WDR73

Summary

WDR73 (WD repeat domain 73, HGNC:25928) is a protein-coding gene on chromosome 15q25.2, encoding Integrator complex assembly factor WDR73 (Q6P4I2). Component of a multiprotein complex required for the assembly of the RNA endonuclease module of the integrator complex. It is a selective cancer dependency (DepMap: 52.6% of cell lines).

The protein encoded by this gene is thought to contain multiple WD40 repeats. WD40 repeats are motifs that contain 40-60 amino acids, and usually end with Trp-Asp (WD). This protein is found in the cytoplasm during interphase, but accumulates at the spindle poles and astral microtubules during mitosis. Reduced expression of this gene results in abnormalities in the size and morphology of the nucleus. Mutations in this gene have been associated with Galloway-Mowat syndrome PMID: 25466283), which is a rare autosomal recessive disorder that affects both the central nervous system and kidneys. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 84942 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Galloway-Mowat syndrome 1 (Strong, GenCC) — +2 more curated relationships
• GWAS associations: 8
• Clinical variants (ClinVar): 291 total — 17 pathogenic, 13 likely-pathogenic
• Phenotypes (HPO): 85
• Cancer dependency (DepMap): dependent in 52.6% of screened cell lines
• MANE Select transcript: NM_032856

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25928
Approved symbol	WDR73
Name	WD repeat domain 73
Location	15q25.2
Locus type	gene with protein product
Status	Approved
Aliases	FLJ14888, HSPC264
Ensembl gene	ENSG00000177082
Ensembl biotype	protein_coding
OMIM	616144
Entrez	84942

Gene structure

Transcript identifiers

Ensembl transcripts: 25 — 14 retained_intron, 5 protein_coding, 3 protein_coding_CDS_not_defined, 3 nonsense_mediated_decay

ENST00000398528, ENST00000434634, ENST00000558019, ENST00000558487, ENST00000558521, ENST00000558608, ENST00000559015, ENST00000559126, ENST00000559178, ENST00000559224, ENST00000559452, ENST00000559877, ENST00000559994, ENST00000560088, ENST00000560182, ENST00000560252, ENST00000560835, ENST00000560966, ENST00000561329, ENST00000561434, ENST00000561447, ENST00000873649, ENST00000915865, ENST00000948302, ENST00000948303

RefSeq mRNA: 1 — MANE Select: NM_032856 NM_032856

CCDS: CCDS45339

Canonical transcript exons

ENST00000434634 — 8 exons

Exon	Start	End
ENSE00001518926	84639285	84643723
ENSE00002574888	84654234	84654283
ENSE00003485764	84647890	84647954
ENSE00003529496	84648537	84648625
ENSE00003565332	84653632	84653699
ENSE00003581757	84646184	84646348
ENSE00003589480	84652714	84652802
ENSE00003673986	84645471	84645836

Expression profiles

Bgee: expression breadth ubiquitous, 275 present calls, max score 91.61.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 12.6694 / max 117.1167, expressed in 1784 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
151332	12.0793	1778
151330	0.3330	154
151331	0.2571	124

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right uterine tube	UBERON:0001302	91.61	gold quality
right lobe of thyroid gland	UBERON:0001119	91.40	gold quality
pituitary gland	UBERON:0000007	90.79	gold quality
adenohypophysis	UBERON:0002196	90.45	gold quality
epithelium of bronchus	UBERON:0002031	90.23	gold quality
bronchial epithelial cell	CL:0002328	90.04	gold quality
left lobe of thyroid gland	UBERON:0001120	90.00	gold quality
bronchus	UBERON:0002185	90.00	gold quality
right adrenal gland	UBERON:0001233	89.83	gold quality
right adrenal gland cortex	UBERON:0035827	89.68	gold quality
thyroid gland	UBERON:0002046	89.60	gold quality
left adrenal gland cortex	UBERON:0035825	88.97	gold quality
left adrenal gland	UBERON:0001234	88.90	gold quality
metanephros cortex	UBERON:0010533	88.90	gold quality
left ovary	UBERON:0002119	88.89	gold quality
adrenal cortex	UBERON:0001235	88.83	gold quality
body of uterus	UBERON:0009853	88.49	gold quality
right ovary	UBERON:0002118	88.46	gold quality
cardia of stomach	UBERON:0001162	88.43	gold quality
endocervix	UBERON:0000458	88.38	gold quality
adrenal gland	UBERON:0002369	88.19	gold quality
body of pancreas	UBERON:0001150	87.85	gold quality
ventricular zone	UBERON:0003053	87.80	gold quality
left uterine tube	UBERON:0001303	87.66	gold quality
caput epididymis	UBERON:0004358	87.56	gold quality
corpus epididymis	UBERON:0004359	87.41	gold quality
apex of heart	UBERON:0002098	87.39	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	86.97	gold quality
adrenal tissue	UBERON:0018303	86.89	gold quality
muscle layer of sigmoid colon	UBERON:0035805	86.88	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.94
E-MTAB-6142	no	179.27

