NKIRAS2

Chr 17

NFKB inhibitor interacting Ras like 2

Also known as: KBRAS2, kappaB-Ras2

NCBI Gene: 28511ENSG00000168256UniProt: Q9NYR9

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]

0
Active trials
6
Pathogenic / LP
31
ClinVar variants
6
Pubs (1 yr)
1.0
Missense Z
1.01
LOEUF
Clinical Summary— NKIRAS2
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.01) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
6 Pathogenic / Likely Pathogenic· 20 VUS of 31 total submissions
Some data sources returned errors (1)

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
1.01LOEUF
pLI 0.007
Z-score 1.56
OE 0.48 (0.25–1.01)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
1.03Z-score
OE missense 0.74 (0.62–0.88)
91 obs / 123.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.48 (0.25–1.01)
0≤0.351.4
Missense OE0.74 (0.62–0.88)
0≤0.61.4
Synonymous OE1.12
0≤1.21.6
LoF obs/exp: 5 / 10.4Missense obs/exp: 91 / 123.2Syn Z: -0.65
GOFDN
DN
0.78top 25%
GOF
0.80top 10%
LOF
0.2776th %ile

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

GOFprediction above median
DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

31 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic6
VUS20
Likely Benign4
Benign1
6
Pathogenic
20
VUS
4
Likely Benign
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
6
0
6
Likely Pathogenic
0
0
0
0
0
VUS
0
19
1
0
20
Likely Benign
1
2
0
1
4
Benign
0
0
1
0
1
Total1218131

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

NKIRAS2 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Top 3 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
4-Hydroxybenzyl Alcohol Mitigates Hyperlipidemia-Associated Depression by Inhibiting Neuroinflammation via the NKIRAS2/NF-κB Pathway.
Zhang Y et al.·Adv Sci (Weinh)
2026
MIR4726EccDNA drives bortezomib resistance in multiple myeloma by enhancing MIR4726-5p/NXF1/NKIRAS2 axis dependent autophagy.
Li F et al.·Cell Commun Signal
2025Open Access
Molecular insight into the potential functional role of pseudoenzyme GFOD1 via interaction with NKIRAS2.
Shi J et al.·Acta Biochim Biophys Sin (Shanghai)
2024Open AccessFunctional
Systems and Computational Screening identifies SRC and NKIRAS2 as Baseline Correlates of Risk (CoR) for Live Attenuated Oral Typhoid Vaccine (TY21a) associated Protection.
Naidu A et al.·Mol Immunol
2024
Circ_0001955 promotes non-small cell lung cancer cell proliferation and invasion by regulating MiR-29a-3p/NKIRAS2 axis to activate the nuclear factor-κB pathway.
Zhou X et al.·Pathol Int
2023
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients