KANSL1

Chr 17

KAT8 regulatory NSL complex subunit 1

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

NCBI Gene: 284058ENSG00000120071UniProt: Q7Z3B3

This gene encodes a nuclear protein that is a subunit of two protein complexes involved with histone acetylation, the MLL1 complex and the NSL1 complex. The encoded protein has been implicated in a variety of cellular processes including enhancer regulation, cell proliferation, and mitosis. Mutations in this gene are associated with Koolen-de Vries Syndrome. [provided by RefSeq, May 2022]

Primary Disease Associations & Inheritance

UniProtKoolen-De Vries syndrome
574
ClinVar variants
62
Pathogenic / LP
1.00
pLI score· haploinsufficient
1
Active trials
Clinical Summary— KANSL1
🧬
Gene-Disease Validity (ClinGen)
Koolen-de Vries syndrome · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
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
62 Pathogenic / Likely Pathogenic· 334 VUS of 574 total submissions
💊
Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
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?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
1.23Z-score
OE missense 0.86 (0.80–0.93)
551 obs / 638.3 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.12 (0.07–0.24)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.86 (0.80–0.93)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.07
0≤1.21.6
LoF obs/exp: 6 / 49.8Missense obs/exp: 551 / 638.3Syn Z: -0.81

ClinVar Variant Classifications

574 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic36
Likely Pathogenic26
VUS334
Likely Benign125
Benign42
Conflicting11
36
Pathogenic
26
Likely Pathogenic
334
VUS
125
Likely Benign
42
Benign
11
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
21
1
14
0
36
Likely Pathogenic
13
2
11
0
26
VUS
13
280
36
5
334
Likely Benign
0
11
46
68
125
Benign
0
5
36
1
42
Conflicting
—11
Total4729914374574

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.

Gene2Phenotype Curations

KANSL1-related chromosome 17q21.31 microdeletion syndrome

definitive
ADLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype

OMIM

No OMIM entries found.

📖
GeneReview available — KANSL1
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
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
Transcriptome-directed analysis for Mendelian disease diagnosis overcomes limitations of conventional genomic testing.
Murdock DR et al.·J Clin Invest
2021Clinical trial
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
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)
2024Review
Shared Genetics and Comorbid Genes of Amyotrophic Lateral Sclerosis and Parkinson's Disease.
Tian Y et al.·Mov Disord
2023
Adult phenotype in Koolen-de Vries/KANSL1 haploinsufficiency syndrome.
Amenta S et al.·J Med Genet
2022
The clinical phenotype of Koolen-de Vries syndrome in Turkish patients and literature review.
Karamik G et al.·Am J Med Genet A
2023Review
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
Shared genetic risk loci between Alzheimer's disease and related dementias, Parkinson's disease, and amyotrophic lateral sclerosis.
Wainberg M et al.·Alzheimers Res Ther
2023
Pathogenic variants in chromatin-related genes: Linking immune dysregulation to neuroregression and acute neuropsychiatric disorders.
Dale RC et al.·Dev Med Child Neurol
2025
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
16P11.2 Deletion Syndrome16p11.2 Duplications1Q21.1 Deletion

Online Study of People Who Have Genetic Changes and Features of Autism: Simons Searchlight

RECRUITING
NCT01238250Simons SearchlightStarted 2010-10

External Resources

Links to major genomics databases and tools