MYSM1

Chr 1AR

Myb like, SWIRM and MPN domains 1

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

NCBI Gene: 114803ENSG00000162601UniProt: Q5VVJ2

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. [provided by Alliance of Genome Resources, Jul 2025]

Primary Disease Associations & Inheritance

Bone marrow failure syndrome 4MIM #618116
AR
575
ClinVar variants
25
Pathogenic / LP
0.04
pLI score
0
Active trials
Clinical Summary— MYSM1
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.26) despite low pLI — interpret in context.
📋
ClinVar Variants
25 Pathogenic / Likely Pathogenic· 98 VUS of 575 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.41LOEUF
pLI 0.043
Z-score 4.90
OE 0.26 (0.17–0.41)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
1.22Z-score
OE missense 0.83 (0.76–0.91)
353 obs / 423.6 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.26 (0.17–0.41)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.83 (0.76–0.91)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.95
0≤1.21.6
LoF obs/exp: 13 / 50.6Missense obs/exp: 353 / 423.6Syn Z: 0.44

ClinVar Variant Classifications

575 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic21
Likely Pathogenic4
VUS98
Likely Benign121
Benign24
Conflicting5
21
Pathogenic
4
Likely Pathogenic
98
VUS
121
Likely Benign
24
Benign
5
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
3
1
17
0
21
Likely Pathogenic
3
0
1
0
4
VUS
0
89
7
2
98
Likely Benign
0
5
51
65
121
Benign
0
6
15
3
24
Conflicting
—5
Total61019170273

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.

Gene2Phenotype Curations

MYSM1-related congenital bone marrow failure

limited
ARLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Bone marrow failure syndrome 4

MIM #618116

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
MYSM1 attenuates DNA damage signals triggered by physiologic and genotoxic DNA breaks.
Mathias B et al.·J Allergy Clin Immunol
2024
MYSM1 inhibits human colorectal cancer tumorigenesis by activating miR-200 family members/CDH1 and blocking PI3K/AKT signaling.
Chen X et al.·J Exp Clin Cancer Res
2021
[A novel compound heterozygous mutation in MYSM1 gene in a 1-month-old girl: a bone marrow failure syndrome 4 family survey and literature review].
Huang J et al.·Zhonghua Xue Ye Xue Za Zhi
2021Review
MYSM1 acts as a novel co-activator of ERα to confer antiestrogen resistance in breast cancer.
Luan R et al.·EMBO Mol Med
2024
Clinical Course and Family History of Adult Patient with Novel MYSM1 Variant.
Sakovich IS et al.·J Clin Immunol
2023
Expression of MYSM1 is associated with tumor progression in colorectal cancer.
Li Y et al.·PLoS One
2017
Myb-like, SWIRM, and MPN domains 1 (MYSM1) deficiency: Genotoxic stress-associated bone marrow failure and developmental aberrations.
Bahrami E et al.·J Allergy Clin Immunol
2017Case report
An in vivo genetic reversion highlights the crucial role of Myb-Like, SWIRM, and MPN domains 1 (MYSM1) in human hematopoiesis and lymphocyte differentiation.
Le Guen T et al.·J Allergy Clin Immunol
2015Case report
Identification of Copy Number Variants in a Southern Chinese Cohort of Patients with Congenital Scoliosis.
Lai W et al.·Genes (Basel)
2021Cohort
Further delineation of bone marrow failure syndrome caused by novel compound heterozygous variants of MYSM1.
Li N et al.·Gene
2020Case report
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
MYSM1-mediated epigenetic modification dysregulation leads to immunosuppression and secondary infections in sepsis.
Xiong J et al.·PLoS Pathog
2026🔓 Open Access
MYSM1 regulates the proliferation and differentiation of bovine skeletal muscle satellite cells via BRG1-mediated activation of the AKT/mTOR/NF-κB signaling pathway.
Zhang C et al.·Anim Biosci
2025
MYSM1 promotes lung adenocarcinoma progression via TRAF2/3-mediated activation of MAPK and non-canonical NF-κB pathways.
Yu W et al.·NPJ Precis Oncol
2025🔓 Open Access
Genetic and Clinical Progression of MYSM1 Related Bone Marrow Failure into Myeloid Malignancies: Case Series and Review of Literature.
Haroon A et al.·Clin Hematol Int
2025🔓 Open AccessReview
MiR-129-5p alleviates depression and anxiety by increasing astrocyte ATP production partly through targeting deubiquitinase Mysm1.
Qin Q et al.·PLoS One
2025🔓 Open Access
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools