PHF8

Chr XXLR

PHD finger protein 8

Also known as: JHDM1F, KDM7B, MRXSSD, ZNF422

NCBI Gene: 23133 ENSG00000172943 UniProt: Q9UPP1 OMIM: 300560

The protein functions as a histone lysine demethylase that removes methyl groups from histones to activate gene transcription, requiring Fe(2+), 2-oxoglutarate, and oxygen for catalytic activity. Loss-of-function mutations cause X-linked syndromic intellectual disability of the Siderius type, which is inherited in an X-linked recessive pattern. The pathogenic mechanism involves disrupted chromatin remodeling and transcriptional regulation due to impaired histone demethylase activity.

OMIM ResearchSummary from RefSeq, OMIM, UniProt, Mechanism

The protein encoded by this gene is a histone lysine demethylase that preferentially acts on histones in the monomethyl or dimethyl states. The encoded protein requires Fe(2+) ion, 2-oxoglutarate, and oxygen for its catalytic activity. The protein has an N-terminal PHD finger and a central Jumonji C domain. This gene is thought to function as a transcription activator. Defects in this gene are a cause of syndromic X-linked Siderius type intellectual disability (MRXSSD) and over-expression of this gene is associated with several forms of cancer. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2017]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Intellectual developmental disorder, X-linked syndromic, Siderius typeMIM #300263

XLR

Clinical highlights

Gene-disease validity (ClinGen)

syndromic X-linked intellectual disability Siderius type · XLDefinitivesufficient evidence for diagnostic panels

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype) and the gene is intolerant of it in the population — truncating, frameshift and canonical splice variants carry more prior weight here than missense.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

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P/LP submissions

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P/LP missense

0.26

LOEUF· LoF intol.

LOF

Mechanism· G2P