ZFX

Chr XX-linked

zinc finger protein X-linked

Also known as: MRXS37, ZNF926

NCBI Gene: 7543 ENSG00000005889 UniProt: P17010 OMIM: 314980

ZFX encodes a transcriptional activator containing 13 zinc fingers that regulates stem cell self-renewal in hematopoietic and other tissues. Mutations cause X-linked syndromic intellectual developmental disorder 37. The gene is highly constrained against loss-of-function variants (pLI = 1.0, LOEUF = 0.16), indicating intolerance to functional disruption.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene on the X chromosome is structurally similar to a related gene on the Y chromosome. It encodes a member of the krueppel C2H2-type zinc-finger protein family. The full-length protein contains an acidic transcriptional activation domain (AD), a nuclear localization sequence (NLS) and a DNA binding domain (DBD) consisting of 13 C2H2-type zinc fingers. Studies in mouse embryonic and adult hematopoietic stem cells showed that this gene was required as a transcriptional regulator for self-renewal of both stem cell types, but it was dispensable for growth and differentiation of their progeny. Multiple alternatively spliced transcript variants encoding different isoforms have been identified, but the full-length nature of some variants has not been determined. [provided by RefSeq, May 2010]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Intellectual developmental disorder, X-linked syndromic 37MIM #301118

X-linked

Clinical highlights

Gene-disease validity (ClinGen)

X-linked syndromic complex neurodevelopmental disorder · XLStrongappropriate for clinical testing

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.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

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LOEUF

LOF

Mechanism· G2P

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