Table 1.

Identification of Heterozygous Variants in GREB1L (GenBank: NM_001142966.2) in 16 CAKUT-Affected Case Subjects and Families

Fam	NGS	Case Subjects with Kidney Phenotype	Other Defects	Mutation (Chrom Position)a	Mutation (Nucleotide)	Substitution (Amino Acid)	GnomAD	Nucleotide Conservation (phred)	Amino Acid Conservation	PP2	Sift	Grantham	CADD (phred)	Inheritance
1	WES	2 fetuses: BKA (M/F) 1 child: UKA (M)	male fetus: clinodactyly (5th fingers) female fetus: clinodactyly (5th fingers), absence of uterus; mother: unicornuated uterus	18:19029659	c.1582delC	p.Gln528Argfs∗12	absent	–	–	–	–	–	34	maternalb
2	WES	2 fetuses: BKA (M/F)	male fetus: thickened left ventricular wall, 10 pairs of ribs female fetus: absence of uterus	18:19088078	c.4369−1G>C	–	absent	–	–	–	–	–	25.2	maternalb
3	TES	2 fetuses: BKA (M/F) 1 child: UKA+VUR (F) mother: UKA	female fetus: absence of uterus and fallopian trumps affected child: ovarian hernia mother: absence of uterine left artery	18:19031043	c.1780G>T	p.Glu594∗	absent	–	–	–	–	–	40	maternal
4	TES	2 fetuses: BKA (M/M) 1 child: UKA (M) mother: UKA	none	18:19070208	c.2926C>T	p.Gln976∗	absent	–	–	–	–	–	40	maternal
5	TES	2 fetuses: BKA (F), UKA+MCD (M) mother: horseshoe kidney	female fetus: 11 pairs of ribs, absence of uterus	18:19088424	c.4607A>G	p.His1536Arg	absent	4.81	zebrafish	0.955	0.07	29	23.3	maternal
6	TES	fetus: BKA (M)	retro-esophageal subclavian artery, adrenal gland hypoplasia, enlarged thymus, one pair of cervical ribs	18:19088215	c.4505T>C	p.Met1502Thr	absent	3.11	zebrafish	0.892	0	81	24.8	maternalc
7	TES	fetus: BKA (F)	none	18:19088489	c.4672C>A	p.Arg1558Ser	absent	3.51	zebrafish	0.908	0.01	110	34	maternalb
8	TES	2 fetuses: BKA mother: unilateral hypoplasia	mother: unicornuated uterus	18:19053060	c.2251C>T	p.Arg751Cys	absent	3.51	zebrafish	0.998	0	180	34	maternal
9	TES	fetus: BKA (M) mother: UKA	mother: ID diabetes, unique fallopian trump and ovary	18:18981153	c.575G>T	p.Arg192Leu	absent	6.26	zebrafish	0.999	0.34	102	26.1	maternal
10	TES	fetus: BKA (M)	auricular tag, hypertrophic left ventricle, aortic stenosis	18:19088544	c.4727C>T	p.Ala1576Val	absent	5.86	tetraodon	0.947	0	64	33	UNK
11	TES	fetus: BKA (M)	adrenal cytomegaly	18:19088236	c.4526A>T	p.Asp1509Val	6.584 × 10−6	2.06	zebrafish	0.835	0	152	26.3	UNK
12	TES	fetus: BKA (M)	preauricular tag, lop ear	18:19098046	c.5323 G>A	p.Asp1775Asn	absent	5.69	zebrafish	0.999	0	23	34	UNK
13	TES	fetus: UKA+MCD, megaurethra (M)	hepatic portal fibrosis	18:19053061	c.2252 G>A	p.Arg751His	2.697 × 10−5	6.34	zebrafish	0.996	0	29	34	maternalc
14	TES	fetus: pelvic kidney+MCD (M) mother: VUR	none	18:19020263	c.983G>A	p.Arg328Gln	absent	4.64	zebrafish	0.999	0.01	43	34	maternal
15	TES	adult: UKA+multilocular cyst (F)	blind ending hemi-vagina and bicornuated uterus	18:19031076	c.1813A>C	p.Ser605Arg	absent	4.81	zebrafish	0.992	0.07	110	24.8	paternalb
16	TES	child: VUR (M)	iris anomaly	18:19034490	c.2148 G>T	p.Leu716Phe	absent	3.84	zebrafish	0.525	0.04	22	24.5	UNK

Abbreviations are as follows: Fam, family; NGS, next generation sequencing; WES, whole-exome sequencing; TES, targeted exome sequencing; BKA, bilateral kidney agenesis; UKA, unilateral kidney agenesis; MCD, multicystic dysplasia; VUR, vesicoureteral reflux; M, male; F, female; ID, insulin-dependent; UNK, unknown; PP2, PolyPhen2; CADD, Combined Annotation Dependent Depletion.

^aPosition on GRCh37/hg19 human genome assembly.

^bParent with normal renal ultrasound.

^cMother with renal status non ascertained by renal ultrasound.