When families receive genetic testing results, words like de novo, likely gene-disrupting, and penetrance can be hard to parse. This article summarizes publicly curated autism gene lists where new (non-inherited) mutations are a major part of the evidence—so you can orient yourself before speaking with a genetic counselor or clinician.
Not medical or genetic advice.This article summarizes public research databases for orientation and learning. It does not interpret your child's test results. Always discuss variants with a genetic counselor or clinician.
Key terms
- De novo
- A variant that arose new in the child and was not inherited from either parent.
- Likely gene-disrupting (LGD)
- Often a stop-gain, frameshift, splice, or strongly damaging missense change—variants thought to severely affect the protein.
- Penetrance
- Not everyone with a given variant develops autism; risk is probabilistic and varies by gene and variant.
- NDD
- Neurodevelopmental disorder—a broader label that often includes intellectual disability, epilepsy, or speech delay alongside autism traits.
Public studies and databases
- SFARI Gene — Category 1 (May 2026)
245 high-confidence autism-associated genes; scoring typically requires multiple de novo likely-gene-disrupting reports.
- Zhou et al., Nature Genetics 2022
Meta-analysis of 42,607 autism cases; 60 exome-wide significant genes; highlights genes driven primarily by de novo variants (e.g. MARK2).
- Fu et al., Nature Genetics 2022
72 genes at stringent FDR; roughly 57.5% of association evidence from de novo protein-truncating variants.
- Wang et al., PNAS 2021
46,612 parent–child trios; large-scale de novo enrichment across neurodevelopmental genes.
Tier 1 — Highest-confidence genes (SFARI Category 1)
SFARI Gene Category 1 lists 245 genes (May 2026) with clear autism links, usually supported by multiple de novo likely-gene-disrupting mutations. Below are grouped highlights; the full alphabetical list is at the end.
Synaptic and neuronal signaling
| Gene | Why it appears here |
|---|---|
| SHANK3 | Postsynaptic scaffold; 22q13 region; among the strongest ASD signals. |
| SHANK2 | Related synaptic scaffold; recurrent de novo hits. |
| NRXN1 | Neurexin; presynaptic adhesion. |
| NRXN2 | Neurexin family. |
| NRXN3 | Neurexin family. |
| NLGN2 | Neuroligin. |
| NLGN3 | Neuroligin. |
| NLGN4X | X-linked neuroligin. |
| SYNGAP1 | Synaptic Ras-GAP; ID, epilepsy, and ASD overlap. |
| DLG4 | PSD-95; postsynaptic density. |
| GRIN2B | NMDA receptor subunit; classic recurrent de novo gene. |
| GRIN2A | NMDA receptor subunit. |
| GRIN1 | NMDA receptor subunit. |
| GRIA2 | AMPA receptor subunit. |
| GABRB3 | GABA-A receptor. |
| GABRB2 | GABA-A receptor. |
| SCN2A | Sodium channel; top penetrant de novo gene in many cohorts. |
| SCN1A | Sodium channel; epilepsy and NDD overlap. |
| SCN8A | Sodium channel. |
| CACNA1C | Calcium channel. |
| CACNA1A | Calcium channel. |
| CACNA1E | Calcium channel. |
| STXBP1 | Synaptic vesicle release. |
| RELN | Reelin signaling. |
Chromatin remodeling and transcription
| Gene | Why it appears here |
|---|---|
| CHD8 | Top-tier de novo ASD gene; macrocephaly often reported. |
| CHD2 | CHD family helicase. |
| CHD7 | CHARGE syndrome region; NDD overlap. |
| CHD3 | CHD family helicase. |
| ARID1B | SWI/SNF chromatin remodeling. |
| SMARCA4 | SWI/SNF. |
| SMARCA2 | SWI/SNF. |
| SMARCC2 | SWI/SNF. |
| KMT2A | Histone methyltransferase. |
| KMT2C | Histone methyltransferase. |
| KMT2E | Histone methyltransferase. |
| KDM5B | Histone demethylase. |
| KDM5C | X-linked histone demethylase. |
| KDM6B | Histone demethylase. |
| DNMT3A | DNA methylation. |
| EHMT1 | Kleefstra-related chromatin gene. |
| CREBBP | CREB-binding protein. |
| EP300 | p300 histone acetyltransferase. |
| CTCF | Genome architecture / insulator protein. |
| YY1 | Transcription factor; genome regulation. |
| ASH1L | Histone methyltransferase. |
| SETD5 | Chromatin regulator. |
| SETD1A | Chromatin regulator. |
Brain development and neuronal specification
| Gene | Why it appears here |
|---|---|
| DYRK1A | 21q22 kinase; microcephaly association in some cases. |
| TBR1 | T-box TF; OMIM documents de novo TBR1 variants with autism and speech delay. |
| FOXP1 | Forkhead transcription factor. |
| FOXP2 | Speech and language development. |
| FOXG1 | Forebrain development. |
| MEF2C | Cortical development. |
| SATB2 | SATB2-associated syndrome. |
| POGZ | High-impact developmental regulator. |
| PHIP | Developmental disorder gene. |
| ADNP | Helsmoortel–van der Aa syndrome; strong ASD link. |
| BCL11A | Cortical interneuron development. |
Cytoskeleton, migration, and Rho signaling
| Gene | Why it appears here |
|---|---|
| TRIO | Rho GEF; de novo enrichment in autism studies. |
| NCKAP1 | Neurite migration. |
| WDFY3 | Neurite and synaptic development. |
| DYNC1H1 | Dynein; axonal transport. |
| DPYSL2 | CRMP family; axon guidance. |
RNA processing and regulation
| Gene | Why it appears here |
|---|---|
| DDX3X | X-linked; intellectual disability and ASD. |
| HNRNPU | hnRNP family. |
| HNRNPH2 | X-linked hnRNP. |
| CELF4 | RNA regulation. |
| UPF3B | Nonsense-mediated decay; X-linked. |
| SON | RNA-binding; enriched in NDD/ASD cohorts. |
Syndromic genes with strong autism and de novo overlap
| Gene | Why it appears here |
|---|---|
| FMR1 | Fragile X. |
| MECP2 | Rett syndrome (X-linked). |
| TSC1 | Tuberous sclerosis. |
| TSC2 | Tuberous sclerosis. |
| PTEN | PTEN hamartoma; macrocephaly/autism. |
| NF1 | Neurofibromatosis type 1. |
| UBE3A | 15q11 region (Angelman context). |
| CDKL5 | Epileptic encephalopathy (X-linked). |
| PCDH19 | Epileptic encephalopathy (X-linked). |
| RAI1 | Smith–Magenis (17p11.2). |
| ANKRD11 | KBG syndrome. |
Tier 2 — Landmark recurrent de novo genes
Early large trio exome studies (e.g. Sanders 2012, De Rubeis 2014) highlighted these six genes as recurrent de novo contributors to sporadic autism risk.
| Gene | Why it appears here |
|---|---|
| CHD8 | Chromatin remodeling. |
| DYRK1A | Kinase; 21q22 region. |
| GRIN2B | Glutamate signaling. |
| TBR1 | T-box transcription factor. |
| PTEN | PI3K pathway / tumor suppressor. |
| TBL1XR1 | Transducin beta-like protein. |
Tier 3 — Findings from large meta-analyses (2021–2022)
Primarily supported by de novo variants (Zhou et al. 2022)
| Gene | Why it appears here |
|---|---|
| MARK2 | Primarily de novo; also NDD, epilepsy, Tourette overlap. |
| ITSN1 | De novo and inherited; endocytosis. |
| SCAF1 | De novo and inherited. |
| HNRNPUL2 | De novo and inherited; RNA processing. |
Also exome-wide significant in large meta-analyses
Includes established de novo drivers such as CHD8, SHANK3, SCN2A, ADNP, and FOXP1. Some genes (e.g. NAV3) are driven more by inherited loss-of-function than classic de novo hits.
| Gene | Why it appears here |
|---|---|
| SHANK3 | Established de novo driver. |
| SCN2A | Established de novo driver. |
| ADNP | Established de novo driver. |
| FOXP1 | Established de novo driver. |
| NAV3 | Mostly inherited LoF in Zhou 2022—not a classic de novo list gene. |
Full list — SFARI Category 1 (alphabetical)
242 gene symbols from the public Category 1 export. Search any symbol on gene.sfari.org for variant reports and scores.
