UniProtKB/Swiss-Prot Q96J66: Variant p.Val648Ile

• Variant information
• Sequence information
• Literature citations
• All

Variant information

Variant position: 648 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant: LB/B 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 Valine (V) to Isoleucine (I) at position 648 (V648I, p.Val648Ile). 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: Similar physico-chemical property. Both residues are medium size and hydrophobic. 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
Polymorphism: Variations in ABCC11 gene may affect apocrine gland secretion, which determines earwax type, axillary osmidrosis, and colostrum secretion [MIM:117800] (PubMed:16444273). The wet, cerumen-containing earwax type is a dominant trait, while the dry type, characterized by the lack of oily components, is recessive. The dry type is frequently observed (80-95%) among East Asians, but is uncommon (0-3%) in populations of European and African origins. Intermediate frequencies (30-50%) are seen in populations of Southern Asia, the Pacific Islands, Central Asia and Asia Minor, as well as among the Native North Americans and Inuit. The variant p.Gly180Arg is associated with dry earwax phenotype and lack of axillary odor (PubMed:16444273, PubMed:19383836, PubMed:19710689). It has been suggested that the selective advantage of variant p.Gly180Arg might be related to an adaptation to a cold climate (PubMed:20937735). Additional information on the polymorphism described.
Variant description: No effect on glycosylation; no effect on transport activity; no effect on plasma membrane localization. Any additional useful information about the variant.
Other resources: Links to websites of interest for the variant.

• Variant rs16945930 [ dbSNP | Ensembl ]

Sequence information

Variant position: 648 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: 1382 The length of the canonical sequence.
Location on the sequence: GERGLNLSGGQKQRISLARA V YSDRQIYLLDDPLSAVDAHV 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.
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 – 1382	ATP-binding cassette sub-family C member 11
Topological domain	439 – 806	Cytoplasmic
Domain	508 – 732	ABC transporter 1

Literature citations

Earwax, osmidrosis, and breast cancer: why does one SNP (538G>A) in the human ABC transporter ABCC11 gene determine earwax type?
Toyoda Y.; Sakurai A.; Mitani Y.; Nakashima M.; Yoshiura K.; Nakagawa H.; Sakai Y.; Ota I.; Lezhava A.; Hayashizaki Y.; Niikawa N.; Ishikawa T.;
FASEB J. 23:2001-2013(2009)
Cited for: VARIANT ARG-180; CHARACTERIZATION OF VARIANTS HIS-19; ARG-180; GLU-317; MET-546; TRP-630; ILE-648; ILE-687; ARG-735; VAL-970; 1313-ASP--ARG-1321 DEL AND ARG-1344; FUNCTION; SUBCELLULAR LOCATION; TOPOLOGY; TISSUE SPECIFICITY; GLYCOSYLATION AT ASN-838 AND ASN-844; POLYMORPHISM; MUTAGENESIS OF GLY-180; ASN-838 AND ASN-844; Functional characterization of common protein variants in the efflux transporter ABCC11 and identification of T546M as functionally damaging variant.
Arlanov R.; Lang T.; Jedlitschky G.; Schaeffeler E.; Ishikawa T.; Schwab M.; Nies A.T.;
Pharmacogenomics J. 16:193-201(2016)
Cited for: CHARACTERIZATION OF VARIANTS HIS-19; ARG-180; GLU-317; MET-546; ILE-648 AND ARG-1344; FUNCTION; SUBCELLULAR LOCATION; CATALYTIC ACTIVITY;