Human Gene Module / Chromosome 19 / ZNF865

ZNF865zinc finger protein 865

SFARI Gene Score
1
High Confidence Criteria 1.1
Autism Reports / Total Reports
4 / 5
Rare Variants / Common Variants
22 / 0
Aliases
-
Associated Syndromes
-
Chromosome Band
19q13.42
Associated Disorders
-
Relevance to Autism

Bradbrook et al., 2025 described a cohort of 18 patients with protein-truncating variants in the ZNF865 gene (the majority of which were de novo in origin and clustered toward the C-terminus) presenting with a neurodevelopmental disorder characterized by speech delay, cognitive delay or intellectual disability, hypotonia, brain MRI abnormalities, and dysmorphic features; seven patients were reported to have been diagnosed with autism spectrum disorder, with two additional patients having autistic features without a confirmed diagnosis. Additional de novo variants in ZNF865, including two protein-truncating variants and four missense variants, have been reported in ASD probands from the Simons Simplex Collection, SPARK, the Autism Sequencing Consortium, MSSNG, and a Chinese ASD cohort (Satterstrom et al., 2020; Zhou et al., 2022; Wang et al., 2023).

Molecular Function

Predicted to enable DNA-binding transcription factor activity and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be located in nucleus.

External Links
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Human
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Reports related to ZNF865 (5 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Support Large-Scale Exome Sequencing Study Implicates Both Developmental and Functional Changes in the Neurobiology of Autism Satterstrom FK et al. (2020) Yes -
2 Support - Zhou X et al. (2022) Yes -
3 Support - Wang J et al. (2023) Yes -
4 Primary - Samuel M Bradbrook et al. (2026) No ASD, epilepsy/seizures
5 Support - Richard G Boles et al. (2025) Yes ID
Rare Variants   (22)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.2015C>A p.Ser672Ter stop_gained De novo - - 40936200 Samuel M Bradbrook et al. (2026)
c.2091C>G p.Tyr697Ter stop_gained De novo - - 40936200 Samuel M Bradbrook et al. (2026)
c.2141G>A p.Trp714Ter stop_gained De novo - - 40936200 Samuel M Bradbrook et al. (2026)
c.2142G>A p.Trp714Ter stop_gained De novo - - 40936200 Samuel M Bradbrook et al. (2026)
c.1381G>T p.Ala461Ser missense_variant De novo - Simplex 35982159 Zhou X et al. (2022)
c.2629C>G p.Arg877Gly missense_variant De novo - Simplex 37393044 Wang J et al. (2023)
c.1999C>T p.Leu667= synonymous_variant De novo - Simplex 35982159 Zhou X et al. (2022)
c.539C>T p.Pro180Leu missense_variant De novo - Multiplex 35982159 Zhou X et al. (2022)
c.1256C>T p.Ala419Val missense_variant De novo - - 31981491 Satterstrom FK et al. (2020)
c.1718C>T p.Thr573Met missense_variant De novo - - 41010044 Richard G Boles et al. (2025)
c.2304_2305delTG p.Gly770Ter stop_gained De novo - - 40936200 Samuel M Bradbrook et al. (2026)
c.2038del p.Asp680IlefsTer6 frameshift_variant De novo - Simplex 35982159 Zhou X et al. (2022)
c.2952del p.Pro985ArgfsTer97 frameshift_variant De novo - Simplex 35982159 Zhou X et al. (2022)
c.2395C>T p.Gln799Ter stop_gained Unknown Not maternal - 40936200 Samuel M Bradbrook et al. (2026)
c.194del p.Pro65ArgfsTer98 frameshift_variant De novo - - 40936200 Samuel M Bradbrook et al. (2026)
c.1616del p.Gly539GlufsTer27 frameshift_variant De novo - - 40936200 Samuel M Bradbrook et al. (2026)
c.2339del p.Gly780ValfsTer29 frameshift_variant De novo - - 40936200 Samuel M Bradbrook et al. (2026)
c.2351del p.Gly784ValfsTer25 frameshift_variant De novo - - 40936200 Samuel M Bradbrook et al. (2026)
c.2363del p.Gly788AlafsTer21 frameshift_variant De novo - - 40936200 Samuel M Bradbrook et al. (2026)
c.1951del p.Ala651ProfsTer17 frameshift_variant Familial - - 40936200 Samuel M Bradbrook et al. (2026)
c.2398_2399del p.Ser800PhefsTer163 frameshift_variant De novo - - 40936200 Samuel M Bradbrook et al. (2026)
c.1573_1574dup p.His526ProfsTer41 frameshift_variant Unknown Not maternal - 40936200 Samuel M Bradbrook et al. (2026)
Common Variants  

No common variants reported.

SFARI Gene score
1

High Confidence

Score Delta: Score remained at 1

criteria met
See SFARI Gene'scoring criteria
1

High Confidence

See all Category 1 Genes

We considered a rigorous statistical comparison between cases and controls, yielding genome-wide statistical significance, with independent replication, to be the strongest possible evidence for a gene. These criteria were relaxed slightly for category 2.

10/1/2025
icon
1

Increased from to 1

Zhang D Score

Score -0.24083939987115

Ranking 16212/20870 scored genes


[Show Scoring Methodology]
The DAMAGES score (disease-associated mutation analysis using gene expression signatures), or D score, was developed to combine evidence from de novo loss-of- function mutation with evidence from cell-type- specific gene expression in the mouse brain (specifically translational profiles of 24 specific mouse CNS cell types isolated from 6 different brain regions). Genes with positive D scores are more likely to be associated with autism risk, with higher-confidence genes having higher D scores. This statistic was first presented by Zhang & Shen (Hum Mutat 38, 204- 215 (2017), and D scores for more than 20,000 RefSeq genes can be found in column M in supplementary table 2 from that paper.
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