KANSL1

Chr 17AD

KAT8 regulatory NSL complex subunit 1

Also known as: C17DELq21.31, CENP-36, DEL17Q21.31, KDVS, KIAA1267, MSL1v1, NSL1, hMSL1v1

NCBI Gene: 284058ENSG00000120071UniProt: Q7Z3B3OMIM: 612452

This gene encodes a nuclear protein that functions as a subunit of the MLL1 and NSL1 complexes, which regulate histone acetylation, enhancer function, cell proliferation, and mitosis. Loss-of-function mutations cause Koolen-de Vries syndrome through an autosomal dominant inheritance pattern. The gene is highly intolerant to loss-of-function variants, indicating haploinsufficiency as the disease mechanism.

GeneReviewsOMIMResearchSummary from RefSeq, OMIM, UniProt, Mechanism
LOFmechanismADLOEUF 0.241 OMIM phenotype
Clinical Summary— KANSL1
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Gene-Disease Validity (ClinGen)
Koolen-de Vries syndrome · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

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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
59 unique Pathogenic / Likely Pathogenic· 222 VUS of 600 total submissions
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Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available
Explore recent and relevant literature in Research Assistant →
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GeneReview available — KANSL1
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint
0.24LOEUF
pLI 1.000
Z-score 5.75
OE 0.12 (0.07–0.24)
Highly constrained

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

Missense Constraint
1.23Z-score
OE missense 0.86 (0.80–0.93)
551 obs / 638.3 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.12 (0.07–0.24)
0≤0.351.4
Missense OE0.86 (0.80–0.93)
0≤0.61.4
Synonymous OE1.07
0≤1.21.6
LoF obs/exp: 6 / 49.8Missense obs/exp: 551 / 638.3Syn Z: -0.81
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveKANSL1-related chromosome 17q21.31 microdeletion syndromeLOFAD
DN
0.2299th %ile
GOF
0.2398th %ile
LOF
0.88top 5%

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

LOFprediction above median · 1 literature citation · 71% of P/LP variants are LoF · LOEUF 0.24

Literature Evidence

LOFThe microdeletion/microduplication syndromes are now easily identified by chromosomal microarray analysis and include Phelan–McDermid syndrome (chromosome 22q13.3 deletion), MBD5 haploinsufficiency syndrome (chromosome 2q23.1 deletion), and KANSL1 haploinsufficiency syndrome (chromoPMID:24779060

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

600 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic42
Likely Pathogenic17
VUS222
Likely Benign242
Benign36
Conflicting15
42
Pathogenic
17
Likely Pathogenic
222
VUS
242
Likely Benign
36
Benign
15
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
28
2
12
0
42
Likely Pathogenic
14
2
1
0
17
VUS
11
192
15
4
222
Likely Benign
0
31
79
132
242
Benign
0
15
21
0
36
Conflicting
—15
Total53242128136574

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

View in ClinVar →

Protein Context — Lollipop Plot

KANSL1 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold
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
A systematic review and pooled analysis of penetrance estimates of copy-number variants associated with neurodevelopment.
Goh S et al.·Genet Med
2025Review
Recurrent KAT6B/A::KANSL1 Fusions Characterize a Potentially Aggressive Uterine Sarcoma Morphologically Overlapping With Low-grade Endometrial Stromal Sarcoma.
Agaimy A et al.·Am J Surg Pathol
2022
Shared Genetics and Comorbid Genes of Amyotrophic Lateral Sclerosis and Parkinson's Disease.
Tian Y et al.·Mov Disord
2023
Transcriptome-directed analysis for Mendelian disease diagnosis overcomes limitations of conventional genomic testing.
Murdock DR et al.·J Clin Invest
2021Clinical trial
Uterine mesenchymal tumours harboring the KAT6B/A::KANSL1 gene fusion represent a distinct type of uterine sarcoma based on DNA methylation profiles.
Kommoss FKF et al.·Virchows Arch
2024
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
The KANSL1-ARL17A fusion gene generates oncogenic chKANSARL and F-circKA RNAs that synergistically drive lung cancer progression via a novel F-circKA/miR-6860/chKANSARL axis.
Guan X et al.·J Biol Chem
2026Open Access
circKANSL1 promotes immature porcine Sertoli cell growth via recruiting the Vimentin to enhance its parental gene KANSL1 expression.
Yan S et al.·Theriogenology
2026
De Novo HNRNPU Pathogenic Variant Related to Developmental Epileptic Encephalopathy With Inherited KANSL1 Loss-of-Function Variant Resolved by RNA Analysis.
Akimova D et al.·Mol Genet Genomic Med
2025Open Access
Uterine sarcoma with KAT6B/A::KANSL1 fusion: a molecular and clinicopathological study on 9 cases.
Dundr P et al.·Virchows Arch
2025Open AccessCohort
Clinical and genetic characteristics of a case of Koolen-De Vries syndrome caused by KANSL1 gene mutation and literature review: A case report.
Zhang H et al.·Medicine (Baltimore)
2024Open AccessReview
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