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UniProtKB/Swiss-Prot O14672: Variant p.Gln170His

Disintegrin and metalloproteinase domain-containing protein 10
Gene: ADAM10
Variant information

Variant position:  170
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 Glutamine (Q) to Histidine (H) at position 170 (Q170H, p.Gln170His).
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 polar.
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  0
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:  Alzheimer disease 18 (AD18) [MIM:615590]: A late-onset form of Alzheimer disease. Alzheimer disease is a neurodegenerative disorder characterized by progressive dementia, loss of cognitive abilities, and deposition of fibrillar amyloid proteins as intraneuronal neurofibrillary tangles, extracellular amyloid plaques and vascular amyloid deposits. The major constituents of these plaques are neurotoxic amyloid-beta protein 40 and amyloid-beta protein 42, that are produced by the proteolysis of the transmembrane APP protein. The cytotoxic C-terminal fragments (CTFs) and the caspase-cleaved products, such as C31, are also implicated in neuronal death. {ECO:0000269|PubMed:19608551, ECO:0000269|PubMed:24055016}. Note=Disease susceptibility is associated with variations 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 AD18; associated with disease susceptibility; significantly attenuates alpha-secretase activity of the enzyme; shifts APP processing toward beta-secretase-mediated cleavage resulting in enhanced amyloid-beta plaque load and reactive gliosis.
Any additional useful information about the variant.

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



Sequence information

Variant position:  170
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  748
The length of the canonical sequence.

Location on the sequence:   PFHSVIYHEDDINYPHKYGP  Q GGCADHSVFERMRKYQMTGV
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                         PFHSVIYHEDDINYPHKYGPQGGCADHS-------VFERMRKYQMTGV

Mouse                         PFHSVIYHEDDINYPHKYGPQGGCADHS-------VFERMR

Rat                           PFHSVIYHEDDINYPHKYGPQGGCADHS-------VFERMR

Pig                           PFHSVIYHEDDINYPHKYGPQGGCADHS-------VFERMR

Bovine                        PFHSVIYHEDDIKYPHKYGPQGGCADHS-------VFERMR

Xenopus laevis                PFHSVMYHEDDIKYPHKYGSEGGCADSS-------VFKRMK

Caenorhabditis elegans        QYHSIIYRDDEINH-RKWRVKRDAENLSEQMQGCGFSSRVR

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
Propeptide 20 – 213
Topological domain 20 – 672 Extracellular
Metal binding 173 – 173 Zinc; in inhibited form
Alternative sequence 19 – 319 Missing. In isoform 2.


Literature citations

Potential late-onset Alzheimer's disease-associated mutations in the ADAM10 gene attenuate {alpha}-secretase activity.
Kim M.; Suh J.; Romano D.; Truong M.H.; Mullin K.; Hooli B.; Norton D.; Tesco G.; Elliott K.; Wagner S.L.; Moir R.D.; Becker K.D.; Tanzi R.E.;
Hum. Mol. Genet. 18:3987-3996(2009)
Cited for: VARIANTS AD18 HIS-170 AND GLY-181; CHARACTERIZATION OF VARIANTS AD18 HIS-170 AND GLY-181;

ADAM10 missense mutations potentiate beta-amyloid accumulation by impairing prodomain chaperone function.
Suh J.; Choi S.H.; Romano D.M.; Gannon M.A.; Lesinski A.N.; Kim D.Y.; Tanzi R.E.;
Neuron 80:385-401(2013)
Cited for: CHARACTERIZATION OF VARIANTS AD18 HIS-170 AND GLY-181;

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.