. 2020 Mar 5;8(1):6. doi: 10.3390/jdb8010006

Table 1.

Summary of Phenotype Causing Mutations in Human CYP26 genes.

Gene	Nucleotide/AA Change	Change in Enzyme Function	Phenotype	Reference
CYP26A1	R173S	?	None reported	[206]
	F186L	40–80% reduced atRA metabolising activity in COS cells
	C358R
CYP26A1	g.3116delT	reduced atRA metabolising activity	Associated with spina bifida	[208]
CYP26A1	premature stop	reduced atRA metabolising activity	Associated with spina bifida	[208]
CYP26A1	rs4411227 C/G or C/C	?	Increased risk oral and pharyngeal cancer	[209,210,211]
CYP26A1 and CYP26C1	Microdeletion of up to 249–363 kb of chrs. 10q23.33	Haploinsufficiency	Optic nerve aplasia	[213]
CYP26A1 and CYP26C1	Microdeletion of up to 249–363 kb of chrs. 10q23.33	CYP26A1, CYP26C1, EXOC6	Optic nerve aplasia	[213]
CYP26A1 and CYP26C1	8.3 Mb microdel. Chrs 10q23.2–23.33. The 79 deleted genes included CYP26A1 and C1,	Haploinsufficiency CYP26A1, CYP26C1 + 79 other genes	Premature ageing skeletal and dental development, retinal scarring, and autism-spectrum	[214]
CYP26A1 and CYP26C1		Raised plasma RA levels		[214]
CYP26B1	Nine missense or splicing changes	100% loss of function	Neural tube, limb, craniofacial, skeletal, heart, kidney and lung defects	[207]
	(samples collected during gestation)
	583C > T Arg195Met (1)
	589c > A Leu197Met (3)
	704G > A Arg235Gln (1)
	712C > G Gln238Glu (1)
	715G > A Ala237Thr (3)
CYP26B1	Splicing variant with loss of exon 2	30% loss of function	Expressed in atherosclerotic lesion vascular cells	[215]
CYP26B1	rs3768647/9309462	?	Increased risk oral and pharyngeal cancer	[209,210,211,212]
	C/C or C/T
	rs138478634 G/A change in exon 5
CYP26B1	rs2241057T/T (major allele	Lower CYP26B1 activity	Increased risk of Crohn’s disease	[217]
	rs2241057C/C (minor allele)	Higher CYP26B1 activity	Larger macrophage-rich atherosclerotic	[216]
	L264S		lesions
CYP26B1	3 c.1088G > T	100% loss of function by affecting the K-helix	Craniofacial, skull, pelvic, limb long bone skeletal defects	[202]
	homozygous
	p.Arg363Leu
	1 died in utero/2 terminations
CYP26B1	c.436T > C	31% loss of function	Defects similar to Antley–Bixler and Pfeiffer Syndromes	[202]
	homozygous		Skull, digit and joint skeletal defects
	p.Ser146Pro
	Died at 5 months
CYP26B1	c.1303G > A	Predicted loss of function	Skull and long bone skeletal defects, intellectual disability	[218]
	p.Gly435Ser
	homozygous
	(survived to adulthood)
CYP26B1	0.78–4 Mb microdeletion 0.78–4 Mb chrs.2p13.2–13.3	8% induction of CYP26B1 mRNA by RA compared to controls	Intellectual disability, language delay, hyperactivity, dysmorphic facies and vertebral and/or craniofacial abnormalities	[219]
CYP26B1	CYP26B1 and EXOC6B haploinsufficient	8% induction of CYP26B1 mRNA by RA compared to controls		[219]
CYP26C1	Missense p.Phe508Cys	Loss of function	Confers increased severity of SHOX p.Val161Ala mutation skeletal and short stature phenotype	[223]
CYP26C1	Missense c.148C > T, Pro50Ser;	Loss of function	Short stature phenotype	[224]
	c.356A > C, p.Gln119Pro; c.910G > A, Ala304 The
	Splice variant truncation
	c.706-A > C
CYP26C1	Duplication > frameshift	100% loss of function	Focal facial dermal dysplasia	[225]
	> premature stop
	c.844–851dupCCATGCA
	p.Glu284fsX128 (maternal)
	homozygous and compound heterozygous
	Missense c.1433G > A p.Arg478His (paternal)
	compound heterozygous
POR	Missense, nonsense, frameshift, splicing and exon deletions	Loss of function	Antley–Bixler like skeletal defects and deficient steroidal profiles	[220,221,222]