GREB1L

Summary

GREB1L (GREB1 like retinoic acid receptor coactivator, HGNC:31042) is a protein-coding gene on chromosome 18q11.1-q11.2, encoding GREB1-like protein (Q9C091). Plays a major role in early metanephros and genital development.

Acts upstream of or within kidney development. Predicted to be located in membrane. Implicated in autosomal dominant nonsyndromic deafness 80 and renal agenesis.

Source: NCBI Gene 80000 — RefSeq curated summary.

At a glance

• Gene–disease (curated): renal hypodysplasia/aplasia 3 (Definitive, GenCC) — +3 more curated relationships
• GWAS associations: 3
• Clinical variants (ClinVar): 517 total — 37 pathogenic, 43 likely-pathogenic
• Phenotypes (HPO): 32
• MANE Select transcript: NM_001142966

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:31042
Approved symbol	GREB1L
Name	GREB1 like retinoic acid receptor coactivator
Location	18q11.1-q11.2
Locus type	gene with protein product
Status	Approved
Aliases	FLJ13687, C18orf6
Ensembl gene	ENSG00000141449
Ensembl biotype	protein_coding
OMIM	617782
Entrez	80000

Gene structure

Transcript identifiers

Ensembl transcripts: 13 — 8 protein_coding, 4 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000269218, ENST00000424526, ENST00000578368, ENST00000578383, ENST00000578955, ENST00000579454, ENST00000580384, ENST00000580683, ENST00000580732, ENST00000581327, ENST00000584446, ENST00000861016, ENST00000942000

RefSeq mRNA: 3 — MANE Select: NM_001142966 NM_001142966, NM_001410867, NM_001410868

CCDS: CCDS45836, CCDS92442, CCDS92443

Canonical transcript exons

ENST00000424526 — 33 exons

Exon	Start	End
ENSE00001242851	21366027	21366136
ENSE00001615927	21473031	21473211
ENSE00003458499	21449510	21449836
ENSE00003461816	21518034	21518234
ENSE00003475310	21485620	21485753
ENSE00003481525	21384206	21384403
ENSE00003509587	21439521	21439637
ENSE00003511368	21505412	21505567
ENSE00003513982	21395385	21395561
ENSE00003527464	21441400	21441537
ENSE00003532915	21513821	21513986
ENSE00003538708	21490012	21490351
ENSE00003539043	21520688	21520823
ENSE00003540691	21444224	21444409
ENSE00003541039	21500540	21500642
ENSE00003557799	21403872	21403994
ENSE00003564898	21495670	21495785
ENSE00003573776	21499729	21500306
ENSE00003574644	21454366	21454563
ENSE00003575997	21477164	21477356
ENSE00003582540	21440269	21440388
ENSE00003594071	21516613	21516754
ENSE00003608466	21508387	21508591
ENSE00003612553	21515417	21515644
ENSE00003624342	21401150	21401326
ENSE00003629616	21452083	21452217
ENSE00003632474	21508118	21508279
ENSE00003641093	21505810	21505949
ENSE00003642120	21496454	21496698
ENSE00003651837	21451023	21451151
ENSE00003694289	21383510	21383675
ENSE00003932836	21242232	21242393
ENSE00003937374	21522658	21526112

Expression profiles

Bgee: expression breadth ubiquitous, 184 present calls, max score 87.27.

FANTOM5 (CAGE): breadth broad, TPM avg 7.4715 / max 627.8758, expressed in 842 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
169593	5.6975	771
169594	1.0998	453
169597	0.3758	94
169592	0.1720	72
169596	0.1063	43
169598	0.0202	7

