NKAIN4

Chr 20

sodium/potassium transporting ATPase interacting 4

Also known as: C20orf58, FAM77A, bA261N11.2

NCBI Gene: 128414ENSG00000101198UniProt: Q8IVV8OMIM: 612873

The protein interacts with the beta subunit of Na,K-ATPase and is part of a family with similarity to Drosophila Nkain proteins. Mutations cause autosomal recessive neurodevelopmental disorder with seizures, microcephaly, and brain atrophy. The gene shows low constraint to loss-of-function variation, consistent with its recessive inheritance pattern.

OMIMResearchSummary from RefSeq
MultiplemechanismLOEUF 0.99
Clinical Summary— NKAIN4
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.01) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
48 unique Pathogenic / Likely Pathogenic· 66 VUS of 125 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
0.99LOEUF
pLI 0.007
Z-score 1.60
OE 0.47 (0.24–0.99)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
-0.06Z-score
OE missense 1.02 (0.87–1.19)
110 obs / 108.2 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.47 (0.24–0.99)
0≤0.351.4
Missense OE1.02 (0.87–1.19)
0≤0.61.4
Synonymous OE0.87
0≤1.21.6
LoF obs/exp: 5 / 10.6Missense obs/exp: 110 / 108.2Syn Z: 0.69
DN
0.79top 25%
GOF
0.83top 10%
LOF
0.1994th %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

125 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic40
Likely Pathogenic8
VUS66
Likely Benign6
40
Pathogenic
8
Likely Pathogenic
66
VUS
6
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
40
0
40
Likely Pathogenic
0
0
8
0
8
VUS
0
42
24
0
66
Likely Benign
0
5
1
0
6
Benign
0
0
0
0
0
Total047730120

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

View in ClinVar →

Protein Context — Lollipop Plot

NKAIN4 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
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

No open access results found

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