UniProtKB/Swiss-Prot P08397: Variant p.Asp178Asn

Porphobilinogen deaminase
Gene: HMBS
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Variant information Variant position:

178 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant:

US 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 Aspartate (D) to Asparagine (N) at position 178 (D178N, p.Asp178Asn). 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 acidic (D) to medium size and polar (N) 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; uncertain significance; slightly decreased hydroxymethylbilane synthase activity corresponding to 80% of wild-type activity. Any additional useful information about the variant.
Other resources:

Links to websites of interest for the variant.

Variant rs536814318 [ dbSNP | Ensembl ]

Sequence information Variant position:

178 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:

FPHLEFRSIRGNLNTRLRKL D EQQEFSAIILATAGLQRMGW 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                         FPHLEFRSIRGNLNTRLRKLDE-QQEFSAIILATAGLQRMGW

Mouse                         FPHLEFKSIRGNLNTRLRKLDE-LQEFSAIVLAVAGLQRMG

Rat                           FPHLEFKSIRGNLNTRLRKLDE-QLEFSAIILAVAGLQRMG

Bovine                        FPHLEFKSIRGNLNTRLRKLDE-LQEFSAIILATAGLQRMG

Slime mold                    YPHLQFKDIRGNLNTRFKKLEDDSNGYDGMILAVAGLERME

Baker's yeast                 YPHLKFESVRGNIQTRLQKLDDPKSPYQCIILASAGLMRMG

Fission yeast                 FPHLRFVDIRGNVGTRLAKLDAPDSQFDCLVLAAAGLFRLG

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	195 – 195	R -> A. Loss of hydroxymethylbilane synthase activity.
Helix	170 – 179

Literature citations
Molecular epidemiology and diagnosis of PBG deaminase gene defects in acute intermittent porphyria.
Puy H.; Deybach J.-C.; Lamoril J.; Robreau A.-M.; Da Silva V.; Gouya L.; Grandchamp B.; Nordmann Y.;
Am. J. Hum. Genet. 60:1373-1383(1997)
Cited for: VARIANTS AIP SER-24; ASN-28; ASP-124; ASN-178; HIS-217; ALA-250; VAL-250; TYR-256; MET-267; ASP-270 AND ASP-335; Acute intermittent porphyria in Sweden. Molecular, functional and clinical consequences of some new mutations found in the porphobilinogen deaminase gene.
Floderus Y.; Shoolingin-Jordan P.M.; Harper P.;
Clin. Genet. 62:288-297(2002)
Cited for: VARIANTS AIP CYS-26; HIS-26; VAL-86; PRO-92; GLY-99; ARG-111; THR-113; GLN-173; ASN-178; GLN-225; GLY-225; TYR-256; ASP-260 AND PRO-343; Correlation between biochemical findings, structural and enzymatic abnormalities in mutated HMBS identified in six Israeli families with acute intermittent porphyria.
Ulbrichova D.; Schneider-Yin X.; Mamet R.; Saudek V.; Martasek P.; Minder E.I.; Schoenfeld N.;
Blood Cells Mol. Dis. 42:167-173(2009)
Cited for: VARIANT AIP PRO-32; CHARACTERIZATION OF VARIANTS AIP PRO-32 AND ASN-178; FUNCTION; CATALYTIC ACTIVITY; PATHWAY;

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.