MSL2

Chr 3AD

MSL complex subunit 2

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

NCBI Gene: 55167ENSG00000174579UniProt: Q9HCI7

Enables histone H2B ubiquitin ligase activity. Involved in DNA damage response and protein monoubiquitination. Located in nucleus. Part of MSL complex. Is active in chromatin. [provided by Alliance of Genome Resources, Jul 2025]

Primary Disease Associations & Inheritance

Karayol-Borroto-Haghshenas neurodevelopmental syndromeMIM #620985
AD
0
Active trials
33
Pathogenic / LP
120
ClinVar variants
3
Pubs (1 yr)
2.0
Missense Z
0.48
LOEUF
Clinical Summary— MSL2
⚡
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.62) — some intolerance to loss-of-function variants.
📋
ClinVar Variants
33 Pathogenic / Likely Pathogenic· 79 VUS of 120 total submissions

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
LOF
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 · 18% 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

120 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic24
Likely Pathogenic9
VUS79
Likely Benign7
Conflicting1
24
Pathogenic
9
Likely Pathogenic
79
VUS
7
Likely Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
1
2
21
0
24
Likely Pathogenic
5
0
4
0
9
VUS
9
61
9
0
79
Likely Benign
0
4
0
3
7
Benign
0
0
0
0
0
Conflicting
—1
Total1567343120

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

View in ClinVar →

MSL2 · protein map & ClinVar variants

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

Gene2Phenotype Curations

MSL2-related developmental disorder

definitive
ADLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Landmark / reviewRecent case evidence
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
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
Prenatal Diagnosis of MSL2-Related Ventriculomegaly in Association With an Inherited 15q13 Microduplication.
Zgheib O et al.·Clin Genet
2026Case report
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