KALRN
protein-codingkalirin RhoGEF kinase, the group of MicroRNA protein coding host genes|Fibronectin type III domain containing|I-set domain containing|Dbl family Rho GEFs
Gene summary
Huntington's disease (HD), a neurodegenerative disorder characterized by loss of striatal neurons, is caused by an expansion of a polyglutamine tract in the HD protein huntingtin. This gene encodes a protein that interacts with the huntingtin-associated protein 1, which is a huntingtin binding protein that may function in vesicle trafficking. [provided by RefSeq, Apr 2016]
- HAPIP
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~693.0 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AD
Disease ID:MONDO:0005010
Submitter: PanelApp Australia
Inheritance Pattern: AR
Disease ID:MONDO:0001071
Submitter: PanelApp Australia
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to KALRN variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001388419.1. 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 | 5 | 17 | 9 | 31 | ||
| missense | 33 | 8 | 6 | 47 | ||
| nonsense | 2 | 2 | ||||
| start loss | 0 | |||||
| frameshift | 4 | 4 | ||||
| splice donor/acceptor (+/-2bp) | 10 | 1 | 11 | |||
| Total | 0 | 0 | 54 | 26 | 15 | 95 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001375348.1 | 60 | MANE Select | |
| Ensembl | ENSP00000508359.1 | 60 | MANE Select | |
| RefSeq | NP_001019831.2 | 60 | Standard | |
| RefSeq | NP_001309917.1 | 49 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| kalrna | Danio rerio | Structure: thrombocyte Quality: decreased amount abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Developmental Biology
- Signaling by GPCR
- Signal Transduction
- MAPK6/MAPK4 signaling
- EPH-Ephrin signaling
Biological Process
- protein phosphorylation
- signal transduction
- G protein-coupled receptor signaling pathway
- nervous system development
- neuromuscular junction development
Molecular Function
- protein serine/threonine kinase activity
- guanyl-nucleotide exchange factor activity
- Rho guanyl-nucleotide exchange factor activity
- GTPase activator activity
- ATP binding
Cellular Component
- nucleoplasm
- cytosol
- actin cytoskeleton
- extracellular exosome
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000240874
- Coding exons
- 34
- Length
- 646303
- Individuals with no LoFs
- 125737
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 11
- Defined
- 125748
- p
- 0.0000437
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 4.36 | 590 | 973 | 0.607 | 0.0000593 | 10992 |
| Missense (PolyPhen) | 108 | 254.12 | 0.42499 | 2918 | ||
| Synonymous | -0.0284 | 392 | 391 | 1.00 | 0.0000240 | 3113 |
| Loss of Function | 8.26 | 8 | 94.7 | 0.0845 | 0.00000469 | 1037 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000063 | 0.000062 | rare |
| Latino/Admixed American | 0.000029 | 0.000029 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00011 | 0.00011 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000035 | 0.000035 | rare |
| South Asian | 0.000067 | 0.000065 | rare |
| Other | 0.00033 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Promotes the exchange of GDP by GTP. Activates specific Rho GTPase family members, thereby inducing various signaling mechanisms that regulate neuronal shape, growth, and plasticity, through their effects on the actin cytoskeleton. Induces lamellipodia independent of its GEF activity. {ECO:0000269|PubMed:10023074}.;
- Disease
- DISEASE: Coronary heart disease 5 (CHDS5) [MIM:608901]: A multifactorial disease characterized by an imbalance between myocardial functional requirements and the capacity of the coronary vessels to supply sufficient blood flow. Decreased capacity of the coronary vessels is often associated with thickening and loss of elasticity of the coronary arteries. {ECO:0000269|PubMed:17357071}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.;
Intolerance Scores
- LoFtool
- 0.415
- RVIS EVS
- -3.65
- RVIS percentile EVS
- 0.27
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.780
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |