GLIS2

Summary

GLIS2 (GLIS family zinc finger 2, HGNC:29450) is a protein-coding gene on chromosome 16p13.3, encoding Zinc finger protein GLIS2 (Q9BZE0). Can act either as a transcriptional repressor or as a transcriptional activator, depending on the cell context.

This gene is a member of the GLI-similar zinc finger protein family and encodes a nuclear transcription factor with five C2H2-type zinc finger domains. The protein encoded by this gene is widely expressed at low levels in the neural tube and peripheral nervous system and likely promotes neuronal differentiation. It is abundantly expressed in the kidney and may have a role in the regulation of kidney morphogenesis. p120 regulates the expression level of this protein and induces the cleavage of this protein’s C-terminal zinc finger domain. This protein also promotes the nuclear translocation of p120. Mutations in this gene cause nephronophthisis (NPHP), an autosomal recessive kidney disease characterized by tubular basement membrane disruption, interstitial lymphohistiocytic cell infiltration, and development of cysts at the corticomedullary border of the kidneys.

Source: NCBI Gene 84662 — RefSeq curated summary.

At a glance

• Gene–disease (curated): nephronophthisis 7 (Strong, GenCC) — +1 more curated relationship
• GWAS associations: 10
• Clinical variants (ClinVar): 360 total — 1 pathogenic
• Phenotypes (HPO): 4
• MANE Select transcript: NM_032575

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29450
Approved symbol	GLIS2
Name	GLIS family zinc finger 2
Location	16p13.3
Locus type	gene with protein product
Status	Approved
Aliases	NPHP7
Ensembl gene	ENSG00000126603
Ensembl biotype	protein_coding
OMIM	608539
Entrez	84662

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 4 protein_coding

ENST00000262366, ENST00000433375, ENST00000886081, ENST00000927239

RefSeq mRNA: 2 — MANE Select: NM_032575 NM_001318918, NM_032575

CCDS: CCDS10511

Canonical transcript exons

ENST00000433375 — 7 exons

Exon	Start	End
ENSE00000667389	4333347	4333519
ENSE00000667397	4332215	4332452
ENSE00001146267	4335275	4335393
ENSE00001146278	4335060	4335193
ENSE00001146287	4334801	4334977
ENSE00003900334	4336725	4339595
ENSE00003901242	4316067	4316254

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 93.56.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 23.4311 / max 789.5433, expressed in 1546 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
152459	16.7443	1492
152458	5.6029	1417
152457	0.5545	367
152456	0.5295	325

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right coronary artery	UBERON:0001625	93.56	gold quality
metanephros cortex	UBERON:0010533	91.80	gold quality
ascending aorta	UBERON:0001496	91.20	gold quality
thoracic aorta	UBERON:0001515	91.12	gold quality
descending thoracic aorta	UBERON:0002345	90.66	gold quality
popliteal artery	UBERON:0002250	90.29	gold quality
tibial artery	UBERON:0007610	90.28	gold quality
adult mammalian kidney	UBERON:0000082	90.24	gold quality
left coronary artery	UBERON:0001626	89.73	gold quality
apex of heart	UBERON:0002098	89.06	gold quality
right lung	UBERON:0002167	88.99	gold quality
cortex of kidney	UBERON:0001225	88.46	gold quality
mucosa of stomach	UBERON:0001199	87.88	gold quality
left adrenal gland cortex	UBERON:0035825	86.91	gold quality
right atrium auricular region	UBERON:0006631	86.74	gold quality
left adrenal gland	UBERON:0001234	86.69	gold quality
upper lobe of left lung	UBERON:0008952	86.61	gold quality
right ovary	UBERON:0002118	86.55	gold quality
lower esophagus muscularis layer	UBERON:0035833	86.54	gold quality
kidney	UBERON:0002113	86.48	gold quality
adenohypophysis	UBERON:0002196	86.48	gold quality
lower esophagus	UBERON:0013473	86.46	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	85.88	gold quality
left uterine tube	UBERON:0001303	85.65	gold quality
right adrenal gland	UBERON:0001233	85.48	gold quality
left ovary	UBERON:0002119	85.40	gold quality
ovary	UBERON:0000992	85.38	gold quality
endocervix	UBERON:0000458	85.18	gold quality
right adrenal gland cortex	UBERON:0035827	85.09	gold quality
body of uterus	UBERON:0009853	84.16	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.43

Regulation

Is transcription factor: yes

JASPAR motifs

Motif	Name	Family
MA0736.1	GLIS2	More than 3 adjacent zinc fingers

JASPAR matrix evidence (PMIDs): PMID:22391303

miRNA regulators (miRDB)

88 targeting GLIS2, 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-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-185-3P	99.95	67.01	1743
HSA-MIR-1-3P	99.93	72.35	1914
HSA-MIR-206	99.93	72.50	1893
HSA-MIR-22-3P	99.93	68.13	917
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-329-3P	99.91	66.56	1234
HSA-MIR-362-3P	99.91	66.38	1267
HSA-MIR-613	99.91	71.50	1710
HSA-MIR-1343-3P	99.89	66.78	1815
HSA-MIR-6783-3P	99.89	67.92	2059
HSA-MIR-137-3P	99.87	74.74	2401
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-3065-3P	99.87	70.25	1407
HSA-MIR-4779	99.86	66.50	1583
HSA-MIR-765	99.84	68.24	2442
HSA-MIR-1321	99.84	65.30	1811
HSA-MIR-4756-5P	99.84	64.98	1809
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-11181-3P	99.75	66.38	2205
HSA-MIR-92A-2-5P	99.75	67.01	2164

Literature-anchored findings (GeneRIF, showing 19)

• Characterization of Glis2, a novel gene encoding a Gli-related, Kruppel-like transcription factor with transactivation and repressor functions (PMID:11741991)
• Glis2 functions as a negative modulator of beta-catenin/TCF-mediated transcription. (PMID:17289029)
• identification of Gli-similar 2 (Glis2) as a novel binding protein for p120 catenin (PMID:17344476)
• Study identified Glis2 as a transcription factor mutated in Nephronophthisis and demonstrate its essential role for the maintenance of renal tissue architecture through prevention of apoptosis and fibrosis. (PMID:17618285)
• Glis2 can function as a transcriptional activator and that post-translational modification within its DNA-binding domain can regulate its transcriptional activity (PMID:21127075)
• Identification of a cryptic chromosome 16 inversion (inv(16)(p13.3q24.3)) in 27% of pediatric acute megakaryoblastic leukemia cases, which encodes a CBFA2T3-GLIS2 fusion protein. (PMID:23153540)
• Recessive mutation in GLIS2 gene is associated with Caroli disease. (PMID:23559409)
• Findings are unprecedented and indicate that the DHH-RHEBL1 fusion transcript is a novel recurrent feature in the changing landscape of CBFA2T3-GLIS2-positive childhood AML. (PMID:24127550)
• BBS11 promotes accumulation of NPHP7, changing the properties of NPHP7. TRIM32 Modulates the Transcriptional Activities of Glis2 (PMID:24500717)
• Glis2/NPHP7 is extensively modified by post-translational modifications (PMID:26083374)
• Nephronophthisis 7-related mutation C175R affects both localization and function of GLIS2 protein. (PMID:26374130)
• Clinical courses of pediatric patients with AMKL harboring the CBFA2T3-GLIS2 fusion gene are poor due to resistance to chemotherapies and SCT. New treatment strategies are necessary. (PMID:27094503)
• CBFA2T3-GLIS2 fusion is associated with acute megakaryoblastic leukemia in non-Down syndrome. (PMID:28063190)
• specific interference with ETO2-GLIS2 oligomerization reverses the transcriptional activation at enhancers and promotes megakaryocytic differentiation, providing a relevant interface to target in this poor-prognosis pediatric leukemia. (PMID:28292442)
• Study confirmed that high expression of GLIS2 is significantly associated with chemoresistance and a worse prognosis in gastric cancer, and that this high expression is likely to be an important biomarker. (PMID:30320360)
• Gene of the month: GLIS1-3. (PMID:32699115)
• Circular RNA GLIS2 promotes colorectal cancer cell motility via activation of the NF-kappaB pathway. (PMID:32968054)
• Glis2 inhibits the epithelial-mesenchymal transition and apoptosis of renal tubule cells by regulating the beta-catenin signalling pathway in diabetic kidney disease. (PMID:35367831)
• GLIS2 and CCND1 expression levels in breast cancer patients. (PMID:37574724)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	glis2a	ENSDARG00000078388
danio_rerio	glis2b	ENSDARG00000100232
mus_musculus	Glis2	ENSMUSG00000014303
rattus_norvegicus	Glis2	ENSRNOG00000004766
drosophila_melanogaster	sug	FBGN0033782

Paralogs (14): ZIC2 (ENSG00000043355), ZXDC (ENSG00000070476), GLI2 (ENSG00000074047), GLI3 (ENSG00000106571), GLIS3 (ENSG00000107249), GLI1 (ENSG00000111087), AEBP2 (ENSG00000139154), ZIC5 (ENSG00000139800), ZIC1 (ENSG00000152977), ZIC3 (ENSG00000156925), GLIS1 (ENSG00000174332), ZIC4 (ENSG00000174963), ZXDA (ENSG00000198205), ZXDB (ENSG00000198455)

Protein

Protein identifiers

Zinc finger protein GLIS2 — Q9BZE0 (reviewed: Q9BZE0)

Alternative names: GLI-similar 2, Neuronal Krueppel-like protein

All UniProt accessions (1): Q9BZE0

UniProt curated annotations — full annotation on UniProt →

Function. Can act either as a transcriptional repressor or as a transcriptional activator, depending on the cell context. Acts as a repressor of the Hedgehog signaling pathway. Represses the Hedgehog-dependent expression of Wnt4. Necessary to maintain the differentiated epithelial phenotype in renal cells through the inhibition of SNAI1, which itself induces the epithelial-to-mesenchymal transition. Represses transcriptional activation mediated by CTNNB1 in the Wnt signaling pathway. May act by recruiting the corepressors CTBP1 and HDAC3. May be involved in neuron differentiation.

Subunit / interactions. Interacts with CTBP1 and HDAC3. Interacts with CTNNB1. Interacts with SUFU. Interacts with CTNND1.

Subcellular location. Nucleus speckle. Cytoplasm.

Tissue specificity. Expressed at high levels in kidney and at low levels in heart, lung and placenta. Expressed in colon.

Post-translational modifications. C-terminus cleavage is induced by interaction with CTNND1 and enhanced by Src tyrosine kinase.

Disease relevance. Nephronophthisis 7 (NPHP7) [MIM:611498] An autosomal recessive disorder resulting in end-stage renal disease during childhood or adolescence. It is a progressive tubulo-interstitial kidney disorder histologically characterized by modifications of the tubules with thickening of the basement membrane, interstitial fibrosis and, in the advanced stages, medullary cysts. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. The C2H2-type zinc finger 1 has a major repressor function and is required for CTNNB1 binding.

Similarity. Belongs to the GLI C2H2-type zinc-finger protein family.

RefSeq proteins (2): NP_001305847, NP_115964* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR013087	Znf_C2H2_type	Domain
IPR036236	Znf_C2H2_sf	Homologous_superfamily
IPR043359	GLI-like	Family
IPR056436	Znf-C2H2_ZIC1-5/GLI1-3-like	Domain

Pfam: PF00096, PF23561

UniProt features (17 total): region of interest 6, zinc finger region 5, compositionally biased region 2, chain 1, site 1, sequence variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BZE0-F1	55.47	0.00

Functional residue map

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

Catalytic / active sites (1): 287–288 (cleavage)

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 134 (showing top): GSE45365_CTRL_VS_MCMV_INFECTION_NK_CELL_UP, TGGTGCT_MIR29A_MIR29B_MIR29C, PEREZ_TP63_TARGETS, GOBP_POSITIVE_REGULATION_OF_PROTEIN_LOCALIZATION, GCAAGGA_MIR502, CHANDRAN_METASTASIS_DN, GOBP_POSITIVE_REGULATION_OF_PROTEIN_LOCALIZATION_TO_NUCLEUS, GOBP_CELL_DIFFERENTIATION_INVOLVED_IN_KIDNEY_DEVELOPMENT, SCHAEFFER_PROSTATE_DEVELOPMENT_48HR_DN, GOBP_NEGATIVE_REGULATION_OF_SMOOTHENED_SIGNALING_PATHWAY, GOBP_REGULATION_OF_SMOOTHENED_SIGNALING_PATHWAY, PEREZ_TP53_AND_TP63_TARGETS, GOBP_PROTEIN_LOCALIZATION_TO_ORGANELLE, GOBP_MULTICELLULAR_ORGANISMAL_LEVEL_HOMEOSTASIS, GOBP_SMOOTHENED_SIGNALING_PATHWAY

GO Biological Process (13): negative regulation of transcription by RNA polymerase II (GO:0000122), central nervous system development (GO:0007417), negative regulation of smoothened signaling pathway (GO:0045879), negative regulation of DNA-templated transcription (GO:0045892), positive regulation of DNA-templated transcription (GO:0045893), positive regulation of transcription by RNA polymerase II (GO:0045944), cell differentiation involved in kidney development (GO:0061005), hematopoietic stem cell homeostasis (GO:0061484), positive regulation of protein localization to nucleus (GO:1900182), kidney development (GO:0001822), regulation of transcription by RNA polymerase II (GO:0006357), nervous system development (GO:0007399), cell differentiation (GO:0030154)

GO Molecular Function (11): transcription cis-regulatory region binding (GO:0000976), RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), DNA-binding transcription repressor activity, RNA polymerase II-specific (GO:0001227), DNA-binding transcription activator activity, RNA polymerase II-specific (GO:0001228), zinc ion binding (GO:0008270), sequence-specific double-stranded DNA binding (GO:1990837), RNA polymerase II transcription regulatory region sequence-specific DNA binding (GO:0000977), DNA binding (GO:0003677), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (5): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), nuclear speck (GO:0016607), non-motile cilium (GO:0097730)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
RNA polymerase II transcription regulatory region sequence-specific DNA binding	4
regulation of transcription by RNA polymerase II	3
transcription by RNA polymerase II	3
regulation of DNA-templated transcription	3
system development	2
DNA-templated transcription	2
DNA-binding transcription factor activity, RNA polymerase II-specific	2
cellular anatomical structure	2
negative regulation of DNA-templated transcription	1
nervous system development	1
smoothened signaling pathway	1
regulation of smoothened signaling pathway	1
negative regulation of signal transduction	1
negative regulation of RNA biosynthetic process	1
positive regulation of RNA biosynthetic process	1
positive regulation of DNA-templated transcription	1
kidney development	1
cell differentiation	1
homeostasis of number of cells	1
protein localization to nucleus	1
regulation of protein localization to nucleus	1
positive regulation of protein localization	1
animal organ development	1
renal system development	1
cellular developmental process	1
transcription regulatory region nucleic acid binding	1
sequence-specific double-stranded DNA binding	1
cis-regulatory region sequence-specific DNA binding	1
chromatin	1
DNA-binding transcription factor activity	1
negative regulation of transcription by RNA polymerase II	1
DNA-binding transcription repressor activity	1
DNA-binding transcription activator activity	1
positive regulation of transcription by RNA polymerase II	1
transition metal ion binding	1
double-stranded DNA binding	1
sequence-specific DNA binding	1
transcription cis-regulatory region binding	1
nucleic acid binding	1
binding	1

Protein interactions and networks

STRING

1402 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GLIS2	CBFA2T3	O75081	797
GLIS2	KIR2DL4	P78400	761
GLIS2	NPHP1	O15259	735
GLIS2	NCR3	O14931	706
GLIS2	KIR3DL1	P43629	692
GLIS2	TYROBP	O43914	641
GLIS2	CTNND1	O60716	632
GLIS2	BBS1	Q8NFJ9	609
GLIS2	KLRK1	P26718	576
GLIS2	NEK8	Q86SG6	568
GLIS2	INVS	Q9Y283	562
GLIS2	GPSM2	P81274	527
GLIS2	TMEM67	Q5HYA8	513
GLIS2	KLRC1	P26715	509
GLIS2	KLRD1	Q13241	508

IntAct

178 interactions, top by confidence:

A	B	Type	Score
GLIS2	CTNNB1	psi-mi:“MI:0915”(physical association)	0.580
CTNNB1	GLIS2	psi-mi:“MI:0915”(physical association)	0.580
GLIS2	KRTAP19-7	psi-mi:“MI:0915”(physical association)	0.560
GMNN	GLIS2	psi-mi:“MI:0915”(physical association)	0.560
PRKAR1B	GLIS2	psi-mi:“MI:0915”(physical association)	0.560
GLIS2	ZRANB1	psi-mi:“MI:0915”(physical association)	0.560
PRR20D	GLIS2	psi-mi:“MI:0915”(physical association)	0.560
	GLIS2	psi-mi:“MI:0915”(physical association)	0.560
GLIS2	NME7	psi-mi:“MI:0915”(physical association)	0.560
VAC14	GLIS2	psi-mi:“MI:0915”(physical association)	0.560
RBPMS	GLIS2	psi-mi:“MI:0915”(physical association)	0.560
CRX	GLIS2	psi-mi:“MI:0915”(physical association)	0.560
ACTN3	GLIS2	psi-mi:“MI:0915”(physical association)	0.560
GOLGA6L9	GLIS2	psi-mi:“MI:0915”(physical association)	0.560
BCAR1	GLIS2	psi-mi:“MI:0915”(physical association)	0.560
VENTX	GLIS2	psi-mi:“MI:0915”(physical association)	0.560
POU6F2	GLIS2	psi-mi:“MI:0915”(physical association)	0.560
FOSB	GLIS2	psi-mi:“MI:0915”(physical association)	0.560
TLE5	GLIS2	psi-mi:“MI:0915”(physical association)	0.560
KRTAP6-1	GLIS2	psi-mi:“MI:0915”(physical association)	0.560
FAM168B	GLIS2	psi-mi:“MI:0915”(physical association)	0.560
ACTMAP	GLIS2	psi-mi:“MI:0915”(physical association)	0.560
SHOX	GLIS2	psi-mi:“MI:0915”(physical association)	0.560
KRTAP6-2	GLIS2	psi-mi:“MI:0915”(physical association)	0.560
GLIS2	PLEKHB1	psi-mi:“MI:0915”(physical association)	0.560
KRTAP19-3	GLIS2	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (110): GLIS2 (Affinity Capture-RNA), GLIS2 (Reconstituted Complex), BCAR1 (Affinity Capture-Western), BCAR1 (Far Western), AKT1 (FRET), BECN1 (FRET), CCNE1 (FRET), CDK4 (FRET), CDK6 (FRET), EPHA2 (FRET), ERBB2 (FRET), FGFR4 (FRET), GLIS2 (FRET), MET (FRET), MYC (FRET)

ESM2 similar proteins: A0PJY2, A1YPR0, A2A935, B0K011, B0X9H6, B7ZRU9, O13089, O15090, O15156, O75626, O88939, O93567, O95365, P14404, P25932, P41183, P56260, Q03112, Q08DS3, Q0IHB8, Q1L8W0, Q2VWH6, Q32NK7, Q3T135, Q5XJQ7, Q60636, Q64321, Q6AY34, Q6DBW0, Q6F2E4, Q802Y8, Q8I7Z8, Q8K083, Q8N9L1, Q8NAP8, Q8TBJ5, Q8VCZ7, Q8VDL9, Q98T94, Q99PV8

Diamond homologs: A0A5K4F1D0, A0JC51, A4FV57, O57311, O60481, O73689, O95409, P08151, P10070, P10071, P19538, P34708, P39768, P46684, P47806, P55878, P55879, Q0VGT2, Q15915, Q17308, Q5IS56, Q61467, Q61602, Q62520, Q62521, Q6DJQ6, Q6GR30, Q6XP49, Q6ZN18, Q7JNM3, Q7K0S9, Q7SXV2, Q7TQ40, Q8JJC0, Q8K1M4, Q8N9L1, Q8NBF1, Q8NEA6, Q8SV95, Q8VDL9

SIGNOR signaling

4 interactions.

A	Effect	B	Mechanism
SUFU	down-regulates	GLIS2	relocalization
RAB23	down-regulates	GLIS2
PRKACA	“down-regulates activity”	GLIS2	phosphorylation
CSNK1A1L	up-regulates	GLIS2

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 67 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

GO biological processes:

GO term	Partners	Fold	FDR
negative regulation of cell population proliferation	8	5.7×	7e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	229
Likely benign	69
Benign	22

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
242364	NM_032575.3(GLIS2):c.775+1G>T	Pathogenic

SpliceAI

1402 predictions. Top by Δscore:

Variant	Effect	Δscore
16:4332314:C:G	donor_gain	1.0000
16:4332394:G:GT	donor_gain	1.0000
16:4332448:CTCAG:C	donor_loss	1.0000
16:4332449:TCAGG:T	donor_loss	1.0000
16:4332450:CAGG:C	donor_loss	1.0000
16:4332451:AGGT:A	donor_loss	1.0000
16:4332452:GG:G	donor_loss	1.0000
16:4332453:G:C	donor_loss	1.0000
16:4332454:T:G	donor_loss	1.0000
16:4333342:CTCA:C	acceptor_loss	1.0000
16:4333343:TCAG:T	acceptor_loss	1.0000
16:4333344:CA:C	acceptor_loss	1.0000
16:4333345:A:AG	acceptor_gain	1.0000
16:4333345:AG:A	acceptor_gain	1.0000
16:4333346:G:GA	acceptor_gain	1.0000
16:4333346:GG:G	acceptor_gain	1.0000
16:4333346:GGC:G	acceptor_gain	1.0000
16:4333346:GGCT:G	acceptor_gain	1.0000
16:4333346:GGCTT:G	acceptor_gain	1.0000
16:4333520:G:A	donor_loss	1.0000
16:4333520:G:GG	donor_gain	1.0000
16:4334796:CCCA:C	acceptor_loss	1.0000
16:4334797:CCA:C	acceptor_loss	1.0000
16:4334799:A:AG	acceptor_gain	1.0000
16:4334799:AG:A	acceptor_gain	1.0000
16:4334800:G:GG	acceptor_gain	1.0000
16:4334800:GG:G	acceptor_gain	1.0000
16:4334975:AAGGT:A	donor_loss	1.0000
16:4334976:AGG:A	donor_loss	1.0000
16:4334978:G:GA	donor_loss	1.0000

