ZFP57

protein-coding

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

Gene summary

The protein encoded by this gene is a zinc finger protein containing a KRAB domain. Studies in mouse suggest that this protein may function as a transcriptional repressor. Mutations in this gene have been associated with transient neonatal diabetes mellitus type 1 (TNDM1).[provided by RefSeq, Sep 2009]

Previous symbols:

C6orf40

MANE transcript

NM_001109809.5

Inheritance

AR, AD

ClinVar variants

P:15U:91B:40

Top phenotype

Diabetes mellitus, transient neonatal, 1

gnomAD constraint

pLI —, LoF o/e 0.68

Max pathogenic AF

—

Genomic locus

chr6:29,672,483-29,681,155

External References & Databases

Ensembl (ENSG00000204644)

Transcript & Mutation Effects

hg38 • Region Span ~8.7 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

diabetes mellitus, transient neonatal, 1DEFINITIVE

Inheritance Pattern: AR

Disease ID:MONDO:0011073

Submitter: G2P

diabetes mellitus, transient neonatal, 1STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0011073

Submitter: Labcorp Genetics (formerly Invitae)

diabetes mellitus, transient neonatal, 1STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0011073

Submitter: PanelApp Australia

transient neonatal diabetes mellitusSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0020525

Submitter: Genomics England PanelApp

transient neonatal diabetes mellitusSUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0020525

Submitter: Orphanet

diabetes mellitus, transient neonatal, 1STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0011073

Submitter: Genomics England PanelApp

diabetes mellitus, transient neonatal, 1MODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0011073

Submitter: Ambry Genetics

Clinical Genomic Database (CGD)

Diabetes mellitus, transient neonatal, 1AD

Manifestation: Endocrine

Intervention: Endocrine

Rationale: Individuals present early in life with failure to thrive, hyperglycemia, and dehydration, and prompt recognition and treatment can reduce morbidity

Comments: The pathogenesis can involve imprinting defects (eg, paternal UPD, paternal duplication, methylation defects)

Refs: 18622393

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to ZFP57 variants in ClinVar

9 Conditions Cataloged

Inborn genetic diseasesTotal: 65

not providedTotal: 61

Diabetes mellitus, transient neonatal, 1Total: 42

not specifiedTotal: 20

ZFP57-related disorderTotal: 12

Monogenic diabetesTotal: 10

Transitory neonatal diabetes mellitusTotal: 2

Monogenic short statueTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001109809.5. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			4 clinvar	22 clinvar		26
missense	4 clinvar	1 clinvar	86 clinvar	15 clinvar	3 clinvar	109
nonsense	1 clinvar	1 clinvar	1 clinvar			3
start loss						0
frameshift	6 clinvar	2 clinvar				8
splice donor/acceptor (+/-2bp)						0
Total	11	4	91	37	3	146

Highest pathogenic variant AF is 0.000010540557

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 15 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001109809.5	RefSeq	NP_001103279.2	4	MANE Select
ENST00000376883.2	Ensembl	ENSP00000366080.2	4	MANE Select
NM_001366333.2	RefSeq	NP_001353262.1	3	Standard
ENST00000488757.6	Ensembl	ENSP00000418259.2	3	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

regulation of gene expression by genetic imprinting
regulation of transcription by RNA polymerase II
DNA methylation involved in embryo development

Molecular Function

DNA-binding transcription factor activity, RNA polymerase II-specific
DNA binding
metal ion binding

Cellular Component

nucleus

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000488757
Coding exons: 4
Length: 8719
Individuals with no LoFs: 124811
Homozygous LoFs: 0
Heterozygous LoFs: 9
Defined: 124820
p: 0.0000361

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.38	219	285	0.770	0.0000152	3556
Missense (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

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00028	0.00026	rare
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00011	0.00011	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0	0.0	absent
South Asian	0.000066	0.000065	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

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

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.00277

Gene Damage Prediction

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