P4HTM

Chr 3

prolyl 4-hydroxylase, transmembrane

Also known as: EGLN4, HIDEA, HIFPH4, P4H-TM, PH-4, PH4, PHD4

NCBI Gene: 54681 ENSG00000178467 UniProt: Q9NXG6

The protein catalyzes 4-hydroxyproline formation in hypoxia-inducible factor (HIF) alpha proteins and functions as a cellular oxygen sensor that targets HIF for proteasomal degradation under normoxic conditions. Biallelic mutations cause an autosomal recessive multisystem disorder characterized by hypotonia, hypoventilation, intellectual disability, dysautonomia, epilepsy, and eye abnormalities. This gene is extremely intolerant to loss-of-function variants, indicating that normal protein function is critical for development and cellular homeostasis.

ResearchSummary from OMIM, UniProt

The product of this gene belongs to the family of prolyl 4-hydroxylases. This protein is a prolyl hydroxylase that may be involved in the degradation of hypoxia-inducible transcription factors under normoxia. It plays a role in adaptation to hypoxia and may be related to cellular oxygen sensing. Alternatively spliced variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]

ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtHypotonia, hyperventilation, impaired intellectual development, dysautonomia, epilepsy, and eye abnormalities

Clinical highlights

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)

—

P/LP submissions

—

P/LP missense

1.00

LOEUF

LOF

Mechanism· G2P

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429