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

49 targeting WDR73, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-10401-5P	99.99	65.79	948
HSA-MIR-520G-5P	99.99	66.76	658
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-3934-3P	99.76	65.51	1351
HSA-MIR-1296-3P	99.72	64.04	636
HSA-MIR-1283	99.69	72.42	3009
HSA-MIR-1303	99.65	69.77	1662
HSA-MIR-6134	99.63	65.68	1537
HSA-MIR-3975	99.62	65.97	697
HSA-MIR-4649-3P	99.56	66.90	1783
HSA-MIR-4735-5P	99.43	68.49	1780
HSA-MIR-377-3P	99.37	70.18	1905
HSA-MIR-19A-5P	99.36	66.93	1675
HSA-MIR-19B-1-5P	99.36	67.07	1669
HSA-MIR-19B-2-5P	99.36	67.07	1669
HSA-MIR-329-5P	99.27	68.11	1597
HSA-MIR-6504-3P	99.17	69.31	2891
HSA-MIR-10399-5P	99.17	69.87	2610
HSA-MIR-7151-3P	99.04	69.72	2370
HSA-MIR-6506-5P	99.04	65.66	1386
HSA-MIR-6877-3P	98.98	65.83	560
HSA-MIR-6819-3P	98.95	65.57	572
HSA-MIR-3190-5P	98.87	64.89	1345
HSA-MIR-3611	98.76	68.76	1290
HSA-MIR-7851-3P	98.72	64.88	980
HSA-MIR-4680-3P	98.64	68.60	2093

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 52.6% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 8)

• WDR73 plays a crucial role in the maintenance of cell architecture and cell survival. (PMID:25466283)
• Nonsense mutation in the WDR73 gene is associated with Galloway-Mowat syndrome (PMID:25873735)
• WDR73 interacts with mitotic microtubules to regulate cell cycle progression, proliferation and survival in brain (PMID:26070982)
• We document postnatal onset of CA, a retinopathy, basal ganglia degeneration, and short stature as novel features of WDR73-related disease, and define WDR73-related disease as a new entity of infantile neurodegeneration. (PMID:26123727)
• WDR73 as a candidate gene of severe intellectual disability and cerebellar hypoplasia. (PMID:27983999)
• We expanded the clinical phenotype of GMS with WDR73 gene defect to include retinal dysfunction with missense mutation and developmental dysplasia of the hip. (PMID:29929488)
• A new homozygous missense mutation was identified in two siblings with Galloway-Mowat syndrome. (PMID:30315938)
• Disruption of pathways regulated by Integrator complex in Galloway-Mowat syndrome due to WDR73 mutations. (PMID:33686175)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	wdr73	ENSDARG00000023152
mus_musculus	Wdr73	ENSMUSG00000025722
rattus_norvegicus	Wdr73	ENSRNOG00000010664

Paralogs (9): ERCC8 (ENSG00000049167), GEMIN5 (ENSG00000082516), RBBP7 (ENSG00000102054), WDR59 (ENSG00000103091), GRWD1 (ENSG00000105447), PEX7 (ENSG00000112357), WDR77 (ENSG00000116455), WDR24 (ENSG00000127580), RBBP4 (ENSG00000162521)

Protein

Protein identifiers

Integrator complex assembly factor WDR73 — Q6P4I2 (reviewed: Q6P4I2)

Alternative names: WD repeat-containing protein 73

All UniProt accessions (4): Q6P4I2, H0YLH0, H0YMT3, H0YMX2

UniProt curated annotations — full annotation on UniProt →

Function. Component of a multiprotein complex required for the assembly of the RNA endonuclease module of the integrator complex. Associates with INTS9 and INTS11 in the cytoplasm, stabilizing the INTS9-INTS11 heterodimer and blocking the active site of INTS11. BRAT1 then joins the complex and plugs the active site of INTS11, leading to WDR73 release and nuclear import of INTS9 and INTS11.

