MYSM1

Summary

MYSM1 (Myb like, SWIRM and MPN domains 1, HGNC:29401) is a protein-coding gene on chromosome 1p32.1, encoding Deubiquitinase MYSM1 (Q5VVJ2). Metalloprotease with deubiquitinase activity that plays important regulator roles in hematopoietic stem cell function, blood cell production and immune response.

Enables deubiquitinase activity; histone binding activity; and transcription coactivator activity. Involved in chromatin remodeling; positive regulation of transcription by RNA polymerase II; and regulation of hemopoiesis. Located in nucleolus and nucleoplasm. Part of protein-containing complex. Implicated in diabetic retinopathy.

Source: NCBI Gene 114803 — RefSeq curated summary.

At a glance

• Gene–disease (curated): bone marrow failure syndrome 4 (Definitive, ClinGen)
• GWAS associations: 4
• Clinical variants (ClinVar): 528 total — 27 pathogenic, 7 likely-pathogenic
• Phenotypes (HPO): 46
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity no evidence
• MANE Select transcript: NM_001085487

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29401
Approved symbol	MYSM1
Name	Myb like, SWIRM and MPN domains 1
Location	1p32.1
Locus type	gene with protein product
Status	Approved
Aliases	KIAA1915
Ensembl gene	ENSG00000162601
Ensembl biotype	protein_coding
OMIM	612176
Entrez	114803

Gene structure

Transcript identifiers

Ensembl transcripts: 27 — 14 retained_intron, 5 nonsense_mediated_decay, 4 protein_coding_CDS_not_defined, 4 protein_coding

ENST00000401044, ENST00000472487, ENST00000481973, ENST00000483003, ENST00000489282, ENST00000493821, ENST00000655340, ENST00000659108, ENST00000659812, ENST00000660611, ENST00000665648, ENST00000697250, ENST00000697251, ENST00000697252, ENST00000697253, ENST00000697254, ENST00000697255, ENST00000697256, ENST00000697257, ENST00000697258, ENST00000697259, ENST00000697260, ENST00000697261, ENST00000697262, ENST00000697263, ENST00000697264, ENST00000930864

RefSeq mRNA: 1 — MANE Select: NM_001085487 NM_001085487

CCDS: CCDS41343

Canonical transcript exons

ENST00000472487 — 20 exons

Exon	Start	End
ENSE00001883052	58699985	58700062
ENSE00001921295	58654743	58660155
ENSE00003459685	58676926	58677056
ENSE00003460867	58675477	58675580
ENSE00003470515	58665499	58665631
ENSE00003498130	58692861	58692931
ENSE00003503666	58668632	58668682
ENSE00003513791	58690226	58690249
ENSE00003514539	58681785	58682545
ENSE00003519045	58668984	58669038
ENSE00003581750	58695129	58695207
ENSE00003588544	58689038	58689116
ENSE00003608082	58690340	58690417
ENSE00003615364	58667847	58667921
ENSE00003621849	58661406	58661511
ENSE00003637292	58673573	58673650
ENSE00003670100	58685153	58685251
ENSE00003673680	58661170	58661227
ENSE00003683830	58671870	58671958
ENSE00003686426	58667038	58667226

Expression profiles

Bgee: expression breadth ubiquitous, 252 present calls, max score 95.51.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 20.1178 / max 430.6084, expressed in 1797 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
12567	20.1178	1797

