UniProtKB/Swiss-Prot P13569: Variant p.Ile148Thr

Cystic fibrosis transmembrane conductance regulator
Gene: CFTR
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Variant information Variant position:

148 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant:

US The variants are classified into three categories: LP/P, LB/B and US.

LP/P: likely pathogenic or pathogenic.
LB/B: likely benign or benign.
US: uncertain significance

Residue change:

From Isoleucine (I) to Threonine (T) at position 148 (I148T, p.Ile148Thr). 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 medium size and polar (T) 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
Variant description:

In CF; uncertain significance; loss of bicarbonate transport; decreased inhibition of epithelial sodium channel (ENaC), when tested in a heterologous system; no effect on protein maturation, subcellular location at the plasma membrane, nor on chloride channel activity. Any additional useful information about the variant.
Other resources:

Links to websites of interest for the variant.

Variant rs35516286 [ dbSNP | Ensembl ]

Sequence information Variant position:

148 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length:

1480 The length of the canonical sequence.
Location on the sequence:

CLLFIVRTLLLHPAIFGLHH I GMQMRIAMFSLIYKKTLKLS 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                         CLLFIVRTLLLHPAIFGLHHIGMQMRIAMFSLIYKKTLKLS

Gorilla                       CLLFIVRTLLLHPAIFGLHHIGMQMRIAMFSLIYKKTLKLS

                              CLLFIMRPLLLHPAIFGLHHIGMQIRIAMFSLIYKKTLKLS

Rhesus macaque                CLLFIVRTLLLHPAIFGLHHIGMQMRIAMFSLIYKKTLKLS

Chimpanzee                    CLLFIVRTLLLHPAIFGLHHIGMQMRIAMFSLIYKKTLKLS

Mouse                         CLLFIVRTLLLHPAIFGLHRIGMQMRTAMFSLIYKKTLKLS

Rat                           CLLFIVRTLLLHPAIFGLHHIGMQMRIAMFSLIYKKTLKLS

Pig                           CLLFIVRTLLLHPAIFGPHHIGMQMRIAMFSLIYKKTLKLS

Bovine                        CLLFIVRTLLLHPAIFGLHHIGMQMRIAMFSLIYKKTLKLS

Rabbit                        CLLFVVRTLLLHPAIFGLHHIGMQMRIAMFSLIYKKTLKLS

Sheep                         CLLFIVRTLLLHPAIFGLHHIGMQMRIAMFSLIYKKTLKLS

Horse                         CLLFIVRTLLLHPAIFGLHHIGMQMRIAMFSLIYKKTLKLS

Xenopus laevis                CLLFVVRMLLLHPAIFGLHHIGMQMRIAMFSLIYKKTLKLS

Zebrafish                     GLLFTARFLLLQPAMFGLHHLGMQIRIALFSIIYKKTLKLS

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.

Type	Positions	Description
Chain	1 – 1480	Cystic fibrosis transmembrane conductance regulator
Topological domain	147 – 195	Cytoplasmic
Domain	81 – 365	ABC transmembrane type-1 1
Helix	120 – 164

Literature citations
Aberrant CFTR-dependent HCO3- transport in mutations associated with cystic fibrosis.
Choi J.Y.; Muallem D.; Kiselyov K.; Lee M.G.; Thomas P.J.; Muallem S.;
Nature 410:94-97(2001)
Cited for: CHARACTERIZATION OF VARIANTS CF HIS-117; THR-148; ARG-178; LYS-193; ASP-551; SER-551; GLN-620; VAL-648; GLY-800; TYR-949; THR-1067; GLN-1070; GLU-1244; PRO-1255 AND ASP-1349; The I148T CFTR allele occurs on multiple haplotypes: a complex allele is associated with cystic fibrosis.
Rohlfs E.M.; Zhou Z.; Sugarman E.A.; Heim R.A.; Pace R.G.; Knowles M.R.; Silverman L.M.; Allitto B.A.;
Genet. Med. 4:319-323(2002)
Cited for: VARIANTS CF THR-148; PHE-508 DEL; 890-GLN--LEU-1480 DEL; 1023-ILE-VAL-1024 DEL AND LYS-1303; Abnormal regulatory interactions of I148T-CFTR and the epithelial Na+ channel in Xenopus oocytes.
Suaud L.; Yan W.; Rubenstein R.C.;
Am. J. Physiol. 292:C603-C611(2007)
Cited for: CHARACTERIZATION OF VARIANT CF THR-148;

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.