Human Gene Module / Chromosome 8 / NEFL

NEFLNeurofilament, light polypeptide

Score
5
Hypothesized Criteria 5.1
Autism Reports / Total Reports
1 / 2
Rare Variants / Common Variants
1 / 1
Aliases
NEFL, CMT1F,  CMT2E,  NF-L,  NF68,  NFL
Associated Syndromes
Tourette syndrome
Genetic Category
Rare Single Gene Mutation, Genetic Association
Chromosome Band
8p21.2
Associated Disorders
-
Relevance to Autism

NEFL showed consistently reduced expression in three brain regions (anterior cingulate gyrus, motor cortex, and thalamus) following gene expression analysis of postmortem brain tissue of autism patients. NEFL also showed genetic association with autism in Caucasian families (P=0.038; Z-score 2.066) (Anitha et al., 2012).

Molecular Function

Neurofilaments usually contain three intermediate filament proteins: L, M, and H which are involved in the maintenance of neuronal caliber. Defects in NEFL are the cause of Charcot-Marie-Tooth disease type 1F (CMT1F) [MIM:607734] and Charcot-Marie-Tooth disease type 2E (CMT2E) [MIM:607684].

Reports related to NEFL (2 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Primary Brain region-specific altered expression and association of mitochondria-related genes in autism. Anitha A , et al. (2012) Yes -
2 Positive association De Novo Coding Variants Are Strongly Associated with Tourette Disorder. Willsey AJ , et al. (2017) No -
Rare Variants   (1)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.1137G>T p.Lys379Asn missense_variant De novo - Simplex 28472652 Willsey AJ , et al. (2017)
Common Variants   (1)
Status Allele Change Residue Change Variant Type Inheritance Pattern Paternal Transmission Family Type PubMed ID Author, Year
c.*1256G>A - 3_prime_UTR_variant - - - 23116158 Anitha A , et al. (2012)
SFARI Gene score
5

Hypothesized

NEFL showed consistently reduced expression in three brain regions (anterior cingulate gyrus, motor cortex, and thalamus) following gene expression analysis of postmortem brain tissue of autism patients and also showed genetic association with autism in Caucasian families (P=0.038; Z-score 2.066) in PMID 23116158.

Score Delta: Score remained at 5

5

Hypothesized

See all Category 5 Genes

Category 5.1 includes genes for which the only evidence comes from studies of model organisms, without statistical or genetic support in human studies.

1/1/2016
5
icon
5

Score remained at 5

Description

NEFL showed consistently reduced expression in three brain regions (anterior cingulate gyrus, motor cortex, and thalamus) following gene expression analysis of postmortem brain tissue of autism patients and also showed genetic association with autism in Caucasian families (P=0.038; Z-score 2.066) in PMID 23116158.

1/1/2017
5
icon
5

Score remained at 5

Description

NEFL showed consistently reduced expression in three brain regions (anterior cingulate gyrus, motor cortex, and thalamus) following gene expression analysis of postmortem brain tissue of autism patients and also showed genetic association with autism in Caucasian families (P=0.038; Z-score 2.066) in PMID 23116158.

10/1/2015
5
icon
5

Score remained at 5

Description

NEFL showed consistently reduced expression in three brain regions (anterior cingulate gyrus, motor cortex, and thalamus) following gene expression analysis of postmortem brain tissue of autism patients and also showed genetic association with autism in Caucasian families (P=0.038; Z-score 2.066) in PMID 23116158.

10/1/2016
5
icon
5

Score remained at 5

Description

NEFL showed consistently reduced expression in three brain regions (anterior cingulate gyrus, motor cortex, and thalamus) following gene expression analysis of postmortem brain tissue of autism patients and also showed genetic association with autism in Caucasian families (P=0.038; Z-score 2.066) in PMID 23116158.

10/1/2017
5
icon
5

Score remained at 5

Description

NEFL showed consistently reduced expression in three brain regions (anterior cingulate gyrus, motor cortex, and thalamus) following gene expression analysis of postmortem brain tissue of autism patients and also showed genetic association with autism in Caucasian families (P=0.038; Z-score 2.066) in PMID 23116158.

4/1/2016
5
icon
5

Score remained at 5

Description

NEFL showed consistently reduced expression in three brain regions (anterior cingulate gyrus, motor cortex, and thalamus) following gene expression analysis of postmortem brain tissue of autism patients and also showed genetic association with autism in Caucasian families (P=0.038; Z-score 2.066) in PMID 23116158.

4/1/2017
5
icon
5

Score remained at 5

Description

NEFL showed consistently reduced expression in three brain regions (anterior cingulate gyrus, motor cortex, and thalamus) following gene expression analysis of postmortem brain tissue of autism patients and also showed genetic association with autism in Caucasian families (P=0.038; Z-score 2.066) in PMID 23116158.

7/1/2015
icon
5

Increased from to 5

Description

NEFL showed consistently reduced expression in three brain regions (anterior cingulate gyrus, motor cortex, and thalamus) following gene expression analysis of postmortem brain tissue of autism patients and also showed genetic association with autism in Caucasian families (P=0.038; Z-score 2.066) in PMID 23116158.

7/1/2016
5
icon
5

Increased from 5 to 5

Description

NEFL showed consistently reduced expression in three brain regions (anterior cingulate gyrus, motor cortex, and thalamus) following gene expression analysis of postmortem brain tissue of autism patients and also showed genetic association with autism in Caucasian families (P=0.038; Z-score 2.066) in PMID 23116158.

7/1/2017
5
icon
5

Increased from 5 to 5

Description

NEFL showed consistently reduced expression in three brain regions (anterior cingulate gyrus, motor cortex, and thalamus) following gene expression analysis of postmortem brain tissue of autism patients and also showed genetic association with autism in Caucasian families (P=0.038; Z-score 2.066) in PMID 23116158.

Krishnan Probability Score

Score 0.6151615269736

Ranking 123/25841 scored genes


[Show Scoring Methodology]
Krishnan and colleagues generated probability scores genome-wide by using a machine learning approach on a human brain-specific gene network. The method was first presented in Nat Neurosci 19, 1454-1462 (2016), and scores for more than 25,000 RefSeq genes can be accessed in column G of supplementary table 3 (see: http://www.nature.com/neuro/journal/v19/n11/extref/nn.4353-S5.xlsx). A searchable browser, with the ability to view networks of associated ASD risk genes, can be found at asd.princeton.edu.
Sanders TADA Score

Score 0.93947151541217

Ranking 14222/18665 scored genes


[Show Scoring Methodology]
The TADA score ('Transmission and De novo Association') was introduced by He et al. PLoS Genet 9(8):e1003671 (2013), and is a statistic that integrates evidence from both de novo and transmitted mutations. It forms the basis for the claim of 65 individual genes being strongly associated with autism risk at a false discovery rate of 0.1 (Sanders et al. Neuron 87, 1215-1233 (2015)). The calculated TADA score for 18,665 RefSeq genes can be found in column P of Supplementary Table 6 in the Sanders et al. paper (the column headed 'tadaFdrAscSscExomeSscAgpSmallDel'), which represents a combined analysis of exome data and small de novo deletions (see www.cell.com/cms/attachment/2038545319/2052606711/mmc7.xlsx).
Larsen Cumulative Evidence Score

Score 1

Ranking 427/461 scored genes


[Show Scoring Methodology]
Larsen and colleagues generated gene scores based on the sum of evidence for all available ASD-associated variants in a gene, with assessments based on mode of inheritance, effect size, and variant frequency in the general population. The approach was first presented in Mol Autism 7:44 (2016), and scores for 461 genes can be found in column I in supplementary table 4 from that paper.
Zhang D Score

Score 0.048111537591037

Ranking 7284/20870 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.
CNVs associated with NEFL(1 CNVs)
8p21.2 7 Deletion-Duplication 15  /  215
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