IZUMO1
protein-codingizumo sperm-oocyte fusion 1, the group of Ig-like cell adhesion molecule family|IZUMO family
Gene summary
The sperm-specific protein Izumo, named for a Japanese shrine dedicated to marriage, is essential for sperm-egg plasma membrane binding and fusion (Inoue et al., 2005 [PubMed 15759005]).[supplied by OMIM, Mar 2008]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~6.1 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 IZUMO1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_182575.3. 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 | 0 | |||||
| missense | 39 | 2 | 41 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 39 | 2 | 0 | 41 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_872381.2 | 9 | MANE Select | |
| Ensembl | ENSP00000327786.2 | 9 | MANE Select | |
| RefSeq | NP_001308793.1 | 7 | Standard | |
| RefSeq | NP_001308794.1 | 4 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Fertilization
- Reproduction
- Sperm:Oocyte Membrane Binding
Biological Process
- cell adhesion
- single fertilization
- fusion of sperm to egg plasma membrane involved in single fertilization
- heterotypic cell-cell adhesion
- sperm-egg recognition
Molecular Function
- signaling receptor binding
- protein binding
- protein homodimerization activity
- protein binding involved in heterotypic cell-cell adhesion
Cellular Component
- acrosomal membrane
- plasma membrane
- integral component of membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000332955
- Coding exons
- 9
- Length
- 6058
- Individuals with no LoFs
- 125691
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 57
- Defined
- 125748
- p
- 0.000227
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.10 | 165 | 210 | 0.786 | 0.0000121 | 2290 |
| Missense (PolyPhen) | 54 | 67.365 | 0.80161 | 761 | ||
| Synonymous | 1.04 | 78 | 90.6 | 0.861 | 0.00000616 | 671 |
| Loss of Function | 1.01 | 14 | 18.7 | 0.748 | 9.93e-7 | 205 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00012 | 0.00012 | rare |
| Latino/Admixed American | 0.00064 | 0.00064 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00027 | 0.00027 | rare |
| Finnish | 0.000092 | 0.000092 | rare |
| European (Non-Finnish) | 0.00011 | 0.00011 | rare |
| South Asian | 0.00029 | 0.00029 | rare |
| Other | 0.00065 | 0.00065 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Essential sperm cell-surface protein required for fertilization by acting as a ligand for IZUMO1R/JUNO receptor on egg. The IZUMO1:IZUMO1R/JUNO interaction is a necessary adhesion event between sperm and egg that is required for fertilization but is not sufficient for cell fusion. The ligand-receptor interaction probably does not act as a membrane 'fusogen'. {ECO:0000269|PubMed:15759005}.;
Recessive Scores
- pRec
- 0.140
Intolerance Scores
- LoFtool
- 0.608
- RVIS EVS
- -0.23
- RVIS percentile EVS
- 37.32
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.225
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |