Table 1 Selected genes with greatest LOEUF difference between values calculated with either DoS or pLoF variation

From: Functionally constrained human proteins are less prone to mutational instability from single amino acid substitutions

Gene

Length (nt)

Transcript

Missense DoF

GnomAD pLoF

OMIM Phenotype-Genotype (MIM numbers)

Observed Variants

Expected Varaints

LOEUF

Observed Variants

Expected Variants

LOEUF

HLA genes - high missense variants, antigenic diversity

 HLA-DRB1

798

ENST00000360004

78

31.00

2

6

10.24

1.16

 

 HLA-B

1086

ENST00000412585

128

60.05

2

10

18.59

0.91

 

Appear constrained in GnomAD, due to very few observed LoF

 RGS1

627

ENST00000367459

43

29.25

1.86

1

9.39

0.51

 

 AQP9

885

ENST00000219919

139

81.23

1.94

3

11.72

0.66

 

 RAD23B

1227

ENST00000358015

84

67.79

1.48

1

20.92

0.23

 

 PRPS1L1

954

ENST00000506618

103

29.87

2

2

8.01

0.79

 

 LAMTOR3

372

ENST00000499666

31

23.53

1.76

1

8.66

0.55

 

Appear unconstrained in GnomAD, but with penetrant mutant phenotypes

 KLLN

534

ENST00000445946

22

52.18

0.6

3

2.62

1.89

615107, 612105

 SDHAF1

345

ENST00000378887

28

66.18

0.58

1

0.91

1.90

619166, 612848