Top tissues by expression

255 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
calcaneal tendon	UBERON:0003701	95.51	gold quality
cardiac muscle of right atrium	UBERON:0003379	95.13	silver quality
sural nerve	UBERON:0015488	94.84	gold quality
tibia	UBERON:0000979	92.59	gold quality
tendon	UBERON:0000043	91.81	gold quality
oviduct epithelium	UBERON:0004804	91.01	gold quality
ileal mucosa	UBERON:0000331	90.90	gold quality
rectum	UBERON:0001052	90.83	gold quality
skin of hip	UBERON:0001554	90.75	gold quality
left ventricle myocardium	UBERON:0006566	90.20	silver quality
body of pancreas	UBERON:0001150	89.89	gold quality
upper leg skin	UBERON:0004262	89.77	gold quality
minor salivary gland	UBERON:0001830	89.62	gold quality
tibial nerve	UBERON:0001323	89.34	gold quality
mucosa of stomach	UBERON:0001199	89.32	gold quality
adrenal tissue	UBERON:0018303	89.23	gold quality
Brodmann (1909) area 23	UBERON:0013554	89.15	gold quality
endometrium	UBERON:0001295	89.06	gold quality
body of uterus	UBERON:0009853	88.97	gold quality
vermiform appendix	UBERON:0001154	88.93	gold quality
left ovary	UBERON:0002119	88.89	gold quality
small intestine Peyer’s patch	UBERON:0003454	88.76	gold quality
right ovary	UBERON:0002118	88.75	gold quality
monocyte	CL:0000576	88.59	gold quality
transverse colon	UBERON:0001157	88.49	gold quality
smooth muscle tissue	UBERON:0001135	88.47	gold quality
gall bladder	UBERON:0002110	88.46	gold quality
left lobe of thyroid gland	UBERON:0001120	88.39	gold quality
right lung	UBERON:0002167	88.34	gold quality
subcutaneous adipose tissue	UBERON:0002190	88.33	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.94

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): GFI1, RUNX1

miRNA regulators (miRDB)

301 targeting MYSM1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-4682	100.00	68.89	1258
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-4514	99.99	67.10	1870

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 14)

• The SWIRM structure of human MYb-like, Swirm and Mpn domain-containing protein-1 (MYSM1), is reported. (PMID:17428495)
• The identification of histone H2A deubiquitinase (2A-DUB, or KIAA1915/MYSM1) specific for monoubiquitinated H2A (uH2A) that helps in delineating a strategy for specific regulatory pathways of gene activation, is reported. (PMID:17707232)
• the biallelic truncation of MYSM1 likely represents the cause of an inherited bone marrow failure syndrome in two siblings (PMID:24288411)
• An in vivo genetic reversion highlights the crucial role of MYSM1 in human hematopoiesis and lymphocyte differentiation (PMID:26220525)
• Data indicate a pathway MYSM1/miR-150/FLT3 that inhibits proliferation of B1a cells, which may be involved in the pathogenesis of systemic lupus erythematosus (SLE). (PMID:27590507)
• this study shows that MYSM1 deficiency is associated with developmental aberrations, progressive bone marrow failure with myelodysplastic features, and increased susceptibility to genotoxic stress (PMID:28115216)
• data suggested that expression of MYSM1 was associated with the progression of CRC and might be a potential biomarker for clinical prognosis (PMID:28498834)
• differentiation of B cells to plasma cells was inhibited after the overexpression of MYSM1 (PMID:31607324)
• MYSM1-AR complex-mediated repression of Akt/c-Raf/GSK-3beta signaling impedes castration-resistant prostate cancer growth. (PMID:31761786)
• Interaction of Deubiquitinase 2A-DUB/MYSM1 with DNA Repair and Replication Factors. (PMID:32466590)
• MYSM1 Represses Innate Immunity and Autoimmunity through Suppressing the cGAS-STING Pathway. (PMID:33086059)
• MYSM1 inhibits human colorectal cancer tumorigenesis by activating miR-200 family members/CDH1 and blocking PI3K/AKT signaling. (PMID:34706761)
• Deubiquitinase catalytic activity of MYSM1 is essential in vivo for hematopoiesis and immune cell development. (PMID:36611064)
• MYSM1 attenuates DNA damage signals triggered by physiologic and genotoxic DNA breaks. (PMID:38065233)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	mysm1	ENSDARG00000034693
mus_musculus	Mysm1	ENSMUSG00000062627
rattus_norvegicus	Mysm1	ENSRNOG00000026299

Paralogs (3): MPND (ENSG00000008382), SMARCC2 (ENSG00000139613), SMARCC1 (ENSG00000173473)

Protein

Protein identifiers

Deubiquitinase MYSM1 — Q5VVJ2 (reviewed: Q5VVJ2)

Alternative names: Myb-like, SWIRM and MPN domain-containing protein 1

All UniProt accessions (7): A0A590UJD8, A0A590UJT8, A0A590UJW2, A0A590UK32, A0A8V8TKW8, A0A8V8TMF1, Q5VVJ2

