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UniProtKB/Swiss-Prot Q7Z6J9: Variant p.Ala307Ser

tRNA-splicing endonuclease subunit Sen54
Gene: TSEN54
Variant information

Variant position:  307
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 Serine (S) at position 307 (A307S, p.Ala307Ser).
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 small size and polar (S)
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:  Pontocerebellar hypoplasia 4 (PCH4) [MIM:225753]: A disorder characterized by an abnormally small cerebellum and brainstem, severe neonatal encephalopathy, microcephaly, myoclonus and muscular hypertonia. There is a severe inferior olivary and pontine neuronal loss and a diffuse white matter gliosis. {ECO:0000269|PubMed:18711368, ECO:0000269|PubMed:21824568}. 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:  Pontocerebellar hypoplasia 2A (PCH2A) [MIM:277470]: A disorder characterized by an abnormally small cerebellum and brainstem, and progressive microcephaly from birth combined with extrapyramidal dyskinesia. Severe chorea occurs and epilepsy is frequent. There are no signs of spinal cord anterior horn cells degeneration. {ECO:0000269|PubMed:18711368, ECO:0000269|PubMed:23307886}. 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 PCH2A and PCH4.
Any additional useful information about the variant.

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



Sequence information

Variant position:  307
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  526
The length of the canonical sequence.

Location on the sequence:   GVTGAGKRRWNFEQISFPNM  A SDSRHTLLRAPAPELLPANV
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                         GVTGAGKRRWNFEQISFPNMASDSRHTLLRAPAPELLPANV

Mouse                         GAKGTPKLRWNFEQISFPNMASDSRHTFLPAPAPELLPANV

Baker's yeast                 LFSGFFYSKWNFFFRKYT-----------TSPQLYQGLNRL

Fission yeast                 ILQTFNFRKLAFPFSKRRRQSILLHDTFYTYEEVYHDLQIV

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 – 526 tRNA-splicing endonuclease subunit Sen54
Modified residue 316 – 316 Omega-N-methylarginine
Alternative sequence 178 – 526 Missing. In isoform 2.


Literature citations

tRNA splicing endonuclease mutations cause pontocerebellar hypoplasia.
Budde B.S.; Namavar Y.; Barth P.G.; Poll-The B.T.; Nuernberg G.; Becker C.; van Ruissen F.; Weterman M.A.J.; Fluiter K.; te Beek E.T.; Aronica E.; van der Knaap M.S.; Hoehne W.; Toliat M.R.; Crow Y.J.; Steinling M.; Voit T.; Roelenso F.; Brussel W.; Brockmann K.; Kyllerman M.; Boltshauser E.; Hammersen G.; Willemsen M.; Basel-Vanagaite L.; Kraegeloh-Mann I.; de Vries L.S.; Sztriha L.; Muntoni F.; Ferrie C.D.; Battini R.; Hennekam R.C.M.; Grillo E.; Beemer F.A.; Stoets L.M.E.; Wollnik B.; Nuernberg P.; Baas F.;
Nat. Genet. 40:1113-1118(2008)
Cited for: VARIANT PCH2A SER-307; VARIANTS PCH4 PRO-93 AND SER-307;

Novel mutations in TSEN54 in pontocerebellar hypoplasia type 2.
Battini R.; D'Arrigo S.; Cassandrini D.; Guzzetta A.; Fiorillo C.; Pantaleoni C.; Romano A.; Alfei E.; Cioni G.; Santorelli F.M.;
J. Child Neurol. 29:520-525(2014)
Cited for: VARIANTS PCH2A ASP-119 AND SER-307;

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.