UniProtKB/Swiss-Prot P08397: Variant p.Arg116Trp

Porphobilinogen deaminase
Gene: HMBS
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Variant information Variant position:

116 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 Tryptophan (W) at position 116 (R116W, p.Arg116Trp). 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 large size and aromatic (W) 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
Variant description:

In AIP; severely decreased, if any, hydroxymethylbilane synthase activity; affects protein conformation; lower thermal stability than wild-type enzyme. Any additional useful information about the variant.
Other resources:

Links to websites of interest for the variant.

Variant rs118204094 [ dbSNP | Ensembl ]

Sequence information Variant position:

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

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

SLKDLPTVLPPGFTIGAICK R ENPHDAVVFHPKFVGKTLET 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                         SLKDLPTVLPPGFTIGAICKRENPHDAVVFHPKFVGKT--LET

Mouse                         SLKDVPTILPPGFTIGAICKRENPCDAVVFHPKFIGKT--L

Rat                           SLKDVPTILPPGFTIGAICKRENPCDAVVFHPKFIGKT--L

Bovine                        SLKDLPTVLPPGFTIGAVCKRESPYDAVVFHPKFVGKT--L

Slime mold                    SLKDIPTKLPDGLKLGAITKRYNTSDAFIANAKKHGKNCKL

Baker's yeast                 SLKDMPTLLPEGFELGGITKRVDPTDCLVMPFYSAYKS--L

Fission yeast                 SLKDLPSEMPDGMVIACIPKRSCPLDAIVFKAGSHYKT--V

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 – 361	Porphobilinogen deaminase
Mutagenesis	120 – 120	H -> A. Decreased hydroxymethylbilane synthase activity.
Mutagenesis	120 – 120	H -> P. Loss of hydroxymethylbilane synthase activity.

Literature citations
Acute intermittent porphyria: identification and expression of exonic mutations in the hydroxymethylbilane synthase gene. An initiation codon missense mutation in the housekeeping transcript causes 'variant acute intermittent porphyria' with normal expression of the erythroid-specific enzyme.
Chen C.-H.; Astrin K.H.; Lee G.; Anderson K.E.; Desnick R.J.;
J. Clin. Invest. 94:1927-1937(1994)
Cited for: VARIANTS AIP PHE-93; TRP-116; TRP-201 AND PHE-247; Acute intermittent porphyria in Finland: 19 mutations in the porphobilinogen deaminase gene.
Kauppinen R.; Mustajoki S.; Pihlaja H.; Peltonen L.; Mustajoki P.;
Hum. Mol. Genet. 4:215-222(1995)
Cited for: VARIANTS AIP CYS-26; ARG-98; TRP-116; TRP-167; GLN-173; TRP-173; CYS-195; GLY-225; ARG-238; PHE-247 AND ARG-280; Genetic investigation of the porphobilinogen deaminase gene in Swedish acute intermittent porphyria families.
Lundin G.; Lee J.-S.; Thunell S.; Anvret M.;
Hum. Genet. 100:63-66(1997)
Cited for: VARIANTS AIP TRP-116; LEU-119; GLN-167; TRP-167; TRP-173; TRP-201 AND ASP-216; Identification and expression of mutations in the hydroxymethylbilane synthase gene causing acute intermittent porphyria (AIP).
Solis C.; Lopez-Echaniz I.; Sefarty-Graneda D.; Astrin K.H.; Desnick R.J.;
Mol. Med. 5:664-671(1999)
Cited for: VARIANTS AIP ARG-111; TRP-116; TRP-167; TRP-173 AND VAL-212; CHARACTERIZATION OF VARIANT AIP VAL-212; Porphobilinogen deaminase gene in African and Afro-Caribbean ethnic groups: mutations causing acute intermittent porphyria and specific intragenic polymorphisms.
Robreau-Fraolini A.M.; Puy H.; Aquaron C.; Bogard C.; Traore M.; Nordmann Y.; Aquaron R.; Deybach J.-C.;
Hum. Genet. 107:150-159(2000)
Cited for: VARIANTS AIP TRP-116 AND GLY-270; Conformational stability and activity analysis of two hydroxymethylbilane synthase mutants, K132N and V215E, with different phenotypic association with acute intermittent porphyria.
Bustad H.J.; Vorland M.; Ronneseth E.; Sandberg S.; Martinez A.; Toska K.;
Biosci. Rep. 33:0-0(2013)
Cited for: VARIANT ASN-132; CHARACTERIZATION OF VARIANTS AIP TRP-116; TRP-167; TRP-173 AND GLU-215; CHARACTERIZATION OF VARIANT ASN-132; FUNCTION; CATALYTIC ACTIVITY; BIOPHYSICOCHEMICAL PROPERTIES; From a dominant to an oligogenic model of inheritance with environmental modifiers in acute intermittent porphyria.
Lenglet H.; Schmitt C.; Grange T.; Manceau H.; Karboul N.; Bouchet-Crivat F.; Robreau A.M.; Nicolas G.; Lamoril J.; Simonin S.; Mirmiran A.; Karim Z.; Casalino E.; Deybach J.C.; Puy H.; Peoc'h K.; Gouya L.;
Hum. Mol. Genet. 27:1164-1173(2018)
Cited for: VARIANTS AIP PHE-30 AND GLU-235; CHARACTERIZATION OF VARIANTS AIP SER-24; CYS-26; HIS-26; ASN-28; PHE-30; MET-35; PHE-96; ARG-111; TRP-116; ASP-124; GLN-149; LEU-149; HIS-217; GLU-235; ARG-247; ALA-250; GLN-250; VAL-250; TYR-256 AND MET-267;

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.