UniProtKB/SwissProt variant VAR

Carbonic anhydrase 2
Gene: CA2
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Variant information Variant position:

107 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 Histidine (H) to Tyrosine (Y) at position 107 (H107Y, p.His107Tyr). 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 polar (H) to large size and aromatic (Y) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score:

2 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 OPTB3. Any additional useful information about the variant.
Other resources:

Links to websites of interest for the variant.

Variant rs118203933 [ dbSNP | Ensembl ]

Sequence information Variant position:

107 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length:

260 The length of the canonical sequence.
Location on the sequence:

TYRLIQFHFHWGSLDGQGSE H TVDKKKYAAELHLVHWNTKY 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                         TYRLIQFHFHWGSLD--GQGSEHTVDKKKYAAELHLVHWNTK-Y

Mouse                         SYRLIQFHFHWGSSD--GQGSEHTVNKKKYAAELHLVHWNT

Rat                           SYRLIQFHFHWGSSD--GQGSEHTVNKKKYAAELHLVHWNT

Bovine                        TYRLVQFHFHWGSSD--DQGSEHTVDRKKYAAELHLVHWNT

Rabbit                        TYRLIQFHFHWGSSD--GQGSEHTVNKKKYAAELHLVHWNT

Sheep                         TYRLVQFHFHWGSSD--DQGSEHTVDRKKYAAELHLVHWNT

Chicken                       VYRLVQFHIHWGSCE--GQGSEHTVDGVKYDAELHIVHWNV

Caenorhabditis elegans        RYKLHQISVHFGRADEGEKGSEHTVDRVRFPAEIQLLAYNS

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.

Type	Positions	Description
Chain	2 – 260	Carbonic anhydrase 2
Domain	3 – 259	Alpha-carbonic anhydrase
Binding site	94 – 94
Binding site	96 – 96
Binding site	119 – 119
Site	92 – 92	Involved in the binding of some activators, including histamine and L-histidine
Mutagenesis	94 – 94	H -> CDENQ. Strongly reduced CO(2) hydrase and p-nitrophenyl acetate esterase activities, impaired stability of zinc binding.
Mutagenesis	106 – 106	E -> AQ. Strongly reduced CO(2) hydrase activity.
Mutagenesis	106 – 106	E -> D. Normal CO(2) hydrase activity.
Mutagenesis	117 – 117	E -> Q. Strongly reduced activity and sulfonamide affinity.
Mutagenesis	119 – 119	H -> DNQ. Reduced activity.
Mutagenesis	119 – 119	H -> E. Strongly reduced activity.
Mutagenesis	121 – 121	V -> AGILS. Reduced CO(2) hydrase and p-nitrophenyl acetate esterase activities.
Mutagenesis	121 – 121	V -> KR. Strongly reduced CO(2) hydrase and p-nitrophenyl acetate esterase activities.
Beta strand	106 – 109

Literature citations
Carbonic anhydrase II deficiency syndrome in a Belgian family is caused by a point mutation at an invariant histidine residue (107 His-->Tyr): complete structure of the normal human CA II gene.
Venta P.J.; Welty R.J.; Johnson T.M.; Sly W.S.; Tashian R.E.;
Am. J. Hum. Genet. 49:1082-1090(1991)
Cited for: VARIANT OPTB3 TYR-107; Molecular basis of human carbonic anhydrase II deficiency.
Roth D.E.; Venta P.J.; Tashian R.E.; Sly W.S.;
Proc. Natl. Acad. Sci. U.S.A. 89:1804-1808(1992)
Cited for: VARIANT OPTB3 TYR-107; A point mutation in exon 3 (His 107-->Tyr) in two unrelated Japanese patients with carbonic anhydrase II deficiency with central nervous system involvement.
Soda H.; Yukizane S.; Yoshida I.; Koga Y.; Aramaki S.; Kato H.;
Hum. Genet. 97:435-437(1996)
Cited for: VARIANT OPTB3 TYR-107; Carbonic anhydrase II deficiency syndrome (osteopetrosis with renal tubular acidosis and brain calcification): novel mutations in CA2 identified by direct sequencing expand the opportunity for genotype-phenotype correlation.
Shah G.N.; Bonapace G.; Hu P.Y.; Strisciuglio P.; Sly W.S.;
Hum. Mutat. 24:272-272(2004)
Cited for: VARIANTS OPTB3 PRO-92; TYR-94; TYR-107 AND ARG-144; FUNCTION; CATALYTIC ACTIVITY; CHARACTERIZATION OF VARIANTS TYR-94 AND ARG-144;

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.

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P00918: Variant p.His107Tyr