ABCE1, ACTB, ADNP, ADSL, AFF2, AHDC1, ALDH5A1, ANK2, ANK3, ANKRD11, ANP32A, AP2S1, ARF3, ARHGEF9, ARID1B, ARX, ASH1L, ASTN1, ASXL3, ATRX, AUTS2, BAZ2B, BCKDK, BCL11A, BRAF, BRSK2, CACNA1A, CACNA1C, CACNA1E, CACNA2D3, CAMK2A, CAMTA2, CAPRIN1, CASK, CASZ1, CDKL5, CELF4, CHAMP1, CHD2, CHD3, CHD7, CHD8, CIC, CNOT3, CORO1A, CPSF7, CREBBP, CSDE1, CSNK2A1, CTCF, CTNNB1, CUL3, DDX3X, DEAF1, DHCR7, DIP2A, DLG4, DMPK, DNMT3A, DPYSL2, DSCAM, DYNC1H1, DYRK1A, EBF3, EHMT1, EIF3G, ELAVL3, EP300, FMR1, FOXG1, FOXP1, FOXP2, GABRB2, GABRB3, GFAP, GIGYF1, GIGYF2, GNAI1, GRIA2, GRIN1, GRIN2A, GRIN2B, HDLBP, HECTD4, HIVEP2, HNRNPH2, HNRNPU, HRAS, IQSEC2, IRF2BPL, KANSL1, KATNAL2, KCNB1, KCNQ2, KCNQ3, KDM2B, KDM3B, KDM5B, KDM5C, KDM6B, KIAA0232, KLHL20, KMT2A, KMT2C, KMT2E, KMT5B, LDB1, LRRC4C, LZTR1, MAGEC3, MAGEL2, MAP1A, MBD5, MBOAT7, MECP2, MED13, MED13L, MEF2C, MEIS2, MKX, MSL3, MTOR, MYCBP2, MYT1L, NAA15, NACC1, NBEA, NCKAP1, NCOA1, NEXMIF, NF1, NIPBL, NLGN2, NLGN3, NLGN4X, NR3C2, NR4A2, NRXN1, NRXN2, NRXN3, NSD1, NUP155, PACS1, PAH, PAX5, PCCB, PCDH19, PHF12, PHF2, PHF21A, PHF3, PHIP, POGZ, POMGNT1, PPP1R9B, PPP2R5D, PPP5C, PRMT9, PRR12, PRR14L, PSMD11, PSMD12, PSMD6, PTCHD1, PTEN, PTK7, PTPN11, RAI1, RALGAPB, RELN, RERE, RFX3, RIMS1, RORB, RUNX1T1, SATB1, SATB2, SCN1A, SCN2A, SCN8A, SETBP1, SETD1A, SETD2, SETD5, SF1, SHANK2, SHANK3, SIN3A, SKI, SLC6A1, SLC9A6, SMARCA1, SMARCA2, SMARCA4, SMARCC2, SON, SOS2, SOX5, SPAST, SRCAP, SRPRA, STXBP1, SYN1, SYNGAP1, TANC2, TAOK1, TBCEL, TBCK, TBL1XR1, TBR1, TCF20, TCF4, TCF7L2, TEK, TLE3, TLK2, TM9SF4, TRAF7, TRIM23, TRIO, TRIP12, TRRAP, TSC1, TSC2, TSHZ1, TSHZ3, UBAP2L, UBE3A, UBR1, UPF3B, USP9X, VEZF1, VPS13B, WAC, WDFY3, YY1, ZBTB20, ZBTB21, ZMYND8, ZNF292, ZNF462, ZNF865
Category 2 genes (often two reported de novo LGD hits) are not listed here. Browse them on SFARI Category 2.
Look up any gene
- SFARI Gene — Autism-specific gene scores and reported variants.
- ClinVar — Clinical classifications of specific variants.
- gnomAD — How rare a variant is in the general population.
- OMIM — Gene–disease entries and references.
- GeneMatcher — Connect families and clinicians studying the same gene.
- DECIPHER — Developmental disorders, CNVs, and phenotype sharing.
Important limitations
- This is not a complete catalog of every possible de novo gene. Thousands of genes can carry rare new mutations; only a subset reach statistical and clinical confidence for autism.
- Many de novo variants are benign. Pathogenicity depends on the specific change, not the gene name alone.
- Inherited variants also contribute substantially to autism risk in large studies—not only de novo changes.
- A gene on this list does not mean your child has that mutation. Always interpret results with a qualified genetic counselor or clinician.
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