GeneBe

MSL2

protein-coding

MSL complex subunit 2, the group of Ring finger proteins|MSL histone acetyltransferase complex

Gene summary

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]

Previous symbols:
  • RNF184
  • MSL2L1

MANE transcript

NM_018133.4

Inheritance

AD

ClinVar variants

P:19U:80B:16

Top phenotype

Karayol-Borroto-Haghshenas neurodevelopmental syndrome

gnomAD constraint

pLI —, LoF o/e 0.19

Max pathogenic AF

—

Genomic locus

chr3:136,148,917-136,197,241

External References & Databases

Ensembl (ENSG00000174579)NCBI Gene (55167)OMIM (614802)HGNC:25544GenCCUniProt (Q9HCI7)AlphaFoldClinVar (MSL2)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~48.3 kb
Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

complex neurodevelopmental disorderSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0100038

Submitter: Ambry Genetics

Karayol-Borroto-Haghshenas neurodevelopmental syndromeSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0975836

Submitter: PanelApp Australia

Karayol-Borroto-Haghshenas neurodevelopmental syndromeDEFINITIVE

Inheritance Pattern: AD

Disease ID:MONDO:0975836

Submitter: G2P

Clinical Genomic Database (CGD)

Karayol-Borroto-Haghshenas neurodevelopmental syndromeAD

Manifestation: Craniofacial; Musculoskeletal; Neurologic; Ophthalmologic

Intervention: General

Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing

Refs: 38815585Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to MSL2 variants in ClinVar

6 Conditions Cataloged
not specifiedTotal: 60
not providedTotal: 48
Karayol-Borroto-Haghshenas neurodevelopmental syndromeTotal: 13
Syndromic neurodevelopmental disorderTotal: 3
AutismTotal: 2
MSL2-related disordersTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_018133.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

EffectPLPVUSLBBSum
synonymous
8
clinvar
 8
missense
1
clinvar
68
clinvar
8
clinvar
 77
nonsense
4
clinvar
3
clinvar
2
clinvar
 9
start loss
1
clinvar
1
clinvar
 2
frameshift
2
clinvar
8
clinvar
8
clinvar
 18
splice donor/acceptor (+/-2bp)
1
clinvar
 1
Total71280160115

Highest pathogenic variant AF is 0.0000012393663

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 13 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_018133.4RefSeqNP_060603.22MANE Select
ENST00000309993.3EnsemblENSP00000311827.22MANE Select
NM_001145417.2RefSeqNP_001138889.11Standard
ENST00000434835.2EnsemblENSP00000387948.21Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

  • Chromatin modifying enzymes
  • TCR
  • HATs acetylate histones
  • Chromatin organization

Biological Process

  • protein ubiquitination
  • histone H4-K16 acetylation

Molecular Function

  • metal ion binding
  • ubiquitin protein ligase activity

Cellular Component

  • nucleoplasm
  • MSL complex

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000309993
Coding exons
2
Length
48320
Individuals with no LoFs
125737
Homozygous LoFs
0
Heterozygous LoFs
4
Defined
125741
p
0.0000159
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense2.002103090.6790.00001663789
Missense (PolyPhen)3896.4250.394091227
Synonymous-2.271461151.270.000006191164
Loss of Function3.03316.10.1869.73e-7226

Population LoF Frequency

PopulationCAFp-valueStatus
African00.0absent
Latino/Admixed American0.0000290.000029rare
Ashkenazi Jewish00.0absent
East Asian00.0absent
Finnish0.0000460.000046rare
European (Non-Finnish)0.0000180.000018rare
South Asian00.0absent
Other00.0absent

dbNSFP Gene Annotations

Source: dbNSFP

Function
FUNCTION: Component of histone acetyltransferase complex responsible for the majority of histone H4 acetylation at lysine 16 which is implicated in the formation of higher-order chromatin structure. Acts as an E3 ubiquitin ligase that promotes monoubiquitination of histone H2B at 'Lys-35' (H2BK34Ub), but not that of H2A. This activity is greatly enhanced by heterodimerization with MSL1. H2B ubiquitination in turn stimulates histine H3 methylation at 'Lys-4' (H3K4me) and 'Lys-79' (H3K79me) and leads to gene activation, including that of HOXA9 and MEIS1. {ECO:0000269|PubMed:21726816}.;

Recessive Scores

pRec
0.118

Intolerance Scores

LoFtool
0.00717
RVIS EVS
-0.53
RVIS percentile EVS
20.7

Essentials

Essential (CRISPR)
N
Essential (CRISPR2)
N
Essential (gene trap)
E
Indispensability pred.
E
Indispensability score
0.903

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium
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