.2019000468. PMID 30917958.
^ Hsu YC, Chen TC, Lin CC, Yuan CT, Hsu CL, Hou HA, et al. (August 2019). "Phf6-null hematopoietic stem cells have enhanced self-renewal capacity and oncogenic potentials". Blood Advances. 3 (15): 2355–2367. doi:10.1182/bloodadvances.2019000391. PMC 6693005. PMID 31395598.

External links

PHF6+protein,+human at the U.S. National Library of Medicine Medical Subject Headings (MeSH)

This article incorporates text from the United States National Library of Medicine, which is in the public domain.

This article on a gene on the human X chromosome and/or its associated protein is a stub. You can help Wikipedia by expanding it.

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000156531 - Ensembl, May 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000025626 - 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.

[pmid12415272-5] Lower KM, Turner G, Kerr BA, Mathews KD, Shaw MA, Gedeon AK, et al. (December 2002). "Mutations in PHF6 are associated with Börjeson-Forssman-Lehmann syndrome". Nature Genetics. 32 (4): 661–5. doi:10.1038/ng1040. PMID 12415272. S2CID 10274037.

[entrez-6] "Entrez Gene: PHF6 PHD finger protein 6".

[7] Van Vlierberghe P, Palomero T, Khiabanian H, Van der Meulen J, Castillo M, Van Roy N, et al. (April 2010). "PHF6 mutations in T-cell acute lymphoblastic leukemia". Nature Genetics. 42 (4): 338–42. doi:10.1038/ng.542. PMC 2847364. PMID 20228800.

[8] Van Vlierberghe P, Patel J, Abdel-Wahab O, Lobry C, Hedvat CV, Balbin M, et al. (January 2011). "PHF6 mutations in adult acute myeloid leukemia". Leukemia. 25 (1): 130–4. doi:10.1038/leu.2010.247. PMC 3878659. PMID 21030981.

[9] Chao MM, Todd MA, Kontny U, Neas K, Sullivan MJ, Hunter AG, et al. (October 2010). "T-cell acute lymphoblastic leukemia in association with Börjeson-Forssman-Lehmann syndrome due to a mutation in PHF6". Pediatric Blood & Cancer. 55 (4): 722–4. doi:10.1002/pbc.22574. PMC 2933084. PMID 20806366.

[10] Wendorff AA, Quinn SA, Rashkovan M, Madubata CJ, Ambesi-Impiombato A, Litzow MR, et al. (March 2019). "Phf6 Loss Enhances HSC Self-Renewal Driving Tumor Initiation and Leukemia Stem Cell Activity in T-ALL". Cancer Discovery. 9 (3): 436–451. doi:10.1158/2159-8290.CD-18-1005. PMC 6425751. PMID 30567843.

[:0-11] McRae HM, Garnham AL, Hu Y, Witkowski MT, Corbett MA, Dixon MP, et al. (April 2019). "PHF6 regulates hematopoietic stem and progenitor cells and its loss synergizes with expression of TLX3 to cause leukemia". Blood. 133 (16): 1729–1741. doi:10.1182/blood-2018-07-860726. PMC 6695515. PMID 30755422.

[12] Miyagi S, Sroczynska P, Kato Y, Nakajima-Takagi Y, Oshima M, Rizq O, et al. (June 2019). "The chromatin-binding protein Phf6 restricts the self-renewal of hematopoietic stem cells". Blood. 133 (23): 2495–2506. doi:10.1182/blood.2019000468. PMID 30917958.

[13] Hsu YC, Chen TC, Lin CC, Yuan CT, Hsu CL, Hou HA, et al. (August 2019). "Phf6-null hematopoietic stem cells have enhanced self-renewal capacity and oncogenic potentials". Blood Advances. 3 (15): 2355–2367. doi:10.1182/bloodadvances.2019000391. PMC 6693005. PMID 31395598.

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Mutations

References

Further reading

External links