UniProtKB/SwissProt variant VAR

Variant information

Variant position:

767

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 Arginine (R) to Tryptophan (W) at position 767 (R767W, p.Arg767Trp).

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 basic (R) to large size and aromatic (W)

The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:

-3

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 OPTA2 and OPTB4.

Any additional useful information about the variant.

Other resources:

Links to websites of interest for the variant.

Variant rs121434435 [ dbSNP | Ensembl ]

Sequence information

Variant position:

767

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

Protein sequence length:

805

The length of the canonical sequence.

Location on the sequence:

TVPQEASLPRVFKLFRALGL R HLVVVDNRNQVVGLVTRKDL

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                         TVPQEASLPRVFKLFRALGLRHLVVVDNRNQVVGLVTRKDL

Mouse                         TVPQEASLPRVFKLFRALGLRHLVVVDNHNQVVGLVTRKDL

Rat                           TVPQEASLPRVFKLFRALGLRHLVVVDNHNQVVGLVTRKDL

Bovine                        TVPQEASLPRVFKLFRALGLRHLVVVDNCNQVVGLVTRKDL

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 – 805	H(+)/Cl(-) exchange transporter 7
Topological domain	598 – 805	Cytoplasmic
Domain	741 – 799	CBS 2

Literature citations

Albers-Schonberg disease (autosomal dominant osteopetrosis, type II) results from mutations in the ClCN7 chloride channel gene.
Cleiren E.; Benichou O.; Van Hul E.; Gram J.; Bollerslav J.; Singer F.R.; Beaverson K.; Aledo A.; Whyte M.P.; Yoneyama T.; de Vernejoul M.-C.; Van Hul W.;
Hum. Mol. Genet. 10:2861-2867(2001)
Cited for: VARIANT OPTB4 PRO-766; VARIANT OPTA2 TRP-767;

Chloride channel ClCN7 mutations are responsible for severe recessive, dominant, and intermediate osteopetrosis.
Frattini A.; Pangrazio A.; Susani L.; Sobacchi C.; Mirolo M.; Abinun M.; Andolina M.; Flanagan A.; Horwitz E.M.; Mihci E.; Notarangelo L.D.; Ramenghi U.; Teti A.; Van Hove J.; Vujic D.; Young T.; Albertini A.; Orchard P.J.; Vezzoni P.; Villa A.;
J. Bone Miner. Res. 18:1740-1747(2003)
Cited for: VARIANTS OPTB4 ARG-240; ARG-249; VAL-332; TRP-526; PRO-614; PHE-744; GLN-767 AND TRP-767; VARIANTS OPTA2 ARG-215; GLN-286; PHE-490 AND VAL-677; VARIANT MET-418;

Identification of the CLCN7 gene mutations in two Chinese families with autosomal dominant osteopetrosis (type II).
Zhang Z.L.; He J.W.; Zhang H.; Hu W.W.; Fu W.Z.; Gu J.M.; Yu J.B.; Gao G.; Hu Y.Q.; Li M.; Liu Y.J.;
J. Bone Miner. Metab. 27:444-451(2009)
Cited for: VARIANT OPTA2 TRP-767;

Molecular and clinical heterogeneity in CLCN7-dependent osteopetrosis: report of 20 novel mutations.
Pangrazio A.; Pusch M.; Caldana E.; Frattini A.; Lanino E.; Tamhankar P.M.; Phadke S.; Lopez A.G.; Orchard P.; Mihci E.; Abinun M.; Wright M.; Vettenranta K.; Bariae I.; Melis D.; Tezcan I.; Baumann C.; Locatelli F.; Zecca M.; Horwitz E.; Mansour L.S.; Van Roij M.; Vezzoni P.; Villa A.; Sobacchi C.;
Hum. Mutat. 31:E1071-E1080(2010)
Cited for: VARIANTS OPTB4 PRO-132; SER-214; LEU-227 DEL; ARG-240; GLN-403; ARG-521; GLN-526; TRP-526; PRO-549; PRO-651; TRP-762 AND PRO-767; VARIANTS OPTA2 ARG-215; GLN-286; LEU-318; LEU-758; GLN-762 AND TRP-767;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P51798: Variant p.Arg767Trp