ZNF445

Chr 3

zinc finger protein 445

Also known as: ZFP445, ZKSCAN15, ZNF168, ZSCAN47

This transcription regulator maintains maternal and paternal gene imprinting by controlling DNA methylation at imprinting control regions during early embryonic development. Mutations cause transient neonatal diabetes mellitus with an autosomal recessive inheritance pattern. The gene is highly constrained against loss-of-function variants (pLI=1.0, LOEUF=0.21), indicating that heterozygous loss-of-function mutations are likely not tolerated.

OMIMResearchSummary from RefSeq, UniProt
LOFmechanismLOEUF 0.21
Clinical SummaryZNF445
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
7 unique Pathogenic / Likely Pathogenic· 128 VUS of 157 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.21LOEUF
pLI 1.000
Z-score 5.14
OE 0.08 (0.040.21)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint
1.37Z-score
OE missense 0.84 (0.770.90)
462 obs / 552.6 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.08 (0.040.21)
00.351.4
Missense OE0.84 (0.770.90)
00.61.4
Synonymous OE1.04
01.21.6
LoF obs/exp: 3 / 36.5Missense obs/exp: 462 / 552.6Syn Z: -0.41
DN
0.3892th %ile
GOF
0.3887th %ile
LOF
0.70top 10%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.21

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

157 submitted variants in ClinVar

Classification Summary

Pathogenic6
Likely Pathogenic1
VUS128
Likely Benign7
Benign1
6
Pathogenic
1
Likely Pathogenic
128
VUS
7
Likely Benign
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
6
0
6
Likely Pathogenic
0
0
1
0
1
VUS
1
126
1
0
128
Likely Benign
0
7
0
0
7
Benign
0
1
0
0
1
Total113480143

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

View in ClinVar →

Protein Context — Lollipop Plot

ZNF445 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
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Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC