P4HTM
Prolyl 4-Hydroxylase, Transmembrane
Gene Information Card
| Symbol | P4HTM |
|---|---|
| Full Name | Prolyl 4-Hydroxylase, Transmembrane |
| Gene Type | protein-coding |
| Chromosomal Location | 3p21.31 |
| NCBI Gene ID | 54681 ncbi.nlm.nih.gov/gene/54681 |
| Ensembl ID | ENSG00000163882 |
| UniProt ID | Q9NXG6 |
| OMIM ID | 614584 |
| HGNC ID | 21322 |
| Aliases | P4H-TM, HIF-PH3, EGLN3, PH-4 |
Description
The P4HTM gene encodes a transmembrane prolyl 4-hydroxylase that hydroxylates hypoxia-inducible factor (HIF) alpha subunits, targeting them for proteasomal degradation under normoxic conditions. It belongs to the EGLN family of prolyl hydroxylases and is involved in oxygen sensing, cellular adaptation to hypoxia, and collagen metabolism. Mutations in P4HTM are associated with autosomal recessive intellectual disability and myopathy.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Autosomal recessive intellectual disability with myopathy | Loss-of-function mutations impair HIF hydroxylation, leading to dysregulated hypoxia response and muscle dysfunction | ClinVar, OMIM #614584 |
| Hypoxia-inducible factor pathway dysregulation | Deficient prolyl hydroxylation stabilizes HIF-1α, altering gene expression in oxygen-sensitive tissues | UniProt, NCBI Gene |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 5.2 | Medium |
| Skeletal muscle | 3.8 | Low |
| Heart | 4.1 | Low |
| Kidney | 6.0 | Medium |
| Liver | 2.5 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 4.5 | Moderate expression |
| HeLa | 3.2 | Low expression |
| SH-SY5Y | 6.1 | Moderate expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1A>G (p.Met1?) | Missense | <0.01% | Loss of start codon, likely loss of function |
| c.950G>A (p.Arg317Gln) | Missense | <0.01% | Reduced hydroxylase activity, associated with intellectual disability |
Mutation functional classification
Loss of Function (LOF)
Missense and nonsense mutations that reduce or abolish prolyl hydroxylase activity, leading to HIF stabilization and altered hypoxia response.
Gain of Function (GOF)
Not reported in P4HTM.
Dominant Negative (DN)
Not reported in P4HTM.
View complete mutation data：
Gene Ontology (GO)
| • prolyl 4-hydroxylase activity | • L-ascorbic acid binding |
| • iron ion binding | • hypoxia-inducible factor-alpha hydroxylation |
| • cellular response to hypoxia | • protein hydroxylation |
Pathways
• HIF-1 alpha transcription factor network
• Cellular response to hypoxia
• Proline hydroxylation of HIF-alpha
Protein Summary
P4HTM is a 302-amino acid transmembrane protein with a C-terminal prolyl hydroxylase domain. It localizes to the endoplasmic reticulum and uses Fe2+ and 2-oxoglutarate as cofactors to hydroxylate specific proline residues in HIF-1α and HIF-2α. This modification promotes binding to the von Hippel-Lindau (VHL) ubiquitin ligase complex, leading to HIF degradation. Under hypoxia, P4HTM activity is reduced, allowing HIF accumulation and activation of adaptive genes.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| P4HTM Knockout HEK293 Cell Line | EDJ-KQ11483 | Human | 54681 | Details Get a Quote |
| P4HTM Knockout A-549 Cell Line | EDJ-KQ38465 | Human | 54681 | Details Get a Quote |
| P4HTM Knockout HCT 116 Cell Line | EDJ-KQ39807 | Human | 54681 | Details Get a Quote |
| P4HTM Knockout HeLa Cell Line | EDJ-KQ39808 | Human | 54681 | Details Get a Quote |
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