UniProtKB/Swiss-Prot Q14973: Variant p.Ser267Phe

Hepatic sodium/bile acid cotransporter
Gene: SLC10A1
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Variant information Variant position:

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

LP/P [Disclaimer] 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 Serine (S) to Phenylalanine (F) at position 267 (S267F, p.Ser267Phe). 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 small size and polar (S) to large size and aromatic (F) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score:

-2 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 FHCA2; protective factor against hepatitis B virus infection and chronic hepatitis; unable to transport taurocholate and cholate; does not affect uptake of estrone sulfate; does not affect localization to the cell membrane; disrupts interaction with HBV myristoylated pre-S1 peptide. Any additional useful information about the variant.
Other resources:

Links to websites of interest for the variant.

Variant rs2296651 [ dbSNP | Ensembl ]

Sequence information Variant position:

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

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

NGRCRRTVSMETGCQNVQLC S TILNVAFPPEVIGPLFFFPL 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                         NGRCRRTVSMETGCQNVQLCSTILNVAFPPEVIGPLFFFPL

Mouse                         NPSCRRTISMETGFQNVQLCSTILNVTFPPEVIGPLFFFPL

Rat                           NPSCRRTISMETGFQNIQLCSTILNVTFPPEVIGPLFFFPL

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 – 349	Hepatic sodium/bile acid cotransporter
Transmembrane	248 – 273	Discontinuously helical; Name=8
Mutagenesis	261 – 261	Q -> A. Abolishes interaction with HBV myristoylated pre-S1 peptide.
Mutagenesis	263 – 263	V -> W. Disrupts interaction with HBV myristoylated pre-S1 peptide.
Mutagenesis	264 – 264	Q -> AW. Disrupts interaction with HBV myristoylated pre-S1 peptide, reduces bile acid transport and reduces HBV infection.
Mutagenesis	268 – 268	T -> W. Disrupts interaction with HBV myristoylated pre-S1 peptide, reduces bile acid transport and reduces HBV infection.
Mutagenesis	272 – 272	V -> W. Disrupts interaction with HBV myristoylated pre-S1 peptide, reduces bile acid transport and reduces HBV infection.
Helix	263 – 273

Literature citations
Ethnicity-dependent polymorphism in Na+-taurocholate cotransporting polypeptide (SLC10A1) reveals a domain critical for bile acid substrate recognition.
Ho R.H.; Leake B.F.; Roberts R.L.; Lee W.; Kim R.B.;
J. Biol. Chem. 279:7213-7222(2004)
Cited for: FUNCTION; SUBCELLULAR LOCATION; VARIANTS THR-223; THR-279 AND GLU-314; VARIANT FHCA2 PHE-267; CHARACTERIZATION OF VARIANT FHCA2 PHE-267; CHARACTERIZATION OF VARIANTS THR-279 AND GLU-314; TRANSPORT ACTIVITY; BIOPHYSICOCHEMICAL PROPERTIES; Structure of the bile acid transporter and HBV receptor NTCP.
Asami J.; Kimura K.T.; Fujita-Fujiharu Y.; Ishida H.; Zhang Z.; Nomura Y.; Liu K.; Uemura T.; Sato Y.; Ono M.; Yamamoto M.; Noda T.; Shigematsu H.; Drew D.; Iwata S.; Shimizu T.; Nomura N.; Ohto U.;
Nature 606:1021-1026(2022)
Cited for: STRUCTURE BY ELECTRON MICROSCOPY (3.32 ANGSTROMS) OF 1-319; FUNCTION (MICROBIAL INFECTION); CATALYTIC ACTIVITY; INTERACTION WITH HBV PRE-S1 PEPTIDE; SUBCELLULAR LOCATION; TOPOLOGY; CHARACTERIZATION OF VARIANT PHE-267; MUTAGENESIS OF LYS-20; LEU-27; VAL-202; GLN-261 AND VAL-263; The p.Ser267Phe variant in SLC10A1 is associated with resistance to chronic hepatitis B.
Peng L.; Zhao Q.; Li Q.; Li M.; Li C.; Xu T.; Jing X.; Zhu X.; Wang Y.; Li F.; Liu R.; Zhong C.; Pan Q.; Zeng B.; Liao Q.; Hu B.; Hu Z.X.; Huang Y.S.; Sham P.; Liu J.; Xu S.; Wang J.; Gao Z.L.; Wang Y.;
Hepatology 61:1251-1260(2015)
Cited for: ASSOCIATION OF VARIANT PHE-267 WITH RESISTANCE TO CHRONIC HEPATITIS B; Clinical and molecular study of a pediatric patient with sodium taurocholate cotransporting polypeptide deficiency.
Deng M.; Mao M.; Guo L.; Chen F.P.; Wen W.R.; Song Y.Z.;
Exp. Ther. Med. 12:3294-3300(2016)
Cited for: VARIANT FHCA2 PHE-267; INVOLVEMENT IN FHCA2; NTCP deficiency and persistently raised bile salts: an adult case.
Van Herpe F.; Waterham H.R.; Adams C.J.; Mannens M.; Bikker H.; Vaz F.M.; Cassiman D.;
J. Inherit. Metab. Dis. 40:313-315(2017)
Cited for: VARIANT FHCA2 PHE-267; Sodium taurocholate cotransporting polypeptide (NTCP) deficiency: Identification of a novel SLC10A1 mutation in two unrelated infants presenting with neonatal indirect hyperbilirubinemia and remarkable hypercholanemia.
Qiu J.W.; Deng M.; Cheng Y.; Atif R.M.; Lin W.X.; Guo L.; Li H.; Song Y.Z.;
Oncotarget 8:106598-106607(2017)
Cited for: VARIANTS FHCA2 THR-88 AND PHE-267; Homozygous p.Ser267Phe in SLC10A1 is associated with a new type of hypercholanemia and implications for personalized medicine.
Liu R.; Chen C.; Xia X.; Liao Q.; Wang Q.; Newcombe P.J.; Xu S.; Chen M.; Ding Y.; Li X.; Liao Z.; Li F.; Du M.; Huang H.; Dong R.; Deng W.; Wang Y.; Zeng B.; Pan Q.; Jiang D.; Zeng H.; Sham P.; Cao Y.; Maxwell P.H.; Gao Z.L.; Peng L.; Wang Y.;
Sci. Rep. 7:9214-9214(2017)
Cited for: VARIANT PHE-267; INVOLVEMENT IN FHCA2; Clinical and molecular characterization of four patients with NTCP deficiency from two unrelated families harboring the novel SLC10A1 variant c.595A>C (p.Ser199Arg).
Li H.; Deng M.; Guo L.; Qiu J.W.; Lin G.Z.; Long X.L.; Xiao X.M.; Song Y.Z.;
Mol. Med. Report. 20:4915-4924(2019)
Cited for: VARIANTS FHCA2 ARG-199 AND PHE-267; Clinical characterization of NTCP deficiency in paediatric patients: A case-control study based on SLC10A1 genotyping analysis.
Deng L.J.; Ouyang W.X.; Liu R.; Deng M.; Qiu J.W.; Yaqub M.R.; Raza M.A.; Lin W.X.; Guo L.; Li H.; Chen F.P.; Ouyang Y.; Huang Y.G.; Huang Y.J.; Long X.L.; Huang X.L.; Li S.J.; Song Y.Z.;
Liver Int. 41:2720-2728(2021)
Cited for: VARIANTS FHCA2 THR-88; ARG-199 AND PHE-267;

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.