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 (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 (134 variants)
not_provided (80 variants)
PHF6-related_disorder (47 variants)
Inborn_genetic_diseases (26 variants)
not_specified (9 variants)
Intellectual_disability (4 variants)
See_cases (2 variants)
Obesity (1 variants)
Horseshoe_kidney (1 variants)
Pulmonary_arterial_hypertension (1 variants)
Hereditary_spastic_paraplegia_4 (1 variants)
Hirsutism (1 variants)
Hypoplasia_of_penis (1 variants)
Global_developmental_delay (1 variants)
Neuroblastoma (1 variants)
Bilateral_cryptorchidism (1 variants)
Enlarged_cisterna_magna (1 variants)
Abnormality_of_neuronal_migration (1 variants)
Rib_fusion (1 variants)
Neurodevelopmental_abnormality (1 variants)
Macrocephaly (1 variants)
Developmental_disorder (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. These statistics are base on transcript: NM_001015877.2. Only rare variants are included in the table.

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.

Effect	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous			2 clinvar	32 clinvar	3 clinvar	37
missense	10 clinvar	12 clinvar	79 clinvar	6 clinvar		107
nonsense	14 clinvar	3 clinvar				17
start loss	2					2
frameshift	5 clinvar	2 clinvar	3 clinvar			10
splice donor/acceptor (+/-2bp)	3 clinvar	2 clinvar				5
Total	34	19	84	38	3

Highest pathogenic variant AF is 9.156478e-7

Loading clinvar variants...

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