P3H3
protein-codingprolyl 3-hydroxylase 3, the group of Prolyl 3-hydroxylase family
Gene summary
The protein encoded by this gene belongs to the leprecan family of proteoglycans, which function as collagen prolyl hydroxylases that are required for proper collagen biosynthesis, folding and assembly. This protein, like other family members, is thought to reside in the endoplasmic reticulum. Epigenetic inactivation of this gene is associated with breast and other cancers, suggesting that it may function as a tumor suppressor. [provided by RefSeq, Aug 2013]
- LEPREL2
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~11.4 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to P3H3 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_014262.5. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 4 | 3 | 7 | |||
| missense | 49 | 4 | 53 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 4 | 4 | ||||
| Total | 0 | 0 | 57 | 7 | 0 | 64 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_055077.2 | 15 | MANE Select | |
| Ensembl | ENSP00000478600.1 | 15 | MANE Select | |
| Ensembl | ENSP00000583313.1 | 15 | Standard | |
| Ensembl | ENSP00000583313.1 | 15 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Collagen biosynthesis and modifying enzymes
- Collagen formation
- Extracellular matrix organization
Biological Process
- negative regulation of cell population proliferation
- peptidyl-lysine hydroxylation
- peptidyl-proline hydroxylation
- collagen metabolic process
- collagen biosynthetic process
Molecular Function
- iron ion binding
- procollagen-proline 3-dioxygenase activity
- L-ascorbic acid binding
Cellular Component
- endoplasmic reticulum
- catalytic complex
gnomAD Constraint
Source:
- Gene type
- polymorphic_pseudogene
- Transcript type
- protein_coding
- Transcript
- ENST00000396725
- Coding exons
- 16
- Length
- 11447
- Individuals with no LoFs
- 124545
- Homozygous LoFs
- 1
- Heterozygous LoFs
- 113
- Defined
- 124659
- p
- 0.000457
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.0383 | 363 | 361 | 1.01 | 0.0000230 | 4568 |
| Missense (PolyPhen) | 162 | 148.17 | 1.0934 | 1807 | ||
| Synonymous | 0.167 | 137 | 140 | 0.982 | 0.00000811 | 1564 |
| Loss of Function | 1.51 | 22 | 31.1 | 0.707 | 0.00000149 | 383 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00033 | 0.00032 | rare |
| Latino/Admixed American | 0.00067 | 0.00064 | rare |
| Ashkenazi Jewish | 0.00050 | 0.00050 | rare |
| East Asian | 0.00051 | 0.00050 | rare |
| Finnish | 0.00020 | 0.00019 | rare |
| European (Non-Finnish) | 0.00030 | 0.00029 | rare |
| South Asian | 0.0012 | 0.0011 | notable |
| Other | 0.00017 | 0.00017 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Part of a complex composed of PLOD1, P3H3 and P3H4 that catalyzes hydroxylation of lysine residues in collagen alpha chains and is required for normal assembly and cross-linkling of collagen fibrils. Required for normal hydroxylation of lysine residues in type I collagen chains in skin, bone, tendon, aorta and cornea. Required for normal skin stability via its role in hydroxylation of lysine residues in collagen alpha chains and in collagen fibril assembly. Apparently not required for normal prolyl 3-hydroxylation on collagen chains, possibly because it functions redundantly with other prolyl 3-hydroxylases. {ECO:0000250|UniProtKB:Q8CG70}.;
Recessive Scores
- pRec
- 0.305