UniProt curated annotations — full annotation on UniProt →

Function. Metalloprotease with deubiquitinase activity that plays important regulator roles in hematopoietic stem cell function, blood cell production and immune response. Participates in the normal programming of B-cell responses to antigen after the maturation process. Within the cytoplasm, plays critical roles in the repression of innate immunity and autoimmunity. Removes ‘Lys-63’-linked polyubiquitins from TRAF3 and TRAF6 complexes. Attenuates NOD2-mediated inflammation and tissue injury by promoting ‘Lys-63’-linked deubiquitination of RIPK2 component. Suppresses the CGAS-STING1 signaling pathway by cleaving STING1 ‘Lys-63’-linked ubiquitin chains. In the nucleus, acts as a hematopoietic transcription regulator derepressing a range of genes essential for normal stem cell differentiation including EBF1 and PAX5 in B-cells, ID2 in NK-cell progenitor or FLT3 in dendritic cell precursors. Deubiquitinates monoubiquitinated histone H2A, a specific tag for epigenetic transcriptional repression, leading to dissociation of histone H1 from the nucleosome.

Subunit / interactions. Component of a large chromatin remodeling complex, at least composed of MYSM1, PCAF, RBM10 and KIF11/TRIP5. Binds histones. Interacts with NFIL3; this interaction is critical for their correct recruitment to the ID2 locus during natural killer cell maturation.

Subcellular location. Nucleus. Cytoplasm.

Disease relevance. Bone marrow failure syndrome 4 (BMFS4) [MIM:618116] A form of bone marrow failure syndrome, a heterogeneous group of life-threatening disorders characterized by hematopoietic defects in association with a range of variable extra-hematopoietic manifestations. BMFS4 is characterized by early-onset anemia, leukopenia, decreased B cells, and developmental aberrations including facial dysmorphism, mild skeletal anomalies, and neurodevelopmental delay. BMFS4 inheritance is autosomal recessive. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. Contains an N-terminal SANT domain that mediates histone/DNA binding, a central SWIRM domain to mediate interaction with chromatin associated proteins, and a C-terminal MPN domain that contains the metalloprotease activity.

Induction. By DNA from viral infection and intracellular DNA.

Similarity. Belongs to the peptidase M67A family. MYSM1 subfamily.

Isoforms (3)

UniProt ID	Names	Canonical?
Q5VVJ2-1	1	yes
Q5VVJ2-2	2
Q5VVJ2-3	3

RefSeq proteins (1): NP_001078956* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000555	JAMM/MPN+_dom	Domain
IPR001005	SANT/Myb	Domain
IPR007526	SWIRM	Domain
IPR009057	Homeodomain-like_sf	Homologous_superfamily
IPR017884	SANT_dom	Domain
IPR017930	Myb_dom	Domain
IPR036388	WH-like_DNA-bd_sf	Homologous_superfamily
IPR037518	MPN	Domain
IPR050242	JAMM_MPN+_peptidase_M67A	Family

Pfam: PF00249, PF01398, PF04433

UniProt features (42 total): helix 8, modified residue 6, sequence variant 5, strand 4, domain 3, binding site 3, sequence conflict 3, splice variant 2, short sequence motif 2, chain 1, cross-link 1, mutagenesis site 1, turn 1, region of interest 1, compositionally biased region 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
2CU7	SOLUTION NMR
2DCE	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q5VVJ2-F1	64.69	0.24

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (3): 669; 656; 658

Post-translational modifications (7): 110, 218, 236, 242, 267, 340, 187

Mutagenesis-validated functional residues (1):

Position	Phenotype
669	abolishes h2a deubiquitination.

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-5689901	Metalloprotease DUBs
R-HSA-392499	Metabolism of proteins
R-HSA-5688426	Deubiquitination
R-HSA-597592	Post-translational protein modification

MSigDB gene sets: 227 (showing top): GOBP_EPITHELIUM_DEVELOPMENT, GOMF_METALLOPEPTIDASE_ACTIVITY, GOBP_REGULATION_OF_HAIR_CYCLE, GOBP_REGULATION_OF_HAIR_FOLLICLE_DEVELOPMENT, GOBP_PIGMENTATION, GOBP_REGULATION_OF_HEMOPOIESIS, GOBP_MOLTING_CYCLE, GOBP_EPIDERMIS_DEVELOPMENT, NAKAMURA_TUMOR_ZONE_PERIPHERAL_VS_CENTRAL_DN, LASTOWSKA_NEUROBLASTOMA_COPY_NUMBER_DN, GOBP_CHROMATIN_REMODELING, GOBP_SKIN_DEVELOPMENT, GOBP_REGULATION_OF_CELL_DEVELOPMENT, LEE_RECENT_THYMIC_EMIGRANT, GOBP_PROTEOLYSIS

GO Biological Process (9): immune system process (GO:0002376), chromatin remodeling (GO:0006338), proteolysis (GO:0006508), regulation of cell migration (GO:0030334), pigmentation (GO:0043473), positive regulation of transcription by RNA polymerase II (GO:0045944), regulation of hair follicle development (GO:0051797), regulation of hemopoiesis (GO:1903706), chromatin organization (GO:0006325)

GO Molecular Function (10): DNA binding (GO:0003677), transcription coactivator activity (GO:0003713), histone binding (GO:0042393), metal ion binding (GO:0046872), metal-dependent deubiquitinase activity (GO:0140492), histone H2A deubiquitinase activity (GO:0140950), protein binding (GO:0005515), peptidase activity (GO:0008233), metallopeptidase activity (GO:0008237), hydrolase activity (GO:0016787)

GO Cellular Component (5): nucleus (GO:0005634), nucleoplasm (GO:0005654), nucleolus (GO:0005730), cytoplasm (GO:0005737), protein-containing complex (GO:0032991)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Deubiquitination	1
Post-translational protein modification	1
Metabolism of proteins	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
biological_process	2
positive regulation of DNA-templated transcription	2
regulation of multicellular organismal development	2
nuclear lumen	2
cellular anatomical structure	2
chromatin organization	1
protein metabolic process	1
cell migration	1
regulation of cell motility	1
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
hair follicle development	1
regulation of hair cycle	1
regulation of immune system process	1
hemopoiesis	1
regulation of cell development	1
cellular component organization	1
nucleic acid binding	1
transcription coregulator activity	1
protein binding	1
cation binding	1
metallopeptidase activity	1
deubiquitinase activity	1
histone deubiquitinase activity	1
binding	1
hydrolase activity	1
catalytic activity, acting on a protein	1
peptidase activity	1
catalytic activity	1
intracellular membrane-bounded organelle	1
intracellular membraneless organelle	1
intracellular anatomical structure	1
cellular_component	1

Protein interactions and networks

STRING

5982 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MYSM1	KAT2B	Q92831	885
MYSM1	RBM10	P98175	663
MYSM1	H2AC20	Q16777	649
MYSM1	H2AC19	P20670	648
MYSM1	USP16	Q9Y5T5	630
MYSM1	USP21	Q9UK80	630
MYSM1	USP3	Q9Y6I4	621
MYSM1	STAMBPL1	Q96FJ0	612
MYSM1	USP4	Q13107	606
MYSM1	ZUP1	Q96AP4	602
MYSM1	USP22	Q9UPT9	596
MYSM1	USP5	P45974	595
MYSM1	BRCC3	P46736	583
MYSM1	USP11	P51784	582
MYSM1	USP15	Q9Y4E8	579
MYSM1	STAMBP	O95630	579

IntAct

12 interactions, top by confidence:

A	B	Type	Score
CDK8	MED19	psi-mi:“MI:2364”(proximity)	0.850
MPP7	MYSM1	psi-mi:“MI:0915”(physical association)	0.560
H3C1	SMCHD1	psi-mi:“MI:2364”(proximity)	0.410
TCEAL9	DIRAS1	psi-mi:“MI:0914”(association)	0.350
LMNA	SMCHD1	psi-mi:“MI:2364”(proximity)	0.270
NPM1	SBNO1	psi-mi:“MI:2364”(proximity)	0.270
MPP7	MYSM1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (177): HIST2H2AC (Biochemical Activity), MYSM1 (Proximity Label-MS), MYSM1 (Proximity Label-MS), MYSM1 (Proximity Label-MS), MYSM1 (Two-hybrid), H2AFX (Co-localization), ACTBL2 (Affinity Capture-MS), UBTF (Affinity Capture-MS), IPO4 (Affinity Capture-MS), PPIB (Affinity Capture-MS), HSP90AB2P (Affinity Capture-MS), H2AFY (Affinity Capture-MS), TK1 (Affinity Capture-MS), BRAT1 (Affinity Capture-MS), HELLS (Affinity Capture-MS)

