MSL2

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

Basic information

Region (hg38): 3:136148917-136197241

Previous symbols: [ "RNF184", "MSL2L1" ]

Links

ENSG00000174579 ∙ NCBI:55167 ∙ OMIM:614802 ∙ HGNC:25544 ∙ Uniprot:Q9HCI7 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• complex neurodevelopmental disorder (Strong), mode of inheritance: AD
• neurodevelopmental disorder (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Karayol-Borroto-Haghshenas neurodevelopmental syndrome	AD	General	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	Craniofacial; Musculoskeletal; Neurologic; Ophthalmologic	38815585

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the MSL2 gene.

• not specified (2 variants)
• Autism (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the MSL2 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous						0
missense			32	1		33
nonsense	1		2			3
start loss						0
frameshift	2		7			9
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	3	0	41	1	0

Variants in MSL2

This is a list of pathogenic ClinVar variants found in the MSL2 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
3-136151169-A-G		not specified	Uncertain significance (Apr 12, 2024)
3-136151239-C-G			Uncertain significance (Feb 08, 2023)
3-136151244-A-G		not specified	Uncertain significance (Jan 22, 2024)
3-136151256-C-A			Uncertain significance (Feb 08, 2023)
3-136151262-C-T			Likely benign (Apr 01, 2025)
3-136151311-T-A			Uncertain significance (Mar 12, 2024)
3-136151356-T-G		not specified	Uncertain significance (May 27, 2022)
3-136151401-T-C		not specified	Uncertain significance (Oct 26, 2024)
3-136151402-A-T			Pathogenic (Dec 18, 2024)
3-136151430-T-C			Uncertain significance (Feb 14, 2024)
3-136151466-CT-C			Uncertain significance (Apr 06, 2022)
3-136151499-CCTTT-C			Likely pathogenic (Oct 17, 2024)
3-136151532-T-C			Uncertain significance (Feb 20, 2024)
3-136151549-C-T		not specified	Uncertain significance (Jul 26, 2022)
3-136151560-G-C		not specified	Uncertain significance (Oct 26, 2021)
3-136151584-C-T		not specified	Likely benign (Apr 07, 2023)
3-136151619-G-C			Uncertain significance (Oct 18, 2024)
3-136151653-T-C		not specified	Uncertain significance (Dec 19, 2022)
3-136151658-A-G		not specified	Uncertain significance (Oct 26, 2022)
3-136151671-A-ATTACT		Karayol-Borroto-Haghshenas neurodevelopmental syndrome	Likely pathogenic (Mar 04, 2025)
3-136151673-A-G		not specified	Uncertain significance (Nov 07, 2024)
3-136151687-G-T		not specified	Uncertain significance (Dec 08, 2023)
3-136151695-T-C		not specified	Uncertain significance (Sep 20, 2023)
3-136151716-G-A		not specified	Uncertain significance (Sep 14, 2022)
3-136151746-T-TG			Uncertain significance (Feb 04, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
MSL2	protein_coding	protein_coding	ENST00000309993	2	48320

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.624	0.376	125737	0	4	125741	0.0000159

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.00	210	309	0.679	0.0000166	3789
Missense in Polyphen		38	96.425	0.39409		1227
Synonymous	-2.27	146	115	1.27	0.00000619	1164
Loss of Function	3.03	3	16.1	0.186	9.73e-7	226

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000289	0.0000289
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.0000176	0.0000176
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

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}.
• Pathway: Chromatin modifying enzymes;TCR;HATs acetylate histones;Chromatin organization (Consensus)

Recessive Scores

• pRec: 0.118

Intolerance Scores

• loftool: 0.00717
• rvis_EVS: -0.53
• rvis_percentile_EVS: 20.7

Haploinsufficiency Scores

• pHI: 0.972
• hipred: Y
• hipred_score: 0.775
• ghis: 0.578

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.903

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Msl2

Gene ontology

• Biological process: protein ubiquitination;histone H4-K16 acetylation
• Cellular component: nucleoplasm;MSL complex
• Molecular function: metal ion binding;ubiquitin protein ligase activity