UniProtKB/Swiss-Prot P35670: Variant p.Ile1148Thr

Copper-transporting ATPase 2
Gene: ATP7B
Feedback?

Variant information Variant position:

1148 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 Isoleucine (I) to Threonine (T) at position 1148 (I1148T, p.Ile1148Thr). 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
Variant description:

In WD; yeast complementation assays show that the variant mildly rescue iron-uptake deficiency of yeast mutant ccc2. Any additional useful information about the variant.
Other resources:

Links to websites of interest for the variant.

Variant rs60431989 [ dbSNP | Ensembl ]

Sequence information Variant position:

1148 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length:

1465 The length of the canonical sequence.
Location on the sequence:

NEAGSLPAEKDAVPQTFSVL I GNREWLRRNGLTISSDVSDA 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                         NEAGSLPAEKDAVPQTFSVLIGNREWLRRNGLTISSDVSDA

Mouse                         VGVGNPPTGEGAGPQTFSVLIGNREWMRRNGLTISSDISDA

Rat                           IGVGNPPIGEGTGPQTFSVLIGNREWMRRNGLTISSDISDA

Sheep                         NRVGSEPSETDAATQTFSVLIGNREWMRRNGLTVTSDVRDA

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 – 1465	Copper-transporting ATPase 2
Topological domain	995 – 1322	Cytoplasmic
Alternative sequence	234 – 1465	RPLSSANQNFNNSETLGHQGSHVVTLQLRIDGMHCKSCVLNIEENIGQLLGVQSIQVSLENKTAQVKYDPSCTSPVALQRAIEALPPGNFKVSLPDGAEGSGTDHRSSSSHSPGSPPRNQVQGTCSTTLIAIAGMTCASCVHSIEGMISQLEGVQQISVSLAEGTATVLYNPSVISPEELRAAIEDMGFEASVVSESCSTNPLGNHSAGNSMVQTTDGTPTSVQEVAPHTGRLPANHAPDILAKSPQSTRAVAPQKCFLQIKGMTCASCVSNIERNLQKEAGVLSVLVALMAGKAEIKYDPEVIQPLEIAQFIQDLGFEAAVMEDYAGSDGNIELTITGMTCASCVHNIESKLTRTNGITYASVALATSKALVKFDPEIIGPRDIIKIIEEIGFHASLAQRNPNAHHLDHKMEIKQWKKSFLCSLVFGIPVMALMIYMLIPSNEPHQSMVLDHNIIPGLSILNLIFFILCTFVQLLGGWYFYVQAYKSLRHRSANMDVLIVLATSIAYVYSLVILVVAVAEKAERSPVTFFDTPPMLFVFIALGRWLEHLAKSKTSEALAKLMSLQATEATVVTLGEDNLIIREEQVPMELVQRGDIVKVVPGGKFPVDGKVLEGNTMADESLITGEAMPVTKKPGSTVIAGSINAHGSVLIKATHVGNDTTLAQIVKLVEEAQMSKAPIQQLADRFSGYFVPFIIIMSTLTLVVWIVIGFIDFGVVQRYFPNPNKHISQTEVIIRFAFQTSITVLCIACPCSLGLATPTAVMVGTGVAAQNGILIKGGKPLEMAHKIKTVMFDKTGTITHGVPRVMRVLLLGDVATLPLRKVLAVVGTAEASSEHPLGVAVTKYCKEELGTETLGYCTDFQAVPGCGIGCKVSNVEGILAHSERPLSAPASHLNEAGSLPAEKDAVPQTFSVLIGNREWLRRNGLTISSDVSDAMTDHEMKGQTAILVAIDGVLCGMIAIADAVKQEAALAVHTLQSMGVDVVLITGDNRKTARAIATQVGINKVFAEVLPSHKVAKVQELQNKGKKVAMVGDGVNDSPALAQADMGVAIGTGTDVAIEAADVVLIRNDLLDVVASIHLSKRTVRRIRINLVLALIYNLVGIPIAAGVFMPIGIVLQPWMGSAAMAASSVSVVLSSLQLKCYKKPDLERYEAQAHGHMKPLTASQVSVHIGMDDRWRDSPRATPWDQVSYVSQVSLSSLTSDKPSRHSAAADDDGDKWSLLLNGRDEEQYI -> ETFIFC. In isoform 5.
Beta strand	1145 – 1149

