MSL3

MSL complex subunit 3, the group of MSL histone acetyltransferase complex

Basic information

Region (hg38): X:11758158-11775772

Previous symbols: [ "MSL3L1" ]

Links

ENSG00000005302 ∙ NCBI:10943 ∙ OMIM:300609 ∙ HGNC:7370 ∙ Uniprot:Q8N5Y2 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Basilicata-Akhtar syndrome (Strong), mode of inheritance: XL
• Basilicata-Akhtar syndrome (Strong), mode of inheritance: XL
• Basilicata-Akhtar syndrome (Definitive), mode of inheritance: XL

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Basilicata-Akhtar syndrome	XL	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	30224647

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the MSL3 gene.

• not provided (38 variants)
• Basilicata-Akhtar syndrome (21 variants)
• Inborn genetic diseases (16 variants)
• Intellectual disability (8 variants)
• MSL3-related condition (5 variants)
• not specified (2 variants)
• Global developmental delay (1 variants)
• MSL3-Related Disorder (1 variants)
• X-linked neurodevelopmental delay, dysmorphism, and progressive neurological disorder (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the MSL3 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				4		4
missense		1	35	6	1	43
nonsense	5	3	1			9
start loss						0
frameshift	8	5				13
inframe indel			2			2
splice donor/acceptor (+/-2bp)	1	2				3
splice region				3	1	4
non coding			3	1		4
Total	14	11	41	11	1

Variants in MSL3

This is a list of pathogenic ClinVar variants found in the MSL3 region.

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

Position	Type	Phenotype	Significance	ClinVar
X-11758268-G-A		Inborn genetic diseases	Uncertain significance (Nov 07, 2022)
X-11758279-G-A		Inborn genetic diseases	Uncertain significance (May 31, 2023)
X-11758324-G-A		MSL3-related disorder	Uncertain significance (Jul 16, 2023)
X-11758727-C-T		MSL3-related disorder	Uncertain significance (Mar 07, 2023)
X-11758742-C-T		Inborn genetic diseases	Likely benign (Aug 22, 2022)
X-11758803-C-T			Likely benign (Apr 01, 2023)
X-11760438-G-C		Basilicata-Akhtar syndrome	Uncertain significance (-)
X-11760446-G-C			Uncertain significance (Oct 25, 2022)
X-11760495-G-A			Uncertain significance (Jul 18, 2022)
X-11760863-G-A		Basilicata-Akhtar syndrome	Uncertain significance (Jun 30, 2021)
X-11760875-C-G			Uncertain significance (Jan 01, 2023)
X-11760913-G-A		MSL3-related disorder	Likely benign (Nov 17, 2022)
X-11760922-G-C		Basilicata-Akhtar syndrome	Uncertain significance (Jan 28, 2022)
X-11761501-A-G			Likely benign (Dec 01, 2021)
X-11761513-C-T		MSL3-related disorder	Benign (Oct 22, 2019)
X-11761531-C-G		MSL3-related disorder	Uncertain significance (Aug 29, 2023)
X-11762130-AAAG-A		not specified	Uncertain significance (May 04, 2022)
X-11762152-C-A		MSL3-related disorder	Uncertain significance (Feb 27, 2023)
X-11762184-A-G		Inborn genetic diseases • MSL3-related disorder	Benign/Likely benign (Dec 01, 2023)
X-11762211-C-T		Basilicata-Akhtar syndrome	Pathogenic (Jan 25, 2023)
X-11762834-CAGTT-C		Basilicata-Akhtar syndrome	Pathogenic (Aug 07, 2022)
X-11762855-C-T		Basilicata-Akhtar syndrome	Pathogenic (Dec 19, 2019)
X-11762903-A-G		Inborn genetic diseases	Uncertain significance (Mar 14, 2023)
X-11762948-G-A		Inborn genetic diseases	Uncertain significance (Jul 08, 2021)
X-11762950-T-TATGCCAC		Inborn genetic diseases	Pathogenic (Dec 11, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
MSL3	protein_coding	protein_coding	ENST00000312196	13	17593

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.997	0.00335	0	0	0	0	0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.93	121	197	0.613	0.0000157	3439
Missense in Polyphen		24	69.397	0.34584		1335
Synonymous	0.672	63	70.2	0.898	0.00000554	942
Loss of Function	3.80	0	16.8	0.00	0.00000113	351

LoF frequencies by population

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

dbNSFP

Source: dbNSFP

• Function: FUNCTION: May be involved in chromatin remodeling and transcriptional regulation. May have a role in X inactivation. Component of the MSL complex which is responsible for the majority of histone H4 acetylation at 'Lys-16' which is implicated in the formation of higher-order chromatin structure. Specifically recognizes histone H4 monomethylated at 'Lys-20' (H4K20Me1) in a DNA-dependent manner and is proposed to be involved in chromosomal targeting of the MSL complex. {ECO:0000269|PubMed:16227571, ECO:0000269|PubMed:20018852, ECO:0000269|PubMed:20657587, ECO:0000269|PubMed:20943666, ECO:0000269|PubMed:21217699, ECO:0000269|PubMed:22547026}.
• Pathway: Chromatin modifying enzymes;HATs acetylate histones;Chromatin organization (Consensus)

Recessive Scores

• pRec: 0.0976

Intolerance Scores

• rvis_EVS: -0.23
• rvis_percentile_EVS: 37.32

Haploinsufficiency Scores

• pHI: 0.241
• hipred: Y
• hipred_score: 0.746
• ghis: 0.528

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.872

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Msl3

Gene ontology

• Biological process: chromatin silencing;histone acetylation;histone deacetylation;histone H4 acetylation;histone H2A acetylation;histone H4-K16 acetylation
• Cellular component: histone acetyltransferase complex;nucleoplasm;NuA4 histone acetyltransferase complex;MSL complex
• Molecular function: DNA binding;methylated histone binding