Subunit / interactions. Interacts with INTS9 and INTS11; the interaction is direct. Part of the multiprotein complex composed of BRAT1, WDR73, as well as integrator complex subunits INTS9 and INTS11.

Subcellular location. Cytoplasm. Cytoskeleton. Spindle. Spindle pole. Cleavage furrow.

Tissue specificity. Expressed in kidney and brain. In the kidney, expressed in glomeruli, most probably in podocytes, and in tubules (at protein level). In the brain, expressed in the cerebellum, with high levels in Purkinje cells and their projecting axons, in the deep cerebellar nuclei and in pyramidal neurons of the cerebral cortex (at protein level). In the white matter, mainly present in astrocytes, but not in oligodendrocytes (at protein level). Also highly expressed in endothelial cells of cerebral capillaries (at protein level).

Disease relevance. Galloway-Mowat syndrome 1 (GAMOS1) [MIM:251300] A form of Galloway-Mowat syndrome, a severe renal-neurological disease characterized by early-onset nephrotic syndrome associated with microcephaly, central nervous system abnormalities, developmental delays, and a propensity for seizures. Brain anomalies include gyration defects ranging from lissencephaly to pachygyria and polymicrogyria, and cerebellar hypoplasia. Most patients show facial dysmorphism characterized by a small, narrow forehead, large/floppy ears, deep-set eyes, hypertelorism and micrognathia. Additional variable features are visual impairment and arachnodactyly. Patients may die in early childhood. GAMOS1 inheritance is autosomal recessive. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the WD repeat WDR73 family.

RefSeq proteins (1): NP_116245* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001680	WD40_rpt	Repeat
IPR015943	WD40/YVTN_repeat-like_dom_sf	Homologous_superfamily
IPR036322	WD40_repeat_dom_sf	Homologous_superfamily
IPR042795	Wdr73	Family

UniProt features (18 total): sequence variant 9, repeat 6, chain 1, mutagenesis site 1, sequence conflict 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
8R22	ELECTRON MICROSCOPY	3.9

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6P4I2-F1	87.81	0.68

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Mutagenesis-validated functional residues (1):

Position	Phenotype
8	abolished interaction with ints9 and ints11.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 250 (showing top): GOBP_CYTOPLASMIC_MICROTUBULE_ORGANIZATION, LINDGREN_BLADDER_CANCER_CLUSTER_3_DN, GOBP_NUCLEUS_ORGANIZATION, GCM_NUMA1, IVANOVA_HEMATOPOIESIS_INTERMEDIATE_PROGENITOR, GOCC_SPINDLE, GOCC_CELL_DIVISION_SITE, GOCC_PLASMA_MEMBRANE_REGION, SCGGAAGY_ELK1_02, MGGAAGTG_GABP_B, MARTENS_TRETINOIN_RESPONSE_DN, HIRSCH_CELLULAR_TRANSFORMATION_SIGNATURE_DN, BRUINS_UVC_RESPONSE_MIDDLE, GOBP_MICROTUBULE_CYTOSKELETON_ORGANIZATION, KRIEG_KDM3A_TARGETS_NOT_HYPOXIA

GO Biological Process (2): nucleus organization (GO:0006997), cytoplasmic microtubule organization (GO:0031122)

GO Molecular Function (2): protein-macromolecule adaptor activity (GO:0030674), protein binding (GO:0005515)

GO Cellular Component (6): spindle pole (GO:0000922), cytoplasm (GO:0005737), cleavage furrow (GO:0032154), spindle (GO:0005819), cytosol (GO:0005829), cytoskeleton (GO:0005856)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
intracellular membraneless organelle	2
organelle organization	1
microtubule cytoskeleton organization	1
supramolecular fiber organization	1
protein binding	1
molecular adaptor activity	1
binding	1
spindle	1
intracellular anatomical structure	1
cell division site	1
plasma membrane region	1
microtubule cytoskeleton	1
cytoplasm	1

Protein interactions and networks

STRING

2536 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
WDR73	TP53RK	Q96S44	710
WDR73	WDR4	P57081	646
WDR73	LAGE3	Q14657	628
WDR73	OSGEP	Q9NPF4	614
WDR73	NUP107	P57740	592
WDR73	COQ6	Q9Y2Z9	577
WDR73	NUP133	Q8WUM0	572
WDR73	TTC19	Q6DKK2	533
WDR73	DNAJB12	Q9NXW2	527
WDR73	BLMH	Q13867	519
WDR73	USP37	Q86T82	510
WDR73	PDSS2	Q86YH6	507
WDR73	LYRM4	Q9HD34	500
WDR73	MORF4L1	Q9UBU8	493
WDR73	SMARCAL1	Q9NZC9	487

IntAct

29 interactions, top by confidence:

A	B	Type	Score
CCM2	KRIT1	psi-mi:“MI:0914”(association)	0.960
INTS9	INTS11	psi-mi:“MI:0914”(association)	0.940
ALDH3B1	UBA6	psi-mi:“MI:0914”(association)	0.530
SLC2A14	SLC2A3	psi-mi:“MI:0914”(association)	0.530
WDR73	ANXA7	psi-mi:“MI:0915”(physical association)	0.370
CDKN1A	WDR73	psi-mi:“MI:0915”(physical association)	0.370
WDR73	DAZAP2	psi-mi:“MI:0915”(physical association)	0.370
WDR73	SMN1	psi-mi:“MI:0915”(physical association)	0.370
WDR73	TK1	psi-mi:“MI:0915”(physical association)	0.370
WDR73	TNFRSF14	psi-mi:“MI:0915”(physical association)	0.370
WDR73	TSC22D1	psi-mi:“MI:0915”(physical association)	0.370
RFPL2	BACH1	psi-mi:“MI:0914”(association)	0.350
DNAJC11	PDE6D	psi-mi:“MI:0914”(association)	0.350
HDAC7	ZMYM6	psi-mi:“MI:0914”(association)	0.350
SLC2A14	SLC2A3	psi-mi:“MI:0914”(association)	0.350
INTS9	GRN	psi-mi:“MI:0914”(association)	0.350
KCNQ3	AKT2	psi-mi:“MI:0914”(association)	0.350
PHETA1	CTNND1	psi-mi:“MI:0914”(association)	0.350
VWA2	RECQL4	psi-mi:“MI:0914”(association)	0.350
ALDH3B1	PIK3R2	psi-mi:“MI:0914”(association)	0.350
CIAO2A	MAP2K7	psi-mi:“MI:0914”(association)	0.350
LY86	MAP2K7	psi-mi:“MI:0914”(association)	0.350
NXPH3	NXPH4	psi-mi:“MI:0914”(association)	0.350
SLC25A11	FGL1	psi-mi:“MI:0914”(association)	0.350
TMED5	DGAT1	psi-mi:“MI:0914”(association)	0.350

BioGRID (39): WDR73 (Affinity Capture-MS), WDR73 (Affinity Capture-MS), WDR73 (Affinity Capture-MS), WDR73 (Affinity Capture-MS), WDR73 (Affinity Capture-MS), WDR73 (Affinity Capture-MS), WDR73 (Affinity Capture-MS), WDR73 (Affinity Capture-MS), WDR73 (Affinity Capture-MS), WDR73 (Affinity Capture-MS), WDR73 (Affinity Capture-MS), WDR73 (Affinity Capture-MS), WDR73 (Two-hybrid), WDR73 (Affinity Capture-MS), WDR73 (Affinity Capture-MS)

ESM2 similar proteins: A0JP70, A2CEI4, A5D8Q8, A8Q2R5, A9X1C6, B3MET8, B3NSK1, B4GIJ0, B4HND9, B4J8H6, B4KRQ4, B4MFM2, B4P7H8, B4QB64, O65555, Q13216, Q16MY0, Q1LZ08, Q28YY2, Q3SXM0, Q3U821, Q4KLQ5, Q4QR85, Q566T0, Q567G2, Q58DC2, Q5BIM8, Q5FVP5, Q6DFC6, Q6NPN9, Q6NUD0, Q6P4I2, Q6TEN6, Q6ZJW8, Q6ZJX0, Q7ZVR1, Q8BX17, Q8CFJ9, Q8IZU2, Q8L4M1

Diamond homologs: A5D8Q8, Q567G2, Q6P4I2, Q9CWR1

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	17
Likely pathogenic	13
Uncertain significance	139
Likely benign	63
Benign	23

