MSL2

Chr 3AD

MSL complex subunit 2

Also known as: KBHS, MSL-2, MSL2L1, RNF184

NCBI Gene: 55167ENSG00000174579UniProt: Q9HCI7OMIM: 614802

MSL2 encodes a non-catalytic component of the MSL histone acetyltransferase complex that mediates histone H4 acetylation and acts as an E3 ubiquitin ligase for histone H2B, playing essential roles in chromatin regulation, gene dosage compensation, and DNA damage response. Mutations cause Karayol-Borroto-Haghshenas neurodevelopmental syndrome with autosomal dominant inheritance. The gene shows significant constraint against loss-of-function variants (LOEUF 0.481), reflecting its critical role in cellular function.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismADLOEUF 0.481 OMIM phenotype
Clinical Summary— MSL2
⚡
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.62) — some intolerance to loss-of-function variants.
📋
ClinVar Variants
33 unique Pathogenic / Likely Pathogenic· 78 VUS of 127 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
0.48LOEUF
pLI 0.624
Z-score 3.03
OE 0.19 (0.08–0.48)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
2.00Z-score
OE missense 0.68 (0.61–0.76)
210 obs / 309.1 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.19 (0.08–0.48)
0≤0.351.4
Missense OE0.68 (0.61–0.76)
0≤0.61.4
Synonymous OE1.27
0≤1.21.6
LoF obs/exp: 3 / 16.1Missense obs/exp: 210 / 309.1Syn Z: -2.27
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveMSL2-related developmental disorderLOFAD
DN
0.2698th %ile
GOF
0.1999th %ile
LOF
0.77top 5%

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

LOFprediction above median · 30% of P/LP variants are LoF · LOEUF 0.48

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

127 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic24
Likely Pathogenic9
VUS78
Likely Benign6
Benign2
Conflicting3
24
Pathogenic
9
Likely Pathogenic
78
VUS
6
Likely Benign
2
Benign
3
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
4
2
18
0
24
Likely Pathogenic
6
0
3
0
9
VUS
12
61
5
0
78
Likely Benign
0
3
0
3
6
Benign
0
1
1
0
2
Conflicting
—3
Total2267273122

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

View in ClinVar →

Protein Context — Lollipop Plot

MSL2 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
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
MSL2 variants lead to a neurodevelopmental syndrome with lack of coordination, epilepsy, specific dysmorphisms, and a distinct episignature.
Karayol R et al.·Am J Hum Genet
2024
Prenatal Diagnosis of MSL2-Related Ventriculomegaly in Association With an Inherited 15q13 Microduplication.
Zgheib O et al.·Clin Genet
2026Case report
Novel protein-truncating variants of a chromatin-modifying gene MSL2 in syndromic neurodevelopmental disorders.
Lu X et al.·Eur J Hum Genet
2024Case report
Hepatitis B virus X protein-elevated MSL2 modulates hepatitis B virus covalently closed circular DNA by inducing degradation of APOBEC3B to enhance hepatocarcinogenesis.
Gao Y et al.·Hepatology
2017
Nonrandom occurrence of multiple de novo coding variants in a proband indicates the existence of an oligogenic model in autism.
Du Y et al.·Genet Med
2020Functional
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
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