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UniProtKB/Swiss-Prot O00429: Variant p.Arg403Cys

Dynamin-1-like protein
Gene: DNM1L
Chromosomal location: 12p11.21
Variant information

Variant position:  403
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 Arginine (R) to Cysteine (C) at position 403 (R403C, p.Arg403Cys).
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 large size and basic (R) to medium size and polar (C)
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  -3
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:  Encephalopathy due to defective mitochondrial and peroxisomal fission 1 (EMPF1) [MIM:614388]: A rare autosomal dominant systemic disorder resulting in lack of neurologic development and death in infancy. After birth, infants present in the first week of life with poor feeding and neurologic impairment, including hypotonia, little spontaneous movement, no tendon reflexes, no response to light stimulation, and poor visual fixation. Other features include mildly elevated plasma concentration of very-long-chain fatty acids, lactic acidosis, microcephaly, deep-set eyes, optic atrophy and hypoplasia, and an abnormal gyral pattern in both frontal lobes associated with dysmyelination. {ECO:0000269|PubMed:17460227, ECO:0000269|PubMed:26604000, ECO:0000269|PubMed:26992161, ECO:0000269|PubMed:27145208, ECO:0000269|PubMed:27301544, ECO:0000269|PubMed:27328748, ECO:0000269|PubMed:29899447}. 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 EMPF1; the mutation acts in a dominant-negative manner; reduced oligomerization; decreased mitochondrial recruitment; defects observed in mitochondrial fission.
Any additional useful information about the variant.

Other resources:  
Links to websites of interest for the variant.



Sequence information

Variant position:  403
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  736
The length of the canonical sequence.

Location on the sequence:   PLGGLNTIDILTAIRNATGP  R PALFVPEVSFELLVKRQIKR
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                         PLGGLNTIDILTAIRNATGPRPALFVPEVSFELLVKRQIKR

Mouse                         PLGGLNTIDILTAIRNATGPRPALFVPEVSFELLVKRQIKR

Rat                           PLGGLNTIDILTAIRNATGPRPALFVPEVSFELLVKRQIKR

Bovine                        PLGGLNTIDILTAIRNATGPRPALFVPEVSFELLVKRQIKR

Zebrafish                     PLGGLTTIDVLTAIRNATGPRPALFVPEVSFELLVKRQVKR

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 – 736 Dynamin-1-like protein
Region 344 – 489 Middle domain
Mutagenesis 401 – 404 GPRP -> AAAA. Impairs formation of higher order oligomers, but not homodimerization.


Literature citations

A novel de novo dominant negative mutation in DNM1L impairs mitochondrial fission and presents as childhood epileptic encephalopathy.
Fahrner J.A.; Liu R.; Perry M.S.; Klein J.; Chan D.C.;
Am. J. Med. Genet. A 170:2002-2011(2016)
Cited for: VARIANT EMPF1 CYS-403; CHARACTERIZATION OF VARIANTS EMPF1 ASP-395 AND CYS-403; FUNCTION; SUBUNIT; SUBCELLULAR LOCATION;

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.