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
162610	NM_032856.5(WDR73):c.129T>G (p.Tyr43Ter)	Pathogenic
1953148	NM_032856.5(WDR73):c.674_675del (p.Arg225fs)	Pathogenic
208466	NM_032856.5(WDR73):c.400_401del (p.Trp136fs)	Pathogenic
208467	NM_032856.5(WDR73):c.1039C>T (p.His347Tyr)	Pathogenic
208469	NM_032856.5(WDR73):c.940C>T (p.Gln314Ter)	Pathogenic
3255490	NM_032856.5(WDR73):c.285_287+1dup	Pathogenic
3370299	NM_032856.5(WDR73):c.475C>T (p.Gln159Ter)	Pathogenic
3390598	NM_032856.5(WDR73):c.82C>T (p.Arg28Ter)	Pathogenic
3628185	NM_032856.5(WDR73):c.466C>T (p.Arg156Ter)	Pathogenic
4076325	NM_032856.5(WDR73):c.717_847del (p.Ser240fs)	Pathogenic
4717466	NM_032856.5(WDR73):c.618del (p.Gln207fs)	Pathogenic
4819331	NM_032856.5(WDR73):c.753T>A (p.Cys251Ter)	Pathogenic
807718	NM_032856.5(WDR73):c.706_719dup (p.Ser240fs)	Pathogenic
812996	NM_032856.5(WDR73):c.681T>A (p.Cys227Ter)	Pathogenic
812997	NM_032856.5(WDR73):c.42-1G>C	Pathogenic
817296	NM_032856.5(WDR73):c.750_751del (p.Cys251fs)	Pathogenic
817321	NM_032856.5(WDR73):c.568_569del (p.Thr190fs)	Pathogenic
1180827	NM_032856.5(WDR73):c.173_174del (p.Leu58fs)	Likely pathogenic
1344892	NM_032856.5(WDR73):c.1096_1097del (p.Leu366fs)	Likely pathogenic
208468	NM_032856.5(WDR73):c.68T>A (p.Leu23Gln)	Likely pathogenic
242543	NM_032856.5(WDR73):c.293T>C (p.Leu98Pro)	Likely pathogenic
2434648	NM_032856.5(WDR73):c.41+1G>C	Likely pathogenic
2664753	NM_032856.5(WDR73):c.6_9del (p.Asp2fs)	Likely pathogenic
3577818	NM_032856.5(WDR73):c.1086_1089delinsCAGCA (p.Asp363fs)	Likely pathogenic
3577833	NM_032856.5(WDR73):c.699G>A (p.Trp233Ter)	Likely pathogenic
3577846	NM_032856.5(WDR73):c.388_391del (p.Glu130fs)	Likely pathogenic
4077743	NM_032856.5(WDR73):c.294_298delinsTCAGAAT (p.Val99fs)	Likely pathogenic
620324	NM_032856.5(WDR73):c.872T>A (p.Leu291Ter)	Likely pathogenic
620573	NM_032856.5(WDR73):c.1046G>A (p.Trp349Ter)	Likely pathogenic
635182	NM_032856.5(WDR73):c.767G>A (p.Arg256Gln)	Likely pathogenic

SpliceAI

1666 predictions. Top by Δscore:

Variant	Effect	Δscore
15:84646346:CAT:C	acceptor_gain	1.0000
15:84646348:TCT:T	acceptor_loss	1.0000
15:84646349:C:CC	acceptor_gain	1.0000
15:84646349:CTAG:C	acceptor_loss	1.0000
15:84652712:A:AT	donor_loss	1.0000
15:84652713:CCTT:C	donor_loss	1.0000
15:84652800:CTC:C	acceptor_gain	1.0000
15:84652803:C:CC	acceptor_gain	1.0000
15:84652803:CTGG:C	acceptor_loss	1.0000
15:84652804:T:A	acceptor_loss	1.0000
15:84653569:AGCT:A	donor_gain	1.0000
15:84643539:AGT:A	donor_gain	0.9900
15:84643541:T:TA	donor_gain	0.9900
15:84643596:C:A	donor_gain	0.9900
15:84643645:A:AC	donor_gain	0.9900
15:84643646:C:CC	donor_gain	0.9900
15:84646178:CGGTA:C	donor_loss	0.9900
15:84646179:GGTA:G	donor_loss	0.9900
15:84646180:GTA:G	donor_loss	0.9900
15:84646181:TA:T	donor_loss	0.9900
15:84646182:A:C	donor_loss	0.9900
15:84646183:C:A	donor_loss	0.9900
15:84646344:GACAT:G	acceptor_gain	0.9900
15:84646345:ACAT:A	acceptor_gain	0.9900
15:84646346:CATC:C	acceptor_gain	0.9900
15:84646347:AT:A	acceptor_gain	0.9900
15:84648624:CC:C	acceptor_gain	0.9900
15:84648625:CC:C	acceptor_gain	0.9900
15:84652721:T:TA	donor_gain	0.9900
15:84652798:GACTC:G	acceptor_gain	0.9900

