Variant information:

(Click the titles to show more 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.

• SeattleSNPs
• NIEHS-SNPs
• Enbrel; Clinical information on Enbrel
• Variant rs1061622 [ dbSNP | Ensembl ]

Sequence information:

(Click the titles to show more 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.

Type	Positions	Description
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;