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UniProtKB/Swiss-Prot Q9H1D0: Variant p.Ile223Thr

Transient receptor potential cation channel subfamily V member 6
Gene: TRPV6
Variant information

Variant position:  223
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 223 (I223T, p.Ile223Thr).
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 HRPTTN; decreased localization at the plasma membrane; no change in calcium ion import across plasma membrane.
Any additional useful information about the variant.



Sequence information

Variant position:  223
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  765
The length of the canonical sequence.

Location on the sequence:   GEHPLSFAACVNSEEIVRLL  I EHGADIRAQDSLGNTVLHIL
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                         GEHPLSFAACVNSEEIVRLLIEHGADIRAQDSLGNTVLHIL

Mouse                         GEHPLSFAACVGSEEIVRLLIEHGADIRAQDSLGNTVLHIL

Rat                           GEHPLSFAACVGSEEIVRLLIEHGADIRAQDSLGNTVLHIL

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 – 765 Transient receptor potential cation channel subfamily V member 6
Topological domain 1 – 367 Cytoplasmic
Repeat 202 – 231 ANK 4
Alternative sequence 65 – 232 Missing. In isoform 2.
Helix 216 – 223


Literature citations

TRPV6 Variants Interfere with Maternal-Fetal Calcium Transport through the Placenta and Cause Transient Neonatal Hyperparathyroidism.
Suzuki Y.; Chitayat D.; Sawada H.; Deardorff M.A.; McLaughlin H.M.; Begtrup A.; Millar K.; Harrington J.; Chong K.; Roifman M.; Grand K.; Tominaga M.; Takada F.; Shuster S.; Obara M.; Mutoh H.; Kushima R.; Nishimura G.;
Am. J. Hum. Genet. 102:1104-1114(2018)
Cited for: VARIANTS HRPTTN TYR-212; THR-223; GLN-425; ARG-428; GLU-451 AND TRP-483; VARIANT SER-18; CHARACTERIZATION OF VARIANTS HRPTTN TYR-212; THR-223; GLN-425; GLU-451; ARG-428 AND TRP-483; CHARACTERIZATION OF VARIANT SER-18; INVOLVEMENT IN HRPTTN; FUNCTION; SUBCELLULAR LOCATION;

TRPV6 gene mutation in a dizygous twin with transient neonatal hyperparathyroidism.
Yamashita S.; Mizumoto H.; Sawada H.; Suzuki Y.; Hata D.;
J. Endocr. Soc. 3:602-606(2019)
Cited for: VARIANTS HRPTTN THR-223 AND ARG-428;

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.