HPR
protein-codinghaptoglobin-related protein, the group of Sushi domain containing
Gene summary
This gene encodes a haptoglobin-related protein that binds hemoglobin as efficiently as haptoglobin. Unlike haptoglobin, plasma concentration of this protein is unaffected in patients with sickle cell anemia and extensive intravascular hemolysis, suggesting a difference in binding between haptoglobin-hemoglobin and haptoglobin-related protein-hemoglobin complexes to CD163, the hemoglobin scavenger receptor. This protein may also be a clinically important predictor of recurrence of breast cancer. [provided by RefSeq, Oct 2011]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~14.1 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 HPR variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_020995.4. 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 | 3 | 3 | 6 | |||
| missense | 67 | 11 | 78 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 67 | 14 | 3 | 84 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_066275.3 | 5 | MANE Select | |
| Ensembl | ENSP00000441828.2 | 5 | MANE Select | |
| RefSeq | NP_001371289.1 | 1 | Standard | |
| Ensembl | ENSP00000462916.1 | 6 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- African trypanosomiasis - Homo sapiens (human)
- Vesicle-mediated transport
- Scavenging of heme from plasma
- Binding and Uptake of Ligands by Scavenger Receptors
Biological Process
- acute inflammatory response
- proteolysis
- receptor-mediated endocytosis
- response to organic substance
- positive regulation of cell death
Molecular Function
- serine-type endopeptidase activity
- hemoglobin binding
Cellular Component
- extracellular region
- extracellular space
- spherical high-density lipoprotein particle
- extracellular exosome
- blood microparticle
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000540303
- Coding exons
- 5
- Length
- 22624
- Individuals with no LoFs
- 124654
- Homozygous LoFs
- 1
- Heterozygous LoFs
- 168
- Defined
- 124823
- p
- 0.000677
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -1.52 | 243 | 185 | 1.31 | 0.0000105 | 2258 |
| Missense (PolyPhen) | 74 | 67.883 | 1.0901 | 793 | ||
| Synonymous | -1.17 | 89 | 76.0 | 1.17 | 0.00000487 | 671 |
| Loss of Function | -0.108 | 14 | 13.6 | 1.03 | 6.88e-7 | 163 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00019 | 0.00019 | rare |
| Latino/Admixed American | 0.00026 | 0.00026 | rare |
| Ashkenazi Jewish | 0.00070 | 0.00070 | rare |
| East Asian | 0.0030 | 0.0030 | notable |
| Finnish | 0.00019 | 0.00019 | rare |
| European (Non-Finnish) | 0.00044 | 0.00044 | rare |
| South Asian | 0.0013 | 0.0013 | notable |
| Other | 0.00067 | 0.00066 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Primate-specific plasma protein associated with apolipoprotein L-I (apoL-I)-containing high-density lipoprotein (HDL). This HDL particle, termed trypanosome lytic factor-1 (TLF- 1), mediates human innate immune protection against many species of African trypanosomes. Binds hemoglobin with high affinity and may contribute to the clearance of cell-free hemoglobin to allow hepatic recycling of heme iron. {ECO:0000269|PubMed:16778136}.;
Recessive Scores
- pRec
- 0.841
Intolerance Scores
- LoFtool
- 0.348
- RVIS EVS
- 0.38
- RVIS percentile EVS
- 75.51
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.781
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |