Allelic Variants of PAH locus:
Genetic variation in Phenylketonuria in OMIM

    Inborn metabolic diseases are often incorrectly thought of as the result of a single "disease" allele, in contrast to a single "normal" allele.  In fact, most human gene loci are highly polymorphic, and there are a number of variant alleles for the medical conditions of interest.  An even greater range of variation remains undetected, because many (most?) nucleotide substitutions (especially third-position changes) do not noticeably affect gene activity.

    For example, as of 2007 OMIM listed 67 allelic variants at the Phenylalanine Hydroxylase (PAH) locus (MGA2_3-29).

Mutation
 #
 %
Non-PKU hyperphenylalanemia
 19
 -
Phenylkentonuria (PKU)
 47
 100
Splice-site mutations
 7
 14
Deletion mutations, including:
12
     Complete exon
 1
     Single triplet
 2
     Five triplets
 1
     single base => premature termination
 2
Non-sense mutations
 9
 18
Miss-sense mutations
 27
 55


In the table below, XXX###YYY describes a missense substitution of amino acid XXX to YYY at position ###;
                                XXX###TER describes a termination (nonsense) at position ###
                                IVS refers to an alteration at an  intervening spacer (intron)


     0001 : PHENYLKETONURIA           Mutation : PAH, IVS12DS, G-A, +1
                [This is the most common PKU-causing variant in Europeans]
     0002 : PHENYLKETONURIA           Mutation : PAH, ARG408TRP
     0003 : PHENYLKETONURIA           Mutation : PAH, LEU311PRO
     0004 : PHENYLKETONURIA           Mutation : PAH, GLU280LYS
     0005 : PHENYLKETONURIA           Mutation : PAH, ARG111TER
     0006 : PHENYLKETONURIA           Mutation : PAH, ARG261GLN
     0007 : PHENYLKETONURIA           Mutation : PAH, ARG252TRP
     0008 : PHENYLKETONURIA           Mutation : PAH, EX3DEL
     0009 : PHENYLKETONURIA           Mutation : PAH, MET1VAL
     0010 : PHENYLKETONURIA           Mutation : PAH, ARG158GLN
     0011 : PHENYLKETONURIA           Mutation : PAH, ARG243TER
     0012 : PHENYLKETONURIA           Mutation : PAH, PRO281LEU
     0013 : PHENYLKETONURIA           Mutation : PAH, TYR204CYS
     0014 : PHENYLKETONURIA           Mutation : PAH, ARG243GLN
     0015 : PHENYLKETONURIA           Mutation : PAH, TRP326TER
     0016 : PHENYLKETONURIA           Mutation : PAH, ARG413PRO
     0018 : PHENYLKETONURIA           Mutation : PAH, SPLICE ACCEPTOR, IVS4, AG-AA
     0019 : PHENYLKETONURIA           Mutation : PAH, TYR356TER
     0020 : PHENYLKETONURIA           Mutation : PAH, TER272GLY
     0021 : PHENYLKETONURIA           Mutation : PAH, LEU364DEL
     0022 : PHENYLKETONURIA           Mutation : PAH, GLY272TER
     0023 : PHENYLKETONURIA           Mutation : PAH, SER273PHE
     0024 : PHENYLKETONURIA           Mutation : PAH, INTRON 4 SPLICE MUTATION
     0025 : PHENYLKETONURIA           Mutation : PAH, IVS7DS, G-A, +1
     0026 : PHENYLKETONURIA           Mutation : PAH, LEU255SER
     0028 : PHENYLKETONURIA           Mutation : PAH, ALA259VAL
     0029 : PHENYLKETONURIA           Mutation : PAH, TYR277ASP
     0030 : PHENYLKETONURIA           Mutation : PAH, ILE94DEL
     0031 : PHENYLKETONURIA           Mutation : PAH, PHE39LEU
     0032 : PHENYLKETONURIA           Mutation : PAH, SER349ARG
     0033 : PHENYLKETONURIA           Mutation : PAH, INTRON 10 SPLICE MUTATION, IVS10NT546
     0034 : PHENYLKETONURIA           Mutation : PAH, LEU48SER
     0035 : PHENYLKETONURIA           Mutation : PAH, GLU221GLY
     0036 : PHENYLKETONURIA           Mutation : PAH, ARG261TER
     0037 : PHENYLKETONURIA           Mutation : PAH, 1-BP DEL, FS60TER
     0038 : PHENYLKETONURIA           Mutation : PAH, ARG408GLN
     0039 : PHENYLKETONURIA           Mutation : PAH, PHE299CYS
     0040 : PHENYLKETONURIA           Mutation : PAH, IVS7DS, T-A, +2
     0041 : PHENYLKETONURIA           Mutation : PAH, SER349PRO
     0045 : PHENYLKETONURIA           Mutation : PAH, VAL388MET
     0046 : PHENYLKETONURIA           Mutation : PAH, 15-BP DEL, EX11
     0047 : PHENYLKETONURIA           Mutation : PAH, PRO244LEU
     0048 : PHENYLKETONURIA           Mutation : PAH, MET1ILE
     0049 : PHENYLKETONURIA           Mutation : PAH, IVS10AS, C-T, -3
     0052 : PHENYLKETONURIA           Mutation : PAH, SER359TER
     0061 : PHENYLKETONURIA           Mutation : PAH, 1-BP DEL, FS399TER
     0062 : PHENYLKETONURIA           Mutation : PAH, PRO407LEU
     0063 : PHENYLKETONURIA           Mutation : PAH, ILE65THR
     0065 : PHENYLKETONURIA           Mutation : PAH, 1197A-T, VAL399VAL

All text & figure material © 2011 by Steven M. Carr