GLIS3

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

Basic information

Region (hg38): 9:3824127-4348392

Previous symbols: [ "ZNF515" ]

Links

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

Transcripts

Transcript IDs starting with ENST are treated as Ensembl, all others as RefSeq. Showing 4 of 31.

Transcript ID	Protein ID	Coding exons	MANE Select	MANE Plus Clinical
NM_001042413.2	NP_001035878.1	10	yes	-
ENST00000381971.8	ENSP00000371398.3	10	yes	-
NM_152629.4	NP_689842.3	9	-	-
NM_001438906.1	NP_001425835.1	10	-	-

Phenotypes

GenCC

Source: genCC

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

• not_provided (293 variants)
• Neonatal_diabetes_mellitus_with_congenital_hypothyroidism (285 variants)
• Inborn_genetic_diseases (158 variants)
• Monogenic_diabetes (29 variants)
• GLIS3-related_disorder (20 variants)
• not_specified (20 variants)
• Transitory_neonatal_diabetes_mellitus (11 variants)
• Diabetes_mellitus (1 variants)
• Congenital_hypothyroidism (1 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. These statistics are base on transcript: NM_001042413.2. Only rare variants are included in the table.

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.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			13	117	3	133
missense	2		341	37	5	385
nonsense	2	5	3			10
start loss		1	1			2
frameshift	2	5				7
splice donor/acceptor (+/-2bp)		1	4			5
Total	6	12	362	154	8

Highest pathogenic variant AF is 0.000027262307

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
		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

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

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