GLIS2

GLIS family zinc finger 2, the group of Zinc fingers C2H2-type

Basic information

Region (hg38): 16:4314761-4339597

Links

ENSG00000126603 ∙ NCBI:84662 ∙ OMIM:608539 ∙ HGNC:29450 ∙ Uniprot:Q9BZE0 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• nephronophthisis 7 (Strong), mode of inheritance: AR
• nephronophthisis 7 (Limited), mode of inheritance: AR
• nephronophthisis 1 (Supportive), mode of inheritance: AR
• nephronophthisis 7 (Strong), mode of inheritance: AR
• nephronophthisis 7 (Limited), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Nephronophthisis 7	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Renal	17618285; 23559409
Renal transplantation has been described

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the GLIS2 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the GLIS2 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			8	39	4	51
missense			80	4	3	87
nonsense						0
start loss						0
frameshift						0
inframe indel			1			1
splice donor/acceptor (+/-2bp)			1			1
splice region			1	1		2
non coding			47	17	16	80
Total	0	0	137	60	23

Variants in GLIS2

This is a list of pathogenic ClinVar variants found in the GLIS2 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
16-4332064-T-C			Benign (Jul 14, 2018)
16-4332270-G-A		not specified • Nephronophthisis 7	Benign (Jul 05, 2018)
16-4332272-C-G			Uncertain significance (Jul 18, 2014)
16-4332295-C-T		GLIS2-related disorder	Uncertain significance (May 07, 2014)
16-4332298-G-A		Nephronophthisis	Likely benign (Mar 15, 2017)
16-4332331-C-G		Nephronophthisis	Likely benign (Oct 17, 2022)
16-4332336-C-T		Nephronophthisis 7 • Nephronophthisis	Uncertain significance (Nov 13, 2022)
16-4332337-G-A		Nephronophthisis	Likely benign (Oct 27, 2022)
16-4332337-G-T			Likely benign (Feb 09, 2018)
16-4332350-C-A		Nephronophthisis • not specified • Nephronophthisis 7	Benign/Likely benign (Mar 01, 2024)
16-4332351-G-A		not specified	Uncertain significance (Jun 29, 2022)
16-4332360-C-T		not specified	Uncertain significance (Mar 21, 2023)
16-4332380-C-T		Nephronophthisis	Uncertain significance (Sep 01, 2021)
16-4332381-G-A		Nephronophthisis • Nephronophthisis 7	Uncertain significance (Jul 06, 2022)
16-4332406-G-A		Nephronophthisis	Likely benign (Feb 06, 2023)
16-4332407-G-A		Nephronophthisis 7	Uncertain significance (Jan 13, 2018)
16-4332409-G-A		Nephronophthisis	Likely benign (Oct 22, 2023)
16-4332444-C-T		Nephronophthisis	Uncertain significance (Mar 09, 2021)
16-4332445-G-A		Nephronophthisis	Likely benign (Aug 02, 2023)
16-4332466-G-A		Nephronophthisis	Likely benign (Feb 23, 2023)
16-4332606-T-G			Benign (Jul 09, 2018)
16-4332652-G-T			Benign (Jul 10, 2018)
16-4333330-C-G		Nephronophthisis	Likely benign (May 09, 2022)
16-4333331-T-C		Nephronophthisis	Benign (Jan 08, 2024)
16-4333369-C-T		Nephronophthisis	Likely benign (May 12, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
GLIS2	protein_coding	protein_coding	ENST00000262366	6	24837

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.858	0.142	125542	0	5	125547	0.0000199

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.792	290	331	0.877	0.0000227	3295
Missense in Polyphen		57	89.877	0.6342		971
Synonymous	-0.943	168	153	1.10	0.0000109	1154
Loss of Function	3.14	2	15.2	0.132	7.47e-7	187

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000579	0.0000579
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000178	0.0000176
Middle Eastern	0.00	0.00
South Asian	0.0000327	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: 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 (By similarity). Represses the Hedgehog-dependent expression of Wnt4 (By similarity). Necessary to maintain the differentiated epithelial phenotype in renal cells through the inhibition of SNAI1, which itself induces the epithelial-to-mesenchymal transition (By similarity). 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 (By similarity). {ECO:0000250}.
• Disease: DISEASE: 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. {ECO:0000269|PubMed:17618285}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: HH-Core (Consensus)

Recessive Scores

• pRec: 0.0798

Intolerance Scores

• loftool: 0.0975
• rvis_EVS: -0.18
• rvis_percentile_EVS: 40.36

Haploinsufficiency Scores

• pHI: 0.229
• hipred: Y
• hipred_score: 0.806
• ghis: 0.502

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.825

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Glis2
• Phenotype: renal/urinary system phenotype; immune system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); homeostasis/metabolism phenotype; cellular phenotype

Zebrafish Information Network

• Gene name: glis2a
• Affected structure: pronephros
• Phenotype tag: abnormal
• Phenotype quality: cystic

Gene ontology

• Biological process: negative regulation of transcription by RNA polymerase II;nervous system development;central nervous system development;negative regulation of DNA-binding transcription factor activity;negative regulation of smoothened signaling pathway;negative regulation of transcription, DNA-templated;positive regulation of transcription, DNA-templated;positive regulation of transcription by RNA polymerase II;regulation of transcription from RNA polymerase II promoter involved in kidney development;cell differentiation involved in kidney development;positive regulation of protein localization to nucleus
• Cellular component: nucleus;cytoplasm;nuclear speck;non-motile cilium
• Molecular function: RNA polymerase II regulatory region sequence-specific DNA binding;DNA-binding transcription factor activity, RNA polymerase II-specific;DNA-binding transcription activator activity, RNA polymerase II-specific;protein binding;transcription regulatory region DNA binding;metal ion binding