NKIRAS2
protein-codingNFKB inhibitor interacting Ras like 2, the group of RAS type GTPase family
Gene summary
Predicted to enable GTPase activating protein binding activity. Predicted to be involved in Ral protein signal transduction. Predicted to act upstream of or within several processes, including lung alveolus development; regulation of signal transduction; and surfactant homeostasis. Predicted to be located in cytoplasm. [provided by Alliance of Genome Resources, Jul 2025]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~14.3 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 NKIRAS2 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_017595.6. 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 | 4 | 4 | ||||
| missense | 20 | 20 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 0 | 21 | 4 | 0 | 25 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_060065.2 | 3 | MANE Select | |
| Ensembl | ENSP00000377463.3 | 3 | MANE Select | |
| RefSeq | NP_001001349.1 | 3 | Standard | |
| RefSeq | NP_001138399.1 | 3 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Toll Like Receptor 7/8 (TLR7/8) Cascade
- Signaling by Interleukins
- Cytokine Signaling in Immune system
- Toll Like Receptor 9 (TLR9) Cascade
- MyD88 cascade initiated on plasma membrane
Biological Process
- I-kappaB kinase/NF-kappaB signaling
Molecular Function
- GTPase activity
- GTP binding
Cellular Component
- cellular_component
- cytoplasm
- membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000307641
- Coding exons
- 3
- Length
- 14260
- Individuals with no LoFs
- 125722
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 26
- Defined
- 125748
- p
- 0.000103
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.03 | 91 | 123 | 0.739 | 0.00000802 | 1236 |
| Missense (PolyPhen) | 28 | 48.414 | 0.57835 | 512 | ||
| Synonymous | -0.653 | 57 | 51.1 | 1.12 | 0.00000322 | 382 |
| Loss of Function | 1.56 | 5 | 10.4 | 0.479 | 6.99e-7 | 99 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000062 | 0.000062 | rare |
| Latino/Admixed American | 0.000058 | 0.000058 | rare |
| Ashkenazi Jewish | 0.000099 | 0.000099 | rare |
| East Asian | 0.00016 | 0.00016 | rare |
| Finnish | 0.000046 | 0.000046 | rare |
| European (Non-Finnish) | 0.00012 | 0.00012 | rare |
| South Asian | 0.00013 | 0.00013 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Atypical Ras-like protein that acts as a potent regulator of NF-kappa-B activity by preventing the degradation of NF-kappa-B inhibitor beta (NFKBIB) by most signals, explaining why NFKBIB is more resistant to degradation. May act by blocking phosphorylation of NFKBIB and nuclear localization of p65/RELA NF- kappa-B subunit. It is unclear whether it acts as a GTPase. Both GTP- and GDP-bound forms block phosphorylation of NFKBIB (By similarity). {ECO:0000250}.;
Recessive Scores
- pRec
- 0.118
Intolerance Scores
- LoFtool
- 0.670
- RVIS EVS
- -0.21
- RVIS percentile EVS
- 38.28
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.404
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Low | Low |
| Primary Immunodeficiency | Medium | Low | Medium |
| Cancer | Medium | Low | Medium |