P3H2
protein-codingprolyl 3-hydroxylase 2, the group of Prolyl 3-hydroxylase family
Gene summary
This gene encodes a member of the prolyl 3-hydroxylase subfamily of 2-oxo-glutarate-dependent dioxygenases. These enzymes play a critical role in collagen chain assembly, stability and cross-linking by catalyzing post-translational 3-hydroxylation of proline residues. Mutations in this gene are associated with nonsyndromic severe myopia with cataract and vitreoretinal degeneration, and downregulation of this gene may play a role in breast cancer. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Dec 2011]
- LEPREL1
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~165.7 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:0013670
Submitter: Ambry Genetics
Inheritance Pattern: AR
Disease ID:MONDO:0013670
Submitter: PanelApp Australia
Inheritance Pattern: AR
Disease ID:MONDO:0013670
Submitter: G2P
Clinical Genomic Database (CGD)
Manifestation: Ophthalmologic
Intervention: General
Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to P3H2 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_018192.4. 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 | 153 | 2 | 159 | ||
| missense | 3 | 333 | 23 | 3 | 362 | |
| nonsense | 11 | 10 | 4 | 25 | ||
| start loss | 0 | |||||
| frameshift | 17 | 10 | 2 | 29 | ||
| splice donor/acceptor (+/-2bp) | 12 | 3 | 15 | |||
| Total | 28 | 35 | 346 | 176 | 5 | 590 |
Highest pathogenic variant AF is 0.00015986616
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_060662.2 | 15 | MANE Select | |
| Ensembl | ENSP00000316881.5 | 15 | MANE Select | |
| RefSeq | NP_001127890.1 | 14 | Standard | |
| Ensembl | ENSP00000394326.1 | 3 | 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-proline hydroxylation
- collagen metabolic process
- oxidation-reduction process
Molecular Function
- iron ion binding
- procollagen-proline 3-dioxygenase activity
- L-ascorbic acid binding
Cellular Component
- basement membrane
- endoplasmic reticulum
- endoplasmic reticulum lumen
- Golgi apparatus
- sarcoplasmic reticulum
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000319332
- Coding exons
- 15
- Length
- 165710
- Individuals with no LoFs
- 125606
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 142
- Defined
- 125748
- p
- 0.000565
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.235 | 389 | 376 | 1.03 | 0.0000201 | 4529 |
| Missense (PolyPhen) | 110 | 98.896 | 1.1123 | 1182 | ||
| Synonymous | -0.643 | 155 | 145 | 1.07 | 0.00000792 | 1383 |
| Loss of Function | 0.771 | 34 | 39.2 | 0.867 | 0.00000227 | 451 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00050 | 0.00049 | rare |
| Latino/Admixed American | 0.00035 | 0.00035 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00016 | 0.00016 | rare |
| Finnish | 0.00032 | 0.00032 | rare |
| European (Non-Finnish) | 0.00083 | 0.00083 | rare |
| South Asian | 0.00046 | 0.00046 | rare |
| Other | 0.00065 | 0.00065 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Prolyl 3-hydroxylase that catalyzes the post- translational formation of 3-hydroxyproline on collagens (PubMed:18487197). Contributes to proline 3-hydroxylation of collagen COL4A1 and COL1A1 in tendons, the eye sclera and in the eye lens capsule (By similarity). Has high activity with the type IV collagen COL4A1, and lower activity with COL1A1 (PubMed:18487197). Catalyzes hydroxylation of the first Pro in Gly-Pro-Hyp sequences where Hyp is 4-hydroxyproline (PubMed:18487197). Has no activity on substrates that lack 4- hydroxyproline in the third position (PubMed:18487197). {ECO:0000250|UniProtKB:Q8CG71, ECO:0000269|PubMed:18487197}.;
Recessive Scores
- pRec
- 0.132
Intolerance Scores
- RVIS EVS
- -0.55
- RVIS percentile EVS
- 19.8
Essentials
- Essential (gene trap)
- N