ZFP57

Chr 6ADAR

ZFP57 zinc finger protein

Also known as: C6orf40, TNDM1, ZNF698, bA145L22, bA145L22.2

NCBI Gene: 346171ENSG00000204644UniProt: Q9NU63

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]

Primary Disease Associations & Inheritance

Diabetes mellitus, transient neonatal 1MIM #601410
ADAR
166
ClinVar variants
20
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— ZFP57
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
20 Pathogenic / Likely Pathogenic· 87 VUS of 166 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
1.34LOEUF
pLI 0.001
Z-score 0.88
OE 0.68 (0.37–1.34)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
1.38Z-score
OE missense 0.77 (0.69–0.86)
219 obs / 284.5 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.68 (0.37–1.34)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.77 (0.69–0.86)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.85
0≤1.21.6
LoF obs/exp: 6 / 8.8Missense obs/exp: 219 / 284.5Syn Z: 1.21

ClinVar Variant Classifications

166 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic15
Likely Pathogenic5
VUS87
Likely Benign25
Benign23
Conflicting11
15
Pathogenic
5
Likely Pathogenic
87
VUS
25
Likely Benign
23
Benign
11
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
5
3
7
0
15
Likely Pathogenic
2
1
2
0
5
VUS
0
80
4
3
87
Likely Benign
0
6
4
15
25
Benign
0
4
19
0
23
Conflicting
—11
Total7943618166

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

ZFP57 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

ZFP57-related diabetes mellitus, transient neonatal

definitive
ARLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Diabetes mellitus, transient neonatal 1

MIM #601410

Molecular basis of disorder known

Autosomal dominantAutosomal recessive
📖
GeneReview available — ZFP57
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Transient neonatal diabetes mellitus and hypomethylation at additional imprinted loci: novel ZFP57 mutation and review on the literature.
Touati A et al.·Acta Diabetol
2019Review
Is ZFP57 binding to H19/IGF2:IG-DMR affected in Silver-Russell syndrome?
Sparago A et al.·Clin Epigenetics
2018
Mutational Alterations of DNA Methylation-related Genes CTCF, ZFP57, and ATF7IP Genes in Colon Cancers.
Moon SW et al.·Appl Immunohistochem Mol Morphol
2022
Genes, assisted reproductive technology and trans-illumination.
Dias RP et al.·Epigenomics
2013Review
The role of ZFP57 and additional KRAB-zinc finger proteins in the maintenance of human imprinted methylation and multi-locus imprinting disturbances.
Monteagudo-Sánchez A et al.·Nucleic Acids Res
2020
The Embryonic Stem Cell-Specific Transcription Factor ZFP57 Promotes Liver Metastasis of Colorectal Cancer.
Shoji Y et al.·J Surg Res
2019
Unraveling the genetic basis of MODY: insights from next-generation sequencing.
Eser M et al.·J Appl Genet
2025
Molecular and Clinical Profiles of Pediatric Monogenic Diabetes Subtypes: Comprehensive Genetic Analysis of 138 Patients.
Zhou Q et al.·J Clin Endocrinol Metab
2025Cohort
The stem cell transcription factor ZFP57 induces IGF2 expression to promote anchorage-independent growth in cancer cells.
Tada Y et al.·Oncogene
2015
DNA methylation and stroke prognosis: an epigenome-wide association study.
Jiménez-Balado J et al.·Clin Epigenetics
2024Meta-analysis
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
ZFP57 is a regulator of postnatal growth and life-long health.
Hanin G et al.·Nat Commun
2026🔓 Open Access
An epigenome-wide association study in the case-control study to explore early development identifies differential DNA methylation near ZFP57 as associated with autistic traits.
Howerton EM et al.·J Neurodev Disord
2025🔓 Open Access
ZFP57 promotes ovarian cancer progression by transcriptionally regulating BRCA1 and managing G1 checkpoint.
Fan W et al.·J Cancer
2023🔓 Open Access
ZFP57 regulates DNA methylation of imprinted genes to facilitate embryonic development of somatic cell nuclear transfer embryos in Holstein cows.
Yu T et al.·J Dairy Sci
2023
High-fat diet and palmitate inhibits FNDC5 expression via AMPK-Zfp57 pathway in mouse muscle cells.
Guo Q et al.·Chem Biol Interact
2023Functional
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools