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UniProtKB/Swiss-Prot Q16637: Variant p.Ile116Phe

Survival motor neuron protein
Gene: SMN2
Variant information

Variant position:  116
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 Isoleucine (I) to Phenylalanine (F) at position 116 (I116F, p.Ile116Phe).
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 hydrophobic (I) to large size and aromatic (F)
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:  Spinal muscular atrophy 1 (SMA1) [MIM:253300]: A form of spinal muscular atrophy, a group of neuromuscular disorder characterized by degeneration of the anterior horn cells of the spinal cord, leading to symmetrical muscle weakness and atrophy. Autosomal recessive forms are classified according to the age of onset, the maximum muscular activity achieved, and survivorship. The severity of the disease is mainly determined by the copy number of SMN2, a copy gene which predominantly produces exon 7-skipped transcripts and only low amount of full-length transcripts that encode for a protein identical to SMN1. Only about 4% of SMA patients bear one SMN1 copy with an intragenic mutation. SMA1 is a severe form, with onset before 6 months of age. SMA1 patients never achieve the ability to sit. {ECO:0000269|PubMed:10732817, ECO:0000269|PubMed:14715275, ECO:0000269|PubMed:15249625, ECO:0000269|PubMed:15580564, ECO:0000269|PubMed:21088113, ECO:0000269|PubMed:21389246, ECO:0000269|PubMed:7813012, ECO:0000269|PubMed:9147655}. 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 SMA1; abolishes the interaction with ELAVL4.
Any additional useful information about the variant.

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



Sequence information

Variant position:  116
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  294
The length of the canonical sequence.

Location on the sequence:   DKCSAIWSEDGCIYPATIAS  I DFKRETCVVVYTGYGNREEQ
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                         DKCSAIWSEDGCIYPATIASIDFKRETCVVVYTGYGNREEQ

                              DKCSAVWSEDGCIYPATIASIDFKRETCVVVYTGYGNREEQ

Mouse                         DKCSAVWSEDGCIYPATITSIDFKRETCVVVYTGYGNREEQ

Rat                           DKCSAVWSEDGCVYPATITSVDLKRETCVVVYTGYGNKEEQ

Bovine                        DNCCAIWSEDGCIYPATIASIDFKRETCVVVYTGYGNREEQ

Cat                           DKCSAIWSEDGCVYPATIASIDFKRETCVVVYTGYGNREEQ

Drosophila                    DYARATYV-DGVDYEGAVVSINEEKGTCVLRYLGYENEQEV

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 – 294 Survival motor neuron protein
Domain 91 – 151 Tudor
Region 97 – 209 Required for interaction with RPP20/POP7
Mutagenesis 134 – 134 E -> K. Reduces SMN binding to RPP20/POP7. Abolishes the interaction with ELAVL4.
Beta strand 108 – 117


Literature citations

Detection of novel mutations in the SMN Tudor domain in type I SMA patients.
Cusco I.; Barcelo M.J.; del Rio E.; Baiget M.; Tizzano E.F.;
Neurology 63:146-149(2004)
Cited for: VARIANTS SMA1 PHE-116 AND GLU-136;

HuD interacts with survival motor neuron protein and can rescue spinal muscular atrophy-like neuronal defects.
Hubers L.; Valderrama-Carvajal H.; Laframboise J.; Timbers J.; Sanchez G.; Cote J.;
Hum. Mol. Genet. 20:553-579(2011)
Cited for: INTERACTION WITH ELAVL4; SUBCELLULAR LOCATION; CHARACTERIZATION OF VARIANTS SMA2 GLU-111; SMA1 PHE-116 AND SMA1 GLU-136; MUTAGENESIS OF GLU-134;

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.