KIRREL2
protein-codingkirre like nephrin family adhesion molecule 2, the group of I-set domain containing|C2-set domain containing
Gene summary
This gene encodes a type I transmembrane protein and member of the immunoglobulin superfamily of cell adhesion molecules. The encoded protein localizes to adherens junctions in pancreatic beta cells and regulates insulin secretion. Autoantibodies against the encoded protein have been detected in serum from patients with type 1 diabetes. This gene may also play a role in glomerular development and decreased expression of this gene has been observed in human glomerular diseases. This gene and the related opposite-strand gene nephrin (GeneID: 527362) are regulated by a bidirectional promoter. [provided by RefSeq, Jul 2016]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~11.3 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 KIRREL2 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_199180.4. 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 | 4 | 4 | ||||
| missense | 112 | 2 | 1 | 115 | ||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 1 | 1 | ||||
| splice donor/acceptor (+/-2bp) | 3 | 3 | ||||
| Total | 0 | 0 | 117 | 6 | 1 | 124 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_954649.3 | 15 | MANE Select | |
| Ensembl | ENSP00000353331.4 | 15 | MANE Select | |
| RefSeq | NP_001316459.1 | 14 | Standard | |
| RefSeq | NP_001350596.1 | 14 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Primary Focal Segmental Glomerulosclerosis FSGS
- Nephrin family interactions
- Cell-Cell communication
Biological Process
- negative regulation of protein phosphorylation
- cell adhesion
- cell-cell adhesion
Molecular Function
- protein binding
- identical protein binding
Cellular Component
- plasma membrane
- cell-cell junction
- integral component of membrane
- slit diaphragm
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000360202
- Coding exons
- 15
- Length
- 11249
- Individuals with no LoFs
- 125307
- Homozygous LoFs
- 2
- Heterozygous LoFs
- 439
- Defined
- 125748
- p
- 0.00176
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.605 | 392 | 427 | 0.918 | 0.0000238 | 4405 |
| Missense (PolyPhen) | 92 | 104.28 | 0.88223 | 1102 | ||
| Synonymous | 0.228 | 183 | 187 | 0.979 | 0.0000107 | 1596 |
| Loss of Function | 2.10 | 20 | 33.0 | 0.606 | 0.00000175 | 339 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00082 | 0.00080 | rare |
| Latino/Admixed American | 0.0030 | 0.0027 | notable |
| Ashkenazi Jewish | 0.00020 | 0.00020 | rare |
| East Asian | 0.00033 | 0.00033 | rare |
| Finnish | 0.00015 | 0.00014 | rare |
| European (Non-Finnish) | 0.0026 | 0.0026 | notable |
| South Asian | 0.00085 | 0.00085 | rare |
| Other | 0.0011 | 0.0011 | notable |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: May regulate basal insulin secretion. {ECO:0000250|UniProtKB:Q7TSU7}.;
Recessive Scores
- pRec
- 0.111
Intolerance Scores
- LoFtool
- 0.895
- RVIS EVS
- 0.67
- RVIS percentile EVS
- 84.7
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.120
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |