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UniProtKB/Swiss-Prot Q5VVJ2: Variant p.His656Arg

Histone H2A deubiquitinase MYSM1
Gene: MYSM1
Chromosomal location: 1p32.1
Variant information

Variant position:  656
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Type of variant:  Disease [Disclaimer]
The variants are classified into three categories: Disease, Polymorphism and Unclassified.
  • Disease: Variants implicated in disease according to literature reports.
  • Polymorphism: Variants not reported to be implicated in disease.
  • Unclassified: Variants with uncertain implication in disease according to literature reports. Evidence against or in favor of a pathogenic role is limited and/or conflicting.

Residue change:  From Histidine (H) to Arginine (R) at position 656 (H656R, p.His656Arg).
Indicates the amino acid change of the variant. The one-letter and three-letter codes for amino acids used in UniProtKB/Swiss-Prot are those adopted by the commission on Biochemical Nomenclature of the IUPAC-IUB.

Physico-chemical properties:  Change from medium size and polar (H) to large size and basic (R)
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  0
The score within a Blosum matrix for the corresponding wild-type to variant amino acid change. The log-odds score measures the logarithm for the ratio of the likelihood of two amino acids appearing by chance. The Blosum62 substitution matrix is used. This substitution matrix contains scores for all possible exchanges of one amino acid with another:
  • Lowest score: -4 (low probability of substitution).
  • Highest score: 11 (high probability of substitution).
More information can be found on the following page

Involvement in disease:  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 features. 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. {ECO:0000269|PubMed:24288411, ECO:0000269|PubMed:26220525, ECO:0000269|PubMed:28115216}. Note=The disease is caused by mutations affecting the gene represented in this entry.
The name and a short description of the disease associated with the variant. For more information about the disease, the user can refer to OMIM, following the link provided after the disease acronym.

Variant description:  In BMFS4.
Any additional useful information about the variant.



Sequence information

Variant position:  656
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  828
The length of the canonical sequence.

Location on the sequence:   SQTQASETLAVRGFSVIGWY  H SHPAFDPNPSLRDIDTQAKY
The residue change on the sequence. Unless the variant is located at the beginning or at the end of the protein sequence, both residues upstream (20) and downstream (20) of the variant will be shown.

Residue conservation: 
The multiple alignment of the region surrounding the variant against various orthologous sequences.

Human                         SQTQASETLAVRGFSVIGWYHSHPAFDPNPSLRDIDTQAKY

Mouse                         SQTQASETLALRGYSVIGWYHSHPAFDPNPSLRDIDTQAKY

Chicken                       SQTQASETLAARGYSVIGWYHSHPAFDPNPSIRDIDTQAKY

Xenopus laevis                SQTQASEALASRGYSVIGWYHSHPAFDPNPSIRDIDTQAKY

Zebrafish                     SQTQASEVLGVKGLSVVGWYHSHPAFDPNPSLRDIDTQAKY

Sequence annotation in neighborhood:  
The regions or sites of interest surrounding the variant. In general the features listed are posttranslational modifications, binding sites, enzyme active sites, local secondary structure or other characteristics reported in the cited references. The "Sequence annotation in neighborhood" lines have a fixed format:
  • Type: the type of sequence feature.
  • Positions: endpoints of the sequence feature.
  • Description: contains additional information about the feature.

TypePositionsDescription
Chain 1 – 828 Histone H2A deubiquitinase MYSM1
Domain 577 – 709 MPN
Motif 656 – 669 JAMM motif
Metal binding 656 – 656 Zinc; catalytic
Metal binding 658 – 658 Zinc; catalytic
Metal binding 669 – 669 Zinc; catalytic
Mutagenesis 669 – 669 D -> N. Abolishes H2A deubiquitination.


Literature citations

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.; Touzot F.; Andre-Schmutz I.; Lagresle-Peyrou C.; France B.; Kermasson L.; Lambert N.; Picard C.; Nitschke P.; Carpentier W.; Bole-Feysot C.; Lim A.; Cavazzana M.; Callebaut I.; Soulier J.; Jabado N.; Fischer A.; de Villartay J.P.; Revy P.;
J. Allergy Clin. Immunol. 136:1619-1626(2015)
Cited for: FUNCTION; INVOLVEMENT IN BMFS4; VARIANT BMFS4 ARG-656;

Disclaimer: Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. They are not in any way intended to be used as a substitute for professional medical advice, diagnostic, treatment or care.