Top tissues by expression

272 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
buccal mucosa cell	CL:0002336	87.27	silver quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	84.00	gold quality
gastrocnemius	UBERON:0001388	81.45	gold quality
muscle of leg	UBERON:0001383	81.07	gold quality
hindlimb stylopod muscle	UBERON:0004252	79.85	gold quality
muscle organ	UBERON:0001630	78.40	gold quality
skeletal muscle organ	UBERON:0014892	78.39	gold quality
decidua	UBERON:0002450	78.25	gold quality
right atrium auricular region	UBERON:0006631	77.96	gold quality
secondary oocyte	CL:0000655	77.54	gold quality
cardiac atrium	UBERON:0002081	76.56	gold quality
apex of heart	UBERON:0002098	76.42	gold quality
left lobe of thyroid gland	UBERON:0001120	75.36	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	75.25	gold quality
descending thoracic aorta	UBERON:0002345	74.98	gold quality
left ovary	UBERON:0002119	74.60	gold quality
diaphragm	UBERON:0001103	74.30	gold quality
thyroid gland	UBERON:0002046	74.26	gold quality
right lobe of thyroid gland	UBERON:0001119	73.92	gold quality
cauda epididymis	UBERON:0004360	73.50	gold quality
left uterine tube	UBERON:0001303	73.29	gold quality
caput epididymis	UBERON:0004358	73.23	gold quality
right ovary	UBERON:0002118	73.15	gold quality
calcaneal tendon	UBERON:0003701	73.08	gold quality
popliteal artery	UBERON:0002250	72.99	gold quality
tibial artery	UBERON:0007610	72.94	gold quality
stromal cell of endometrium	CL:0002255	72.92	gold quality
aorta	UBERON:0000947	72.66	gold quality
heart left ventricle	UBERON:0002084	72.63	gold quality
heart	UBERON:0000948	72.48	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-CURD-119	yes	9.78
E-GEOD-93593	yes	7.45
E-ANND-3	yes	7.36
E-ENAD-17	no	70.70

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 6)

• A novel autosomal dominant GREB1L variant associated with non-syndromic hearing impairment in Ghana. (PMID:36357908)
• A novel missense mutation in GREB1L identified in a three-generation family with renal hypodysplasia/aplasia-3. (PMID:36371238)
• Rare variant enrichment analysis supports GREB1L as a contributory driver gene in the etiology of Mayer-Rokitansky-Kuster-Hauser syndrome. (PMID:37124138)
• GREB1L overexpression is associated with good clinical outcomes in breast cancer. (PMID:37964281)
• The expanded spectrum of human disease associated with GREB1L likely includes complex congenital heart disease. (PMID:38285371)
• Whole exome sequencing reveals two novel mutations in GREB1L in two Chinese families with renal agenesis. (PMID:38410081)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	greb1l	ENSDARG00000039196
mus_musculus	Greb1l	ENSMUSG00000042942
rattus_norvegicus	Greb1l	ENSRNOG00000023492

Paralogs (1): GREB1 (ENSG00000196208)

Protein

Protein identifiers

GREB1-like protein — Q9C091 (reviewed: Q9C091)

Alternative names: Growth regulation by estrogen in breast cancer 1-like protein

All UniProt accessions (4): Q9C091, J3KRT4, J3QQW0, J3QR03

UniProt curated annotations — full annotation on UniProt →

Function. Plays a major role in early metanephros and genital development.

Subcellular location. Membrane.

Tissue specificity. Widely expressed, with prominent expression in the cochlea. Expressed at high levels in fetal kidney. In adult tissues, highest levels in vagina, cervix and epididymis.

Disease relevance. Renal hypodysplasia/aplasia 3 (RHDA3) [MIM:617805] A severe, autosomal dominant disease encompassing a spectrum of kidney development defects. Clinical manifestations are highly variable and include bilateral or unilateral renal agenesis, renal aplasia, hypoplasia, (cystic) dysplasia, severe obstructive uropathy, and vesicoureteral reflux. Bilateral renal agenesis is almost invariably fatal in utero or in the perinatal period. Unilateral renal agenesis can lead to future health issues including end-stage renal disease. The disease is caused by variants affecting the gene represented in this entry. Deafness, autosomal dominant, 80 (DFNA80) [MIM:619274] A form of non-syndromic, sensorineural hearing loss. Sensorineural hearing loss results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information. DFNA80 is characterized by severe inner ear malformations, bilateral cochlear aplasia and absent eighth cranial nerve. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the GREB1 family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q9C091-1	1	yes
Q9C091-3	3
Q9C091-4	4

RefSeq proteins (3): NP_001136438, NP_001397796, NP_001397797 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR028422	GREB1	Family
IPR046926	GREB1_N	Domain
IPR046927	GREB1-like_C	Domain
IPR048657	GREB1-like_cpSF2	Domain
IPR048659	GREB1-like_2nd	Domain
IPR049100	TAGT	Domain

