Table 3.

Pathogenicity of missense mutations of amino acids in NIPAL4 gene (Ref Seq: NG_016626.1)

Amino acid change			G142V	A176D	E178D	S208F	G230R	H237D	G297R
Nucleotide change			425G>T	527C>A	534A>C	623C>T	688G>A	709C>G	889G>A
Bioinformatics analysis	Proveana	Prediction Score	Deleterious −6.612	Deleterious −3.407	Deleterious −2.893	Deleterious −5.689	Deleterious −7.965	Deleterious −8.983	Deleterious −7.975
	Siftb	Prediction Score	Damaging 0	Tolerated 0.15	Damaging 0	Damaging 0	Damaging 0	Damaging 0	Damaging 0
	Mutation Tasterc	Prediction	Disease causing	Disease causing	Disease causing	Disease causing	Disease causing	Disease causing	Disease causing
	Mutpredd	Prediction Score	Probably Damaging 0.797	Probably Damaging 0.804	Probably Damaging 0.857	Probably Damaging 0.751	Probably Damaging 0.901	Probably Damaging 0.855	Probably Damaging 0.764
	PhD‐SNPe	Prediction	Disease	Disease	Disease	Disease	Disease	Disease	Disease
Phenotype			Ichthyosis, autosomal recessive
Reference			Lefèvre et al. (2004)	Lefèvre et al. (2004)	Our study	Lefèvre et al. (2004)	Dahlqvist et al., (2007)	Lefèvre et al. (2004)	Lefèvre et al. (2004)

^aPROVEAN (Protein Variation Effect Analyzer) v1.1: Classify substitutions as “deleterious” (PROVEAN score ≤ −2.5), and as a “neutral” effect if the PROVEAN score>−2.5.

^bSIFT (Sorting Intolerant From Tolerant) classify substitutions as damaging (SIFT score < 0.05) or tolerant (SIFT score > 0.05)

^cMutation Taster is a structural testing method: classify substitutions as “disease causing” or “polymorphism”

^dMutpred classify an amino acid substitution as deleterious/disease‐associated or neutral, based on the evolutionary conservation of the protein sequence, the protein structure and dynamics, and in functional properties.

^ePhD‐SNP (predictor of Human Deleterious Single Nucleotide Polymorphisms) classify substitutions as disease‐related (Disease) or as neutral polymorphism (Neutral).