Human Gene Module / Chromosome 4 / CRMP1

CRMP1collapsin response mediator protein 1

SFARI Gene Score
3
Suggestive Evidence Criteria 3.1
Autism Reports / Total Reports
7 / 9
Rare Variants / Common Variants
10 / 0
Aliases
-
Associated Syndromes
-
Chromosome Band
4p16.2
Associated Disorders
-
Relevance to Autism

De novo variants in the CRMP1 gene have been reported to cause a neurodevelopmental disorder characterized by developmental delay, intellectual disability, and behavioral abnormalities; autism spectrum disorder was diagnosed in an individual with a de novo missense variant that was experimentally shown to impair CRMP1B homo-oligomerization and attenuate neurite outgrowth in mouse cortical neurons in Ravindran et al., 2022 and in an individual with a de novo frameshift variant in Liu et al., 2024. Additional de novo variants in the CRMP1 gene, including two de novo missense variants that were not reported in control databases and were predicted to be damaging by CADD, have been reported in ASD probands from the Simons Simplex Collection, the SPARK cohort, the Autism Sequencing Consortium, and a Korean ASD cohort (Satterstrom et al., 2020; Zhou et al., 2022; Kim et al., 2024). Several studies have previously reported that maternal autoantibody reactivity to CRMP1 was associated with elevated severity of ASD (Braunschweig et al., 2013; Ramirez-Celis et al., 2021; Ramirez-Celis et al., 2022).

Molecular Function

This gene encodes a member of a family of cytosolic phosphoproteins expressed exclusively in the nervous system. The encoded protein is thought to be a part of the semaphorin signal transduction pathway implicated in semaphorin-induced growth cone collapse during neural development.

External Links
Gene CardOpen Targets PlatformgnomAD browserPubMed
Human
Entrez GeneOMIMUniProtHumanBaseVariCarta
Mouse
Entrez GeneMouse Genome InformaticsAllen Brain Atlas
SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to CRMP1 (9 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Support - D Braunschweig et al. (2013) Yes -
2 Support - Naoya Yamashita et al. (2013) No -
3 Support Large-Scale Exome Sequencing Study Implicates Both Developmental and Functional Changes in the Neurobiology of Autism Satterstrom FK et al. (2020) Yes -
4 Support - Alexandra Ramirez-Celis et al. (2021) Yes -
5 Support - Alexandra Ramirez-Celis et al. (2022) Yes -
6 Support - Zhou X et al. (2022) Yes -
7 Support - Ethiraj Ravindran et al. (2022) No ASD
8 Support - Soo-Whee Kim et al. (2024) Yes -
9 Primary - Juan Liu et al. (2024) Yes -
Rare Variants   (10)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.1242G>A p.Ala414= synonymous_variant De novo - - 35982159 Zhou X et al. (2022)
c.564G>A p.Thr188= synonymous_variant De novo - - 39334436 Soo-Whee Kim et al. (2024)
c.1966T>C p.Ser656Pro missense_variant De novo - - 39334436 Soo-Whee Kim et al. (2024)
c.883-6C>T p.? splice_region_variant De novo - - 31981491 Satterstrom FK et al. (2020)
c.1571T>G p.Val524Gly missense_variant De novo - Simplex 35982159 Zhou X et al. (2022)
c.1786G>A p.Val596Ile missense_variant De novo - Simplex 35982159 Zhou X et al. (2022)
c.1052T>C p.Phe351Ser missense_variant De novo - Simplex 36511780 Ethiraj Ravindran et al. (2022)
c.1280C>T p.Thr427Met missense_variant De novo - Simplex 36511780 Ethiraj Ravindran et al. (2022)
c.1766C>T p.Pro589Leu missense_variant De novo - Simplex 36511780 Ethiraj Ravindran et al. (2022)
c.1755delG p.Lys586ArgfsTer75 frameshift_variant De novo - Simplex 39758889 Juan Liu et al. (2024)
Common Variants  

No common variants reported.

SFARI Gene score
3

Suggestive Evidence

criteria met
See SFARI Gene'scoring criteria
3

Suggestive Evidence

See all Category 3 Genes

The literature is replete with relatively small studies of candidate genes, using either common or rare variant approaches, which do not reach the criteria set out for categories 1 and 2. Genes that had two such lines of supporting evidence were placed in category 3, and those with one line of evidence were placed in category 4. Some additional lines of "accessory evidence" (indicated as "acc" in the score cards) could also boost a gene from category 4 to 3.

4/1/2025
3

Initial score established: 3

Krishnan Probability Score

Score 0.61474674162597

Ranking 126/25841 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.
Original Source
ExAC Score

Score 0.95327323476714

Ranking 2626/18225 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
Original Source
Sanders TADA Score

Score 0.93664408318447

Ranking 13263/18665 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).
Original Source
Zhang D Score

Score 0.49916420506196

Ranking 530/20870 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.
Original Source
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