UniProtKB/Swiss-Prot Q9Y6X9: Variant p.Thr424Arg

• Variant information
• Sequence information
• Literature citations
• All

Variant information

Variant position: 424 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant: US The variants are classified into three categories: LP/P, LB/B and US.

• LP/P: likely pathogenic or pathogenic.
• LB/B: likely benign or benign.
• US: uncertain significance

Residue change: From Threonine (T) to Arginine (R) at position 424 (T424R, p.Thr424Arg). 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 (T) to large size and basic (R) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score: -1 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
Variant description: Found in early-onset spinal muscular atrophy-like disease with cerebellar atrophy, cerebellar ataxia and diaphragmatic paralysis; likely pathogenic; increased ATPase activity; increased rate of dimer assembly and disassembly; decreased HUSH-dependent gene silencing. Any additional useful information about the variant.

Sequence information

Variant position: 424 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: 1032 The length of the canonical sequence.
Location on the sequence: GMACGGVVGVVDVPYLVLEP T HNKQDFADAKEYRHLLRAMG 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.
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.

Type	Positions	Description
Chain	2 – 1032	ATPase MORC2
Binding site	427 – 427

Literature citations

MORC2 mutation causes severe spinal muscular atrophy-phenotype, cerebellar atrophy, and diaphragmatic paralysis.
Schottmann G.; Wagner C.; Seifert F.; Stenzel W.; Schuelke M.;
Brain 139:E70-E70(2016)
Cited for: VARIANT ARG-424; De novo p.T362R mutation in MORC2 causes early onset cerebellar ataxia, axonal polyneuropathy and nocturnal hypoventilation.
Zanni G.; Nardella M.; Barresi S.; Bellacchio E.; Niceta M.; Ciolfi A.; Pro S.; D'Arrigo S.; Tartaglia M.; Bertini E.;
Brain 140:E34-E34(2017)
Cited for: VARIANT ARG-424; Neuropathic MORC2 mutations perturb GHKL ATPase dimerization dynamics and epigenetic silencing by multiple structural mechanisms.
Douse C.H.; Bloor S.; Liu Y.; Shamin M.; Tchasovnikarova I.A.; Timms R.T.; Lehner P.J.; Modis Y.;
Nat. Commun. 9:651-651(2018)
Cited for: X-RAY CRYSTALLOGRAPHY (1.81 ANGSTROMS) OF 1-603 OF WILD-TYPE; X-RAY CRYSTALLOGRAPHY (1.81 ANGSTROMS) OF 1-603 OF; X-RAY CRYSTALLOGRAPHY (1.81 ANGSTROMS) OF 1-603 OF VARIANT CMT2Z LEU-87; X-RAY CRYSTALLOGRAPHY (1.81 ANGSTROMS) OF 1-603 OF VARIANT ARG-424 IN COMPLEX WITH ATP; MAGNESIUM AND ZINC; CHARACTERIZATION OF VARIANTS CMT2Z LEU-87 AND TRP-252; CHARACTERIZATION OF VARIANT ARG-424; FUNCTION; CATALYTIC ACTIVITY; SUBUNIT; MUTAGENESIS OF TYR-18; ASN-39; ARG-266; ARG-319; ARG-326; ARG-329; ARG-333; ARG-344; ARG-351 AND ARG-358;