Human Gene Module / Chromosome 7 / NRCAM

NRCAMneuronal cell adhesion molecule

SFARI Gene Score
2
Strong Candidate Criteria 2.1
Autism Reports / Total Reports
4 / 6
Rare Variants / Common Variants
2 / 7
Aliases
NRCAM, KIAA0343,  NgCAM-related cell adhesion molecule,  NrCAM protein,  NrCAM-short,  brav o
Associated Syndromes
-
Chromosome Band
7q31.1
Associated Disorders
-
Relevance to Autism

Genetic association has been found between the NRCAM gene and autism in a Japanese population cohort (Marui et al., 2009). However, no genetic association was found between the NRCAM gene and autism in a US population cohort (Hutcheson et al., 2004).

Molecular Function

The encoded protein is a cell-cell adhesion molecule that participates in neuro nal outgrowth and guidance processes.

SFARI Genomic Platforms
Reports related to NRCAM (6 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Negative Association Examination of NRCAM, LRRN3, KIAA0716, and LAMB1 as autism candidate genes Hutcheson HB , et al. (2004) Yes -
2 Recent Recommendation The shed ectodomain of Nr-CAM stimulates cell proliferation and motility, and confers cell transformation Conacci-Sorrell M , et al. (2005) No -
3 Primary Association of the neuronal cell adhesion molecule (NRCAM) gene variants with autism Marui T , et al. (2008) Yes -
4 Support Exome sequencing of extended families with autism reveals genes shared across neurodevelopmental and neuropsychiatric disorders Cukier HN , et al. (2014) Yes -
5 Support - Zhou X et al. (2022) Yes -
6 Highly Cited Molecular composition of the node of Ranvier: identification of ankyrin-binding cell adhesion molecules neurofascin (mucin+/third FNIII domain-) and NrCAM at nodal axon segments Davis JQ , et al. (1996) No -
Rare Variants   (2)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.1928T>C p.Val643Ala missense_variant De novo - Multiplex 35982159 Zhou X et al. (2022)
c.2557C>T p.Arg853Cys missense_variant Familial - Extended multiplex (at least one pair of ASD affec 24410847 Cukier HN , et al. (2014)
Common Variants   (7)
Status Allele Change Residue Change Variant Type Inheritance Pattern Paternal Transmission Family Type PubMed ID Author, Year
c.-332+13182G>A;c.-390+13182G>A;c.-332+13609G>A - intron_variant - - - 18664314 Marui T , et al. (2008)
c.-332+8364T>A;c.-390+8364T>A;c.-332+8791T>A A to T intron_variant - - - 18664314 Marui T , et al. (2008)
c.1032C>T;c.975C>T;c.1014C>T;c.744C>T p.(=) synonymous_variant, non_coding_transcript_variant - - - 18664314 Marui T , et al. (2008)
c.-106-6865C>A;c.-164-12347C>A - intron_variant - - - 18664314 Marui T , et al. (2008)
c.-106-21769G>C;c.-164-27251G>C - intron_variant - - - 18664314 Marui T , et al. (2008)
c.-331-23058C>G;c.-389-23058C>G T to C intron_variant - - - 18664314 Marui T , et al. (2008)
c.-331-23201A>G;c.-389-23201A>G T to C intron_variant - - - 18664314 Marui T , et al. (2008)
SFARI Gene score
2

Strong Candidate

Multiple (but inconsistent) associations have been reported (Marui et al., 2009 PMID: 18664314; Hutcheson et al., 2004 PMID: 15128462).

Score Delta: Score remained at 2

2

Strong Candidate

See all Category 2 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.

4/1/2022
3
icon
2

Decreased from 3 to 2

Description

Multiple (but inconsistent) associations have been reported (Marui et al., 2009 PMID: 18664314; Hutcheson et al., 2004 PMID: 15128462).

10/1/2019
4
icon
3

Decreased from 4 to 3

New Scoring Scheme
Description

Multiple (but inconsistent) associations have been reported (Marui et al., 2009 PMID: 18664314; Hutcheson et al., 2004 PMID: 15128462).

Reports Added
[New Scoring Scheme]
7/1/2014
No data
icon
4

Increased from No data to 4

Description

Multiple (but inconsistent) associations have been reported (Marui et al., 2009 PMID: 18664314; Hutcheson et al., 2004 PMID: 15128462).

4/1/2014
No data
icon
4

Increased from No data to 4

Description

Multiple (but inconsistent) associations have been reported (Marui et al., 2009 PMID: 18664314; Hutcheson et al., 2004 PMID: 15128462).

Krishnan Probability Score

Score 0.64236093248094

Ranking 49/25841 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.
ExAC Score

Score 0.45648459830867

Ranking 5679/18225 scored genes


[Show Scoring Methodology]
The Exome Aggregation Consortium (ExAC) is a summary database of 60,706 exomes that has been widely used to estimate 'constraint' on mutation for individual genes. It was introduced by Lek et al. Nature 536, 285-291 (2016), and the ExAC browser can be found at exac.broadinstitute.org. The pLI score was developed as measure of intolerance to loss-of- function mutation. A pLI > 0.9 is generally viewed as highly constrained, and thus any loss-of- function mutations in autism in such a gene would be more likely to confer risk. For a full list of pLI scores see: ftp://ftp.broadinstitute.org/pub/ExAC_release/release0.3.1/functional_gene_constraint/fordist_cle aned_exac_nonTCGA_z_pli_rec_null_data.txt
Sanders TADA Score

Score 0.94767460512195

Ranking 17372/18665 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 10

Ranking 189/461 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 0.16379456074717

Ranking 4915/20870 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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