KIRREL1
protein-codingkirre like nephrin family adhesion molecule 1, the group of C2-set domain containing|I-set domain containing
Gene summary
NEPH1 is a member of the nephrin-like protein family, which includes NEPH2 (MIM 607761) and NEPH3 (MIM 607762). The cytoplasmic domains of these proteins interact with the C terminus of podocin (NPHS2; MIM 604766), and the genes are expressed in kidney podocytes, cells involved in ensuring size- and charge-selective ultrafiltration (Sellin et al., 2003 [PubMed 12424224]).[supplied by OMIM, Mar 2008]
- KIRREL
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~107.0 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:0030962
Submitter: PanelApp Australia
Inheritance Pattern: Unknown
Disease ID:MONDO:0030962
Submitter: Labcorp Genetics (formerly Invitae)
Clinical Genomic Database (CGD)
Manifestation: Renal
Intervention: Renal
Rationale: Individuals have been described with early-onset nephrotic syndrome, with remission achieved through medical management
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to KIRREL1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_018240.7. 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 | 20 | 1 | 24 | ||
| missense | 1 | 1 | 118 | 2 | 3 | 125 |
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 2 | 2 | ||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 1 | 1 | 124 | 22 | 4 | 152 |
Highest pathogenic variant AF is 0.0011114608
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_060710.3 | 15 | MANE Select | |
| Ensembl | ENSP00000352138.6 | 15 | MANE Select | |
| RefSeq | NP_001273278.1 | 13 | Standard | |
| Ensembl | ENSP00000353202.4 | 12 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| kirrel1b | Danio rerio | Structure: podocyte Quality: disorganized abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- TCR
- EGFR1
- Nephrin family interactions
- Cell-Cell communication
- Nephrin/Neph1 signaling in the kidney podocyte
Biological Process
- negative regulation of protein phosphorylation
- excretion
- positive regulation of actin filament polymerization
- cell-cell adhesion
Molecular Function
- protein binding
- myosin binding
Cellular Component
- plasma membrane
- cell-cell junction
- integral component of membrane
- cell projection membrane
- dendritic shaft
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000359209
- Coding exons
- 15
- Length
- 106990
- Individuals with no LoFs
- 125742
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 6
- Defined
- 125748
- p
- 0.0000239
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 2.61 | 333 | 496 | 0.671 | 0.0000322 | 4878 |
| Missense (PolyPhen) | 102 | 171.65 | 0.59422 | 1664 | ||
| Synonymous | 0.150 | 199 | 202 | 0.987 | 0.0000134 | 1601 |
| Loss of Function | 5.00 | 4 | 36.7 | 0.109 | 0.00000203 | 381 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00012 | 0.00012 | rare |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000026 | 0.000026 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0.00016 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Plays a significant role in the normal development and function of the glomerular permeability. Signaling protein that needs the presence of TEC kinases to fully trans-activate the transcription factor AP-1 (By similarity). {ECO:0000250}.;
Recessive Scores
- pRec
- 0.127
Intolerance Scores
- RVIS EVS
- -0.73
- RVIS percentile EVS
- 14.14
Essentials
- Essential (gene trap)
- N