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
References
Type
Title
Type of Disorder
Associated Disorders
Author, Year
Primary
Case report: A de novo variant of CRMP1 in an individual with a neurodevelopmental disorder
The homozygous Crmp1 knockout mouse model is viable and shows decreased body weight. The knockout model shows normal grip strength, touch, nociception, gait, anxiety-like behavior, emotional response to fear and defeat, and acoustic startle response. The knockout model shows increased locomotor activity, decreased contextual fear memory (but normal cued fear memory), decreased long-term remote spatial memory (but normal 24-hour spatial memory), decreased prepulse inhibition of acoustic startle and increased methamphetamine-induced dopamine release. Acute treatment with chlorpromazine rescues the prepulse inhibition phenotype.
References
Type
Title
Author, Year
Primary
Mice lacking collapsin response mediator protein 1 manifest hyperactivity, impaired learning and memory, and impaired prepulse inhibition
Model Type:
Genetic
Model Genotype:
Homozygous
Mutation:
Exon 4 of Crmp1 was replaced with an IRES-LacZ-neo cassette (MGI:3701338).
Allele Type: Knockout
Strain of Origin: (129X1/SvJ x 129S1/Sv)F1-Kitl+
Genetic Background: C57BL/6N
ES Cell Line: R1
Mutant ES Cell Line: Model Source: Pappachan Kolattukudy (Universite Claude Bernard, Lyon, France)
Description: Methamphetamine-induced dopamine release is increased in Crmp1 knockout mice.
Exp Paradigm: In vivo microdialysis, following methamphetamine treatment