Pfam: PF15782, PF20267, PF20688, PF20691, PF20692

UniProt features (51 total): sequence variant 35, compositionally biased region 6, splice variant 3, region of interest 3, sequence conflict 2, chain 1, transmembrane region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9C091-F1	72.90	0.29

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 193 (showing top): GSE45365_CTRL_VS_MCMV_INFECTION_NK_CELL_UP, GOBP_CARDIAC_CHAMBER_DEVELOPMENT, GOBP_MORPHOGENESIS_OF_AN_EPITHELIUM, TGGTGCT_MIR29A_MIR29B_MIR29C, GOBP_RIBOSOME_BIOGENESIS, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_MUSCLE_TISSUE_DEVELOPMENT, GOBP_METANEPHROS_DEVELOPMENT, TGCTGCT_MIR15A_MIR16_MIR15B_MIR195_MIR424_MIR497, GOBP_MALE_GENITALIA_DEVELOPMENT, GOBP_STRIATED_MUSCLE_CELL_DIFFERENTIATION, ATGCAGT_MIR217, GOBP_KIDNEY_EPITHELIUM_DEVELOPMENT, CAGCTG_AP4_Q5, GOBP_HORMONE_MEDIATED_SIGNALING_PATHWAY

GO Biological Process (15): metanephros development (GO:0001656), branching involved in ureteric bud morphogenesis (GO:0001658), kidney development (GO:0001822), morphogenesis of an epithelium (GO:0002009), outflow tract morphogenesis (GO:0003151), cardiac ventricle development (GO:0003231), male genitalia development (GO:0030539), embryonic heart tube development (GO:0035050), ribosome biogenesis (GO:0042254), retinoic acid receptor signaling pathway (GO:0048384), cardiac muscle cell differentiation (GO:0055007), uterus development (GO:0060065), paramesonephric duct development (GO:0061205), mesonephric duct development (GO:0072177), epithelial tube morphogenesis (GO:0060562)

GO Molecular Function (0):

GO Cellular Component (1): membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
animal organ development	2
epithelium development	2
tube development	2
kidney development	1
branching morphogenesis of an epithelial tube	1
ureteric bud morphogenesis	1
renal system development	1
tissue morphogenesis	1
heart morphogenesis	1
anatomical structure morphogenesis	1
cardiac chamber development	1
male sex differentiation	1
genitalia development	1
reproductive system development	1
heart development	1
embryonic organ development	1
ribonucleoprotein complex biogenesis	1
hormone-mediated signaling pathway	1
nuclear receptor-mediated signaling pathway	1
cardiocyte differentiation	1
cardiac muscle tissue development	1
striated muscle cell differentiation	1
reproductive structure development	1
developmental process involved in reproduction	1
mesonephric tubule development	1
nephric duct development	1
morphogenesis of an epithelium	1
tube morphogenesis	1
cellular anatomical structure	1

Protein interactions and networks

STRING

598 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GREB1L	VGLL3	A8MV65	503
GREB1L	ROCK1	Q13464	492
GREB1L	TULP4	Q9NRJ4	464
GREB1L	CAAP1	Q9H8G2	460
GREB1L	SLC35D4	Q24JQ0	456
GREB1L	DZIP1L	Q8IYY4	415
GREB1L	ABHD3	Q8WU67	398
GREB1L	SNX13	Q9Y5W8	394
GREB1L	ANKRD29	Q8N6D5	392
GREB1L	TOPAZ1	Q8N9V7	385
GREB1L	QSER1	Q2KHR3	385
GREB1L	FAN1	Q9Y2M0	375
GREB1L	CWC25	Q9NXE8	373
GREB1L	SPIRE1	Q08AE8	360
GREB1L	ZNF853	P0CG23	358

IntAct

14 interactions, top by confidence:

A	B	Type	Score
CLP1	PCF11	psi-mi:“MI:0914”(association)	0.590
GREB1L	RPL4	psi-mi:“MI:0915”(physical association)	0.400
NEK4	E2F8	psi-mi:“MI:0914”(association)	0.350
ESR1	ESYT2	psi-mi:“MI:0914”(association)	0.350
M		psi-mi:“MI:0914”(association)	0.350
CEP192	WASL	psi-mi:“MI:0914”(association)	0.350
ATG16L1	ESYT2	psi-mi:“MI:0914”(association)	0.350
LYPD4	PIK3C2A	psi-mi:“MI:0914”(association)	0.350
TTC9C	PLD2	psi-mi:“MI:0914”(association)	0.350
PNKD	ADD1	psi-mi:“MI:0914”(association)	0.350
TSEN2	TMED8	psi-mi:“MI:0914”(association)	0.350

BioGRID (25): GREB1L (Affinity Capture-RNA), GREB1L (Affinity Capture-RNA), GREB1L (Affinity Capture-MS), GREB1L (Affinity Capture-MS), GREB1L (Affinity Capture-RNA), GREB1L (Affinity Capture-MS), GREB1L (Affinity Capture-RNA), GREB1L (Affinity Capture-MS), GREB1L (Proximity Label-MS), GREB1L (Proximity Label-MS), GREB1L (Affinity Capture-MS), GREB1L (Affinity Capture-MS), GREB1L (Affinity Capture-MS), GREB1L (Affinity Capture-MS), GREB1L (Affinity Capture-MS)

ESM2 similar proteins: A0A140LFM6, A0A1B0GUA6, A0JMD2, A2VCZ5, A5WUT8, A6H5Y1, A6NKB5, B8JKP6, D3ZJ47, F1M5M3, F1MJR8, M0R5D6, O14513, O60284, P0CAX8, Q0P4S0, Q15468, Q1LV19, Q1RMQ5, Q4V7H1, Q5DU28, Q5DW34, Q5REU9, Q5SW75, Q5SWW4, Q5U4U4, Q5ZM13, Q60664, Q60988, Q6P9N1, Q6ZPK7, Q76I76, Q76I79, Q80TA9, Q80TY4, Q8BLN6, Q8BYM7, Q8IWB6, Q8JGS1, Q8K2J4

Diamond homologs: B8JKP6, B9EJV3, Q3UHK3, Q4ZG55, Q9C091

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

517 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	37
Likely pathogenic	43
Uncertain significance	228
Likely benign	141
Benign	32

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1013396	NM_001142966.3(GREB1L):c.1735C>T (p.Arg579Ter)	Pathogenic
1064690	NM_001142966.3(GREB1L):c.705G>T (p.Trp235Cys)	Pathogenic
1172553	NM_001142966.3(GREB1L):c.3977del (p.Lys1326fs)	Pathogenic
1172554	NM_001142966.3(GREB1L):c.3983del (p.Gly1328fs)	Pathogenic
1684664	NM_001142966.3(GREB1L):c.4992T>A (p.Tyr1664Ter)	Pathogenic
2084026	NM_001142966.3(GREB1L):c.4115_4118dup (p.Trp1373fs)	Pathogenic
2113840	NM_001142966.3(GREB1L):c.3574dup (p.Gln1192fs)	Pathogenic
2444475	NM_001142966.3(GREB1L):c.3146+1G>A	Pathogenic
2444485	NM_001142966.3(GREB1L):c.5396_5397del (p.Lys1799fs)	Pathogenic
2581335	NM_001142966.3(GREB1L):c.570dup (p.Phe191fs)	Pathogenic
2626752	NM_001142966.3(GREB1L):c.1975C>T (p.Gln659Ter)	Pathogenic
3061184	NM_001142966.3(GREB1L):c.1907_1910dup (p.Pro638fs)	Pathogenic
3601152	NM_001142966.3(GREB1L):c.1144G>T (p.Glu382Ter)	Pathogenic
3601155	NM_001142966.3(GREB1L):c.1498_1499del (p.Val500fs)	Pathogenic
3601157	NM_001142966.3(GREB1L):c.2556+1G>A	Pathogenic
3601159	NM_001142966.3(GREB1L):c.5562dup (p.Asp1855Ter)	Pathogenic
3601160	NM_001142966.3(GREB1L):c.5761_5762insAT (p.Arg1921fs)	Pathogenic
3641419	NM_001142966.3(GREB1L):c.4509del (p.Leu1504fs)	Pathogenic
3722079	NM_001142966.3(GREB1L):c.5220del (p.Lys1740fs)	Pathogenic
3727887	NM_001142966.3(GREB1L):c.4860_4861del (p.Val1622fs)	Pathogenic
3894532	NM_001142966.3(GREB1L):c.2173C>T (p.Arg725Ter)	Pathogenic
4291137	NM_001142966.3(GREB1L):c.2491_2492del (p.Leu831fs)	Pathogenic
446526	NM_001142966.3(GREB1L):c.982C>T (p.Arg328Ter)	Pathogenic
446527	NM_001142966.3(GREB1L):c.4368G>T (p.Gln1456His)	Pathogenic
453273	NM_001142966.3(GREB1L):c.5378T>G (p.Leu1793Arg)	Pathogenic
453274	NM_001142966.3(GREB1L):c.5608+1del	Pathogenic
453275	NM_001142966.3(GREB1L):c.4000dup (p.Leu1334fs)	Pathogenic
453276	NM_001142966.3(GREB1L):c.4680C>A (p.Tyr1560Ter)	Pathogenic
453280	NM_001142966.3(GREB1L):c.1582del (p.Gln528fs)	Pathogenic
453281	NM_001142966.3(GREB1L):c.4369-1G>C	Pathogenic

SpliceAI

7562 predictions. Top by Δscore:

Variant	Effect	Δscore
18:21350756:G:GT	donor_gain	1.0000
18:21350757:A:T	donor_gain	1.0000
18:21383497:T:TA	acceptor_gain	1.0000
18:21383498:G:A	acceptor_gain	1.0000
18:21384195:T:TA	acceptor_gain	1.0000
18:21384201:C:G	acceptor_gain	1.0000
18:21384201:CCCA:C	acceptor_loss	1.0000
18:21384202:CCA:C	acceptor_loss	1.0000
18:21384204:A:AG	acceptor_gain	1.0000
18:21384204:AGAT:A	acceptor_gain	1.0000
18:21384205:G:GG	acceptor_gain	1.0000
18:21384205:GA:G	acceptor_gain	1.0000
18:21384205:GAT:G	acceptor_gain	1.0000
18:21384205:GATG:G	acceptor_gain	1.0000
18:21384205:GATGT:G	acceptor_gain	1.0000
18:21384400:GATG:G	donor_gain	1.0000
18:21384403:GGT:G	donor_loss	1.0000
18:21384404:G:GA	donor_loss	1.0000
18:21384405:T:A	donor_loss	1.0000
18:21384415:T:G	donor_gain	1.0000
18:21395371:AAACT:A	acceptor_gain	1.0000
18:21395373:ACT:A	acceptor_gain	1.0000
18:21395375:T:A	acceptor_gain	1.0000
18:21395383:A:AG	acceptor_gain	1.0000
18:21395383:A:G	acceptor_loss	1.0000
18:21395384:G:GG	acceptor_gain	1.0000
18:21395384:GGTT:G	acceptor_gain	1.0000
18:21395384:GGTTT:G	acceptor_gain	1.0000
18:21395557:TTTAG:T	donor_gain	1.0000
18:21395558:TTAG:T	donor_gain	1.0000

AlphaMissense

12615 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
18:21384391:T:A	C115S	1.000
18:21384391:T:C	C115R	1.000
18:21384392:G:A	C115Y	1.000
18:21384392:G:C	C115S	1.000
18:21384393:C:G	C115W	1.000
18:21384403:G:C	G119R	1.000
18:21395385:G:A	G119D	1.000
18:21395390:T:A	C121S	1.000
18:21395390:T:C	C121R	1.000
18:21395390:T:G	C121G	1.000
18:21395391:G:A	C121Y	1.000
18:21395391:G:C	C121S	1.000
18:21395391:G:T	C121F	1.000
18:21395392:T:G	C121W	1.000
18:21395399:G:A	G124R	1.000
18:21395399:G:C	G124R	1.000
18:21395400:G:A	G124E	1.000
18:21395400:G:T	G124V	1.000
18:21395405:G:C	D126H	1.000
18:21395406:A:C	D126A	1.000
18:21395406:A:T	D126V	1.000
18:21395409:T:C	L127S	1.000
18:21395411:C:A	R128S	1.000
18:21395412:G:C	R128P	1.000
18:21395415:T:C	L129S	1.000
18:21395456:T:C	F143L	1.000
18:21395457:T:C	F143S	1.000
18:21395458:C:A	F143L	1.000
18:21395458:C:G	F143L	1.000
18:21395466:T:A	V146E	1.000

