KANSL1L

Chr 2

KAT8 regulatory NSL complex subunit 1 like

Also known as: C2orf67, MSL1v2

NCBI Gene: 151050 ENSG00000144445 UniProt: A0AUZ9 OMIM: 613833

The protein is predicted to bind histone acetyltransferases and participate in the NSL complex, which regulates gene expression through chromatin modification. This gene is highly constrained against loss-of-function variants (LOEUF 0.352), suggesting that mutations would likely cause significant developmental effects, though specific disease associations have not yet been established in humans.

OMIM ResearchSummary from RefSeq

Predicted to enable histone acetyltransferase binding activity. Predicted to be located in intracellular membrane-bounded organelle. Predicted to be part of NSL complex. [provided by Alliance of Genome Resources, Apr 2025]

OMIM ResearchGenerating clinical summary…

LOFmechanismLOEUF 0.35

Clinical Summary— KANSL1L

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Population Constraint (gnomAD)

Moderately constrained gene (pLI 0.66) — some intolerance to loss-of-function variants.

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ClinVar Variants

128 VUS of 155 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.35LOEUF

pLI 0.657

Z-score 5.25

OE 0.21 (0.13–0.35)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

0.25Z-score

OE missense 0.97 (0.90–1.04)

470 obs / 485.2 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.21 (0.13–0.35)

0≤0.351.4

Missense OE?0.97 (0.90–1.04)

0≤0.61.4

Synonymous OE?1.11

0≤1.21.6

LoF obs/exp: 11 / 51.8Missense obs/exp: 470 / 485.2Syn Z: -1.15

This gene — mechanism propensity

0.4784th %ile

GOF

0.3094th %ile

LOF

0.74top 10%

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

LOFprediction above median · LOEUF 0.35

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

155 submitted variants in ClinVar

ClinVar

Classification Summary

VUS128

Likely Benign5

Benign2

128

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Synonymous	Total
Pathogenic	0	0	0
Likely Pathogenic	0	0	0
VUS	128	0	128
Likely Benign	4	1	5
Benign	1	1	2
Total	133	2	135

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

View in ClinVar →

25 pathogenic / likely-pathogenic (of 31) ClinVar copy-number / structural variants overlap KANSL1L — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →