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UniProtKB/Swiss-Prot Q9NSK7: Variant p.Ala63Pro

Protein C19orf12
Gene: C19orf12
Variant information

Variant position:  63
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 Alanine (A) to Proline (P) at position 63 (A63P, p.Ala63Pro).
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 small size and hydrophobic (A) to medium size and hydrophobic (P)
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

Involvement in disease:  Neurodegeneration with brain iron accumulation 4 (NBIA4) [MIM:614298]: A neurodegenerative disorder associated with iron accumulation in the brain, primarily in the basal ganglia. NBIA4 results in speech difficulty, extrapyramidal signs, oromandibular and generalized dystonia, and parkinsonism. Most patients have progressive involvement of the corticospinal tract, with spasticity, hyperreflexia, and extensor plantar responses. {ECO:0000269|PubMed:21981780, ECO:0000269|PubMed:22508347, ECO:0000269|PubMed:22584950, ECO:0000269|PubMed:22704260, ECO:0000269|PubMed:23269600, ECO:0000269|PubMed:23278385, ECO:0000269|PubMed:23521069, ECO:0000269|PubMed:23857908, ECO:0000269|PubMed:25592411, ECO:0000269|PubMed:26136767, ECO:0000269|PubMed:26187298}. 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.

Involvement in disease:  Spastic paraplegia 43, autosomal recessive (SPG43) [MIM:615043]: A form of spastic paraplegia, a neurodegenerative disorder characterized by a slow, gradual, progressive weakness and spasticity of the lower limbs. Rate of progression and the severity of symptoms are quite variable. Initial symptoms may include difficulty with balance, weakness and stiffness in the legs, muscle spasms, and dragging the toes when walking. In some forms of the disorder, bladder symptoms (such as incontinence) may appear, or the weakness and stiffness may spread to other parts of the body. SP43 is characterized by childhood onset of progressive spasticity affecting the lower and upper limbs. {ECO:0000269|PubMed:23857908}. 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 NBIA4 and SPG43; impairs subcellular localization to the endoplasmic reticulum or mitochondrion.
Any additional useful information about the variant.

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



Sequence information

Variant position:  63
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  152
The length of the canonical sequence.

Location on the sequence:   ALVTGAMAFVGGLVGGPPGL  A VGGAVGGLLGAWMTSGQFKP
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                         ALVTGAMAFVGGLVGGPPGLAVGGAVGGLLGAWMTSGQFKP

Mouse                         AMVAGAMAFVGGLVGGPPGIAVGGTVGGLLGAWMTSGQFKP

Bovine                        ALVTGAVAFVGGLVGGPPGLAVGGAVGGLLGAWMTSGQFKP

Xenopus tropicalis            ALVAAAGAFLGGLVGGPPGIAVGGAVGGAMGAWMTSGQFKP

Zebrafish                     AAAAGGLAFAGGLIGGPLGIAVGGAVGGLLGCWMKSGQFKP

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 – 152 Protein C19orf12
Transmembrane 51 – 71 Helical
Alternative sequence 1 – 75 Missing. In isoform 2.


Literature citations

Hereditary spastic paraplegia type 43 (SPG43) is caused by mutation in C19orf12.
Landoure G.; Zhu P.P.; Lourenco C.M.; Johnson J.O.; Toro C.; Bricceno K.V.; Rinaldi C.; Meilleur K.G.; Sangare M.; Diallo O.; Pierson T.M.; Ishiura H.; Tsuji S.; Hein N.; Fink J.K.; Stoll M.; Nicholson G.; Gonzalez M.A.; Speziani F.; Durr A.; Stevanin G.; Biesecker L.G.; Accardi J.; Landis D.M.; Gahl W.A.; Traynor B.J.; Marques W. Jr.; Zuchner S.; Blackstone C.; Fischbeck K.H.; Burnett B.G.;
Hum. Mutat. 34:1357-1360(2013)
Cited for: VARIANT SPG43 PRO-63; VARIANTS NBIA4 PRO-63 AND GLY-66 DEL; SUBCELLULAR LOCATION; CHARACTERIZATION OF VARIANTS SPG43 PRO-63; CHARACTERIZATION OF VARIANTS NBIA4 PRO-63; GLY-66 DEL AND ARG-69;

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.