AlphaMissense

2443 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
15:84643562:A:G	W349R	0.992
15:84643562:A:T	W349R	0.992
15:84653647:A:G	W32R	0.991
15:84653647:A:T	W32R	0.991
15:84643502:A:G	W369R	0.986
15:84643502:A:T	W369R	0.986
15:84647946:A:T	V99D	0.986
15:84643560:C:A	W349C	0.985
15:84643560:C:G	W349C	0.985
15:84643708:A:T	V300D	0.985
15:84652793:A:T	V40D	0.985
15:84653678:G:C	F21L	0.985
15:84653678:G:T	F21L	0.985
15:84653680:A:G	F21L	0.985
15:84643632:G:C	F325L	0.984
15:84643632:G:T	F325L	0.984
15:84643634:A:G	F325L	0.984
15:84643500:C:A	W369C	0.983
15:84643500:C:G	W369C	0.983
15:84645480:C:G	A292P	0.983
15:84647911:A:G	W111R	0.982
15:84647911:A:T	W111R	0.982
15:84648603:A:G	F74S	0.979
15:84652751:A:G	L54P	0.979
15:84652757:A:G	L52P	0.979
15:84652790:G:T	A41D	0.978
15:84643723:C:T	G295D	0.977
15:84645479:G:T	A292D	0.977
15:84652760:A:G	I51T	0.976
15:84648558:A:G	L89P	0.972

dbSNP variants (sampled 300 via entrez): RS1000101391 (15:84654331 G>A,T), RS1000892590 (15:84640349 C>T), RS1001034862 (15:84651077 T>C), RS1001144384 (15:84644938 G>A,T), RS1001339276 (15:84642096 C>A,G), RS1001409227 (15:84645305 G>A,T), RS1001504094 (15:84640566 C>A), RS1001789354 (15:84642291 G>C), RS1001873633 (15:84641917 C>G,T), RS1001892330 (15:84646012 T>C), RS1002147212 (15:84649508 AG>A), RS1002356176 (15:84638892 G>A), RS1002470242 (15:84640675 G>A), RS1002515820 (15:84641514 CTTTATT>C), RS1002524708 (15:84643369 C>A,G)

Disease associations

OMIM: gene MIM:616144 | disease phenotypes: MIM:251300

GenCC curated gene-disease

Disease	Classification	Inheritance
Galloway-Mowat syndrome 1	Strong	Autosomal recessive
Galloway-Mowat syndrome	Supportive	Autosomal recessive
CAMOS syndrome	Supportive	Autosomal recessive

Mondo (6): Galloway-Mowat syndrome 1 (MONDO:0033005), congenital nervous system disorder (MONDO:0002320), nephrotic syndrome (MONDO:0005377), Galloway-Mowat syndrome (MONDO:0009627), dystonic disorder (MONDO:0003441), CAMOS syndrome (MONDO:0019374)

Orphanet (2): Galloway-Mowat syndrome (Orphanet:2065), CAMOS syndrome (Orphanet:83472)

HPO phenotypes

85 total (30 of 85 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000083	Renal insufficiency
HP:0000093	Proteinuria
HP:0000097	Focal segmental glomerulosclerosis
HP:0000100	Nephrotic syndrome
HP:0000112	Nephropathy
HP:0000154	Wide mouth
HP:0000164	Abnormality of the dentition
HP:0000218	High palate
HP:0000252	Microcephaly
HP:0000286	Epicanthus
HP:0000316	Hypertelorism
HP:0000340	Sloping forehead
HP:0000347	Micrognathia
HP:0000369	Low-set ears
HP:0000400	Macrotia
HP:0000418	Narrow nasal ridge
HP:0000448	Prominent nose
HP:0000486	Strabismus
HP:0000508	Ptosis
HP:0000518	Cataract
HP:0000568	Microphthalmia
HP:0000601	Hypotelorism
HP:0000639	Nystagmus
HP:0000648	Optic atrophy
HP:0000750	Delayed speech and language development
HP:0000951	Abnormality of the skin
HP:0001010	Hypopigmentation of the skin
HP:0001181	Adducted thumb
HP:0001188	Hand clenching

