UniProtKB/Swiss-Prot P05543: Variant p.Ile116Asn

Thyroxine-binding globulin
Gene: SERPINA7
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Variant information Variant position:

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

LB/B 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 Asparagine (N) at position 116 (I116N, p.Ile116Asn). 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 (N) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score:

-3 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
Polymorphism:

Genetic variants in SERPINA7 influence the serum levels of thyroxine-binding globulin and define the thyroxine-binding globulin quantitative trait locus (TBGQTL) [MIM:300932]. Individuals with low or high serum levels of thyroxine-binding globulin show, respectively, reduced or elevated protein-bound iodine but are euthyroid and do not manifest major metabolic alterations (PubMed:1294376, PubMed:1515456, PubMed:1901689, PubMed:1906047, PubMed:2155256, PubMed:2501669). Two qualitative TBG variants occur in particular populations. TBG-A is found in 40% of Australian aborigines, it has reduced affinity for thyroxine and triiodothyroxine and increased susceptibility to inactivation by heat or acid (PubMed:2495303). TBG-S ('s' for slow shift on isoelectic focusing) is found in blacks, Eskimos, Melanesians, Polynesians and Indonesians, but not in Caucasians; TBG-S is slightly more thermolabile (PubMed:2115061). Additional information on the polymorphism described.
Variant description:

Gary; severe thyroxine-binding globulin deficiency. Any additional useful information about the variant.
Other resources:

Links to websites of interest for the variant.

Variant rs28933689 [ dbSNP | Ensembl ]

Sequence information Variant position:

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

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

LGFNLTDTPMVEIQHGFQHL I CSLNFPKKELELQIGNALFI 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                         LGFNLTDTPMVEIQHGFQHLICSLNFPKKELELQIGNALFI

Chimpanzee                    LGFNLTDTPMVEIQHGFQHLICSLNFPKKELELQIGNALFI

Mouse                         LGFNLTDTPVTELQQGFQHLICSLNFPKNELELQMGNAVFI

Rat                           LGFNLTDTPVKELQQGFQHLICSLNFPNNELELQMGNAVFI

Pig                           LGYNLTEMPMAEIQQGFQHLICSLNFPKKELELQMGNALFI

Bovine                        LGFNLTDTPVAEIQQGFQHLICSLNFPKKELELQMGNALFI

Sheep                         LGFNLTDTPMAEIQQGFQHLICSLNFPKKELELQMGNALFI

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	21 – 415	Thyroxine-binding globulin
Glycosylation	99 – 99	N-linked (GlcNAc...) asparagine
Glycosylation	116 – 116	N-linked (GlcNAc...) asparagine; in variant Gary
Helix	105 – 120

Literature citations
A mutation causing reduced biological activity and stability of thyroxine-binding globulin probably as a result of abnormal glycosylation of the molecule.
Mori Y.; Seino S.; Takeda K.; Flink I.L.; Murata Y.; Bell G.I.; Refetoff S.;
Mol. Endocrinol. 3:575-579(1989)
Cited for: POLYMORPHISM; VARIANT ASN-116;

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.