ZBTB18

zinc finger and BTB domain containing 18, the group of Zinc fingers C2H2-type|BTB domain containing

Basic information

Region (hg38): 1:244048547-244057476

Previous symbols: [ "ZNF238" ]

Links

ENSG00000179456 ∙ NCBI:10472 ∙ OMIM:608433 ∙ HGNC:13030 ∙ Uniprot:Q99592 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• intellectual disability, autosomal dominant 22 (Strong), mode of inheritance: AD
• intellectual disability, autosomal dominant 22 (Definitive), mode of inheritance: AD
• complex neurodevelopmental disorder (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Intellectual developmental disorder, autosomal dominant 22	AD	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	Craniofacial; Neurologic	24193349

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ZBTB18 gene.

• Intellectual disability, autosomal dominant 22 (13 variants)
• not provided (10 variants)
• Inborn genetic diseases (4 variants)
• Intellectual disability (1 variants)
• ZBTB18-related disorder (1 variants)
• ZBTB18-related intellectual disability (1 variants)
• Neurodevelopmental delay (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ZBTB18 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			1	57	5	63
missense	3	20	74	7	10	114
nonsense	7	3	1			11
start loss						0
frameshift	12	10				22
inframe indel			1	1		2
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding				1		1
Total	22	33	77	66	15

Variants in ZBTB18

This is a list of pathogenic ClinVar variants found in the ZBTB18 region.

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

Position	Type	Phenotype	Significance	ClinVar
1-244051441-A-G		Inborn genetic diseases	Uncertain significance (Oct 27, 2022)
1-244051457-A-G			Likely benign (Aug 17, 2023)
1-244053801-T-C			Likely benign (Dec 11, 2023)
1-244053805-G-C			Uncertain significance (Mar 16, 2023)
1-244053806-A-T		Developmental delay	Likely pathogenic (-)
1-244053839-G-A			Uncertain significance (Aug 03, 2022)
1-244053846-C-T			Likely benign (Nov 28, 2022)
1-244053849-G-A			Likely benign (Jun 01, 2023)
1-244053854-G-C		Intellectual disability, autosomal dominant 22	Uncertain significance (Jan 20, 2023)
1-244053876-C-G			Uncertain significance (Nov 25, 2022)
1-244053878-G-A			Uncertain significance (Jan 29, 2024)
1-244053907-C-T		Intellectual disability, autosomal dominant 22	Pathogenic (Feb 09, 2016)
1-244053916-C-G		Intellectual disability, autosomal dominant 22	Conflicting classifications of pathogenicity (May 05, 2023)
1-244053916-C-T		Intellectual disability, autosomal dominant 22	Conflicting classifications of pathogenicity (Apr 08, 2022)
1-244053933-A-G			Likely benign (Dec 11, 2023)
1-244053934-T-C		Intellectual disability, autosomal dominant 22	Likely pathogenic (Dec 01, 2022)
1-244053940-A-G		ZBTB18-related disorder	Uncertain significance (Jan 01, 2024)
1-244053944-A-T		Inborn genetic diseases	Uncertain significance (May 01, 2022)
1-244053945-T-A			Likely pathogenic (Oct 15, 2018)
1-244053975-CAA-C		Intellectual disability, autosomal dominant 22	Likely pathogenic (Aug 25, 2022)
1-244053982-G-A		Intellectual disability, autosomal dominant 22	Uncertain significance (May 08, 2020)
1-244053991-C-G			Uncertain significance (Dec 11, 2023)
1-244054015-G-GC			Pathogenic (Nov 08, 2018)
1-244054015-G-GCCC		Intellectual disability, autosomal dominant 22	Likely pathogenic (Jun 05, 2020)
1-244054020-C-T			Likely benign (Dec 31, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ZBTB18	protein_coding	protein_coding	ENST00000358704	2	6194

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.997	0.00342	0	0	0	0	0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	3.43	150	324	0.463	0.0000194	3542
Missense in Polyphen		27	127.87	0.21116		1382
Synonymous	-0.314	146	141	1.03	0.0000102	1012
Loss of Function	3.79	0	16.7	0.00	9.79e-7	203

LoF frequencies by population

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

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Transcriptional repressor that plays a role in various developmental processes such as myogenesis and brain development. Plays a key role in myogenesis by directly repressing the expression of ID2 and ID3, 2 inhibitors of skeletal myogenesis. Also involved in controlling cell division of progenitor cells and regulating the survival of postmitotic cortical neurons. Specifically binds the consensus DNA sequence 5'- [AC]ACATCTG[GT][AC]-3' which contains the E box core, and acts by recruiting chromatin remodeling multiprotein complexes. May also play a role in the organization of chromosomes in the nucleus. {ECO:0000269|PubMed:9756912}.

Recessive Scores

• pRec: 0.121

Intolerance Scores

• rvis_EVS: -0.78
• rvis_percentile_EVS: 12.77

Haploinsufficiency Scores

• pHI: 0.959
• hipred: Y
• hipred_score: 0.728
• ghis: 0.633

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Zbtb18
• 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); nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); growth/size/body region phenotype; cellular phenotype

Gene ontology

• Biological process: negative regulation of transcription by RNA polymerase II;cellular response to DNA damage stimulus;skeletal muscle tissue development;negative regulation of transcription, DNA-templated;positive regulation of transcription by RNA polymerase II
• Cellular component: nuclear chromosome;nucleus
• Molecular function: DNA-binding transcription factor activity, RNA polymerase II-specific;DNA binding;DNA-binding transcription factor activity;transcription coactivator activity;protein binding;sequence-specific DNA binding;metal ion binding