Literature citations
Distinct clinical courses according to presenting phenotypes and their correlations to ATP7B mutations in a large Wilson's disease cohort.
Lee B.H.; Kim J.H.; Lee S.Y.; Jin H.Y.; Kim K.J.; Lee J.J.; Park J.Y.; Kim G.H.; Choi J.H.; Kim K.M.; Yoo H.W.;
Liver Int. 31:831-839(2011)
Cited for: VARIANTS WD ARG-108; VAL-729; GLN-778; LEU-778; TRP-827; VAL-874; ASP-891; 899-ILE--GLN-907 DEL; GLY-919; ASP-943; SER-943; GLN-969; MET-977; LEU-992; THR-1010; ALA-1024; ILE-1029; ALA-1031; VAL-1035; PHE-1083; TYR-1091; ILE-1106; THR-1148; CYS-1151; SER-1168; SER-1186; MET-1216; ALA-1267; SER-1270; LEU-1273 AND ASP-1295; CHARACTERIZATION OF VARIANTS WD TRP-827; THR-1010; CYS-1151 AND ASP-1295; Mutation analysis in patients with Wilson disease: identification of 4 novel mutations.
Haas R.; Gutierrez-Rivero B.; Knoche J.; Boeker K.; Manns M.P.; Schmidt H.H.-J.;
Hum. Mutat. 14:88-88(1999)
Cited for: VARIANTS WD 670-TYR-MET-671 DEL; TYR-985 AND THR-1148; Delineation of the spectrum of Wilson disease mutations in the Greek population and the identification of six novel mutations.
Loudianos G.; Lovicu M.; Solinas P.; Kanavakis E.; Tzetis M.; Manolaki N.; Panagiotakaki E.; Karpathios T.; Cao A.;
Genet. Test. 4:399-402(2000)
Cited for: VARIANTS WD SER-486; GLY-778; MET-890; GLN-969; GLU-1061; GLN-1069; SER-1099 AND THR-1148; Mutation spectrum and polymorphisms in ATP7B identified on direct sequencing of all exons in Chinese Han and Hui ethnic patients with Wilson's disease.
Gu Y.-H.; Kodama H.; Du S.-L.; Gu Q.-J.; Sun H.-J.; Ushijima H.;
Clin. Genet. 64:479-484(2003)
Cited for: VARIANTS WD VAL-85; GLY-765; LEU-778; MET-890; GLY-919; MET-935; TYR-975; LEU-992; ARG-1098; THR-1148; LYS-1173 AND ASN-1248; VARIANTS ASP-14; ALA-406; LEU-456; ARG-832; ALA-1140; ASN-1143 AND SER-1245; Wilson disease: high prevalence in a mountainous area of Crete.
Dedoussis G.V.Z.; Genschel J.; Sialvera T.-E.; Bochow B.; Manolaki N.; Manios Y.; Tsafantakis E.; Schmidt H.;
Ann. Hum. Genet. 69:268-274(2005)
Cited for: VARIANTS WD THR-1148 AND ARG-1176; Mutation analysis of the ATP7B gene and genotype/phenotype correlation in 227 patients with Wilson disease.
Vrabelova S.; Letocha O.; Borsky M.; Kozak L.;
Mol. Genet. Metab. 86:277-285(2005)
Cited for: VARIANTS WD SER-641; SER-710; ARG-737; GLY-778; GLU-918; GLN-969; MET-977; VAL-1018; SER-1033; TRP-1041; VAL-1063; LYS-1064; GLN-1069; THR-1102; ASP-1111; THR-1148; ARG-1176; SER-1186; ASN-1271; LEU-1273; PRO-1305; ASP-1341 AND CYS-1355; VARIANTS LEU-456; ARG-832 AND ALA-1140; Functional analysis of mutations in the ATP loop of the Wilson disease copper transporter, ATP7B.
Luoma L.M.; Deeb T.M.; Macintyre G.; Cox D.W.;
Hum. Mutat. 31:569-577(2010)
Cited for: VARIANTS WD MET-991; ARG-1000; PRO-1043; ARG-1101; THR-1102; THR-1148; GLY-1173; GLU-1176; THR-1228; GLY-1239; VAL-1267 AND SER-1287; CHARACTERIZATION OF VARIANTS WD MET-991; ARG-1000; PRO-1043; ARG-1101; THR-1102; THR-1148; GLY-1173; GLU-1176; THR-1228; GLY-1239; VAL-1267 AND SER-1287;

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.