GWAS associations

8 associations (top):

Study	Trait	p-value
GCST002126_24	Periodontitis (CDC/AAP)	2.000000e-06
GCST004521_253	Autism spectrum disorder or schizophrenia	6.000000e-11
GCST006803_69	Schizophrenia	9.000000e-10
GCST008058_225	Estimated glomerular filtration rate	5.000000e-12
GCST008059_153	Estimated glomerular filtration rate	2.000000e-11
GCST008103_25	Bipolar disorder	3.000000e-08
GCST009600_133	Anorexia nervosa, attention-deficit/hyperactivity disorder, autism spectrum disorder, bipolar disorder, major depression, obsessive-compulsive disorder, schizophrenia, or Tourette syndrome (pleiotropy)	5.000000e-14
GCST90011899_116	Aspartate aminotransferase levels	1.000000e-09

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004736	aspartate aminotransferase measurement

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D020821	Dystonic Disorders	C10.228.662.300
D009404	Nephrotic Syndrome	C12.050.351.968.419.630.643; C12.200.777.419.630.643; C12.950.419.630.643
C537548	Galloway Mowat syndrome (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

24 total (human), top 24 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, increases expression	3
GSK-J4	decreases expression	1
beta-lapachone	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
sodium arsenite	decreases expression	1
cobaltous chloride	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
abrine	increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Atrazine	decreases expression	1
Cadmium	increases abundance, increases expression	1
Carbamazepine	affects expression	1
Doxorubicin	decreases expression	1
Ivermectin	decreases expression	1
Plant Extracts	affects cotreatment, increases expression	1
Rotenone	decreases expression	1
Silicon Dioxide	increases expression	1
Thiram	decreases expression	1
Urethane	decreases expression	1
Vanadates	decreases expression	1
Aflatoxin B1	increases expression	1
Antirheumatic Agents	decreases expression	1
Cadmium Chloride	increases abundance, increases expression	1
Copper Sulfate	decreases expression	1

