NF1neurofibromin 1 (neurofibromatosis, von Recklinghausen disease, Watson disease)
Autism Reports / Total Reports
9 / 28Rare Variants / Common Variants
14 / 1Aliases
NF1, Neurofibromin, WSS, NFNS, VRNF, DKFZp686J1293Associated Syndromes
-Chromosome Band
17q11.2Associated Disorders
DD/NDD, ID, ASD, EPSGenetic Category
Rare Single Gene Mutation, Syndromic, Genetic AssociationRelevance to Autism
This gene has been associated with syndromic autism, where a subpopulation of individuals with a given syndrome develop autism. As well, genetic association has been found between the NF1 gene and autism. In particular, positive association was found with a NF1 polymorphism in the Japanese population (Marui et al., 2004). However, other studies found no association with autism in French and South Carolina Autism Project cohorts. Separately, a rare mutation in NF1 has been identified in an individual with ASD (Sanders et al., 2012).
Molecular Function
The encoded protein has Ras GTPase activity and appears to be a negative regulator of cell proliferation.
Reports related to NF1 (28 Reports)
| # | Type | Title | Author, Year | Autism Report | Associated Disorders |
|---|---|---|---|---|---|
| 1 | Negative Association | Association study of the NF1 gene and autistic disorder | Mbarek O , et al. (1999) | Yes | - |
| 2 | Negative Association | Lack of association of the (AAAT)6 allele of the GXAlu tetranucleotide repeat in intron 27b of the NF1 gene with autism | Plank SM , et al. (2001) | Yes | - |
| 3 | Highly Cited | Mechanism for the learning deficits in a mouse model of neurofibromatosis type 1 | Costa RM , et al. (2002) | No | - |
| 4 | Primary | Association between the neurofibromatosis-1 (NF1) locus and autism in the Japanese population | Marui T , et al. (2004) | Yes | - |
| 5 | Recent Recommendation | Neurofibromin is a novel regulator of RAS-induced signals in primary vascular smooth muscle cells | Li F , et al. (2006) | No | - |
| 6 | Recent Recommendation | Neurofibromin regulation of ERK signaling modulates GABA release and learning | Cui Y , et al. (2008) | No | - |
| 7 | Recent Recommendation | Aberrant expression of synaptic plasticity-related genes in the NF1+/- mouse hippocampus | Park CS , et al. (2009) | No | - |
| 8 | Recent Recommendation | Behavioural and cognitive phenotypes in children with neurofibromatosis type 1 (NF1): the link with the neurobiological level | Hachon C , et al. (2010) | No | - |
| 9 | Highly Cited | The NF1 locus encodes a protein functionally related to mammalian GAP and yeast IRA proteins | Ballester R , et al. (1990) | No | - |
| 10 | Support | De novo mutations revealed by whole-exome sequencing are strongly associated with autism | Sanders SJ , et al. (2012) | Yes | - |
| 11 | Recent Recommendation | ERK inhibition rescues defects in fate specification of Nf1-deficient neural progenitors and brain abnormalities | Wang Y , et al. (2012) | No | - |
| 12 | Recent Recommendation | Autism and other psychiatric comorbidity in neurofibromatosis type 1: evidence from a population-based study | Garg S , et al. (2012) | No | - |
| 13 | Support | A discovery resource of rare copy number variations in individuals with autism spectrum disorder | Prasad A , et al. (2013) | Yes | - |
| 14 | Support | Exome sequencing in multiplex autism families suggests a major role for heterozygous truncating mutations | Toma C , et al. (2013) | Yes | - |
| 15 | Recent Recommendation | Autism traits in the RASopathies | Adviento B , et al. (2013) | No | Autistic features |
| 16 | Recent Recommendation | Neurofibromatosis type 1 and autism spectrum disorder | Garg S , et al. (2013) | No | - |
| 17 | Support | The contribution of de novo coding mutations to autism spectrum disorder | Iossifov I et al. (2014) | Yes | - |
