ZFP69

Chr 1

ZFP69 zinc finger protein

Also known as: ZFP69A, ZKSCAN23A, ZNF642, ZSCAN54A

NCBI Gene: 339559 ENSG00000187815 UniProt: Q49AA0 OMIM: 617939

This gene encodes a transcription factor that regulates lipid metabolism through RNA polymerase II-mediated transcription. The gene shows minimal constraint against loss-of-function variants (pLI near 0, LOEUF ~1.1), and no established disease associations have been reported in humans. Currently, there is insufficient evidence to support ZFP69 as a cause of pediatric neurological disorders.

OMIM ResearchSummary from RefSeq, UniProt

Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II transcription regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of lipid metabolic process and regulation of transcription by RNA polymerase II. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

MultiplemechanismLOEUF 1.11

Clinical Summary— ZFP69

⚡

Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

📋

ClinVar Variants

70 VUS of 84 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.11LOEUF

pLI 0.000

Z-score 1.19

OE 0.72 (0.48–1.11)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

1.22Z-score

OE missense 0.80 (0.72–0.89)

229 obs / 287.0 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.72 (0.48–1.11)

0≤0.351.4

Missense OE?0.80 (0.72–0.89)

0≤0.61.4

Synonymous OE?0.82

0≤1.21.6

LoF obs/exp: 15 / 20.9Missense obs/exp: 229 / 287.0Syn Z: 1.42

This gene — mechanism propensity

0.81top 10%

GOF

0.79top 25%

LOF

0.2777th %ile

This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

DNprediction above median

GOFprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

84 submitted variants in ClinVar

ClinVar

Classification Summary

VUS70

Likely Benign4

Benign1

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Synonymous	Total
Pathogenic	0	0	0
Likely Pathogenic	0	0	0
VUS	70	0	70
Likely Benign	3	1	4
Benign	1	0	1
Total	74	1	75

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

View in ClinVar →

9 pathogenic / likely-pathogenic (of 17) ClinVar copy-number / structural variants overlap ZFP69 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →