L3HYPDH
protein-codingtrans-L-3-hydroxyproline dehydratase
Gene summary
The protein encoded by this gene is a dehydratase that converts trans-3-hydroxy-L-proline to delta(1)-pyrroline-2-carboxylate. This enzyme may function to degrade dietary proteins that contain trans-3-hydroxy-L-proline as well as other proteins such as collagen IV. The encoded protein can be converted to an epimerase by changing a threonine to a cysteine at a catalytic site. [provided by RefSeq, Sep 2016]
- C14orf149
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~24.0 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 L3HYPDH variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_144581.2. 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 | 2 | 2 | ||||
| missense | 70 | 1 | 71 | |||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 2 | 2 | ||||
| Total | 0 | 0 | 75 | 1 | 0 | 76 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_653182.1 | 5 | MANE Select | |
| Ensembl | ENSP00000247194.4 | 5 | MANE Select | |
| RefSeq | NP_001318087.1 | 4 | Standard | |
| RefSeq | NP_001318088.1 | 4 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Arginine and proline metabolism - Homo sapiens (human)
Molecular Function
- hydro-lyase activity
- proline racemase activity
- trans-L-3-hydroxyproline dehydratase activity
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000247194
- Coding exons
- 5
- Length
- 24068
- Individuals with no LoFs
- 125658
- Homozygous LoFs
- 1
- Heterozygous LoFs
- 87
- Defined
- 125746
- p
- 0.000350
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.359 | 216 | 202 | 1.07 | 0.00000936 | 2237 |
| Missense (PolyPhen) | 89 | 86.481 | 1.0291 | 898 | ||
| Synonymous | 1.11 | 71 | 83.9 | 0.846 | 0.00000423 | 746 |
| Loss of Function | 0.404 | 10 | 11.5 | 0.871 | 5.74e-7 | 136 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00047 | 0.00043 | rare |
| Latino/Admixed American | 0.00059 | 0.00058 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00044 | 0.00044 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.00030 | 0.00029 | rare |
| South Asian | 0.00056 | 0.00052 | rare |
| Other | 0.00069 | 0.00065 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Catalyzes the dehydration of trans-3-hydroxy-L-proline to Delta(1)-pyrroline-2-carboxylate (Pyr2C). May be required to degrade trans-3-hydroxy-L-proline from the diet and originating from the degradation of proteins such as collagen-IV that contain it. {ECO:0000269|PubMed:22528483}.;
Recessive Scores
- pRec
- 0.102
Intolerance Scores
- RVIS EVS
- 0.33
- RVIS percentile EVS
- 73.41
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |