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UniProtKB/Swiss-Prot O43520: Variant p.Ile661Thr

Phospholipid-transporting ATPase IC
Gene: ATP8B1
Variant information

Variant position:  661
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 Isoleucine (I) to Threonine (T) at position 661 (I661T, p.Ile661Thr).
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 (I) to medium size and polar (T)
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

Involvement in disease:  Cholestasis, benign recurrent intrahepatic, 1 (BRIC1) [MIM:243300]: A disorder characterized by intermittent episodes of cholestasis without progression to liver failure. There is initial elevation of serum bile acids, followed by cholestatic jaundice which generally spontaneously resolves after periods of weeks to months. The cholestatic attacks vary in severity and duration. Patients are asymptomatic between episodes, both clinically and biochemically. {ECO:0000269|PubMed:15239083, ECO:0000269|PubMed:19731236, ECO:0000269|PubMed:9500542, ECO:0000269|PubMed:9918928}. 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.

Involvement in disease:  Cholestasis, progressive familial intrahepatic, 1 (PFIC1) [MIM:211600]: A disorder characterized by early onset of cholestasis that progresses to hepatic fibrosis, cirrhosis, and end-stage liver disease before adulthood. {ECO:0000269|PubMed:11093741, ECO:0000269|PubMed:15239083, ECO:0000269|PubMed:19731236, ECO:0000269|PubMed:20038848, ECO:0000269|PubMed:23197899, ECO:0000269|PubMed:9500542}. 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 BRIC1 and PFIC1; common mutation; reduces interaction with TMEM30A.
Any additional useful information about the variant.

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



Sequence information

Variant position:  661
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  1251
The length of the canonical sequence.

Location on the sequence:   DALDIFANETLRTLCLCYKE  I EEKEFTEWNKKFMAASVAST
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                         DALDIFANETLRTLCLCYKEIEEKEFTEWNKKFMAASVAST

Mouse                         DALDIFASETLRTLCLCYKEIEEKEFTEWNNKFMAASVASS

Xenopus tropicalis            KALDIFANASLRTLCLCYKDINKGDFENWSKKYKQASVATS

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 – 1251 Phospholipid-transporting ATPase IC
Topological domain 412 – 949 Cytoplasmic


Literature citations

A gene encoding a P-type ATPase mutated in two forms of hereditary cholestasis.
Bull L.N.; van Eijk M.J.T.; Pawlikowska L.; DeYoung J.A.; Juijn J.A.; Liao M.; Klomp L.W.J.; Lomri N.; Berger R.; Scharschmidt B.F.; Knisely A.S.; Houwen R.H.J.; Freimer N.B.;
Nat. Genet. 18:219-223(1998)
Cited for: NUCLEOTIDE SEQUENCE [MRNA]; VARIANTS PFIC1 SER-288; VAL-308; 645-ILE--ILE-699 DEL AND ARG-892; VARIANTS BRIC1 THR-661 AND 795-GLY--ARG-797 DEL; VARIANT THR-1152;

Recurrent familial intrahepatic cholestasis in the Faeroe Islands. Phenotypic heterogeneity but genetic homogeneity.
Tygstrup N.; Steig B.A.; Juijn J.A.; Bull L.N.; Houwen R.H.J.;
Hepatology 29:506-508(1999)
Cited for: VARIANT BRIC1 THR-661;

Characterization of mutations in ATP8B1 associated with hereditary cholestasis.
Klomp L.W.J.; Vargas J.C.; van Mil S.W.C.; Pawlikowska L.; Strautnieks S.S.; van Eijk M.J.T.; Juijn J.A.; Pabon-Pena C.; Smith L.B.; DeYoung J.A.; Byrne J.A.; Gombert J.; van der Brugge G.; Berger R.; Jankowska I.; Pawlowska J.; Villa E.; Knisely A.S.; Thompson R.J.; Freimer N.B.; Houwen R.H.J.; Bull L.N.;
Hepatology 40:27-38(2004)
Cited for: VARIANTS PFIC1 PRO-127; TYR-403; PRO-412; MET-456; HIS-500; PHE-529 DEL; LEU-535; ASN-554; THR-661; GLY-688; ARG-733; SER-853; ARG-892 AND ARG-1040; VARIANTS BRIC1 ASN-70; ASP-308; PHE-344; TYR-453; GLY-454; TRP-600; GLN-600; TRP-628; THR-661; THR-694 AND ARG-892; VARIANT ALA-429;

Differential effects of progressive familial intrahepatic cholestasis type 1 and benign recurrent intrahepatic cholestasis type 1 mutations on canalicular localization of ATP8B1.
Folmer D.E.; van der Mark V.A.; Ho-Mok K.S.; Oude Elferink R.P.; Paulusma C.C.;
Hepatology 50:1597-1605(2009)
Cited for: CHARACTERIZATION OF VARIANTS PFIC1 VAL-308; ASN-554; THR-661 AND ARG-1040; CHARACTERIZATION OF VARIANTS BRIC1 ASN-70 AND THR-661; CHARACTERIZATION OF VARIANT ICP1 CYS-867; MUTAGENESIS OF ASP-454;

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.