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: 284058 ENSG00000120071 OMIM: 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.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt, Mechanism

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]

GeneReviews OMIM ResearchGenerating clinical summary…

LOFmechanismADLOEUF 0.241 OMIM phenotype

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

129 unique Pathogenic / Likely Pathogenic· 541 VUS of 1504 total submissions

💊

Clinical Trials

1 active or recruiting trial — potential therapeutic options may be available

Explore recent and relevant literature in Research Assistant →

📖

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 OE?0.12 (0.07–0.24)

0≤0.351.4

Missense OE?0.86 (0.80–0.93)

0≤0.61.4

Synonymous OE?1.07

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

This gene — mechanism propensity

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 · 91% of P/LP variants are LoF · LOEUF 0.24 · ClinGen HI: Sufficient evidence for dosage pathogenicity

Literature Evidence

LOFThe microdeletion/microduplication syndromes are now easily identified by chromosomal microarray analysis and include PhelanÃÂ¢Ã¢âÂ¬Ã¢â¬ÅMcDermid syndrome (chromosome 22q13.3 deletion), MBD5 haploinsufficiency syndrome (chromosome 2q23.1 deletion), and KANSL1 haploinsufficiency syndrome (chromo1

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

References

1.PMID 24779060 ↗

ClinVar Variant Classifications

1504 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic79

Likely Pathogenic50

VUS541

Likely Benign544

Benign132

Conflicting129

Pathogenic

Likely Pathogenic

541

VUS

544

Likely Benign

132

Benign

129

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	73	2	4	0	79
Likely Pathogenic	44	6	0	0	50
VUS	26	472	37	6	541
Likely Benign	0	139	133	272	544
Benign	0	32	88	12	132
Conflicting	—				129
Total	143	651	262	290	1,475

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

View in ClinVar →

62 pathogenic / likely-pathogenic (of 97) ClinVar copy-number / structural variants overlap KANSL1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →