ZNF668

zinc finger protein 668, the group of Zinc fingers C2H2-type

Basic information

Region (hg38): 16:31060842-31074240

Links

ENSG00000167394 ∙ NCBI:79759 ∙ OMIM:617103 ∙ HGNC:25821 ∙ Uniprot:Q96K58 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• neurodevelopmental disorder with poor growth, large ears, and dysmorphic facies (Limited), mode of inheritance: AR
• neurodevelopmental disorder with poor growth, large ears, and dysmorphic facies (Limited), mode of inheritance: Unknown

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Neurodevelopmental disorder with poor growth, large ears, and dysmorphic facies	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	Craniofacial; Musculoskeletal; Neurologic	26633546; 34313816

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ZNF668 gene.

• Inborn genetic diseases (23 variants)
• not provided (6 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ZNF668 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					3	3
missense			22	1		23
nonsense			1			1
start loss						0
frameshift			1			1
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding			1			1
Total	0	0	25	1	3

Variants in ZNF668

This is a list of pathogenic ClinVar variants found in the ZNF668 region.

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

Position	Type	Phenotype	Significance	ClinVar
16-31061069-C-T		ZNF668-related disorder	Benign/Likely benign (Dec 31, 2019)
16-31061165-C-T		not specified	Uncertain significance (Jun 07, 2023)
16-31061166-G-A		not specified	Uncertain significance (Aug 17, 2021)
16-31061262-G-A		not specified	Uncertain significance (Dec 05, 2022)
16-31061294-G-C		not specified	Uncertain significance (Oct 25, 2022)
16-31061303-C-T		not specified	Uncertain significance (Oct 25, 2023)
16-31061322-G-C		not specified	Uncertain significance (Apr 28, 2022)
16-31061338-C-G		ZNF668-related disorder	Likely benign (Apr 04, 2019)
16-31061379-C-G		Myoepithelial tumor	Uncertain significance (Nov 01, 2022)
16-31061463-C-T		not specified	Uncertain significance (May 18, 2022)
16-31061640-C-A		not specified	Uncertain significance (May 04, 2023)
16-31061652-G-A			Uncertain significance (Aug 18, 2022)
16-31061708-A-C		not specified	Uncertain significance (Apr 07, 2022)
16-31061779-G-C		not specified	Uncertain significance (Dec 15, 2023)
16-31061816-C-T		not specified	Uncertain significance (Nov 10, 2023)
16-31061817-G-A		marked facial dysmorphism;Progressive microcephaly;Failure to thrive;Profound global developmental delay • Neurodevelopmental disorder with poor growth, large ears, and dysmorphic facies	Pathogenic (Jan 10, 2023)
16-31061826-C-G		not specified	Uncertain significance (Nov 30, 2022)
16-31061887-C-T		ZNF668-related disorder	Likely benign (Mar 08, 2019)
16-31061919-T-C			Uncertain significance (Jun 21, 2018)
16-31061973-G-A		marked facial dysmorphism;Progressive microcephaly;Failure to thrive;Profound global developmental delay • Severe short-limb dwarfism • Neurodevelopmental disorder with poor growth, large ears, and dysmorphic facies	Pathogenic (Jan 10, 2023)
16-31062060-A-C		not specified	Uncertain significance (Nov 29, 2023)
16-31062137-A-T		not specified	Uncertain significance (Jan 04, 2024)
16-31062207-A-T		not specified	Uncertain significance (Jul 14, 2021)
16-31062264-G-A		not specified	Uncertain significance (Mar 31, 2022)
16-31063826-G-A		not specified	Uncertain significance (Aug 12, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ZNF668	protein_coding	protein_coding	ENST00000539836	3	13478

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.221	0.779	125725	0	15	125740	0.0000596

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.35	326	469	0.695	0.0000358	4080
Missense in Polyphen		76	168.42	0.45126		1487
Synonymous	0.630	194	206	0.944	0.0000167	1353
Loss of Function	3.14	5	20.2	0.247	0.00000110	224

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000127	0.000123
Ashkenazi Jewish	0.000101	0.0000992
East Asian	0.000164	0.000163
Finnish	0.0000464	0.0000462
European (Non-Finnish)	0.0000731	0.0000703
Middle Eastern	0.000164	0.000163
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: May be involved in transcriptional regulation. {ECO:0000250}.
• Pathway: Gene expression (Transcription);Generic Transcription Pathway;RNA Polymerase II Transcription (Consensus)

Intolerance Scores

• loftool: 0.634
• rvis_EVS: -0.51
• rvis_percentile_EVS: 21.56

Haploinsufficiency Scores

• pHI: 0.183
• hipred: Y
• hipred_score: 0.572
• ghis: 0.527

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.919

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Zfp668

Gene ontology

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