UniProtKB/Swiss-Prot Q14204: Variant p.Ile584Leu

Cytoplasmic dynein 1 heavy chain 1
Gene: DYNC1H1
Chromosomal location: 14q32
Variant information

Variant position:  584
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 have been found in patients and disease-association is reported in literature. However, this classification is not a definitive assessment of variant pathogenicity.
  • Polymorphism: No disease-association has been reported.
  • Unclassified: Variants have been found in patients but disease-association remains unclear.

Residue change:  From Isoleucine (I) to Leucine (L) at position 584 (I584L, p.Ile584Leu).
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:  Similar physico-chemical property. Both residues are medium size and hydrophobic.
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  2
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:  In SMALED1; disrupts dynein complex stability and function.
Any additional useful information about the variant.



Sequence information

Variant position:  584
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  4646
The length of the canonical sequence.

Location on the sequence:   ITARLRDQLGTAKNANEMFR  I FSRFNALFVRPHIRGAIREY
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                         ITARLRDQLGTAKNANEMFRIFSRFNALFVRPHIRGAIREY

Mouse                         ITARLRDQLGTAKNANEMFRIFSRFNALFVRPHIRGAIREY

Rat                           ITARLRDQLGTAKNANEMFRIFSRFNALFVRPHIRGAIREY

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 2 – 4646 Cytoplasmic dynein 1 heavy chain 1
Region 53 – 1867 Stem
Region 448 – 703 Interaction with DYNC1I2


Literature citations

Mutations in the tail domain of DYNC1H1 cause dominant spinal muscular atrophy.
Harms M.B.; Ori-McKenney K.M.; Scoto M.; Tuck E.P.; Bell S.; Ma D.; Masi S.; Allred P.; Al-Lozi M.; Reilly M.M.; Miller L.J.; Jani-Acsadi A.; Pestronk A.; Shy M.E.; Muntoni F.; Vallee R.B.; Baloh R.H.;
Neurology 78:1714-1720(2012)
Cited for: VARIANTS SMALED1 LEU-584; GLU-671 AND CYS-970; CHARACTERIZATION OF VARIANT SMALED1 LEU-584;

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.