ZFP57

ZFP57 zinc finger protein, the group of Zinc fingers C2H2-type

Basic information

Region (hg38): 6:29672482-29681155

Previous symbols: [ "C6orf40" ]

Links

ENSG00000204644 ∙ NCBI:346171 ∙ OMIM:612192 ∙ HGNC:18791 ∙ Uniprot:Q9NU63 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• diabetes mellitus, transient neonatal, 1 (Definitive), mode of inheritance: AR
• diabetes mellitus, transient neonatal, 1 (Strong), mode of inheritance: AR
• transient neonatal diabetes mellitus (Strong), mode of inheritance: AR
• diabetes mellitus, transient neonatal, 1 (Moderate), mode of inheritance: AR
• diabetes mellitus, transient neonatal, 1 (Strong), mode of inheritance: AR
• transient neonatal diabetes mellitus (Supportive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Diabetes mellitus, transient neonatal, 1	AD	Endocrine	Individuals present early in life with failure to thrive, hyperglycemia, and dehydration, and prompt recognition and treatment can reduce morbidity	Endocrine	18622393
The pathogenesis can involve imprinting defects (eg, paternal UPD, paternal duplication, methylation defects)

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ZFP57 gene.

• not provided (60 variants)
• Diabetes mellitus, transient neonatal, 1 (32 variants)
• Inborn genetic diseases (17 variants)
• not specified (10 variants)
• Monogenic diabetes (10 variants)
• Transitory neonatal diabetes mellitus (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ZFP57 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			4	7		11
missense		1	37	2	5	45
nonsense						0
start loss						0
frameshift	3	1				4
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region			1			1
non coding				2	17	19
Total	3	2	41	11	22

Highest pathogenic variant AF is 0.0000132

Variants in ZFP57

This is a list of pathogenic ClinVar variants found in the ZFP57 region.

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

Position	Type	Phenotype	Significance	ClinVar
6-29672507-T-C			Uncertain significance (-)
6-29672526-C-T		ZFP57-related disorder	Likely benign (Aug 06, 2023)
6-29672529-C-A			Uncertain significance (Apr 04, 2024)
6-29672561-C-G		Inborn genetic diseases	Uncertain significance (Mar 23, 2022)
6-29672566-G-C		not specified	Uncertain significance (Aug 05, 2015)
6-29672582-G-T		Inborn genetic diseases	Uncertain significance (Sep 27, 2022)
6-29672590-C-A			Uncertain significance (Apr 08, 2022)
6-29672639-G-C		Diabetes mellitus, transient neonatal, 1 • Monogenic diabetes • ZFP57-related disorder • Inborn genetic diseases	Conflicting classifications of pathogenicity (Dec 28, 2023)
6-29672685-G-A		Inborn genetic diseases	Likely benign (Dec 15, 2023)
6-29672727-AG-A		Diabetes mellitus, transient neonatal, 1	Pathogenic (Aug 01, 2008)
6-29672739-G-C		Diabetes mellitus, transient neonatal, 1	Pathogenic (Aug 01, 2008)
6-29672772-G-T		Inborn genetic diseases	Uncertain significance (Dec 07, 2021)
6-29672828-A-G		Inborn genetic diseases	Uncertain significance (Dec 19, 2022)
6-29672835-T-C		Inborn genetic diseases	Likely benign (Oct 03, 2023)
6-29672858-C-A			Uncertain significance (Dec 07, 2023)
6-29672881-C-T		Diabetes mellitus, transient neonatal, 1	Uncertain significance (Jan 13, 2018)
6-29672930-C-T		Inborn genetic diseases	Uncertain significance (Jun 05, 2023)
6-29672985-C-G			Uncertain significance (Oct 21, 2021)
6-29672993-G-C		Diabetes mellitus, transient neonatal, 1	Conflicting classifications of pathogenicity (Sep 08, 2023)
6-29672999-G-C		Inborn genetic diseases	Uncertain significance (Oct 27, 2021)
6-29673008-T-A		not specified • Diabetes mellitus, transient neonatal, 1	Benign (Feb 01, 2024)
6-29673025-A-G		not specified • Diabetes mellitus, transient neonatal, 1	Benign/Likely benign (Jan 26, 2024)
6-29673078-C-G		Diabetes mellitus, transient neonatal, 1 • Monogenic diabetes • ZFP57-related disorder	Conflicting classifications of pathogenicity (Dec 28, 2023)
6-29673168-T-C		Inborn genetic diseases	Uncertain significance (Mar 03, 2022)
6-29673174-T-C		Diabetes mellitus, transient neonatal, 1 • Monogenic diabetes	Benign (Jan 25, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ZFP57	protein_coding	protein_coding	ENST00000488757	4	8719

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.000546	0.717	124811	0	9	124820	0.0000361

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.38	219	285	0.770	0.0000152	3556
Missense in Polyphen		45	70.997	0.63383		944
Synonymous	1.21	92	108	0.852	0.00000561	1012
Loss of Function	0.876	6	8.81	0.681	3.80e-7	105

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000308	0.000287
Ashkenazi Jewish	0.00	0.00
East Asian	0.000112	0.000111
Finnish	0.00	0.00
European (Non-Finnish)	0.00	0.00
Middle Eastern	0.000112	0.000111
South Asian	0.0000659	0.0000654
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Binds to a 5'-TGCCGC-3' consensus sequence and recognizes the methylated CpG within this element (By similarity). Transcription regulator required to maintain maternal and paternal gene imprinting, a process by which gene expression is restricted in a parent of origin-specific manner by epigenetic modification of genomic DNA and chromatin, including DNA methylation. Acts by controlling DNA methylation during the earliest multicellular stages of development at multiple imprinting control regions. Required for the establishment of maternal methylation imprints at SNRPN locus. Acts as a transcriptional repressor in Schwann cells. {ECO:0000250, ECO:0000269|PubMed:18622393}.
• Disease: DISEASE: Transient neonatal diabetes mellitus 1 (TNDM1) [MIM:601410]: Neonatal diabetes is a form of diabetes mellitus defined by the onset of mild-to-severe hyperglycemia within the first months of life. In about half of the neonates, diabetes is transient and resolves at a median age of 3 months, whereas the rest have a permanent form of diabetes. {ECO:0000269|PubMed:18622393}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Intolerance Scores

• loftool: 0.716
• rvis_EVS: 1.97
• rvis_percentile_EVS: 97.58

Haploinsufficiency Scores

• hipred: N
• hipred_score: 0.247
• ghis: 0.391

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.00277

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Zfp57
• 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); cellular phenotype

Gene ontology

• Biological process: regulation of gene expression by genetic imprinting;regulation of transcription by RNA polymerase II;DNA methylation involved in embryo development
• Cellular component: nucleus
• Molecular function: DNA-binding transcription factor activity, RNA polymerase II-specific;DNA binding;metal ion binding