UniProtKB/Swiss-Prot P20333: Variant p.Met196Arg

Tumor necrosis factor receptor superfamily member 1B
Gene: TNFRSF1B
Chromosomal location: 1p36.2-p36.3
Variant information

Variant position:  196
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Type of variant:  Polymorphism
The variants are classified into three categories: Disease, Polymorphism and Unclassified.
  • Disease: Variants have been found in patients and disease-association is reported in literature. However, this classification is not a definitive assessment of variant pathogenicity.
  • Polymorphism: No disease-association has been reported.
  • Unclassified: Variants have been found in patients but disease-association remains unclear.

Residue change:  From Methionine (M) to Arginine (R) at position 196 (M196R, p.Met196Arg).
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 (M) to large size and basic (R)
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:  Frequent polymorphism; seems to be associated with hyperandrogenism, polycystic ovary syndrome (PCOS) and systemic lupus erythematosus.
Any additional useful information about the variant.

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



Sequence information

Variant position:  196
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  461
The length of the canonical sequence.

Location on the sequence:   TDICRPHQICNVVAIPGNAS  M DAVCTSTSPTRSMAPGAVHL
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                         TDICRPHQICNVVAIPGNASMDAVCTSTSPTRSMAPGAVHL

Mouse                         TDVCRPHRICSILAIPGNASTDAVCAPESPTLSAIPRTLYV

Rat                           TDVCRPHRICSILAIPGNASTDAVCASESPTPSAVPRTIYV

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 23 – 461 Tumor necrosis factor receptor superfamily member 1b, membrane form
Topological domain 23 – 257 Extracellular
Repeat 163 – 201 TNFR-Cys 4
Glycosylation 193 – 193 N-linked (GlcNAc...)
Beta strand 194 – 196


Literature citations

A second tumor necrosis factor receptor gene product can shed a naturally occurring tumor necrosis factor inhibitor.
Kohno T.; Brewer M.T.; Baker S.L.; Schwartz P.E.; King M.W.; Hale K.K.; Squires C.H.; Thompson R.C.; Vannice J.L.;
Proc. Natl. Acad. Sci. U.S.A. 87:8331-8335(1990)
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1); VARIANT ARG-196;

Submission
NIEHS SNPs program;
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]; VARIANTS MET-187; ARG-196; LYS-232; THR-236; PRO-264 AND ARG-295;

Submission
SeattleSNPs variation discovery resource;
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]; VARIANTS ARG-196; LYS-232; PRO-269 AND ARG-301;

Complementary DNA cloning of a receptor for tumor necrosis factor and demonstration of a shed form of the receptor.
Heller R.A.; Song K.; Onasch M.A.; Fischer W.H.; Chang D.; Ringold G.M.;
Proc. Natl. Acad. Sci. U.S.A. 87:6151-6155(1990)
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 116-461 (ISOFORM 1); PARTIAL PROTEIN SEQUENCE; VARIANT ARG-196;

New single nucleotide polymorphisms in the coding region of human TNFR2: association with systemic lupus erythematosus.
Tsuchiya N.; Komata T.; Matsushita M.; Ohashi J.; Tokunaga K.;
Genes Immun. 1:501-503(2000)
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 154-183; VARIANTS ARG-196 AND LYS-232;

Association of tumor necrosis factor receptor type II polymorphism 196R with systemic lupus erythematosus in the Japanese: molecular and functional analysis.
Morita C.; Horiuchi T.; Tsukamoto H.; Hatta N.; Kikuchi Y.; Arinobu Y.; Otsuka T.; Sawabe T.; Harashima S.; Nagasawa K.; Niho Y.;
Arthritis Rheum. 44:2819-2827(2001)
Cited for: VARIANTS ARG-196 AND LYS-232;

Comment: the methionine 196 arginine polymorphism in exon 6 of the TNF receptor 2 gene (TNFRSF1B) is associated with the polycystic ovary syndrome and hyperandrogenism.
Peral B.; San Millan J.L.; Castello R.; Moghetti P.; Escobar-Morreale H.F.;
J. Clin. Endocrinol. Metab. 87:3977-3983(2002)
Cited for: VARIANT ARG-196;

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.