PHF8

Chr Xp11.22

PHD finger protein 8

Aliases:: ZNF422, KIAA1111, JHDM1F, KDM7B
MANE:: ENST00000338154.11

OMIM: 300560 ↗NCBI: 23133 ↗Ensembl ↗

Annotations refreshed 10 hours ago.

Predicted protein structure

AlphaFold predicted structure

PHF8 · Q9UPP1

v62025-08-01

Predicted Aligned Error matrix for PHF8 — diagonal shows residue index, colour shows pairwise prediction confidence (lower is better) — Predicted Aligned Error

Mean pLDDT

62.4/ 100

Low

1,060 residues

Confidence breakdown

Very high(≥ 90)34%
Confident(70–90)9%
Low(50–70)4%
Very low(< 50)53%

Open interactive 3D viewer

AlphaFold (Jumper et al., 2021) · CC BY 4.0

Clinical relevance (Genomics England PanelApp)

Diagnostic Grade (Green)

Clefting
X-LINKED: hemizygous mutation in males, biallelic mutations in females
DDG2P
X-LINKED: hemizygous mutation in males, biallelic mutations in females
Fetal anomalies
X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability
X-LINKED: hemizygous mutation in males, biallelic mutations in females

Disease associations (Open Targets)

syndromic X-linked intellectual disability Siderius type
0.75
X-linked intellectual disability, Siderius type
0.67
hereditary disease
0.42
cleft lip
0.37
neurodegenerative disease
0.37
Intellectual disability
0.35
type 2 diabetes mellitus
0.24
neoplasm
0.11
hepatocellular carcinoma
0.11
breast cancer
0.10

Score is the Open Targets composite evidence score (0-1). Higher = stronger gene-disease association.

Protein function (UniProt)

Histone lysine demethylase PHF8

Histone lysine demethylase with selectivity for mono- and dimethylated residues. It plays an essential role in cell cycle progression and rDNA transcription (PubMed:19843542, PubMed:20531378, PubMed:20548336, PubMed:20622854). Demethylates mono- and dimethylated histone H3 'Lys-9' residue (H3K9Me1 and H3K9Me2) and monomethylated histone H4 'Lys-20' residue (H4K20Me1). Acts as a transcription activator as H3K9Me1, H3K9Me2, H3K27Me2 and H4K20Me1 are epigenetic repressive marks (PubMed:20101266, PubMed:20208542, PubMed:20346720, PubMed:20622853, PubMed:20622854). Displays a very low intrinsic activity toward dimethylated H3 'Lys-27' (H3K27Me2) (PubMed:20346720). May also have weak activity toward dimethylated H3 'Lys-36' (H3K36Me2), however, the relevance of this result remains unsure in vivo (PubMed:19843542, PubMed:20023638, PubMed:20346720). Involved in cell cycle progression by being required to control G1-S transition (PubMed:20622854). Acts as a coactivator of rDNA transcription, by activating polymerase I (pol I) mediated transcription of rRNA genes (PubMed:20531378). 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 (PubMed:20023638, PubMed:20346720, PubMed:20421419). Positively modulates transcription of histone demethylase KDM5C, acting synergistically with transcription factor ARX; synergy may be related to enrichment of histone H3K4me3 in regulatory elements (PubMed:31691806). Required for brain development, probably by regulating expression of neuron-specific genes (By similarity)