KANSL3

Chr 2

KAT8 regulatory NSL complex subunit 3

Also known as: KIAA1310, NSL3, Rcd1

NCBI Gene: 55683 ENSG00000114982 UniProt: Q9P2N6 OMIM: 617742

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.

OMIM ResearchSummary from RefSeq, UniProt

Involved in regulation of mitochondrial transcription. Located in mitochondrion and nucleoplasm. Part of NSL complex. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

LOFmechanismLOEUF 0.16

Clinical Summary— KANSL3

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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.

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ClinVar Variants

104 VUS of 125 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 OE?0.05 (0.02–0.16)

0≤0.351.4

Missense OE?0.69 (0.63–0.75)

0≤0.61.4

Synonymous OE?0.79

0≤1.21.6

LoF obs/exp: 2 / 39.3Missense obs/exp: 335 / 488.7Syn Z: 2.21

This gene — mechanism propensity

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

125 submitted variants in ClinVar

ClinVar

Classification Summary

VUS104

Likely Benign2

104

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Synonymous	Total
Pathogenic	0	0	0	0
Likely Pathogenic	0	0	0	0
VUS	1	102	1	104
Likely Benign	0	2	0	2
Benign	0	0	0	0
Total	1	104	1	106

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

View in ClinVar →

32 pathogenic / likely-pathogenic (of 65) ClinVar copy-number / structural variants overlap KANSL3 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →