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UniProtKB/Swiss-Prot Q9Y6R1: Variant p.Arg554His

Electrogenic sodium bicarbonate cotransporter 1
Gene: SLC4A4
Variant information

Variant position:  554
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 Arginine (R) to Histidine (H) at position 554 (R554H, p.Arg554His).
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 (H)
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 pRTA-OA; mistargeting and altered function.
Any additional useful information about the variant.

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



Sequence information

Variant position:  554
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  1079
The length of the canonical sequence.

Location on the sequence:   VFERLLFNFSKDNNFDYLEF  R LWIGLWSAFLCLILVATDAS
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                         VFERLLFNFSKDNNFDYLEFRLWIGLWSAFLCLILVATDAS

Mouse                         VFERLLFNFSKDHNFDYLEFRLWIGLWSAFMCLVLVATDAS

Rat                           VFERLLFNFSKDHSFDYLEFRLWIGLWSAFMCLILVATDAS

Pig                           VFERLLFNFSKDHNFDYLEFRLWIGLWSAFLCLILVATDAS

Bovine                        VFERLLFNFSKDHNFDYLEFRLWIGLWSAFLCLILVATDAS

Rabbit                        VFERLLFNFSKDHNFDYLEFRLWIGLWSAFLCLILVATDAS

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 – 1079 Electrogenic sodium bicarbonate cotransporter 1
Transmembrane 551 – 571 Helical; Name=4
Mutagenesis 536 – 536 E -> Q. Prevents membrane targeting.
Mutagenesis 552 – 552 E -> N. Prevents membrane targeting.
Mutagenesis 554 – 554 R -> D. Prevents membrane targeting.


Literature citations

Mutations in SLC4A4 cause permanent isolated proximal renal tubular acidosis with ocular abnormalities.
Igarashi T.; Inatomi J.; Sekine T.; Cha S.H.; Kanai Y.; Kunimi M.; Tsukamoto K.; Satoh H.; Shimadzu M.; Tozawa F.; Mori T.; Shiobara M.; Seki G.; Endou H.;
Nat. Genet. 23:264-266(1999)
Cited for: VARIANTS PRTA-OA SER-342 AND HIS-554;

Missense mutations in Na+:HCO3- cotransporter NBC1 show abnormal trafficking in polarized kidney cells: a basis of proximal renal tubular acidosis.
Li H.C.; Szigligeti P.; Worrell R.T.; Matthews J.B.; Conforti L.; Soleimani M.;
Am. J. Physiol. 289:F61-F71(2005)
Cited for: VARIANTS PRTA-OA SER-342; LEU-471 AND HIS-554; MUTAGENESIS OF GLU-135;

Functional analysis of NBC1 mutants associated with proximal renal tubular acidosis and ocular abnormalities.
Horita S.; Yamada H.; Inatomi J.; Moriyama N.; Sekine T.; Igarashi T.; Endo Y.; Dasouki M.; Ekim M.; Al-Gazali L.; Shimadzu M.; Seki G.; Fujita T.;
J. Am. Soc. Nephrol. 16:2270-2278(2005)
Cited for: VARIANTS PRTA-OA SER-342; SER-529; HIS-554; VAL-843 AND CYS-925;

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.