Alleleic variants of PKU in OMIM

Allelic Variants of the PAH locus:
Genetic variation in Phenylketonuria in OMIM
(Online Mendelian Inheritance in Man)

Inborn metabolic diseases are often 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 large numbers of variant alleles for medical conditions of interest. An even greater range of variation remains undetected, because most nucleotide substitutions (especially third-position changes) do not noticeably affect gene activity.

Genetically-influenced traits in humans were first listed in 1966 in book form, Mendelian Inheritance in Man, which grew from a slender single volume to a bulky two-volume 12th edition in 1998 before it went entirely online as OMIM in 2004. Early editions concerned phenotypically observable traits; the latest editions make use of information in the Human Genome Project and are strongly molecularly based.

In 2007, OMIM listed 67 allelic variants at the Phenylalanine Hydroxylase (PAH) locus in the tables below.

Mutation	#	%
Non-PKU hyperphenylalanemia	19	-
Phenylketonuria (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 mis-sense 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)
DEL describes a deletion of a single 3bp triplet, block of bps, or complete exon

     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