MYSM1

Myb like, SWIRM and MPN domains 1, the group of Myb/SANT domain containing|JAMM/MPN+ metallopeptidase family

Basic information

Region (hg38): 1:58643440-58700090

Links

ENSG00000162601 ∙ NCBI:114803 ∙ OMIM:612176 ∙ HGNC:29401 ∙ Uniprot:Q5VVJ2 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• bone marrow failure syndrome 4 (Strong), mode of inheritance: AR
• bone marrow failure syndrome 4 (Limited), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Bone marrow failure syndrome 4	AR	Allergy/Immunology/Infectious	The condition can involve anemia and increased risk of infection, and interventions such as RBC transfusions and early and aggressive treatment of infections may be beneficial; BMT has been described	Allergy/Immunology/Infectious; Craniofacial; Dental; Dermatologic; Hematologic; Neurologic; Ophthalmologic	24288411; 26220525; 28115216

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the MYSM1 gene.

• not provided (15 variants)
• Bone marrow failure syndrome 4 (7 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the MYSM1 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			2	74	4	80
missense			152	6	6	164
nonsense	15		1			16
start loss			1			1
frameshift	4	1				5
inframe indel			1			1
splice donor/acceptor (+/-2bp)		4	1			5
splice region	1		9	15	6	31
non coding				70	12	82
Total	19	5	158	150	22

Highest pathogenic variant AF is 0.0000197

Variants in MYSM1

This is a list of pathogenic ClinVar variants found in the MYSM1 region.

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

Position	Type	Phenotype	Significance	ClinVar
1-58660009-T-C			Likely benign (Dec 15, 2022)
1-58660011-C-T			Benign (Feb 01, 2024)
1-58660016-G-T			Uncertain significance (Apr 29, 2021)
1-58660019-C-CAGTT		not specified	Uncertain significance (Mar 04, 2024)
1-58660030-G-A			Likely benign (Oct 17, 2023)
1-58660031-G-T			Uncertain significance (Aug 31, 2021)
1-58660032-T-C			Uncertain significance (Jul 16, 2022)
1-58660038-C-T		Inborn genetic diseases	Uncertain significance (Sep 14, 2022)
1-58660051-G-A			Likely benign (Jun 04, 2022)
1-58660061-T-C		Inborn genetic diseases • MYSM1-related disorder • not specified	Uncertain significance (Mar 04, 2024)
1-58660062-T-A			Uncertain significance (Jan 13, 2023)
1-58660072-C-T			Likely benign (Oct 05, 2023)
1-58660077-T-A		Inborn genetic diseases	Uncertain significance (Jan 09, 2024)
1-58660079-T-C		Inborn genetic diseases	Uncertain significance (Jan 09, 2024)
1-58660082-A-G			Uncertain significance (Jan 24, 2024)
1-58660093-G-T			Uncertain significance (Apr 16, 2021)
1-58660115-T-C		Inborn genetic diseases	Uncertain significance (Oct 03, 2022)
1-58660136-T-C			Uncertain significance (Mar 07, 2022)
1-58660160-T-G			Likely benign (Dec 27, 2023)
1-58660161-TGAAAA-T			Uncertain significance (Aug 28, 2021)
1-58660162-G-T			Benign (Jan 29, 2024)
1-58660171-A-C			Benign (Jan 20, 2024)
1-58660171-AG-A			Likely benign (Jan 22, 2024)
1-58660173-T-TTTTATATTTATATTTATATATTTATATTTATTTTTAATATATATAATATATATTATATATATTAAATATTATATATATTAAATAATATATATATATATATATATAAATAATATATAATAAATATAATATAATATA			Likely benign (Aug 30, 2022)
1-58660175-T-C			Likely benign (Feb 17, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
MYSM1	protein_coding	protein_coding	ENST00000472487	20	45354

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0434	0.957	124737	0	57	124794	0.000228

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.22	353	424	0.833	0.0000213	5478
Missense in Polyphen		86	132.92	0.647		1632
Synonymous	0.439	132	139	0.953	0.00000664	1430
Loss of Function	4.90	13	50.6	0.257	0.00000267	632

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000455	0.000448
Ashkenazi Jewish	0.000210	0.000199
East Asian	0.000169	0.000167
Finnish	0.0000940	0.0000928
European (Non-Finnish)	0.000359	0.000344
Middle Eastern	0.000169	0.000167
South Asian	0.0000327	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Metalloprotease that specifically deubiquitinates monoubiquitinated histone H2A, a specific tag for epigenetic transcriptional repression, thereby acting as a coactivator. Preferentially deubiquitinates monoubiquitinated H2A in hyperacetylated nucleosomes. Deubiquitination of histone H2A leads to facilitate the phosphorylation and dissociation of histone H1 from the nucleosome. Acts as a coactivator by participating in the initiation and elongation steps of androgen receptor (AR)-induced gene activation. {ECO:0000269|PubMed:17707232}.
• Pathway: Post-translational protein modification;Metabolism of proteins;Metalloprotease DUBs;Deubiquitination (Consensus)

Intolerance Scores

• loftool: 0.748
• rvis_EVS: 0.16
• rvis_percentile_EVS: 64.82

Haploinsufficiency Scores

• pHI: 0.272
• hipred: Y
• hipred_score: 0.637
• ghis: 0.574

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.530

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Mysm1
• Phenotype: growth/size/body region phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); homeostasis/metabolism phenotype; craniofacial phenotype; vision/eye phenotype; hematopoietic system phenotype; pigmentation phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); immune system phenotype; skeleton phenotype; limbs/digits/tail phenotype

Zebrafish Information Network

• Gene name: mysm1
• Affected structure: pharyngeal arch cartilage
• Phenotype tag: abnormal
• Phenotype quality: malformed

Gene ontology

• Biological process: chromatin remodeling;regulation of cell migration;monoubiquitinated histone H2A deubiquitination;pigmentation;positive regulation of transcription by RNA polymerase II;regulation of hair follicle development
• Cellular component: nucleus;nucleoplasm;plasma membrane;protein-containing complex
• Molecular function: DNA-binding transcription factor activity, RNA polymerase II-specific;DNA binding;transcription coactivator activity;thiol-dependent ubiquitin-specific protease activity;metallopeptidase activity;thiol-dependent ubiquitinyl hydrolase activity;histone binding;metal ion binding