PHF6

PHD finger protein 6, the group of PHD finger proteins

Basic information

Region (hg38): X:134373288-134428791

Previous symbols: [ "BFLS", "BORJ" ]

Links

ENSG00000156531 ∙ NCBI:84295 ∙ OMIM:300414 ∙ HGNC:18145 ∙ Uniprot:Q8IWS0 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Borjeson-Forssman-Lehmann syndrome (Definitive), mode of inheritance: XLR
• Borjeson-Forssman-Lehmann syndrome (Strong), mode of inheritance: XL
• Borjeson-Forssman-Lehmann syndrome (Supportive), mode of inheritance: XL
• Borjeson-Forssman-Lehmann syndrome (Strong), mode of inheritance: XL
• Borjeson-Forssman-Lehmann syndrome (Definitive), mode of inheritance: XL
• Borjeson-Forssman-Lehmann syndrome (Definitive), mode of inheritance: XL
• Borjeson-Forssman-Lehmann syndrome (Definitive), mode of inheritance: XL

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Borjeson-Forssman-Lehmann syndrome	XL	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Craniofacial; Endocrine; Musculoskeletal; Neurologic	13871358; 4465467; 12415272; 15241480; 14756673; 15994862; 16912705; 19264739; 22190899; 23906836

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PHF6 gene.

• Borjeson-Forssman-Lehmann syndrome (12 variants)
• not provided (8 variants)
• Inborn genetic diseases (4 variants)
• Hereditary spastic paraplegia 4 (1 variants)
• See cases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PHF6 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			1	28	2	31
missense	2	6	47	2		57
nonsense	10	3				13
start loss	2					2
frameshift	2	2	1			5
inframe indel			5	1		6
splice donor/acceptor (+/-2bp)	2	2				4
splice region			4	4	1	9
non coding				24	12	36
Total	18	13	54	55	14

Variants in PHF6

This is a list of pathogenic ClinVar variants found in the PHF6 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
X-134373472-G-A		Borjeson-Forssman-Lehmann syndrome	Uncertain significance (Jun 23, 2021)
X-134373475-C-T		not specified	Likely benign (Feb 12, 2016)
X-134377233-TTATC-T			Likely benign (Jul 12, 2019)
X-134377619-T-C		Borjeson-Forssman-Lehmann syndrome • Hereditary spastic paraplegia 4	Pathogenic (Jul 22, 2022)
X-134377620-G-T			Pathogenic (Jul 02, 2012)
X-134377626-C-T		PHF6-related disorder	Likely benign (Jun 18, 2021)
X-134377638-GA-G		Hirsutism;Intellectual disability	Pathogenic (Dec 03, 2018)
X-134377638-G-GA		Borjeson-Forssman-Lehmann syndrome	Pathogenic (Mar 01, 2006)
X-134377639-A-T		Borjeson-Forssman-Lehmann syndrome	Pathogenic (Dec 01, 2002)
X-134377641-A-G		PHF6-related disorder	Likely benign (Dec 17, 2019)
X-134377644-A-AGG		Borjeson-Forssman-Lehmann syndrome	Pathogenic (Dec 09, 2017)
X-134377656-A-G		PHF6-related disorder	Likely benign (Nov 23, 2022)
X-134377665-A-G		PHF6-related disorder	Likely benign (Sep 21, 2022)
X-134377682-C-A		Borjeson-Forssman-Lehmann syndrome	Likely pathogenic (Dec 09, 2016)
X-134377688-G-C		Inborn genetic diseases	Uncertain significance (Nov 03, 2023)
X-134377694-A-T			Uncertain significance (Jun 20, 2022)
X-134377701-T-C		Borjeson-Forssman-Lehmann syndrome	Likely benign (Jul 30, 2022)
X-134377702-G-T			Pathogenic (Nov 03, 2021)
X-134377703-G-C		Borjeson-Forssman-Lehmann syndrome	Uncertain significance (Sep 27, 2020)
X-134377705-C-T			Pathogenic (Dec 06, 2022)
X-134377706-A-G		Borjeson-Forssman-Lehmann syndrome	Uncertain significance (Jun 28, 2022)
X-134377728-GA-G		Borjeson-Forssman-Lehmann syndrome	Uncertain significance (Dec 31, 2016)
X-134377731-G-T			Uncertain significance (Jan 01, 2024)
X-134377736-C-A		Neuroblastoma	other (May 01, 2016)
X-134377739-C-T		Borjeson-Forssman-Lehmann syndrome	Uncertain significance (Jul 18, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PHF6	protein_coding	protein_coding	ENST00000332070	9	55538

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.998	0.00216	0	0	0	0	0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.28	57	130	0.437	0.00000914	2412
Missense in Polyphen		5	52.447	0.095334		993
Synonymous	-0.502	48	43.8	1.10	0.00000300	645
Loss of Function	3.93	0	18.0	0.00	0.00000173	281

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.00	0.00
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Transcriptional regulator that associates with ribosomal RNA promoters and suppresses ribosomal RNA (rRNA) transcription. {ECO:0000269|PubMed:23229552}.
• Disease: DISEASE: Boerjeson-Forssman-Lehmann syndrome (BFLS) [MIM:301900]: A X-linked recessive disorder characterized by moderate to severe mental retardation, epilepsy, hypogonadism, hypometabolism, obesity with marked gynecomastia, swelling of subcutaneous tissue of the face, narrow palpebral fissure and large but not deformed ears. {ECO:0000269|PubMed:12415272, ECO:0000269|PubMed:23229552, ECO:0000269|PubMed:23906836}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Mesodermal Commitment Pathway (Consensus)

Recessive Scores

• pRec: 0.163

Intolerance Scores

• loftool: 0.142
• rvis_EVS: -0.03
• rvis_percentile_EVS: 51.04

Haploinsufficiency Scores

• pHI: 0.750
• hipred: Y
• hipred_score: 0.728
• ghis: 0.719

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.114

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Phf6
• Phenotype: mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span)

Gene ontology

• Biological process: negative regulation of transcription by RNA polymerase II;blastocyst hatching
• Cellular component: condensed chromosome kinetochore;nucleus;nucleoplasm;nucleolus
• Molecular function: DNA-binding transcription repressor activity, RNA polymerase II-specific;RNA binding;protein binding;tubulin binding;enzyme binding;histone binding;histone deacetylase binding;ribonucleoprotein complex binding;sequence-specific DNA binding;metal ion binding;phosphoprotein binding;scaffold protein binding