MSL2

Chr 3q22.3

MSL complex subunit 2

Aliases:: FLJ10546, KIAA1585, msl-2
MANE:: ENST00000309993.3

OMIM: 614802 ↗NCBI: 55167 ↗Ensembl ↗

Annotations refreshed 9 hours ago.

Predicted protein structure

AlphaFold predicted structure

MSL2 · Q9HCI7

v62025-08-01

Predicted Aligned Error matrix for MSL2 — diagonal shows residue index, colour shows pairwise prediction confidence (lower is better) — Predicted Aligned Error

Mean pLDDT

55.9/ 100

Low

577 residues

Confidence breakdown

Very high(≥ 90)16%
Confident(70–90)12%
Low(50–70)15%
Very low(< 50)57%

Open interactive 3D viewer

AlphaFold (Jumper et al., 2021) · CC BY 4.0

Clinical relevance (Genomics England PanelApp)

Diagnostic Grade (Green)

DDG2P
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Fetal anomalies
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Intellectual disability
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Disease associations (Open Targets)

Karayol-Borroto-Haghshenas neurodevelopmental syndrome
0.68
neurodegenerative disease
0.54
atrial fibrillation
0.43
autism
0.37
complex neurodevelopmental disorder
0.37
Hypercholesterolemia
0.36
coronary artery disorder
0.35
myocardial ischemia
0.33
myocardial infarction
0.32
metabolic syndrome
0.31

Score is the Open Targets composite evidence score (0-1). Higher = stronger gene-disease association.

Protein function (UniProt)

E3 ubiquitin-protein ligase MSL2

Non-catalytic component of the MSL histone acetyltransferase complex, a multiprotein complex that mediates the majority of histone H4 acetylation at 'Lys-16' (H4K16ac), an epigenetic mark that prevents chromatin compaction (PubMed:16543150, PubMed:33837287). The MSL complex is required for chromosome stability and genome integrity by maintaining homeostatic levels of H4K16ac (PubMed:33837287). The MSL complex is also involved in gene dosage by promoting up-regulation of genes expressed by the X chromosome (By similarity). X up-regulation is required to compensate for autosomal biallelic expression (By similarity). The MSL complex also participates in gene dosage compensation by promoting expression of Tsix non-coding RNA (By similarity). MSL2 plays a key role in gene dosage by ensuring biallelic expression of a subset of dosage-sensitive genes, including many haploinsufficient genes (By similarity). Acts by promoting promoter-enhancer contacts, thereby preventing DNA methylation of one allele and creating a methylation-free environment for methylation-sensitive transcription factors such as SP1, KANSL1 and KANSL3 (By similarity). Also acts as an E3 ubiquitin ligase that promotes monoubiquitination of histone H2B at 'Lys-35' (H2BK34Ub), but not that of H2A (PubMed:21726816, PubMed:30930284). This activity is greatly enhanced by heterodimerization with MSL1 (PubMed:21726816, PubMed:30930284). H2B ubiquitination in turn stimulates histone H3 methylation at 'Lys-4' (H3K4me) and 'Lys-79' (H3K79me) and leads to gene activation, including that of HOXA9 and MEIS1 (PubMed:21726816). Also involved in the DNA damage response by mediating ubiquitination of TP53/p53 and TP53BP1 (PubMed:19033443, PubMed:23874665)