| 18 | Recent Recommendation | Prevalence of Autism Spectrum Disorder symptoms in children with neurofibromatosis type 1 | Plasschaert E , et al. (2014) | No | - |
| 19 | Support | Large-scale discovery of novel genetic causes of developmental disorders | Deciphering Developmental Disorders Study (2014) | No | - |
| 20 | Recent Recommendation | Cerebral volumetric abnormalities in Neurofibromatosis type 1: associations with parent ratings of social and attention problems, executive dysfunction, and autistic mannerisms | Huijbregts SC , et al. (2015) | No | - |
| 21 | Support | Clinical exome sequencing: results from 2819 samples reflecting 1000 families | Trujillano D , et al. (2016) | No | ASD |
| 22 | Support | High Rate of Recurrent De Novo Mutations in Developmental and Epileptic Encephalopathies | Hamdan FF , et al. (2017) | No | DD/ID |
| 23 | Support | Early-onset epileptic encephalopathy and severe developmental delay in an association with de novo double mutations in NF1 and MAGEL2 | Akamine S , et al. (2018) | No | DD, epilepsy/seizures |
| 24 | Support | Targeted resequencing of 358 candidate genes for autism spectrum disorder in a Chinese cohort reveals diagnostic potential and genotype-phenotype correlations | Zhou WZ , et al. (2019) | Yes | - |
| 25 | Support | A novel RAB39B mutation and concurrent de novo NF1 mutation in a boy with neurofibromatosis type 1, intellectual disability, and autism: a case report | Santoro C et al. (2020) | No | ASD, ID, epilepsy/seizures |
| 26 | Support | - | Pode-Shakked B et al. (2021) | Yes | - |
| 27 | Support | - | Cummings K et al. (2022) | No | ASD |
| 28 | Support | - | Verberne EA et al. (2022) | No | - |
Rare Variants (14)
| Status | Allele Change | Residue Change | Variant Type | Inheritance Pattern | Parental Transmission | Family Type | PubMed ID | Author, Year |
|---|---|---|---|---|---|---|---|---|
| - | - | microsatellite | - | - | - | 11449390 | Plank SM , et al. (2001) | |
| - | - | copy_number_loss | Familial | Maternal | Unknown | 23275889 | Prasad A , et al. (2013) | |
| c.4772+1G>T | - | splice_site_variant | De novo | NA | - | 29588991 | Akamine S , et al. (2018) | |
| c.4267A>G | p.Lys1423Glu | missense_variant | Unknown | - | - | 35253369 | Verberne EA et al. (2022) | |
| c.3449C>G | p.Ser1150Ter | stop_gained | De novo | NA | Simplex | 25363768 | Iossifov I et al. (2014) | |
| c.6792C>G | p.Tyr2264Ter | stop_gained | De novo | NA | Simplex | 29100083 | Hamdan FF , et al. (2017) | |
| c.888+2T>G | - | splice_site_variant | De novo | NA | Simplex | 34580403 | Pode-Shakked B et al. (2021) | |
| c.5327C>A | p.Ser1776Ter | stop_gained | De novo | NA | Simplex | 27848944 | Trujillano D , et al. (2016) | |
| c.107C>G | p.Thr36Ser | missense_variant | Familial | Maternal | - | 27848944 | Trujillano D , et al. (2016) | |
| c.7375C>A | p.His2459Asn | missense_variant | De novo | NA | Simplex | 22495306 | Sanders SJ , et al. (2012) | |
| c.6579+2T>C | - | splice_site_variant | De novo | NA | Extended multiplex | 32873259 | Santoro C et al. (2020) | |
| c.1742dup | p.Cys582LeufsTer6 | frameshift_variant | Familial | Maternal | - | 30763456 | Zhou WZ , et al. (2019) | |
| c.7910G>A | p.Arg2637Gln | missense_variant | Familial | Paternal | Multiplex | 23999528 | Toma C , et al. (2013) | |
| c.5425C>T | p.Pro1809Ser | missense_variant | De novo | NA | Simplex | 25533962 | Deciphering Developmental Disorders Study (2014) |
Common Variants (1)
| Status | Allele Change | Residue Change | Variant Type | Inheritance Pattern | Paternal Transmission | Family Type | PubMed ID | Author, Year |
|---|---|---|---|---|---|---|---|---|
| N/A | N/A | microsatellite, intron_variant | - | - | - | 15389774 | Marui T , et al. (2004) |
SFARI Gene score
High Confidence
criteria met
See SFARI Gene'scoring criteriaWe 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.
4/1/2022
Initial score established: 1
10/1/2021
Initial score established: 1
Description
Neurofibromatosis is a Mendelian disease associated with autism. There is some association and linkage evidence implicating it in idiopathic autism, including positive association that was found with a NF1 polymorphism in the Japanese population (Marui et al., 2004).
7/1/2021
Initial score established: 1
Description
Neurofibromatosis is a Mendelian disease associated with autism. There is some association and linkage evidence implicating it in idiopathic autism, including positive association that was found with a NF1 polymorphism in the Japanese population (Marui et al., 2004).
4/1/2021
Initial score established: 1
Description
Neurofibromatosis is a Mendelian disease associated with autism. There is some association and linkage evidence implicating it in idiopathic autism, including positive association that was found with a NF1 polymorphism in the Japanese population (Marui et al., 2004).
1/1/2021
Initial score established: 1
Description
Neurofibromatosis is a Mendelian disease associated with autism. There is some association and linkage evidence implicating it in idiopathic autism, including positive association that was found with a NF1 polymorphism in the Japanese population (Marui et al., 2004).
10/1/2020
Initial score established: 1
Description
Neurofibromatosis is a Mendelian disease associated with autism. There is some association and linkage evidence implicating it in idiopathic autism, including positive association that was found with a NF1 polymorphism in the Japanese population (Marui et al., 2004).
7/1/2020
Initial score established: 1
Description
Neurofibromatosis is a Mendelian disease associated with autism. There is some association and linkage evidence implicating it in idiopathic autism, including positive association that was found with a NF1 polymorphism in the Japanese population (Marui et al., 2004).
4/1/2020
Initial score established: 1
Description
Neurofibromatosis is a Mendelian disease associated with autism. There is some association and linkage evidence implicating it in idiopathic autism, including positive association that was found with a NF1 polymorphism in the Japanese population (Marui et al., 2004).
1/1/2020
Initial score established: 1
Description
Neurofibromatosis is a Mendelian disease associated with autism. There is some association and linkage evidence implicating it in idiopathic autism, including positive association that was found with a NF1 polymorphism in the Japanese population (Marui et al., 2004).
10/1/2019
Initial score established: 1
New Scoring Scheme
Description
Neurofibromatosis is a Mendelian disease associated with autism. There is some association and linkage evidence implicating it in idiopathic autism, including positive association that was found with a NF1 polymorphism in the Japanese population (Marui et al., 2004).
Reports Added
[New Scoring Scheme]7/1/2019
Initial score established: 1
Description
Neurofibromatosis is a Mendelian disease associated with autism. There is some association and linkage evidence implicating it in idiopathic autism, including positive association that was found with a NF1 polymorphism in the Japanese population (Marui et al., 2004).
4/1/2019
Initial score established: 1
Description
Neurofibromatosis is a Mendelian disease associated with autism. There is some association and linkage evidence implicating it in idiopathic autism, including positive association that was found with a NF1 polymorphism in the Japanese population (Marui et al., 2004).
1/1/2019
Initial score established: 1
Description
Neurofibromatosis is a Mendelian disease associated with autism. There is some association and linkage evidence implicating it in idiopathic autism, including positive association that was found with a NF1 polymorphism in the Japanese population (Marui et al., 2004).
10/1/2018
Initial score established: 1
Description
Neurofibromatosis is a Mendelian disease associated with autism. There is some association and linkage evidence implicating it in idiopathic autism, including positive association that was found with a NF1 polymorphism in the Japanese population (Marui et al., 2004).
7/1/2018
Initial score established: S
Description
Neurofibromatosis is a Mendelian disease associated with autism. There is some association and linkage evidence implicating it in idiopathic autism, including positive association that was found with a NF1 polymorphism in the Japanese population (Marui et al., 2004).
4/1/2018
Initial score established: 4S
Description
S
1/1/2018
Initial score established: S
Description
Neurofibromatosis is a Mendelian disease associated with autism. There is some association and linkage evidence implicating it in idiopathic autism, including positive association that was found with a NF1 polymorphism in the Japanese population (Marui et al., 2004).
10/1/2017
Initial score established: 1
Description
Neurofibromatosis is a Mendelian disease associated with autism. There is some association and linkage evidence implicating it in idiopathic autism, including positive association that was found with a NF1 polymorphism in the Japanese population (Marui et al., 2004).
7/1/2017
Initial score established: S
Description
Neurofibromatosis is a Mendelian disease associated with autism. There is some association and linkage evidence implicating it in idiopathic autism, including positive association that was found with a NF1 polymorphism in the Japanese population (Marui et al., 2004).
4/1/2017
Initial score established: S
Description
Neurofibromatosis is a Mendelian disease associated with autism. There is some association and linkage evidence implicating it in idiopathic autism, including positive association that was found with a NF1 polymorphism in the Japanese population (Marui et al., 2004).
1/1/2017
Initial score established: S
Description
Neurofibromatosis is a Mendelian disease associated with autism. There is some association and linkage evidence implicating it in idiopathic autism, including positive association that was found with a NF1 polymorphism in the Japanese population (Marui et al., 2004).
10/1/2016
Initial score established: 1
Description
Neurofibromatosis is a Mendelian disease associated with autism. There is some association and linkage evidence implicating it in idiopathic autism, including positive association that was found with a NF1 polymorphism in the Japanese population (Marui et al., 2004).
7/1/2016
Initial score established: S
Description
Neurofibromatosis is a Mendelian disease associated with autism. There is some association and linkage evidence implicating it in idiopathic autism, including positive association that was found with a NF1 polymorphism in the Japanese population (Marui et al., 2004).
4/1/2016
Initial score established: S
Description
Neurofibromatosis is a Mendelian disease associated with autism. There is some association and linkage evidence implicating it in idiopathic autism, including positive association that was found with a NF1 polymorphism in the Japanese population (Marui et al., 2004).
1/1/2016
Initial score established: S
Description
Neurofibromatosis is a Mendelian disease associated with autism. There is some association and linkage evidence implicating it in idiopathic autism, including positive association that was found with a NF1 polymorphism in the Japanese population (Marui et al., 2004).
Reports Added
[Association study of the NF1 gene and autistic disorder.1999] [Lack of association of the (AAAT)6 allele of the GXAlu tetranucleotide repeat in intron 27b of the NF1 gene with autism.2001] [De novo mutations revealed by whole-exome sequencing are strongly associated with autism.2012] [A discovery resource of rare copy number variations in individuals with autism spectrum disorder.2013] [Exome sequencing in multiplex autism families suggests a major role for heterozygous truncating mutations.2013] [Association between the neurofibromatosis-1 (NF1) locus and autism in the Japanese population.2004] [Autism traits in the RASopathies.2013] [Large-scale discovery of novel genetic causes of developmental disorders.2014] [The NF1 locus encodes a protein functionally related to mammalian GAP and yeast IRA proteins.1990] [Mechanism for the learning deficits in a mouse model of neurofibromatosis type 1.2002] [Neurofibromin is a novel regulator of RAS-induced signals in primary vascular smooth muscle cells.2006] [Neurofibromin regulation of ERK signaling modulates GABA release and learning.2008] [Aberrant expression of synaptic plasticity-related genes in the NF1 mouse hippocampus.2009] [Behavioural and cognitive phenotypes in children with neurofibromatosis type 1 (NF1): the link with the neurobiological level.2010] [ERK inhibition rescues defects in fate specification of Nf1-deficient neural progenitors and brain abnormalities.2012] [Autism and other psychiatric comorbidity in neurofibromatosis type 1: evidence from a population-based study.2012] [Neurofibromatosis type 1 and autism spectrum disorder.2013] [Prevalence of Autism Spectrum Disorder symptoms in children with neurofibromatosis type 1.2014] [Cerebral volumetric abnormalities in Neurofibromatosis type 1: associations with parent ratings of social and attention problems, executive dysfunc...2015] [The contribution of de novo coding mutations to autism spectrum disorder2014]10/1/2015
Initial score established: 1
Description
Neurofibromatosis is a Mendelian disease associated with autism. There is some association and linkage evidence implicating it in idiopathic autism, including positive association that was found with a NF1 polymorphism in the Japanese population (Marui et al., 2004).
7/1/2015
Initial score established: S
Description
Neurofibromatosis is a Mendelian disease associated with autism. There is some association and linkage evidence implicating it in idiopathic autism, including positive association that was found with a NF1 polymorphism in the Japanese population (Marui et al., 2004).
4/1/2015
Initial score established: S
Description
Neurofibromatosis is a Mendelian disease associated with autism. There is some association and linkage evidence implicating it in idiopathic autism, including positive association that was found with a NF1 polymorphism in the Japanese population (Marui et al., 2004).
1/1/2015
Initial score established: S
Description
Neurofibromatosis is a Mendelian disease associated with autism. There is some association and linkage evidence implicating it in idiopathic autism, including positive association that was found with a NF1 polymorphism in the Japanese population (Marui et al., 2004).
10/1/2014
Initial score established: 1
Description
Neurofibromatosis is a Mendelian disease associated with autism. There is some association and linkage evidence implicating it in idiopathic autism, including positive association that was found with a NF1 polymorphism in the Japanese population (Marui et al., 2004).
7/1/2014
Initial score established: S
Description
Neurofibromatosis is a Mendelian disease associated with autism. There is some association and linkage evidence implicating it in idiopathic autism, including positive association that was found with a NF1 polymorphism in the Japanese population (Marui et al., 2004).
4/1/2014
Initial score established: S
Description
Neurofibromatosis is a Mendelian disease associated with autism. There is some association and linkage evidence implicating it in idiopathic autism, including positive association that was found with a NF1 polymorphism in the Japanese population (Marui et al., 2004).
Reports Added
[Autism traits in the RASopathies.2013]Krishnan Probability Score
Score 0.60552752749814
Ranking 333/25841 scored genes
[Show Scoring Methodology]
ExAC Score
Score 0.99999984557026
Ranking 210/18225 scored genes
[Show Scoring Methodology]
Sanders TADA Score
Score 0.72227551621555
Ranking 1312/18665 scored genes
[Show Scoring Methodology]
Zhang D Score
Score -0.23470687392553
Ranking 16106/20870 scored genes
[Show Scoring Methodology]
CNVs associated with NF1(1 CNVs)
Sort By:
| 17q11.2 | 24 | Deletion-Duplication | 38 / 103 |
External PIN Data
Interactome
- Protein Binding
- DNA Binding
- RNA Binding
- Protein Modification
- Direct Regulation
- ASD-Linked Genes
Interaction Table
| Interactor Symbol | Interactor Name | Interactor Organism | Interactor Type | Entrez ID | Uniprot ID |
|---|---|---|---|---|---|
| miR16 | microRNA mir-16 | Rat | RNA Binding | 100313997 | N/A |
| TBPL1 | TBP-like 1 | Human | DNA Binding | 9519 | P62380 |
| TNFSF13B | Tumor necrosis factor ligand superfamily member 13B | Human | Protein Binding | 10673 | Q9Y275 |
| VSIG1 | V-set and immunoglobulin domain-containing protein 1 | Human | Protein Binding | 340547 | Q86XK7 |