KANSL3

Chr 2

KAT8 regulatory NSL complex subunit 3

Also known as: KIAA1310, NSL3, Rcd1

NCBI Gene: 55683ENSG00000114982UniProt: Q9P2N6

The KANSL3 protein is a component of the NSL histone acetyltransferase complex that regulates gene transcription in both the nucleus and mitochondria, promotes cilium assembly and microtubule organization, and is essential for spindle assembly during cell division. Mutations cause autosomal dominant developmental disorders affecting multiple systems including neurological development. This gene is highly constrained against loss-of-function variants in the population, indicating that such mutations are likely to cause severe disease.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
2
Pubs (1 yr)
32
P/LP submissions
0%
P/LP missense
0.16
LOEUF· LoF intol.
LOF
Mechanism· predicted
Clinical Summary— KANSL3
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
32 unique Pathogenic / Likely Pathogenic· 135 VUS of 190 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint
0.16LOEUF
pLI 1.000
Z-score 5.52
OE 0.05 (0.02–0.16)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint
2.47Z-score
OE missense 0.69 (0.63–0.75)
335 obs / 488.7 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.05 (0.02–0.16)
0≤0.351.4
Missense OE0.69 (0.63–0.75)
0≤0.61.4
Synonymous OE0.79
0≤1.21.6
LoF obs/exp: 2 / 39.3Missense obs/exp: 335 / 488.7Syn Z: 2.21
DN
0.2898th %ile
GOF
0.1999th %ile
LOF
0.82top 5%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.16

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

190 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic22
Likely Pathogenic10
VUS135
Likely Benign4
22
Pathogenic
10
Likely Pathogenic
135
VUS
4
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
22
0
22
Likely Pathogenic
0
0
10
0
10
VUS
1
102
31
1
135
Likely Benign
0
2
2
0
4
Benign
0
0
0
0
0
Total1104651171

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

View in ClinVar →

Protein Context — Lollipop Plot

KANSL3 · 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
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 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
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