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UniProtKB/Swiss-Prot Q0IIM8: Variant p.Phe291Ser

TBC1 domain family member 8B
Gene: TBC1D8B
Variant information

Variant position:  291
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Type of variant:  Disease [Disclaimer]
The variants are classified into three categories: Disease, Polymorphism and Unclassified.
  • Disease: Variants implicated in disease according to literature reports.
  • Polymorphism: Variants not reported to be implicated in disease.
  • Unclassified: Variants with uncertain implication in disease according to literature reports. Evidence against or in favor of a pathogenic role is limited and/or conflicting.

Residue change:  From Phenylalanine (F) to Serine (S) at position 291 (F291S, p.Phe291Ser).
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 large size and aromatic (F) to small size and polar (S)
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

Involvement in disease:  Nephrotic syndrome 20 (NPHS20) [MIM:301028]: A form of nephrotic syndrome, a renal disease clinically characterized by severe proteinuria, resulting in complications such as hypoalbuminemia, hyperlipidemia and edema. Kidney biopsies show non-specific histologic changes such as focal segmental glomerulosclerosis and diffuse mesangial proliferation. Some affected individuals have an inherited steroid-resistant form that progresses to end-stage renal failure. NPHS20 is an X-linked, steroid-resistant form with onset at birth or in the first years of life in affected males. Death in childhood may occur in absence of renal transplantation. Carrier females may be unaffected or have a mild disease with proteinuria. {ECO:0000269|PubMed:30661770}. Note=The disease is caused by mutations affecting the gene represented in this entry.
The name and a short description of the disease associated with the variant. For more information about the disease, the user can refer to OMIM, following the link provided after the disease acronym.

Variant description:  In NPHS20; exhibits intracellular vesicular localization; rescues only partially glomerular filtration defects in tbc1d8b knockout fish; reduced podocyte migration; defective vesicular trafficking in podocytes.
Any additional useful information about the variant.



Sequence information

Variant position:  291
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  1120
The length of the canonical sequence.

Location on the sequence:   LQITKRGLENRAHSEQFNAF  F RLPKGESLKEVHECFLWVPF
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                         LQITKRGLENRAHSEQFNAFFRLPKGESLKEVHECFLWVPF

Mouse                         LQITKRGLEYRAHSEQFKAFFRLPKEETLKEVHECFLWVPF

Zebrafish                     LHITQRALEIHARNQSFRSFFRLPQEENLCEVYESFLWVPF

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 1 – 1120 TBC1 domain family member 8B
Domain 285 – 353 GRAM 2


Literature citations

TBC1D8B Loss-of-Function Mutations Lead to X-Linked Nephrotic Syndrome via Defective Trafficking Pathways.
Dorval G.; Kuzmuk V.; Gribouval O.; Welsh G.I.; Bierzynska A.; Schmitt A.; Miserey-Lenkei S.; Koziell A.; Haq S.; Benmerah A.; Mollet G.; Boyer O.; Saleem M.A.; Antignac C.;
Am. J. Hum. Genet. 104:348-355(2019)
Cited for: VARIANTS NPHS20 HIS-246 AND SER-291; CHARACTERIZATION OF VARIANTS NPHS20 HIS-246 AND SER-291; FUNCTION; SUBCELLULAR LOCATION; TISSUE SPECIFICITY; DEVELOPMENTAL STAGE; ALTERNATIVE SPLICING; INTERACTION WITH RAB11B;

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.