UniProtKB/SwissProt variant VAR

Porphobilinogen deaminase
Gene: HMBS
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Variant information Variant position:

167 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 Glutamine (Q) at position 167 (R167Q, p.Arg167Gln). 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 (Q) 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 AIP, ENCEP and LENCEP; decreased hydroxymethylbilane synthase activity due to defective enzyme-intermediate complexes turnover and regeneration of free enzyme molecules. Any additional useful information about the variant.
Other resources:

Links to websites of interest for the variant.

Variant rs118204095 [ dbSNP | Ensembl ]

Sequence information Variant position:

167 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:

SLRRAAQLQRKFPHLEFRSI R GNLNTRLRKLDEQQEFSAII 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                         SLRRAAQLQRKFPHLEFRSIRGNLNTRLRKLDE-QQEFSAII

Mouse                         SLRRVAQLQRKFPHLEFKSIRGNLNTRLRKLDE-LQEFSAI

Rat                           SLRRVAQLQRKFPHLEFKSIRGNLNTRLRKLDE-QLEFSAI

Bovine                        SLRRAAQLQRKFPHLEFKSIRGNLNTRLRKLDE-LQEFSAI

Slime mold                    SLRRVAQLKKAYPHLQFKDIRGNLNTRFKKLEDDSNGYDGM

Baker's yeast                 SVRRSAQLKRKYPHLKFESVRGNIQTRLQKLDDPKSPYQCI

Fission yeast                 SIRRRALLARNFPHLRFVDIRGNVGTRLAKLDAPDSQFDCL

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
Modified residue	147 – 147	Phosphoserine

Literature citations
Two different point G to A mutations in exon 10 of the porphobilinogen deaminase gene are responsible for acute intermittent porphyria.
Delfau M.H.; Picat C.; de Rooij F.W.M.; Hamer K.; Bogard M.; Wilson J.H.P.; Deybach J.-C.; Nordmann Y.; Grandchamp B.;
J. Clin. Invest. 86:1511-1516(1990)
Cited for: VARIANTS AIP GLN-167 AND GLN-173; Homozygous acute intermittent porphyria: compound heterozygosity for adjacent base transitions in the same codon of the porphobilinogen deaminase gene.
Llewellyn D.H.; Smyth S.J.; Elder G.H.; Hutchesson A.C.; Rattenbury J.M.; Smith M.F.;
Hum. Genet. 89:97-98(1992)
Cited for: VARIANTS ENCEP TRP-167 AND GLN-167; INVOLVEMENT IN ENCEP; Detection of seven point mutations in the porphobilinogen deaminase gene in patients with acute intermittent porphyria, by direct sequencing of in vitro amplified cDNA.
Mgone C.S.; Lanyon W.G.; Moore M.R.; Connor J.M.;
Hum. Genet. 90:12-16(1992)
Cited for: VARIANTS AIP LYS-34; GLN-167; ARG-177 AND ASN-256; 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; Human porphobilinogen deaminase mutations in the investigation of the mechanism of dipyrromethane cofactor assembly and tetrapyrrole formation.
Shoolingin-Jordan P.M.; Al-Dbass A.; McNeill L.A.; Sarwar M.; Butler D.;
Biochem. Soc. Trans. 31:731-735(2003)
Cited for: CHARACTERIZATION OF VARIANTS AIP GLY-99; GLN-149; GLN-167 AND GLN-173; Acute intermittent porphyria-related leukoencephalopathy.
Kevelam S.H.; Neeleman R.A.; Waisfisz Q.; Friesema E.C.; Langendonk J.G.; van der Knaap M.S.;
Neurology 87:1258-1265(2016)
Cited for: VARIANTS LENCEP GLN-167 AND GLN-225; INVOLVEMENT IN LENCEP; Expanding the clinical and radiological phenotypes of leukoencephalopathy due to biallelic HMBS mutations.
Stutterd C.A.; Kidd A.; Florkowski C.; Janus E.; Fanjul M.; Raizis A.; Wu T.Y.; Archer J.; Leventer R.J.; Amor D.J.; Lukic V.; Bahlo M.; Gow P.; Lockhart P.J.; van der Knaap M.S.; Delatycki M.B.;
Am. J. Med. Genet. A 185:2941-2950(2021)
Cited for: VARIANTS LENCEP ASP-84; GLN-167 AND GLN-225; CHARACTERIZATION OF VARIANT LENCEP ASP-84;

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 P08397: Variant p.Arg167Gln