dbSNP variants (sampled 300 via entrez): RS1000000560 (18:21327414 A>C), RS1000006705 (18:21473662 C>A,T), RS1000039777 (18:21502097 C>A,T), RS1000045500 (18:21307570 C>G,T), RS1000062315 (18:21280226 C>T), RS1000068603 (18:21488010 CAA>C,CA,CAAA,CAAAA), RS1000074673 (18:21425162 C>A), RS1000093141 (18:21391693 T>C), RS1000096558 (18:21326976 A>C), RS1000137291 (18:21293873 G>A), RS1000137708 (18:21466884 G>A), RS1000148098 (18:21375764 T>C), RS1000162814 (18:21360985 A>G), RS1000202498 (18:21525831 T>C), RS1000207307 (18:21348387 C>T)

Disease associations

OMIM: gene MIM:617782 | disease phenotypes: MIM:617805, MIM:277000, MIM:619274, MIM:601076, MIM:191830, MIM:610805, MIM:181800, MIM:124900

GenCC curated gene-disease

Disease	Classification	Inheritance
renal hypodysplasia/aplasia 3	Definitive	Autosomal dominant
hearing loss, autosomal dominant 80	Strong	Autosomal dominant
bilateral renal agenesis	Supportive	Autosomal recessive
renal agenesis, unilateral	Supportive	Autosomal dominant

Mondo (11): renal hypodysplasia/aplasia 3 (MONDO:0024520), Mayer-Rokitansky-Kuster-Hauser syndrome type 1 (MONDO:0010173), hearing loss, autosomal dominant 80 (MONDO:0030998), Mayer-Rokitansky-Küster-Hauser syndrome type 2 (MONDO:0010989), renal agenesis (MONDO:0018470), congenital anomaly of kidney and urinary tract (MONDO:0019719), scoliosis, isolated, susceptibility to, 1 (MONDO:0008419), Mayer-Rokitansky-Kuster-Hauser syndrome (MONDO:0017771), autosomal dominant nonsyndromic hearing loss (MONDO:0019587), bilateral renal agenesis (MONDO:0015986), renal agenesis, unilateral (MONDO:0019636)

Orphanet (7): Mayer-Rokitansky-Küster-Hauser syndrome type 1 (Orphanet:247775), Mayer-Rokitansky-Küster-Hauser syndrome type 2 (Orphanet:2578), Mayer-Rokitansky-Küster-Hauser syndrome (Orphanet:3109), Renal agenesis (Orphanet:411709), Renal or urinary tract malformation (Orphanet:93545), Male infertility with azoospermia or oligozoospermia due to single gene mutation (Orphanet:399805), Rare autosomal dominant non-syndromic sensorineural deafness type DFNA (Orphanet:90635)

HPO phenotypes

32 total (30 of 32 shown, HPO-id order):

HPO	Term
HP:0000003	Multicystic kidney dysplasia
HP:0000006	Autosomal dominant inheritance
HP:0000008	Abnormal morphology of female internal genitalia
HP:0000076	Vesicoureteral reflux
HP:0000085	Horseshoe kidney
HP:0000104	Renal agenesis
HP:0000110	Renal dysplasia
HP:0000126	Hydronephrosis
HP:0000130	Abnormality of the uterus
HP:0000175	Cleft palate
HP:0000286	Epicanthus
HP:0000316	Hypertelorism
HP:0000369	Low-set ears
HP:0000457	Depressed nasal ridge
HP:0001562	Oligohydramnios
HP:0001563	Fetal polyuria
HP:0001958	Nonketotic hypoglycemia
HP:0002089	Pulmonary hypoplasia
HP:0002242	Abnormal intestine morphology
HP:0002575	Tracheoesophageal fistula
HP:0003577	Congenital onset
HP:0003829	Typified by incomplete penetrance
HP:0005107	Abnormal sacrum morphology
HP:0008527	Congenital sensorineural hearing impairment
HP:0010497	Sirenomelia
HP:0011375	Cochlear aplasia
HP:0011379	Dilated vestibule of the inner ear
HP:0011380	Abnormal semicircular canal morphology
HP:0030680	Abnormal cardiovascular system morphology
HP:0100335	Non-midline cleft of the upper lip

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST010703_44	Brain morphology (MOSTest)	1.000000e-08
GCST90000025_652	Appendicular lean mass	1.000000e-12
GCST90002405_561	Reticulocyte count	2.000000e-09

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004346	neuroimaging measurement
EFO:0004980	appendicular lean mass
EFO:0007986	reticulocyte count

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C566906	Cakut (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

30 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression	5
bisphenol A	decreases expression	2
potassium chromate(VI)	affects cotreatment, decreases expression, increases expression	2
Benzo(a)pyrene	decreases methylation, increases mutagenesis	2
aristolochic acid I	decreases expression	1
bisphenol F	decreases expression	1
alpha phellandrene	increases expression	1
triphenyl phosphate	affects expression	1
propionaldehyde	increases expression	1
arsenite	increases methylation	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
chromium hexavalent ion	affects expression	1
perfluorooctane sulfonic acid	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
jinfukang	affects cotreatment, decreases expression	1
(+)-JQ1 compound	increases expression	1
Cisplatin	affects cotreatment, decreases expression	1
Doxorubicin	decreases expression	1
Estradiol	increases expression	1
Lipopolysaccharides	affects response to substance, increases expression	1
Methotrexate	increases expression	1
Phthalic Acids	increases methylation	1
Thiram	increases expression	1
Tobacco Smoke Pollution	increases expression	1
Tretinoin	decreases expression	1
Urethane	decreases expression	1
Cyclosporine	decreases expression	1
Okadaic Acid	increases expression	1

Clinical trials (associated diseases)

20 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT03277430	PHASE3	UNKNOWN	Uterus Transplantation From Live Donors and From Deceased Donors - Clinical Study
NCT04115345	PHASE1	COMPLETED	A Study of a Renal Autologous Cell Therapy (REACT) in Patients With Chronic Kidney Disease (CKD) From Congenital Anomalies of the Kidney and Urinary Tract (CAKUT).
NCT05694169	PHASE1	TERMINATED	A Study of Participants With Chronic Kidney Disease Previously Treated With REACT
NCT06728228	Not specified	RECRUITING	Amnioinfusion for Fetal Renal Failure
NCT01831141	Not specified	UNKNOWN	Long Term Outcome of Congenital Solitary Kidney
NCT01911884	Not specified	COMPLETED	Assessment of Quality of Global and Sexual Life and Impact of Surgical and Non Surgical Vaginal Aplasia in Patients With a Rokitansky Syndrome
NCT05415540	Not specified	COMPLETED	Evolution of the Quality of Life and Experience of Young Women With Utero-vaginal Aplasia (MRKHPSY)
NCT07186764	Not specified	RECRUITING	Evaluation of the Quality of Life and Gynecological Follow-up of Patients Treated for Mayer-Rokitansky-Küster-Hauser (MRKH) Syndrome
NCT07321782	Not specified	NOT_YET_RECRUITING	Clinical and Imaging Features in MRKH Syndrome
NCT04537364	Not specified	COMPLETED	Prediction of Renal Parenchymal Damage of CAKUT
NCT06921733	Not specified	RECRUITING	Ultrasound Localization Microscopy in Patient With Congenital Anomalies of the Kidney and Urinary Tract (CAKUT)
NCT02967822	Not specified	RECRUITING	Molecular Genetic Study of Mayer-Rokitansky-Kuster-Hauser Syndrome
NCT03252795	Not specified	RECRUITING	Uterus Transplantation From a Multi-organ Donor
NCT03307356	Not specified	ACTIVE_NOT_RECRUITING	The University of Pennsylvania Uterus Transplant for Uterine Factor Infertility Trial
NCT03689842	Not specified	RECRUITING	Feasibility Study of Uterine Transplantation From Living Donors in Terms of Efficacy and Safety in Patients With Mayer-Rokitansky-Küster-Hauser Syndrome (MRKH)
NCT04314869	Not specified	UNKNOWN	Uterus Transplantation Procedure From a Live Donor
NCT04923217	Not specified	COMPLETED	Quality of Life and Sexual Function in Vaginal Aplasia Patients After Davydov Procedure
NCT05263076	Not specified	RECRUITING	Uterine Transplant for Women With Absolute Uterine Factor Infertility (AUFI)
NCT05925361	Not specified	UNKNOWN	Peritoneum Vaginoplasty; Implementation According to IDEAL Framework
NCT06508151	Not specified	NOT_YET_RECRUITING	Neovaginoplasty Using Photoinduced-imine-crosslink Hydrogel in MRKH Patients