Cellosaurus cell lines

6 cell lines: 3 transformed cell line, 2 finite cell line, 1 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_CX83	GM25247	Transformed cell line	Male
CVCL_CX84	GM25248	Finite cell line	Male
CVCL_CX85	GM25249	Transformed cell line	Female
CVCL_IW09	GM25245	Transformed cell line	Female
CVCL_JF29	GM25246	Finite cell line	Female
CVCL_TX92	HAP1 WDR73 (-)	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00308321	PHASE4	UNKNOWN	Long Term Tapering or Standard Steroids for Nephrotic Syndrome
NCT01021540	PHASE4	COMPLETED	Prospective Study Evaluating the Effect of Repository Corticotropin in the Treatment of Various Nephrotic Syndromes
NCT01028287	PHASE4	COMPLETED	Adrenocorticotropic Hormone (ACTH) Treatment of Nephrotic Range Proteinuria in Diabetic Nephropathy (NRDN)
NCT01162005	PHASE4	COMPLETED	Therapeutic Effect of Tacrolimus on Primary Nephrotic Syndrome in Children
NCT01895894	PHASE4	COMPLETED	Mycophenolate Mofetil in Pediatric Steroid Dependent Nephrotic Syndrome
NCT02238418	PHASE4	COMPLETED	Efficacy of Usual Vitamin D Supplementation and Its Impact on Children and Adolescents Calciuria.
NCT02382575	PHASE4	UNKNOWN	Efficacy and Safety of Rituximab to That of Calcineurin Inhibitors in Children With Steroid Resistant Nephrotic Syndrome
NCT02427880	PHASE4	COMPLETED	Role of Acetazolamide and Hydrochlorothiazide Followed by Furosemide in Treating Nephrotic Edema
NCT03210688	PHASE4	COMPLETED	Active Vitamin D And Reduced Dose Prednisolone for Treatment in Minimal Change Nephropathy
NCT03347357	PHASE4	COMPLETED	Pharmacokinetics of Tacrolimus in Children
NCT05696977	PHASE4	UNKNOWN	Effect of Obesity on Cyclosporine Blood Trough Level in Nephrotic Syndrome Patients
NCT05966818	PHASE4	UNKNOWN	Effect of Dapagliflozin in Non-Diabetic Patients With Nephrotic Syndrome.
NCT06026787	PHASE4	COMPLETED	Clinical Value of Adding Dapagliflozin in Patients With Nephrotic Syndrome
NCT00354731	PHASE3	COMPLETED	Efficacy of Pentoxifylline on Primary Nephrotic Syndrome
NCT00615667	PHASE3	COMPLETED	Prospective, Multicenter Study of the Efficacy and Tolerance of Tacrolimus on Refractory Nephrotic Syndrome (RNS)
NCT00981838	PHASE3	COMPLETED	Rituximab in Multirelapsing Minimal Change Disease (MCD) or Focal Segmental Glomerulosclerosis (FSGS)
NCT01197040	PHASE3	COMPLETED	Evaluation of Low Dose Corticosteroids Efficiency, Associated With Myfortic ® in the Treatment of Nephrotic Syndrome
NCT01309477	PHASE3	COMPLETED	The Efficacy and Tolerance of Tacrolimus Sustained-release Capsules on Refractory Nephrotic Syndrome (RNS)
NCT02132195	PHASE3	COMPLETED	Adrenocorticotropic Hormone (ACTH) for Frequently Relapsing and Steroid Dependent Nephrotic Syndrome
NCT02257697	PHASE3	COMPLETED	A Study to Evaluate the Efficacy and Safety of Mizoribine in the Treatment of Refractory Nephrotic Syndrome
NCT02438982	PHASE3	COMPLETED	Efficacy and Safety of Rituximab to That of Calcineurin Inhibitors in Children With Steroid Dependent Nephrotic Syndrome
NCT03141970	PHASE3	COMPLETED	Prednisolone Trial in Children Younger Than 4 Years
NCT03501459	PHASE3	UNKNOWN	Lymphocyte Markers As Predictors Of Responsiveness To Rituximab Among Patients With Idiopathic Nephrotic Syndrome
NCT05079789	PHASE3	TERMINATED	Amiloride in Nephrotic Syndrome
NCT05716880	PHASE3	RECRUITING	Ketoanalogues for Muscle Mass Loss in Nephrotic Syndrome
NCT06635720	PHASE3	ACTIVE_NOT_RECRUITING	REduced-dose Steroid PrOtocol for Childhood Nephrotic SyndromE (RESPONSE)
NCT00001212	PHASE2	COMPLETED	Drug Therapy in Lupus Nephropathy
NCT00001959	PHASE2	COMPLETED	Pirfenidone to Treat Kidney Disease (Focal Segmental Glomerulosclerosis)
NCT00004466	PHASE2	TERMINATED	Pilot Study of Atorvastatin in Children With Chronic Hyperlipidemia Secondary to Nephrotic Syndrome
NCT00004990	PHASE2	COMPLETED	Once-A-Month Steroid Treatment for Patients With Focal Segmental Glomerulosclerosis
NCT00977977	PHASE2	RECRUITING	Rituximab Plus Cyclosporine in Idiopathic Membranous Nephropathy
NCT02394106	PHASE2	TERMINATED	Ofatumumab in Children With Drug Resistant Idiopathic Nephrotic Syndrome
NCT02394119	PHASE2	COMPLETED	Ofatumumab Versus Rituximab in Children With Steroid and Calcineurin Inhibitor Dependent Idiopathic Nephrotic Syndrome
NCT02592798	PHASE2	COMPLETED	Pilot Study to Evaluate the Safety and Efficacy of Abatacept in Adults and Children 6 Years and Older With Excessive Loss of Protein in the Urine Due to Either Focal Segmental Glomerulosclerosis (FSGS) or Minimal Change Disease (MCD)
NCT02966717	PHASE2	UNKNOWN	Rituximab Combined With MSCs in the Treatment of PNS (3-4 Stage of CKD)
NCT03004001	PHASE2	TERMINATED	Effect of PCSK9-Antibody (Alirocumab) on Dyslipidemia Secondary to Nephrotic Syndrome
NCT03949855	PHASE2	RECRUITING	Belimumab With Rituximab for Primary Membranous Nephropathy
NCT05599815	PHASE2	WITHDRAWN	Part 1 - A Clinical Trial in Patients With Frequently Relapsing and Steroid-Dependent Nephrotic Syndrome
NCT05704400	PHASE2	UNKNOWN	Efficacy of Anti-CD20 Ab Associated With Anti-CD38 in the Childhood Multidrug Dependent and Resistant Nephrotic Syndrome
NCT06983028	PHASE2	RECRUITING	Atacicept in Multiple Glomerular Diseases