P4HA2
protein-codingprolyl 4-hydroxylase subunit alpha 2, the group of MicroRNA protein coding host genes
Gene summary
This gene encodes a component of prolyl 4-hydroxylase, a key enzyme in collagen synthesis composed of two identical alpha subunits and two beta subunits. The encoded protein is one of several different types of alpha subunits and provides the major part of the catalytic site of the active enzyme. In collagen and related proteins, prolyl 4-hydroxylase catalyzes the formation of 4-hydroxyproline that is essential to the proper three-dimensional folding of newly synthesized procollagen chains. Alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, Jul 2008]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~105.2 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AD
Disease ID:MONDO:0014982
Submitter: Ambry Genetics
Inheritance Pattern: Unknown
Disease ID:MONDO:0014982
Submitter: Labcorp Genetics (formerly Invitae)
Inheritance Pattern: AD
Disease ID:MONDO:0001384
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 P4HA2 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001017974.2. 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 | 3 | 14 | 17 | |||
| missense | 4 | 86 | 7 | 97 | ||
| nonsense | 4 | 4 | ||||
| start loss | 0 | |||||
| frameshift | 1 | 1 | ||||
| splice donor/acceptor (+/-2bp) | 8 | 1 | 9 | |||
| Total | 0 | 4 | 102 | 22 | 0 | 128 |
Highest pathogenic variant AF is 0.000011773337
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001017974.1 | 14 | MANE Select | |
| Ensembl | ENSP00000353772.3 | 14 | MANE Select | |
| RefSeq | NP_001136070.1 | 14 | Standard | |
| RefSeq | NP_001136071.1 | 14 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Arginine and proline metabolism - Homo sapiens (human)
- miR-targeted genes in epithelium - TarBase
- miR-targeted genes in lymphocytes - TarBase
- miR-targeted genes in muscle cell - TarBase
- miR-targeted genes in squamous cell - TarBase
Biological Process
- peptidyl-proline hydroxylation to 4-hydroxy-L-proline
- electron transport chain
Molecular Function
- procollagen-proline 4-dioxygenase activity
- iron ion binding
- electron transfer activity
- oxidoreductase activity, acting on single donors with incorporation of molecular oxygen, incorporation of two atoms of oxygen
- L-ascorbic acid binding
Cellular Component
- nucleoplasm
- endoplasmic reticulum
- endoplasmic reticulum lumen
- cytosol
- intracellular membrane-bounded organelle
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000401867
- Coding exons
- 14
- Length
- 103478
- Individuals with no LoFs
- 125554
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 194
- Defined
- 125748
- p
- 0.000772
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.821 | 272 | 313 | 0.869 | 0.0000182 | 3479 |
| Missense (PolyPhen) | 135 | 145.02 | 0.9309 | 1579 | ||
| Synonymous | -0.0166 | 123 | 123 | 1.00 | 0.00000726 | 1045 |
| Loss of Function | 3.20 | 16 | 37.0 | 0.433 | 0.00000223 | 369 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.0044 | 0.0044 | notable |
| Latino/Admixed American | 0.00020 | 0.00020 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00027 | 0.00027 | rare |
| Finnish | 0.00051 | 0.00051 | rare |
| European (Non-Finnish) | 0.00074 | 0.00074 | rare |
| South Asian | 0.00036 | 0.00036 | rare |
| Other | 0.00082 | 0.00081 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Catalyzes the post-translational formation of 4- hydroxyproline in -Xaa-Pro-Gly- sequences in collagens and other proteins.;
- Disease
- DISEASE: Myopia 25, autosomal dominant (MYP25) [MIM:617238]: A refractive error of the eye, in which parallel rays from a distant object come to focus in front of the retina, vision being better for near objects than for far. {ECO:0000269|PubMed:25741866}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Recessive Scores
- pRec
- 0.193
Intolerance Scores
- LoFtool
- 0.956
- RVIS EVS
- -1
- RVIS percentile EVS
- 8.47
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- S
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.986
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |