GLIS3

GLIS family zinc finger 3, the group of Zinc fingers C2H2-type

Basic information

Region (hg38): 9:3824126-4348392

Previous symbols: [ "ZNF515" ]

Links

ENSG00000107249 ∙ NCBI:169792 ∙ OMIM:610192 ∙ HGNC:28510 ∙ Uniprot:Q8NEA6 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Tourette syndrome (Limited), mode of inheritance: Unknown
• neonatal diabetes mellitus with congenital hypothyroidism (Definitive), mode of inheritance: AR
• neonatal diabetes mellitus with congenital hypothyroidism (Strong), mode of inheritance: AR
• neonatal diabetes mellitus with congenital hypothyroidism (Strong), mode of inheritance: AR
• neonatal diabetes mellitus with congenital hypothyroidism (Supportive), mode of inheritance: AR
• neonatal diabetes mellitus with congenital hypothyroidism (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Diabetes mellitus, neonatal, with congenital hypothyroidism	AR	Endocrine	Prompt treatment (eg, of ketoacidosis and dehydration) can avoid morbidity; Treatment of congenital hypothyroidism can improve outcome	Endocrine; Gastrointestinal; Musculoskeletal; Neurologic; Ophthalmologic; Renal	12966531; 16715098

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the GLIS3 gene.

• Neonatal diabetes mellitus with congenital hypothyroidism (297 variants)
• not provided (226 variants)
• Inborn genetic diseases (38 variants)
• Monogenic diabetes (29 variants)
• not specified (21 variants)
• Transitory neonatal diabetes mellitus (11 variants)
• Diabetes mellitus (2 variants)
• Congenital aniridia (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the GLIS3 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			11	43	4	58
missense			137	12	6	155
nonsense		1				1
start loss			1			1
frameshift		2				2
inframe indel			1			1
splice donor/acceptor (+/-2bp)			1			1
splice region			6	3		9
non coding			114	41	75	230
Total	0	3	265	96	85

Variants in GLIS3

This is a list of pathogenic ClinVar variants found in the GLIS3 region.

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

Position	Type	Phenotype	Significance	ClinVar
9-3824255-A-G		Neonatal diabetes mellitus with congenital hypothyroidism	Uncertain significance (Jan 13, 2018)
9-3824324-C-A		Neonatal diabetes mellitus with congenital hypothyroidism	Uncertain significance (Jan 13, 2018)
9-3824338-T-C		Neonatal diabetes mellitus with congenital hypothyroidism	Uncertain significance (Jan 12, 2018)
9-3824352-C-T		Neonatal diabetes mellitus with congenital hypothyroidism	Uncertain significance (Jan 13, 2018)
9-3824496-C-G		Neonatal diabetes mellitus with congenital hypothyroidism	Uncertain significance (Jun 14, 2016)
9-3824508-C-T		Neonatal diabetes mellitus with congenital hypothyroidism	Uncertain significance (Jan 12, 2018)
9-3824580-T-A		Neonatal diabetes mellitus with congenital hypothyroidism	Benign (Jan 13, 2018)
9-3824631-T-C		Neonatal diabetes mellitus with congenital hypothyroidism	Uncertain significance (Jan 13, 2018)
9-3824661-A-G		Neonatal diabetes mellitus with congenital hypothyroidism	Uncertain significance (Jan 13, 2018)
9-3824671-G-T		Neonatal diabetes mellitus with congenital hypothyroidism	Likely benign (Jan 13, 2018)
9-3824696-C-T		Neonatal diabetes mellitus with congenital hypothyroidism	Uncertain significance (Jan 13, 2018)
9-3824831-A-G		Neonatal diabetes mellitus with congenital hypothyroidism	Uncertain significance (Jan 13, 2018)
9-3824863-C-T		Neonatal diabetes mellitus with congenital hypothyroidism	Benign (Jan 12, 2018)
9-3824878-A-G		Neonatal diabetes mellitus with congenital hypothyroidism	Uncertain significance (Jan 12, 2018)
9-3824894-CT-C		Neonatal diabetes mellitus with congenital hypothyroidism	Likely benign (Jun 14, 2016)
9-3824919-GCA-G		Neonatal diabetes mellitus with congenital hypothyroidism	Uncertain significance (Jun 14, 2016)
9-3824928-A-T		Neonatal diabetes mellitus with congenital hypothyroidism	Uncertain significance (Jan 15, 2018)
9-3824929-A-T		Neonatal diabetes mellitus with congenital hypothyroidism	Uncertain significance (Jan 13, 2018)
9-3824931-AAAAAT-A		Neonatal diabetes mellitus with congenital hypothyroidism	Uncertain significance (Jun 14, 2016)
9-3824932-A-T		Neonatal diabetes mellitus with congenital hypothyroidism	Uncertain significance (Jan 12, 2018)
9-3824933-A-T		Neonatal diabetes mellitus with congenital hypothyroidism	Uncertain significance (Jan 12, 2018)
9-3824934-A-T		Neonatal diabetes mellitus with congenital hypothyroidism	Uncertain significance (Jan 12, 2018)
9-3824934-AAT-A		Neonatal diabetes mellitus with congenital hypothyroidism	Benign (Jun 14, 2016)
9-3824934-A-AT		Neonatal diabetes mellitus with congenital hypothyroidism	Uncertain significance (Jun 14, 2016)
9-3824935-A-T		Neonatal diabetes mellitus with congenital hypothyroidism	Uncertain significance (Jan 13, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
GLIS3	protein_coding	protein_coding	ENST00000381971	10	524266

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
5.60e-8	0.998	125698	0	50	125748	0.000199

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-3.14	772	563	1.37	0.0000361	5976
Missense in Polyphen		323	254.47	1.2693		2904
Synonymous	-4.73	343	248	1.38	0.0000185	1951
Loss of Function	2.81	18	36.3	0.496	0.00000207	391

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000213	0.000210
Ashkenazi Jewish	0.00	0.00
East Asian	0.000661	0.000653
Finnish	0.000139	0.000139
European (Non-Finnish)	0.000265	0.000264
Middle Eastern	0.000661	0.000653
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Acts as both a repressor and activator of transcription. Binds to the consensus sequence 5'-GACCACCCAC-3' (By similarity). {ECO:0000250}.

Intolerance Scores

• loftool: 0.531
• rvis_EVS: -0.01
• rvis_percentile_EVS: 52.86

Haploinsufficiency Scores

• pHI: 0.596
• hipred: N
• hipred_score: 0.491
• ghis: 0.447

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.744

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Glis3
• Phenotype: cellular phenotype; homeostasis/metabolism phenotype; endocrine/exocrine gland 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); growth/size/body region phenotype; renal/urinary system phenotype

Zebrafish Information Network

• Gene name: glis3
• Affected structure: pancreatic B cell
• Phenotype tag: abnormal
• Phenotype quality: decreased area

Gene ontology

• Biological process: negative regulation of transcription by RNA polymerase II;transcription by RNA polymerase II;positive regulation of transcription by RNA polymerase II
• Cellular component: nucleus
• Molecular function: DNA-binding transcription factor activity, RNA polymerase II-specific;DNA binding;metal ion binding