AlphaMissense

3355 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:4335183:T:C	F216L	1.000
16:4335184:T:C	F216S	1.000
16:4335185:C:A	F216L	1.000
16:4335185:C:G	F216L	1.000
16:4335291:C:A	H225N	1.000
16:4335291:C:G	H225D	1.000
16:4335292:A:G	H225R	1.000
16:4335293:C:A	H225Q	1.000
16:4335293:C:G	H225Q	1.000
16:4335297:C:A	R227S	1.000
16:4335298:G:C	R227P	1.000
16:4335303:C:G	H229D	1.000
16:4335305:C:A	H229Q	1.000
16:4335305:C:G	H229Q	1.000
16:4335327:T:A	C237S	1.000
16:4335327:T:C	C237R	1.000
16:4335328:G:C	C237S	1.000
16:4335329:T:G	C237W	1.000
16:4335336:T:C	C240R	1.000
16:4335337:G:A	C240Y	1.000
16:4335338:C:G	C240W	1.000
16:4335348:T:A	F244I	1.000
16:4335348:T:C	F244L	1.000
16:4335349:T:C	F244S	1.000
16:4335349:T:G	F244C	1.000
16:4335350:C:A	F244L	1.000
16:4335350:C:G	F244L	1.000
16:4335354:C:A	R246S	1.000
16:4335360:G:A	E248K	1.000
16:4335367:T:C	L250P	1.000

dbSNP variants (sampled 300 via entrez): RS1000018481 (16:4314387 T>A), RS1000159135 (16:4340000 C>T), RS1000189230 (16:4324246 T>C), RS1000230839 (16:4339853 G>A), RS1000240399 (16:4319045 G>T), RS1000385737 (16:4314598 G>A), RS1000419160 (16:4319817 G>A), RS1000464076 (16:4335816 C>T), RS1000471602 (16:4319614 C>T), RS1000667240 (16:4324061 A>G), RS1000670741 (16:4313287 T>C,G), RS1000731089 (16:4337130 G>A,C), RS1001042862 (16:4327575 G>A,C,T), RS1001055176 (16:4322689 G>C), RS1001165679 (16:4327885 C>T)

Disease associations

OMIM: gene MIM:608539 | disease phenotypes: MIM:611498, MIM:256100, MIM:614970

GenCC curated gene-disease

Disease	Classification	Inheritance
nephronophthisis 7	Strong	Autosomal recessive
nephronophthisis 1	Supportive	Autosomal recessive

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
nephronophthisis 7	Moderate	AR

Mondo (5): nephronophthisis 7 (MONDO:0012680), nephronophthisis (MONDO:0019005), kidney disorder (MONDO:0005240), Joubert syndrome 20 (MONDO:0013994), nephronophthisis 1 (MONDO:0009728)

Orphanet (2): Nephronophthisis (Orphanet:655), Isolated Joubert syndrome (Orphanet:475)

HPO phenotypes

4 total (4 of 4 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000090	Nephronophthisis
HP:0000092	Renal tubular atrophy
HP:0003774	Stage 5 chronic kidney disease

GWAS associations

10 associations (top):

Study	Trait	p-value
GCST004093_40	Prostate-specific antigen levels	1.000000e-09
GCST006956_6	Erectile dysfunction	2.000000e-06
GCST006979_243	Heel bone mineral density	1.000000e-11
GCST008481_8	Lung function (FEV1/FVC)	7.000000e-06
GCST012227_372	Hip circumference adjusted for BMI	6.000000e-21
GCST012229_175	Hip index	9.000000e-14
GCST012490_98	Femur bone mineral density x serum urate levels interaction	9.000000e-09
GCST90013406_79	Liver enzyme levels (alkaline phosphatase)	6.000000e-14
GCST90020025_138	Waist-to-hip ratio adjusted for BMI	4.000000e-08
GCST90020028_1488	Hip circumference adjusted for BMI	6.000000e-12

