Home  |  Contact

UniProtKB/Swiss-Prot Q8IXQ5: Variant p.Arg420Cys

Kelch-like protein 7
Gene: KLHL7
Variant information

Variant position:  420
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 Arginine (R) to Cysteine (C) at position 420 (R420C, p.Arg420Cys).
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 medium size and polar (C)
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

Involvement in disease:  Crisponi/Cold-induced sweating syndrome 3 (CISS3) [MIM:617055]: A form of cold-induced sweating syndrome, an autosomal recessive disorder characterized by profuse sweating induced by cool surroundings (temperatures of 7 to 18 degrees Celsius). Patients manifest, in the neonatal period, orofacial weakness with impaired sucking and swallowing, resulting in poor feeding. Affected infants show a tendency to startle, with contractions of the facial muscles in response to tactile stimuli or during crying, trismus, abundant salivation, and opisthotonus. These features are referred to as Crisponi syndrome and can result in early death in infancy. Patients who survive into childhood have hyperhidrosis, mainly of the upper body, in response to cold temperatures, and sweat very little with heat. Additional abnormalities include a high-arched palate, nasal voice, depressed nasal bridge, inability to fully extend the elbows and kyphoscoliosis. {ECO:0000269|PubMed:27392078}. 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 CISS3; subcellular localization in punctate structures at the perinuclear region of cytoplasm is similar to wild-type and colocalized with CUL3.
Any additional useful information about the variant.

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



Sequence information

Variant position:  420
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  586
The length of the canonical sequence.

Location on the sequence:   FECYDTRTESWHTKPSMLTQ  R CSHGMVEANGLIYVCGGSLG
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                         FECYDTRTESWHTKPSMLTQRCSHGMVEANGLIYVCGGSLG

Mouse                         FECYDTRTESWHTKPSMLTQRCSHGMVEANGLIYVCGGSLG

Rat                           FECYDTRTESWHTKPSMLTQRCSHGMVEANGLIYVCGGSLG

Chicken                       FECYDTRTESWHTKPSMLTQRCSHGMVEANGLIYVCGGSLG

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 – 586 Kelch-like protein 7
Repeat 383 – 430 Kelch 3
Alternative sequence 167 – 586 Missing. In isoform 3 and isoform 4.


Literature citations

Bi-allelic mutations in KLHL7 cause a Crisponi/CISS1-like phenotype associated with early-onset retinitis pigmentosa.
Angius A.; Uva P.; Buers I.; Oppo M.; Puddu A.; Onano S.; Persico I.; Loi A.; Marcia L.; Hoehne W.; Cuccuru G.; Fotia G.; Deiana M.; Marongiu M.; Atalay H.T.; Inan S.; El Assy O.; Smit L.M.; Okur I.; Boduroglu K.; Utine G.E.; Kilic E.; Zampino G.; Crisponi G.; Crisponi L.; Rutsch F.;
Am. J. Hum. Genet. 99:236-245(2016)
Cited for: VARIANTS CISS3 GLN-372; CYS-420 AND SER-421; CHARACTERIZATION OF VARIANTS CISS3 GLN-372; CYS-420 AND SER-421; INVOLVEMENT IN CISS3; SUBCELLULAR LOCATION;

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.