ESM2 similar proteins: A0A8M3B525, A2AHJ4, A5PJP6, B0KWU8, B2RYM5, B5X8M4, E1C3P4, E9Q4Z2, O00763, O42611, O94967, O95630, P46736, P46737, P48553, Q15386, Q15542, Q3TLI0, Q4VA72, Q5KSL6, Q5R558, Q5R9L6, Q5RAQ5, Q5VVJ2, Q641K1, Q66GV6, Q66H62, Q69Z66, Q6RI45, Q6WKZ8, Q76N33, Q7M757, Q80U95, Q8BPM2, Q8CGF6, Q8IVH8, Q8QFR2, Q8TAT6, Q8VDD9, Q8W206

Diamond homologs: A0A0G3VTN5, A0JMR6, B6MUN4, D4GTS4, P32591, P97496, Q08CH3, Q54Z40, Q5F3F2, Q5RGA4, Q5VVJ2, Q69Z66, Q6CRJ8, Q6PDG5, Q6R0H0, Q84JG2, Q8H0W3, Q8RWU3, Q8SQY3, Q8TAQ2, Q92922, Q9FVU9, Q3TV65, Q8N594, Q8U1Y4, A0A0P0XBU0, B3H5A8, B8A9B2, B8BI93, C0SVG5, F4J2J6, F4K5X6, F4KGY6, P92973, Q54HX6, Q54IF9, Q6R0G4, Q6R0H1, Q7XC51, Q7XC57

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

528 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	27
Likely pathogenic	7
Uncertain significance	213
Likely benign	219
Benign	31

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1031070	NM_001085487.3(MYSM1):c.1885C>T (p.Gln629Ter)	Pathogenic
1394541	NM_001085487.3(MYSM1):c.415A>T (p.Arg139Ter)	Pathogenic
1451828	NM_001085487.3(MYSM1):c.420G>A (p.Trp140Ter)	Pathogenic
1452695	NM_001085487.3(MYSM1):c.1432C>T (p.Arg478Ter)	Pathogenic
1805964	NM_001085487.3(MYSM1):c.1516C>T (p.Arg506Ter)	Pathogenic
1968661	NM_001085487.3(MYSM1):c.1410del (p.Arg470fs)	Pathogenic
2010146	NM_001085487.3(MYSM1):c.391C>T (p.Gln131Ter)	Pathogenic
2023446	NM_001085487.3(MYSM1):c.275dup (p.Asp92fs)	Pathogenic
2026215	NM_001085487.3(MYSM1):c.1477C>T (p.Gln493Ter)	Pathogenic
2423681	NC_000001.10:g.(?59160781)(59165724_?)del	Pathogenic
2501775	NM_001085487.3(MYSM1):c.412C>T (p.Arg138Ter)	Pathogenic
2714130	NM_001085487.3(MYSM1):c.152G>A (p.Trp51Ter)	Pathogenic
2777330	NM_001085487.3(MYSM1):c.1204C>T (p.Gln402Ter)	Pathogenic
2843878	NM_001085487.3(MYSM1):c.775C>T (p.Gln259Ter)	Pathogenic
2848915	NM_001085487.3(MYSM1):c.285dup (p.Tyr96fs)	Pathogenic
2880869	NM_001085487.3(MYSM1):c.664del (p.Glu222fs)	Pathogenic
2905566	NM_001085487.3(MYSM1):c.1709_1710insTTGAAGA (p.Glu570delinsAspTer)	Pathogenic
3622781	NM_001085487.3(MYSM1):c.2089C>T (p.Arg697Ter)	Pathogenic
3725901	NM_001085487.3(MYSM1):c.920_921del (p.Lys307fs)	Pathogenic
4715013	NM_001085487.3(MYSM1):c.1468C>T (p.Gln490Ter)	Pathogenic
4728930	NM_001085487.3(MYSM1):c.2214G>A (p.Trp738Ter)	Pathogenic
4734585	NM_001085487.3(MYSM1):c.2017C>T (p.Gln673Ter)	Pathogenic
4767355	NM_001085487.3(MYSM1):c.252dup (p.Val85fs)	Pathogenic
4810970	NM_001085487.3(MYSM1):c.1194dup (p.Glu399Ter)	Pathogenic
561193	NM_001085487.3(MYSM1):c.1168G>T (p.Glu390Ter)	Pathogenic
561194	NM_001085487.3(MYSM1):c.1967A>G (p.His656Arg)	Pathogenic
807637	NM_001085487.3(MYSM1):c.869C>G (p.Ser290Ter)	Pathogenic
1502993	NM_001085487.3(MYSM1):c.69-2A>G	Likely pathogenic
1514455	NM_001085487.3(MYSM1):c.219-1G>A	Likely pathogenic
2442104	NM_001085487.3(MYSM1):c.1146_1149del (p.Asp382fs)	Likely pathogenic

SpliceAI

3082 predictions. Top by Δscore:

Variant	Effect	Δscore
1:58659985:A:C	donor_gain	1.0000
1:58660005:A:C	donor_gain	1.0000
1:58660010:T:TA	donor_gain	1.0000
1:58661168:A:AC	donor_gain	1.0000
1:58661169:C:CC	donor_gain	1.0000
1:58661169:CTTT:C	donor_gain	1.0000
1:58661172:T:A	donor_gain	1.0000
1:58661223:CGCTG:C	acceptor_gain	1.0000
1:58661225:CTG:C	acceptor_gain	1.0000
1:58661511:CCTA:C	acceptor_loss	1.0000
1:58661512:C:CC	acceptor_gain	1.0000
1:58661512:CTA:C	acceptor_loss	1.0000
1:58661513:T:G	acceptor_loss	1.0000
1:58665497:A:AC	donor_gain	1.0000
1:58665498:C:CC	donor_gain	1.0000
1:58667840:AACTT:A	donor_loss	1.0000
1:58667841:ACTTA:A	donor_loss	1.0000
1:58667842:CTTAC:C	donor_loss	1.0000
1:58667843:TTACT:T	donor_loss	1.0000
1:58667844:TA:T	donor_loss	1.0000
1:58667845:A:AC	donor_gain	1.0000
1:58667845:ACTTC:A	donor_loss	1.0000
1:58667846:C:A	donor_loss	1.0000
1:58667846:C:CC	donor_gain	1.0000
1:58667846:CTT:C	donor_gain	1.0000
1:58667917:GCATG:G	acceptor_gain	1.0000
1:58667918:CATG:C	acceptor_gain	1.0000
1:58667918:CATGC:C	acceptor_gain	1.0000
1:58667919:ATG:A	acceptor_gain	1.0000
1:58667920:TG:T	acceptor_gain	1.0000

AlphaMissense

5516 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:58667062:A:C	D669E	1.000
1:58667062:A:T	D669E	1.000
1:58667063:T:A	D669V	1.000
1:58667063:T:C	D669G	1.000
1:58667063:T:G	D669A	1.000
1:58667086:A:C	F661L	1.000
1:58667086:A:T	F661L	1.000
1:58667088:A:G	F661L	1.000
1:58667103:G:C	H656D	1.000
1:58667109:A:G	W654R	1.000
1:58667109:A:T	W654R	1.000
1:58676936:A:C	N460K	1.000
1:58676936:A:T	N460K	1.000
1:58676958:A:G	L453P	1.000
1:58677026:C:A	K430N	1.000
1:58677026:C:G	K430N	1.000
1:58677028:T:C	K430E	1.000
1:58685233:A:G	W140R	1.000
1:58685233:A:T	W140R	1.000
1:58665584:A:C	S693R	0.999
1:58665584:A:T	S693R	0.999
1:58665586:T:G	S693R	0.999
1:58667064:C:G	D669H	0.999
1:58667072:G:A	S666F	0.999
1:58667075:G:T	P665H	0.999
1:58667095:A:C	H658Q	0.999
1:58667095:A:T	H658Q	0.999
1:58667097:G:C	H658D	0.999
1:58667100:A:G	S657P	0.999
1:58667101:A:C	H656Q	0.999

