ZNF804A

Chr 2

zinc finger protein 804A

Also known as: C2orf10

NCBI Gene: 91752ENSG00000170396UniProt: Q7Z570

The protein encoded by this gene is a zinc finger binding protein. Polymorphisms in this gene, especially rs1344706, are thought to confer increased susceptibility to schizophrenia, bipolar disorder, and heroin addiciton. [provided by RefSeq, Nov 2015]

229
ClinVar variants
26
Pathogenic / LP
0.01
pLI score
0
Active trials
Clinical Summary— ZNF804A
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.30) despite low pLI — interpret in context.
📋
ClinVar Variants
26 Pathogenic / Likely Pathogenic· 162 VUS of 229 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
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.
0.48LOEUF
pLI 0.006
Z-score 4.16
OE 0.30 (0.19–0.48)
Moderately constrained

More LoF-intolerant than ~75% of genes

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.
-0.45Z-score
OE missense 1.05 (0.98–1.12)
630 obs / 598.9 exp
Tolerant

Tolerant to missense variation

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.0.30 (0.19–0.48)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.05 (0.98–1.12)
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.1.02
0≤1.21.6
LoF obs/exp: 12 / 40.6Missense obs/exp: 630 / 598.9Syn Z: -0.20

ClinVar Variant Classifications

229 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic25
Likely Pathogenic1
VUS162
Likely Benign24
Benign16
Conflicting1
25
Pathogenic
1
Likely Pathogenic
162
VUS
24
Likely Benign
16
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
25
0
25
Likely Pathogenic
0
0
1
0
1
VUS
1
157
4
0
162
Likely Benign
0
17
4
3
24
Benign
0
9
1
6
16
Conflicting
—1
Total1183359229

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

View in ClinVar →

Protein Context — Lollipop Plot

ZNF804A · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
The schizophrenia risk gene ZNF804A: clinical associations, biological mechanisms and neuronal functions.
Chang H et al.·Mol Psychiatry
2017Review
Impact of ZNF804A rs1344706 or CACNA1C rs1006737 polymorphisms on cognition in patients with severe mental disorders: A systematic review and meta-analysis.
Novaes de Oliveira Roldan AC et al.·World J Biol Psychiatry
2023Meta-analysis
Replication of ZNF804A gene variant associations with risk of heroin addiction.
Hancock DB et al.·Genes Brain Behav
2015Meta-analysis
Bioinformatic analyses and conceptual synthesis of evidence linking ZNF804A to risk for schizophrenia and bipolar disorder.
Hess JL et al.·Am J Med Genet B Neuropsychiatr Genet
2015Review
Further evidence for the association of genetic variants of ZNF804A with schizophrenia and a meta-analysis for genome-wide significance variant rs1344706.
Zhang R et al.·Schizophr Res
2012Meta-analysis
Polymorphism in the ZNF804A Gene and Variation in D(1) and D(2)/D(3) Dopamine Receptor Availability in the Healthy Human Brain: A Dual Positron Emission Tomography Study.
Hegarty CE et al.·Biol Psychiatry Cogn Neurosci Neuroimaging
2023
The interaction between the ZNF804A gene and cannabis use on the risk of psychosis in a non-clinical sample.
Soler J et al.·Prog Neuropsychopharmacol Biol Psychiatry
2019
ANK3, CACNA1C and ZNF804A gene variants in bipolar disorders and psychosis subphenotype.
Lett TA et al.·World J Biol Psychiatry
2011
Associations of schizophrenia risk genes ZNF804A and CACNA1C with schizotypy and modulation of attention in healthy subjects.
Meller T et al.·Schizophr Res
2019
The effect of psychosis associated CACNA1C, and its epistasis with ZNF804A, on brain function.
Tecelão D et al.·Genes Brain Behav
2019
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
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