PHF8

PHD finger protein 8, the group of Lysine demethylases|PHD finger proteins

Basic information

Region (hg38): X:53936675-54048958

Links

ENSG00000172943 ∙ NCBI:23133 ∙ OMIM:300560 ∙ HGNC:20672 ∙ Uniprot:Q9UPP1 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• syndromic X-linked intellectual disability Siderius type (Definitive), mode of inheritance: XLR
• syndromic X-linked intellectual disability Siderius type (Strong), mode of inheritance: XL
• syndromic X-linked intellectual disability Siderius type (Supportive), mode of inheritance: XL
• syndromic X-linked intellectual disability Siderius type (Definitive), mode of inheritance: XL
• syndromic X-linked intellectual disability Siderius type (Definitive), mode of inheritance: XL

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Intellectual developmental disorder, X-linked, syndrome, Siderius type	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; Musculoskeletal; Neurologic	10398231; 16199551; 17594395; 17661819; 23092983

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PHF8 gene.

• not provided (94 variants)
• Inborn genetic diseases (52 variants)
• Syndromic X-linked intellectual disability Siderius type (24 variants)
• not specified (15 variants)
• PHF8-related condition (3 variants)
• Intellectual disability (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PHF8 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	36	3	40
missense			90	5		95
nonsense	3	1				4
start loss						0
frameshift	5	1	1			7
inframe indel				1		1
splice donor/acceptor (+/-2bp)		3	1			4
splice region	1		3	2	1	7
non coding			2	1	1	4
Total	8	5	95	43	4

Variants in PHF8

This is a list of pathogenic ClinVar variants found in the PHF8 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-53939203-G-A			Likely benign (Jan 01, 2024)
X-53939240-C-T			Uncertain significance (Dec 16, 2022)
X-53940176-G-T			Likely benign (Jan 04, 2019)
X-53940186-C-T			Uncertain significance (Jan 06, 2023)
X-53940197-C-T			Uncertain significance (Aug 03, 2017)
X-53940207-C-T		Syndromic X-linked intellectual disability Siderius type	Uncertain significance (Dec 07, 2021)
X-53940219-G-T		Inborn genetic diseases	Uncertain significance (Aug 04, 2018)
X-53940221-C-T			Uncertain significance (Feb 07, 2023)
X-53940226-G-A			Likely benign (Feb 01, 2023)
X-53940235-G-A		Inborn genetic diseases	Likely benign (Nov 26, 2019)
X-53940257-G-A			Uncertain significance (Feb 24, 2023)
X-53940264-G-A		Inborn genetic diseases	Uncertain significance (Jan 26, 2023)
X-53940270-C-T		Inborn genetic diseases	Uncertain significance (Jan 04, 2022)
X-53940284-A-G		Inborn genetic diseases	Uncertain significance (Sep 16, 2021)
X-53940286-G-C			Likely benign (Jun 29, 2018)
X-53940296-C-T		Inborn genetic diseases	Uncertain significance (Dec 21, 2020)
X-53940303-T-A			Uncertain significance (Nov 03, 2021)
X-53940318-C-T			Uncertain significance (Jan 02, 2021)
X-53940321-G-A		Syndromic X-linked intellectual disability Siderius type • Inborn genetic diseases	Uncertain significance (Jul 30, 2020)
X-53940329-G-A			Uncertain significance (Jul 21, 2022)
X-53940351-C-G			Uncertain significance (Apr 01, 2017)
X-53940356-G-A			Uncertain significance (May 02, 2023)
X-53940357-G-T			Uncertain significance (Nov 04, 2021)
X-53940367-TGAG-T		not specified • Inborn genetic diseases • PHF8-related disorder	Benign/Likely benign (Mar 17, 2020)
X-53940370-G-C			Likely benign (Feb 01, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PHF8	protein_coding	protein_coding	ENST00000357988	22	112283

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.998	0.00215	125738	1	6	125745	0.0000278

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	3.98	199	431	0.461	0.0000347	6924
Missense in Polyphen		13	122.65	0.106		2206
Synonymous	0.430	164	171	0.958	0.0000138	2097
Loss of Function	5.13	5	40.0	0.125	0.00000323	638

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000760	0.0000615
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000723	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.0000490	0.0000352
Middle Eastern	0.0000723	0.0000544
South Asian	0.0000578	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Histone lysine demethylase with selectivity for the di- and monomethyl states that plays a key role cell cycle progression, rDNA transcription and brain development. Demethylates mono- and dimethylated histone H3 'Lys-9' residue (H3K9Me1 and H3K9Me2), dimethylated H3 'Lys-27' (H3K27Me2) and monomethylated histone H4 'Lys-20' residue (H4K20Me1). Acts as a transcription activator as H3K9Me1, H3K9Me2, H3K27Me2 and H4K20Me1 are epigenetic repressive marks. Involved in cell cycle progression by being required to control G1-S transition. Acts as a coactivator of rDNA transcription, by activating polymerase I (pol I) mediated transcription of rRNA genes. Required for brain development, probably by regulating expression of neuron-specific genes. Only has activity toward H4K20Me1 when nucleosome is used as a substrate and when not histone octamer is used as substrate. May also have weak activity toward dimethylated H3 'Lys-36' (H3K36Me2), however, the relevance of this result remains unsure in vivo. Specifically binds trimethylated 'Lys-4' of histone H3 (H3K4me3), affecting histone demethylase specificity: has weak activity toward H3K9Me2 in absence of H3K4me3, while it has high activity toward H3K9me2 when binding H3K4me3. {ECO:0000269|PubMed:19843542, ECO:0000269|PubMed:20023638, ECO:0000269|PubMed:20101266, ECO:0000269|PubMed:20208542, ECO:0000269|PubMed:20346720, ECO:0000269|PubMed:20421419, ECO:0000269|PubMed:20531378, ECO:0000269|PubMed:20548336, ECO:0000269|PubMed:20622853, ECO:0000269|PubMed:20622854}.
• Disease: DISEASE: Mental retardation, X-linked, syndromic, Siderius type (MRXSSD) [MIM:300263]: A syndrome characterized by mild to borderline mental retardation with or without cleft lip/cleft palate. {ECO:0000269|PubMed:16199551, ECO:0000269|PubMed:17661819, ECO:0000269|PubMed:20101266, ECO:0000269|PubMed:20208542, ECO:0000269|PubMed:20346720, ECO:0000269|PubMed:20421419, ECO:0000269|PubMed:20548336, ECO:0000269|PubMed:20622853, ECO:0000269|PubMed:20622854}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Ectoderm Differentiation;HDMs demethylate histones;Chromatin modifying enzymes;Condensation of Prophase Chromosomes;Chromatin organization;Mitotic Prophase;M Phase;Cell Cycle;Cell Cycle, Mitotic (Consensus)

Recessive Scores

• pRec: 0.101

Intolerance Scores

• loftool: 0.352
• rvis_EVS: -0.03
• rvis_percentile_EVS: 51.92

Haploinsufficiency Scores

• pHI: 0.481
• hipred: Y
• hipred_score: 0.695
• ghis: 0.511

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.183

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Phf8

Zebrafish Information Network

• Gene name: phf8
• Affected structure: pharyngeal arch 1
• Phenotype tag: abnormal
• Phenotype quality: decreased size

Gene ontology

• Biological process: G1/S transition of mitotic cell cycle;brain development;histone H3-K9 demethylation;histone H4-K20 demethylation;positive regulation of transcription, DNA-templated;positive regulation of transcription by RNA polymerase I;oxidation-reduction process;negative regulation of chromatin silencing at rDNA;histone H3-K36 demethylation;histone H3-K27 demethylation
• Cellular component: nucleus;nucleoplasm;nucleolus;nuclear membrane
• Molecular function: chromatin binding;iron ion binding;protein binding;zinc ion binding;2-oxoglutarate-dependent dioxygenase activity;histone demethylase activity;histone demethylase activity (H3-K9 specific);methylated histone binding;histone demethylase activity (H4-K20 specific);histone demethylase activity (H3-K36 specific);histone demethylase activity (H3-K27 specific)