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UniProtKB/Swiss-Prot O14746: Variant p.Ala716Thr

Telomerase reverse transcriptase
Gene: TERT
Chromosomal location: 5p15.33
Variant information

Variant position:  716
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 Threonine (T) at position 716 (A716T, p.Ala716Thr).
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 polar (T)
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:  Pulmonary fibrosis, and/or bone marrow failure, telomere-related, 1 (PFBMFT1) [MIM:614742]: A disease associated with shortened telomeres. Pulmonary fibrosis is the most common manifestation. Other manifestations include aplastic anemia due to bone marrow failure, hepatic fibrosis, and increased cancer risk, particularly myelodysplastic syndrome and acute myeloid leukemia. Phenotype, age at onset, and severity are determined by telomere length. {ECO:0000269|PubMed:15814878, ECO:0000269|PubMed:17460043, ECO:0000269|PubMed:21436073, ECO:0000269|PubMed:21483807, ECO:0000269|PubMed:22512499}. 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 PFBMFT1; the mutant protein is demonstrated to cause severely compromised telomerase activity.
Any additional useful information about the variant.

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



Sequence information

Variant position:  716
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  1132
The length of the canonical sequence.

Location on the sequence:   RVRAQDPPPELYFVKVDVTG  A YDTIPQDRLTEVIASIIKPQ
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                         RVRAQDPPPELYFVKVDVTGAYDTIPQDRLTEVIASIIKPQ

                              RIRAQNPAPQLYFVKVDVTGAYDALPQDRLVEVIANVIRPQ

Mouse                         RVRALDQTPRMYFVKADVTGAYDAIPQGKLVEVVANMIRHS

Rat                           RVRALDQTPRMYFVKADVTGAYDAIPQDKLVEIVANIIRRS

Bovine                        PLRARGPAPPLYFVKVDVVGAYDALPQDKLAEVIANVLQPQ

Baker's yeast                 K-KFNNVLPELYFMKFDVKSCYDSIPRMECMRILKDALKNE

Fission yeast                 KHRMFGR--KKYFVRIDIKSCYDRIKQDLMFRIVKKKLKDP

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 – 1132 Telomerase reverse transcriptase
Domain 605 – 935 Reverse transcriptase
Metal binding 712 – 712 Magnesium; catalytic
Modified residue 707 – 707 Phosphotyrosine; by SRC-type Tyr-kinases
Alternative sequence 711 – 722 Missing. In isoform 4.
Mutagenesis 707 – 707 Y -> F. Abolishes oxidative stress-induced phosphorylation and RAN binding. Impaired nuclear export and enhanced antiapoptotic activity against ROS-dependent apoptosis induction. Impaired interaction with PTPN11. No dephosphorylation by PTPN11.
Mutagenesis 712 – 712 D -> A. Loss of telomerase activity. In the absence of TR, no loss of binding to telomeric primers.


Literature citations

Syndrome complex of bone marrow failure and pulmonary fibrosis predicts germline defects in telomerase.
Parry E.M.; Alder J.K.; Qi X.; Chen J.J.; Armanios M.;
Blood 117:5607-5611(2011)
Cited for: VARIANTS PFBMFT1 MET-170; THR-716; PHE-841; ARG-902 AND PHE-1025; CHARACTERIZATION OF VARIANTS PFBMFT1 MET-170; THR-716; PHE-841 AND PHE-1025;

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.