CFHR3
protein-codingcomplement factor H related 3, the group of Sushi domain containing|Complement system regulators and receptors
Gene summary
The protein encoded by this gene is a secreted protein, which belongs to the complement factor H-related protein family. It binds to heparin, and may be involved in complement regulation. Mutations in this gene are associated with decreased risk of age-related macular degeneration, and with an increased risk of atypical hemolytic-uremic syndrome. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2011]
- CFHL3
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~20.6 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: Unknown
Disease ID:MONDO:0009335
Submitter: Labcorp Genetics (formerly Invitae)
Clinical Genomic Database (CGD)
Manifestation: Hematologic; Renal
Intervention: Hematologic; Pharmacogenomic; Renal
Rationale: In Hemolytic-uremic syndrome, the choice of specific treatment modalities (eg, danazol, plasma exchange, plasma therapy), as well as decision to perform renal transplant, may be dictated by genetic diagnosis, and certain agents/precipitating factors should be avoided (eg, certain medications)
Comments: Deletions related to hemolytic-uremic syndrome involve a contiguous deletion with CFHR3 or CFHR4
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to CFHR3 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_021023.6. 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 | 15 | 1 | 18 | ||
| missense | 57 | 11 | 2 | 70 | ||
| nonsense | 3 | 3 | ||||
| start loss | 0 | |||||
| frameshift | 4 | 4 | ||||
| splice donor/acceptor (+/-2bp) | 1 | 2 | 1 | 4 | ||
| Total | 1 | 0 | 68 | 27 | 3 | 99 |
Highest pathogenic variant AF is 0.00002028233
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_066303.2 | 6 | MANE Select | |
| Ensembl | ENSP00000356395.5 | 6 | MANE Select | |
| RefSeq | NP_001160096.1 | 5 | Standard | |
| Ensembl | ENSP00000356397.3 | 5 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Innate Immune System
- Immune System
- Regulation of Complement cascade
- Complement cascade
Cellular Component
- extracellular space
- extracellular exosome
- blood microparticle
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000367425
- Coding exons
- 6
- Length
- 19279
- Individuals with no LoFs
- 118757
- Homozygous LoFs
- 138
- Heterozygous LoFs
- 535
- Defined
- 119430
- p
- 0.00282
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.000941 | 172 | 172 | 1.00 | 0.00000831 | 2112 |
| Missense (PolyPhen) | 87 | 77.832 | 1.1178 | 984 | ||
| Synonymous | -0.369 | 65 | 61.3 | 1.06 | 0.00000314 | 600 |
| Loss of Function | -0.227 | 16 | 15.0 | 1.06 | 7.11e-7 | 196 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00091 | 0.00051 | rare |
| Latino/Admixed American | 0.00052 | 0.00047 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.0013 | 0.0010 | notable |
| Finnish | 0.0022 | 0.0019 | notable |
| European (Non-Finnish) | 0.0039 | 0.0032 | notable |
| South Asian | 0.011 | 0.0083 | notable |
| Other | 0.0043 | 0.0036 | notable |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Might be involved in complement regulation.;
Intolerance Scores
- LoFtool
- 0.531
- RVIS EVS
- 1.73
- RVIS percentile EVS
- 96.56
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.530
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |