MYSM1

Chr 1AR

Myb like, SWIRM and MPN domains 1

Also known as: 2A-DUB, 2ADUB, BMFS4

Encodes a metalloprotease with deubiquitinase activity that regulates hematopoietic stem cell function, blood cell production, and immune responses by removing ubiquitin chains from key signaling proteins and deubiquitinating histone H2A to control gene transcription. Mutations cause bone marrow failure syndrome 4, an autosomal recessive disorder affecting blood cell production. The gene is highly constrained against loss-of-function variants (LOEUF 0.408), reflecting its critical role in hematopoiesis.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismARLOEUF 0.411 OMIM phenotype
Clinical SummaryMYSM1
🧬
Gene-Disease Validity (ClinGen)
bone marrow failure syndrome 4 · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.26) despite low pLI — interpret in context.
📋
ClinVar Variants
45 unique Pathogenic / Likely Pathogenic· 233 VUS of 576 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.41LOEUF
pLI 0.043
Z-score 4.90
OE 0.26 (0.170.41)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
1.22Z-score
OE missense 0.83 (0.760.91)
353 obs / 423.6 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.26 (0.170.41)
00.351.4
Missense OE0.83 (0.760.91)
00.61.4
Synonymous OE0.95
01.21.6
LoF obs/exp: 13 / 50.6Missense obs/exp: 353 / 423.6Syn Z: 0.44

ClinVar Variant Classifications

576 submitted variants in ClinVar

Classification Summary

Pathogenic36
Likely Pathogenic9
VUS233
Likely Benign235
Benign32
Conflicting9
36
Pathogenic
9
Likely Pathogenic
233
VUS
235
Likely Benign
32
Benign
9
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
25
1
10
0
36
Likely Pathogenic
7
0
2
0
9
VUS
2
214
13
4
233
Likely Benign
0
6
114
115
235
Benign
0
7
21
4
32
Conflicting
9
Total34228160123554

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

MYSM1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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