Table 1.

Known and Putative Autism Genes (Organized by Pathogenesis)

Protein Name
Gene Symbol / LocusSelected References
Neuronal cell
function 1
Neuroligin 3 2
(synapse formation and function)
NLGN3 / Xq28Jamain et al [2003]
Chih et al [2004]
Chubykin et al [2005]
Yan et al [2005]
Ylisaukko-oja et al [2005]
Lisé & El-Husseini [2006]
Lintas & Persico [2009]
Neuroligin 4 2
(synapse formation and function)
(NLGN4) / Xp22.33
Jamain et al [2003]
Laumonnier et al [2004]
Talebizadeh et al [2004]
Vincent et al [2004]
Gauthier et al [2005]
Ylisaukko-oja et al [2005]
Kumar et al [2008]
Lintas & Persico [2009]
Neurexin 1
(trans-synaptic binding partner for neuroligins)
NRXN1 / 2p16.3Feng et al [2006]
Lisé & El-Husseini [2006]
Szatmari et al [2007]
Kim et al [2008]
SH3 & multiple ankyrin repeat domains 3
(organizes post-synaptic density & binds neuroligins)
SHANK3 / 22q13Jamain et al [2003]
Durand et al [2007]
Moessner et al [2007]
Contactin-associated protein-like 2
(synaptic binding partner for contactin molecules involved in neuronal migration)
CNTNAP2 / 7q36Alarcón et al [2008]
Arking et al [2008]
Bakkaloglu et al [2008]
O’Roak & State [2008]
Contactin 4 & Contactin 3
(neuronally expressed adhesion molecules)
CNTN4 & CNTN3 / 6p26-p25Fernandez et al [2004]
Fernandez et al [2008]
Roohi et al [2009]
Protocadherin 10
(a cadherin-related neuronal receptor: may play a role in the establishment and function of specific cell-cell connections; essential for normal forebrain axon outgrowth)
PCDH10 / 4q28Morrow et al [2008]
Neuronal cell adhesion moleculeNRCAM / 7q31Hutcheson et al [2004]
Bonora et al [2005]
Sakurai et al [2006]
Methyl CpG binding protein 1
(CAN methylation-dependent transcriptional repressor)
MECP2 / Xq28Campbell et al [2006]
Moretti & Zoghbi [2006]
Lintas & Persico [2009]
Ubiquitin protein ligase E3AUBE3A / 15q11-q13Nurmi et al [2001]
Nurmi et al [2003]
Jiang et al [2004]
Deleted in autismDIA1 (c3orf58) / 3qMorrow et al [2008]
Ataxin 2-binding protein 1A2BP1 / 16p13Martin et al [2007]
Sebat et al [2007]
Bakkaloglu et al [2008]
Engrailed 2
(homeobox gene involved in midbrain and cerebellum development)
EN2 / 7q36Petit et al [1995]
Zhong et al [2003]
Gharani et al [2004]
Benayed et al [2005]
Yang et al [2008]
Homeobox A1
(involved in hindbrain development)
HOXA1 / 17p15.3Ingram et al [2000]
Conciatori et al [2004] 4
Homeobox B1
(involved in hindbrain development)
HOXB1 / 17q21-q22 Ingram et al [2000]
Li et al [2002]
Romano et al [2003]
Gallagher et al [2004]
(signaling protein involved in neuron migration)
RELN / 7q22Persico et al [2001]
Krebs et al [2002]
Zhang et al [2002]
Bonora et al [2003]
Devlin et al [2004]
Li et al [2004]
Skaar et al [2005]
Serajee et al [2006]
Li et al [2008]
(signaling proteins involved in embryonic patterning, cell proliferation, and cell determination)
WNT2 / 7q31Wassink et al [2001]
McCoy et al [2002]
Li et al [2004]
(transcription factor involved in embryogenesis and neural functioning)
FOXP2 / 7q31Wassink et al [2002]
Gauthier et al [2003]
Gong et al [2004]
Li et al [2005]
ARX homeobox gene 5ARX / Xp22.13Stromme et al [2002]
Turner et al [2002]
Chaste et al [2007]
Patched domain containing 1 genePTCHD1 / Xp22.11Marshall et al [2008]
Noor et al [2008]
Sodium channel, voltage-gated, type VIISCN7A / 2qMorrow et al [2008]
Na+/H+ exchanger isoform 9SLC9A9
(NHE9) / 3q24
Morrow et al [2008]
Calcium channel, voltage-dependent, L type, alpha 1C subunit (Timothy syndrome) CACNA1C / 12p13.3Splawski et al [2004]
Barrett & Tsien [2008]
Calcium channel, voltage-dependent, alpha 1H subunit 6CACNA1H / 16p13.3Splawski et al [2006]
Calcium channel, voltage-dependent, L type, alpha 1F subunit 7 CACNA1F / Xp11.23 Hope et al [2005]
Miles et al [2008]
GABA receptor subunits
(major inhibitory transmitter receptors in the brain)
GABRB3, GABRA5, GABRG3 / 15q11.2-q12Cook et al [1998]
Maestrini et al [1999]
Martin et al [2000]
Menold et al [2001]
Buxbaum et al [2002]
McCauley et al [2004a]
Ma et al [2005]
Collins et al [2006]
Serotonin transporterSLC6A4 / 17q11.1-q12Yirmiya et al [2001]
McCauley et al [2004b]
Coutinho et al [2004]
Devlin et al [2005]
Sutcliffe et al [2005]
Cho et al [2007]
Page et al [2009]
MitochondrialMitochondrial aspartate/glutamate transporter
(Mitochondrial function and maintaining ATP levels)
SLC25A12 / 2q24Ramoz et al [2004]
Segurado et al [2005]
Other genesOxytocin receptorOXTR / 3p26.2Wu et al [2005a]
Jacob et al [2007]
Laminin beta 1LAMB1 / 7q31.1Hutcheson et al [2004]
Bonora et al [2005]
RING finger protein 8
(ubiquitin ligase and transcriptional coactivator)
RNF8 / 6p21.3Morrow et al [2008]

Garber [2007]


NLGN4X and NLGN3. Jamain et al [2003] identified a nonsense mutation in NLGN4X in two brothers with autism and Asperger syndrome, both without intellectual disability. Subsequently, Laumonnier et al [2004] identified a two-base-pair deletion in NLGN4X in 12 affected members of a French family with X-linked intellectual disability, some of whom were also autistic. Jamain et al [2003] identified a C-to-T transition in the NLGN3 gene in two brothers, one with autism and the other with Asperger syndrome. The mutation was inherited from the mother and was absent in 200 controls. A number of subsequent studies failed to find mutations in either NLGN3 or NLGN4X in probands with autism [Lintas & Persico 2009]. In addition to ASD, mutations in NLGN4X and NLGN3 have been associated with Tourette syndrome, psychiatric symptoms, and language disability. Individuals with ASD and mutations in NLGN4X and NLGN3 have typically been non-dysmorphic and some have lost of social and verbal milestones at the onset of disease. Molecular genetic testing of NLGN4X and NLGN3 should be considered in families with suspected X-linked inheritance of autism.


Coding for a synaptic protein which binds directly to neuroligins, the SHANK3 gene appears crucial for the development of language and social cognition. Both mutations and small cytogenetic rearrangements have been implicated with an ASD phenotype [Durand et al 2007, Moessner et al 2007]. As with the mutations in NLGN4X and NLGN3, mutations in SHANK3 have been found in a variety of disorders including ADHD and language deficits, as well as in unaffected family members, suggesting they may cause disease by acting synergistically with other susceptibility genes.


Conciatori et al [2004] presented evidence that the HOXA1 G allele correlates with larger head circumferences, explaining approximately 5% of the variance in head circumference in their population.


Family history of X-linked intellectual disability which may be nonsyndromic or associated with seizures, abnormal genitalia, and brain abnormalities. Sequence analysis of all ARX exons and flanking regions did not identify any mutations in 226 males with autism and intellectual disability [Chaste et al 2007].


A study of 461 individuals with ASD found missense deleterious mutations in CACNA1H in six affected individuals and none in 480 ethnically matched controls [Splawski et al 2006].


Mutations in CACNA1F have been associated with autism in two families with congenital stationary night blindness [Hope et al 2005, Miles et al 2008].

From: Autism Spectrum Disorders

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