UniProtKB/Swiss-Prot Q99743: Variant p.Thr394Ala

Neuronal PAS domain-containing protein 2
Gene: NPAS2
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Variant information Variant position:

394 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 Threonine (T) to Alanine (A) at position 394 (T394A, p.Thr394Ala). 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 polar (T) to small size and hydrophobic (A) 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
Polymorphism:

Variants in NPAS2 show a susceptibility to seasonal affective disorder (SAD) [MIM:608516]. SAD is a depressive condition resulting from seasonal changes, and with diurnal preference. Additional information on the polymorphism described.
Variant description:

Probable risk factor for non-Hodgkin's lymphoma and breast cancer. Any additional useful information about the variant.
Other resources:

Links to websites of interest for the variant.

Variant rs2305160 [ dbSNP | Ensembl ]

Sequence information Variant position:

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

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

LHSSALKDKGSSLEPRQHFN T LDVGASGLNTSHSPSASSRS 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                         LHSSALKDKGSSLEPRQHFNTLDVGASGLNTSHSPSASSRS

Mouse                         MHPSAVKEKDSSLEPPQPFNALDMGASGLPSSPSPSASSRS

Chicken                       V-SSALKDSGSSLDPEQHFNALDIGASILSASRTPSVSSRS

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 – 824	Neuronal PAS domain-containing protein 2
Region	367 – 437	Disordered
Compositional bias	388 – 435	Polar residues

Literature citations
Molecular characterization of two mammalian bHLH-PAS domain proteins selectively expressed in the central nervous system.
Zhou Y.-D.; Barnard M.; Tian H.; Li X.; Ring H.Z.; Francke U.; Shelton J.; Richardson J.; Russell D.W.; McKnight S.L.;
Proc. Natl. Acad. Sci. U.S.A. 94:713-718(1997)
Cited for: NUCLEOTIDE SEQUENCE [MRNA]; VARIANTS ALA-394 AND LEU-471; The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).
The MGC Project Team;
Genome Res. 14:2121-2127(2004)
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]; VARIANT ALA-394; Characterization of a subset of the basic-helix-loop-helix-PAS superfamily that interacts with components of the dioxin signaling pathway.
Hogenesch J.B.; Chan W.K.; Jackiw V.H.; Brown R.C.; Gu Y.-Z.; Pray-Grant M.; Perdew G.H.; Bradfield C.A.;
J. Biol. Chem. 272:8581-8593(1997)
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1-626; VARIANT ALA-394; Ala394Thr polymorphism in the clock gene NPAS2: a circadian modifier for the risk of non-Hodgkin's lymphoma.
Zhu Y.; Leaderer D.; Guss C.; Brown H.N.; Zhang Y.; Boyle P.; Stevens R.G.; Hoffman A.; Qin Q.; Han X.; Zheng T.;
Int. J. Cancer 120:432-435(2007)
Cited for: VARIANT ALA-394; Non-synonymous polymorphisms in the circadian gene NPAS2 and breast cancer risk.
Zhu Y.; Stevens R.G.; Leaderer D.; Hoffman A.; Holford T.; Zhang Y.; Brown H.N.; Zheng T.;
Breast Cancer Res. Treat. 107:421-425(2008)
Cited for: VARIANT ALA-394;

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.