dbSNP variants (sampled 300 via entrez): RS1000194916 (1:58690094 A>T), RS1000198152 (1:58690759 G>A), RS1000215747 (1:58694632 TAAC>T), RS1000360939 (1:58683030 C>T), RS1000374510 (1:58661023 T>C), RS1000477747 (1:58658143 C>T), RS1000525107 (1:58672324 T>C), RS1000529246 (1:58678705 CAAGAG>C), RS1000546395 (1:58699395 G>A), RS1000610127 (1:58697737 G>A), RS1000813196 (1:58691954 A>C,G), RS1000878049 (1:58678306 T>C), RS1000881771 (1:58697652 C>T), RS1000982984 (1:58659468 T>C), RS1001041557 (1:58672608 C>G,T)

Disease associations

OMIM: gene MIM:612176 | disease phenotypes: MIM:618116

GenCC curated gene-disease

Disease	Classification	Inheritance
bone marrow failure syndrome 4	Definitive	Autosomal recessive

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
bone marrow failure syndrome 4	Definitive	AR

Mondo (2): bone marrow failure syndrome 4 (MONDO:0020856), congenital progressive bone marrow failure-B-cell immunodeficiency-skeletal dysplasia syndrome (MONDO:0033683)

Orphanet (1): Congenital progressive bone marrow failure-B-cell immunodeficiency-skeletal dysplasia syndrome (Orphanet:508542)

HPO phenotypes

46 total (30 of 46 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000212	Gingival overgrowth
HP:0000243	Trigonocephaly
HP:0000252	Microcephaly
HP:0000280	Coarse facial features
HP:0000365	Hearing impairment
HP:0000369	Low-set ears
HP:0000518	Cataract
HP:0000684	Delayed eruption of teeth
HP:0000765	Abnormal thorax morphology
HP:0000916	Broad clavicles
HP:0000958	Dry skin
HP:0000964	Eczematoid dermatitis
HP:0001156	Brachydactyly
HP:0001249	Intellectual disability
HP:0001263	Global developmental delay
HP:0001482	Subcutaneous nodule
HP:0001635	Congestive heart failure
HP:0001873	Thrombocytopenia
HP:0001875	Decreased total neutrophil count
HP:0001882	Decreased total leukocyte count
HP:0001888	Decreased total lymphocyte count
HP:0001896	Reticulocytopenia
HP:0001903	Anemia
HP:0001999	Abnormal facial shape
HP:0002205	Recurrent respiratory infections
HP:0002783	Recurrent lower respiratory tract infections
HP:0002788	Recurrent upper respiratory tract infections
HP:0002863	Myelodysplasia
HP:0003577	Congenital onset

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST000966_5	Diabetic retinopathy	3.000000e-07
GCST002928_28	Nickel levels	8.000000e-06
GCST003542_175	Night sleep phenotypes	8.000000e-06
GCST009391_1155	Metabolite levels	5.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0010459	aminoadipic acid measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

25 total (human), top 25 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
FR900359	affects phosphorylation	1
bisphenol F	affects cotreatment, increases methylation	1
triphenyl phosphate	affects expression	1
testosterone undecanoate	affects cotreatment, decreases expression	1
sodium arsenite	affects expression	1
potassium chromate(VI)	affects cotreatment, increases expression	1
epigallocatechin gallate	affects cotreatment, increases expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
abrine	increases expression	1
jinfukang	decreases expression	1
Irinotecan	decreases expression	1
Sunitinib	increases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Doxorubicin	decreases expression	1
Endosulfan	increases expression	1
Formaldehyde	increases expression	1
Methyl Methanesulfonate	increases expression	1
Quercetin	decreases phosphorylation	1
Tetrachlorodibenzodioxin	affects expression	1
Dronabinol	increases expression	1
Valproic Acid	decreases expression	1
Vincristine	increases expression	1
Levonorgestrel	affects cotreatment, decreases expression	1
Cadmium Chloride	increases expression	1

Cellosaurus cell lines

3 cell lines: 2 cancer cell line, 1 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B3BP	Abcam HEK293T MYSM1 KO	Transformed cell line	Female
CVCL_SZ67	HAP1 MYSM1 (-) 1	Cancer cell line	Male
CVCL_SZ68	HAP1 MYSM1 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.