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:0009270	heel bone mineral density
EFO:0004713	FEV/FVC ratio
EFO:0008039	BMI-adjusted hip circumference
EFO:0004531	urate measurement
EFO:0004533	alkaline phosphatase measurement
EFO:0007788	BMI-adjusted waist-hip ratio

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D007674	Kidney Diseases	C12.050.351.968.419; C12.200.777.419; C12.950.419
C566930	Nephronophthisis 7 (supp.)
C537699	Nephronophthisis, familial juvenile (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

Binding affinities (BindingDB)

1 measured of 1 human assays (1 total across all organisms); most potent 1 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
N-[3-[[[2-[4-[4-[3-[[2-(2-adamantyl)acetyl]amino]propyl]piperazin-1-yl]-2-methoxyanilino]-5-chloropyrimidin-4-yl]amino]methyl]phenyl]prop-2-enamide	IC50	1820 nM	US-9862688: Hydrophobically tagged janus kinase inhibitors and uses thereof

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression, affects expression, increases methylation	5
trichostatin A	affects cotreatment, decreases expression	3
sodium arsenite	increases expression, increases abundance	3
Air Pollutants	increases abundance, decreases expression	2
Arsenic	increases abundance, increases expression, affects methylation	2
Cyclosporine	increases expression	2
Aflatoxin B1	affects expression, decreases methylation, increases methylation	2
Particulate Matter	decreases expression, increases abundance	2
TAK-243	increases sumoylation	1
urushiol	decreases expression	1
triphenyl phosphate	affects expression	1
butyraldehyde	decreases expression	1
benzo(e)pyrene	increases methylation	1
aflatoxin B2	increases methylation, decreases methylation	1
coumarin	increases phosphorylation	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
bisphenol S	affects cotreatment, decreases methylation	1
Resveratrol	decreases expression, affects cotreatment	1
Sunitinib	increases expression	1
Fulvestrant	affects cotreatment, decreases methylation	1
Acetaminophen	increases expression	1
Cadmium	increases abundance, decreases expression	1
Chelating Agents	affects binding, increases expression	1
Copper	affects binding, increases expression	1
Doxorubicin	increases expression	1
Methapyrilene	increases methylation	1
Niclosamide	increases expression	1
Phthalic Acids	increases methylation	1
Plant Extracts	affects cotreatment, decreases expression	1

