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UniProtKB/Swiss-Prot P01185: Variant p.Ala19Thr

Vasopressin-neurophysin 2-copeptin
Gene: AVP
Variant information

Variant position:  19
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 Alanine (A) to Threonine (T) at position 19 (A19T, p.Ala19Thr).
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 small size and hydrophobic (A) to medium size and polar (T)
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

Variant description:  In NDI; probably causes insufficient processing of precursor.
Any additional useful information about the variant.

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

Sequence information

Variant position:  19
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  164
The length of the canonical sequence.

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.






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.

Signal peptide 1 – 19
Site 28 – 28 Important for agonist activity on V1aR/AVPR1A
Modified residue 28 – 28 Glycine amide
Mutagenesis 28 – 28 G -> V. Gain of antagonist activity on V1aR/AVPR1A (and loss of agonist activity on this receptor). 42-fold decrease in affinity for V1aR/AVPR1A, 2000-fold decrease in affinity for V1bR/AVPR1B, 5-fold decrease in affinity for V2R/AVPR2 and no change in affinity for oxytocin receptor (OXTR).

Literature citations

Familial neurohypophyseal diabetes insipidus associated with a signal peptide mutation.
McLeod J.F.; Kovacs L.; Gaskill M.B.; Rittig S.; Bradley G.S.; Robertson G.L.;
J. Clin. Endocrinol. Metab. 77:599A-599G(1993)
Cited for: VARIANT NDI THR-19;

Possible involvement of inefficient cleavage of preprovasopressin by signal peptidase as a cause for familial central diabetes insipidus.
Ito M.; Oiso Y.; Murase T.; Kondo K.; Saito H.; Chinzei T.; Racchi M.; Lively M.O.;
J. Clin. Invest. 91:2565-2571(1993)
Cited for: VARIANT NDI THR-19;

Identification of 13 new mutations in the vasopressin-neurophysin II gene in 17 kindreds with familial autosomal dominant neurohypophyseal diabetes insipidus.
Rittig S.; Robertson G.L.; Siggaard C.; Kovacs L.; Gregersen N.; Nyborg J.; Pedersen E.B.;
Am. J. Hum. Genet. 58:107-117(1996)
Cited for: VARIANTS NDI PHE-17; THR-19; VAL-19; ARG-45; CYS-51; GLY-78; PRO-81; ARG-88; SER-88; SER-92 AND CYS-96;

Identification of a novel nonsense mutation and a missense substitution in the vasopressin-neurophysin II gene in two Spanish kindreds with familial neurohypophyseal diabetes insipidus.
Calvo B.; Bilbao J.R.; Urrutia I.; Eizaguirre J.; Gaztambide S.; Castano L.;
J. Clin. Endocrinol. Metab. 83:995-997(1998)
Cited for: VARIANT NDI THR-19;

A signal peptide mutation of the arginine vasopressin gene in monozygotic twins.
Boson W.L.; Sarubi J.C.; D'Alva C.B.; Friedman E.; Faria D.; De Marco L.; Wajchenberg B.;
Clin. Endocrinol. (Oxf.) 58:108-110(2003)
Cited for: VARIANT NDI THR-19;

Six novel mutations in the arginine vasopressin gene in 15 kindreds with autosomal dominant familial neurohypophyseal diabetes insipidus give further insight into the pathogenesis.
Christensen J.H.; Siggaard C.; Corydon T.J.; deSanctis L.; Kovacs L.; Robertson G.L.; Gregersen N.; Rittig S.;
Eur. J. Hum. Genet. 12:44-51(2004)
Cited for: VARIANTS NDI THR-19; VAL-19; ARG-54; ALA-67; GLY-78; GLU-78 DEL; ASP-96; CYS-96; GLY-104 AND TRP-116;

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.