Cellosaurus cell lines

10 cell lines: 4 embryonic stem cell, 3 cancer cell line, 2 induced pluripotent stem cell, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_2106	M-07e	Cancer cell line	Female
CVCL_5607	WSU-AML	Cancer cell line
CVCL_A2H2	SEES3-1V human GLIS2, clone1	Embryonic stem cell	Male
CVCL_A2H3	SEES3-1V human GLIS2, clone2	Embryonic stem cell	Male
CVCL_A2H4	SEES3-1V human GLIS2, clone3	Embryonic stem cell	Male
CVCL_HC77	HEK293 eGFP-GLIS2	Transformed cell line	Female
CVCL_RM07	M-07e/TPO	Cancer cell line	Female
CVCL_VL52	PBMC2-iPS4F8 CBFA2T3-GLIS2	Induced pluripotent stem cell	Female
CVCL_WM07	WAe009-A-40	Embryonic stem cell	Female
CVCL_YN83	GENYOi006-A-1	Induced pluripotent stem cell	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00067990	PHASE4	COMPLETED	Angiotensin II Blockade for Chronic Allograft Nephropathy
NCT00117078	PHASE4	COMPLETED	Aranesp® Monthly Preference Study - 2
NCT00117130	PHASE4	COMPLETED	Study to Evaluate Effectiveness of Aranesp®
NCT00132431	PHASE4	COMPLETED	START: Sensipar Treatment Algorithm to Reach K/DOQI Targets in Chronic Kidney Disease Subjects With Secondary Hyperparathyroidism
NCT00140985	PHASE4	COMPLETED	Antiproteinuric Efficacy of Losartan Potassium in Patients With Non-Diabetic Proteinuric Renal Diseases (0954-213)
NCT00246129	PHASE4	COMPLETED	CamTac Trial:Campath-Tacrolimus vs IL2R MoAb/Tacrolimus/MMF in Renal Transplantation
NCT00275535	PHASE4	COMPLETED	The Comparison of Tacrolimus and Sirolimus Immunosuppression Based Drug Regimens in Kidney Transplant Recipients
NCT00282217	PHASE4	COMPLETED	Study Evaluating Sirolimus in the Treatment of Kidney Transplant
NCT00289614	PHASE4	COMPLETED	Patients With Renal Impairment and Diabetes Undergoing Computed Tomography (CT)
NCT00290069	PHASE4	UNKNOWN	Renal Function Optimization With Mycophenolate Mofetil (MMF) Immunosuppressor Regimes (ALHAMBRA)
NCT00338468	PHASE4	TERMINATED	A Study to Assess Disability in Anemic Elderly Patients With Kidney Disease Receiving PROCRIT (Epoetin Alfa)
NCT00368901	PHASE4	COMPLETED	STAAR-2 Clinical Study
NCT00369733	PHASE4	COMPLETED	STAAR-3 Clinical Study
NCT00369772	PHASE4	COMPLETED	STAAR-1 Clinical Study
NCT00379899	PHASE4	COMPLETED	ADVANCE: Study to Evaluate Cinacalcet Plus Low Dose Vitamin D on Vascular Calcification in Subjects With Chronic Kidney Disease Receiving Hemodialysis
NCT00443508	PHASE4	UNKNOWN	Reduction or Discontinuation of CNI’s With Conversion to Everolimus-Based Immunosuppresion
NCT00452478	PHASE4	TERMINATED	Conversion From Standard Phosphate Binder Therapy to Fosrenol® (Lanthanum Carbonate) in Chronic Kidney Disease Stage 5
NCT00492518	PHASE4	COMPLETED	Acetylcysteine, Theophylline, and a Combination of Both in the Prophylaxis of Contrast-Induced Nephropathy
NCT00505102	PHASE4	UNKNOWN	Safe Renal Function In Long Term Heart Transplanted Patients
NCT00526331	PHASE4	COMPLETED	Evaluation of Arterial Pressure Based Cardiac Output for Goal-Directed Perioperative Therapy
NCT00688480	PHASE4	COMPLETED	Do Xanthine Oxidase Inhibitors Reduce Both Left Ventricular Hypertrophy and Endothelial Dysfunction in Cardiovascular Patients With Renal Dysfunction?
NCT00863707	PHASE4	COMPLETED	A Study of the Safety and Tolerance of Regadenoson in Subjects With Renal Impairment
NCT01101698	PHASE4	UNKNOWN	Vitamin K2 and Vessel Calcification in Chronic Kidney Disease Patients
NCT01150201	PHASE4	COMPLETED	Aliskiren Combined With Losartan in Proteinuric, Non-diabetic Chronic Kidney Disease
NCT01155141	PHASE4	COMPLETED	Idiopathic Focal Segmental Glomerulosclerosis (FSGS) and Treatment With ACTH
NCT01228279	PHASE4	COMPLETED	Sympathetic Activity in Patients With End-stage Renal Disease on Peritoneal Dialysis
NCT01334333	PHASE4	COMPLETED	Comparison of Medication Adherence Between Once and Twice Daily Tacrolimus in Stable Renal Transplant Recipients
NCT01437943	PHASE4	TERMINATED	Effect of Short Term Aliskiren Treatment in Kidney Transplant Patients
NCT01545479	PHASE4	COMPLETED	Increased Renal Oxygenation and Angiotensin Converting Enzyme Inhibition
NCT01614431	PHASE4	COMPLETED	N Acetyl Cysteine for Cystinosis Patients
NCT01631149	PHASE4	COMPLETED	Effect of Deep BLock on Intraoperative Surgical Conditions
NCT01722513	PHASE4	UNKNOWN	Efficacy and Safety of Alprostadil Prevent Contrast Induced Nephropathy
NCT01985360	PHASE4	COMPLETED	ISCHEMIA-Chronic Kidney Disease Trial
NCT02311010	PHASE4	UNKNOWN	Practical Use of Advagraf de Novo After Kidney Transplantation According to Recipient Genetic Polymorphism
NCT02413073	PHASE4	COMPLETED	Whole Body Vibration in Kidney Disease
NCT02444013	PHASE4	UNKNOWN	Folic Acid for Prevention of Contrast Induced Nephropathy
NCT02663713	PHASE4	COMPLETED	A Randomized, Pharmacodynamic Comparison of Low Dose Ticagrelor to Clopidogrel in Patients With Prior Myocardial Infarction
NCT02707809	PHASE4	COMPLETED	Effects of Dexmedetomidine on Microcirculation of Kidney Transplant Recipient
NCT02761577	PHASE4	COMPLETED	A Prospective Study on Incidence and Prevention of Contrast-induced Nephropathy in Croatia
NCT03029351	PHASE4	TERMINATED	GLP-1 Receptor Agonist Therapy and Albuminuria in Patients With Type 2 Diabetes