NR1D1nuclear receptor subfamily 1 group D member 1
Autism Reports / Total Reports
3 / 4Rare Variants / Common Variants
7 / 0Aliases
NR1D1, EAR1, THRA1, THRAL, ear-1, hRevAssociated Syndromes
-Chromosome Band
17q21.1Associated Disorders
-Relevance to Autism
Screening of circadian-relevant genes in Japanese ASD patients with or without sleep disorders identified a missense variant in the NR1D1 gene (Yang et al., 2016). Additional screening of Caucasian ASD patients for NR1D1 variants identified several novel missense variants, including a de novo missense variant that failed to rescue defects in the positioning of cortical neurons in the embryonic mouse brain following RNAi-mediated knockdown of endogeneous Nr1d1 (Goto et al., 2017). However, NR1D1 variants identified in these two studies showed incomplete segregation with ASD. Nr1d1-knockout mice were shown to display hyperactivity, impaired response habituation in novel environments, deficiencies in contextual memories, and impaired nest-building activity, suggesting impaired hippocampal function (Jager et al., 2014).
Molecular Function
This gene encodes a transcription factor that is a member of the nuclear receptor subfamily 1. The encoded protein is a ligand-sensitive transcription factor that negatively regulates the expression of core clock proteins. In particular this protein represses the circadian clock transcription factor aryl hydrocarbon receptor nuclear translocator-like protein 1 (ARNTL). This protein may also be involved in regulating genes that function in metabolic, inflammatory and cardiovascular processes.
External Links
SFARI Genomic Platforms
Reports related to NR1D1 (4 Reports)
# | Type | Title | Author, Year | Autism Report | Associated Disorders |
---|---|---|---|---|---|
1 | Support | Behavioral changes and dopaminergic dysregulation in mice lacking the nuclear receptor Rev-erb? | Jager J , et al. (2014) | No | - |
2 | Primary | Circadian-relevant genes are highly polymorphic in autism spectrum disorder patients | Yang Z , et al. (2015) | Yes | - |
3 | Recent Recommendation | Role of a circadian-relevant gene NR1D1 in brain development: possible involvement in the pathophysiology of autism spectrum disorders | Goto M , et al. (2017) | Yes | - |
4 | Support | - | Zhou X et al. (2022) | Yes | - |
Rare Variants (7)
Status | Allele Change | Residue Change | Variant Type | Inheritance Pattern | Parental Transmission | Family Type | PubMed ID | Author, Year |
---|---|---|---|---|---|---|---|---|
c.1153G>A | p.Gly385Arg | missense_variant | De novo | - | - | 35982159 | Zhou X et al. (2022) | |
c.747C>A | p.Pro249%3D | synonymous_variant | De novo | - | - | 35982159 | Zhou X et al. (2022) | |
c.233A>G | p.Asp78Gly | missense_variant | De novo | - | Multiplex | 35982159 | Zhou X et al. (2022) | |
c.1499G>A | p.Arg500His | missense_variant | De novo | - | Multiplex | 28262759 | Goto M , et al. (2017) | |
c.58A>C | p.Ser20Arg | missense_variant | Familial | Paternal | Simplex | 25957987 | Yang Z , et al. (2015) | |
c.1012C>T | p.Pro338Ser | missense_variant | Familial | Maternal | Multiplex | 28262759 | Goto M , et al. (2017) | |
c.1031A>C | p.Asn344Thr | missense_variant | Familial | Maternal | Multiplex | 28262759 | Goto M , et al. (2017) |
Common Variants
No common variants reported.
SFARI Gene score
Strong Candidate


Screening of circadian-relevant genes in Japanese ASD patients with or without sleep disorders identified a missense variant in the NR1D1 gene (Yang et al., 2016). Additional screening of Caucasian ASD patients for NR1D1 variants identified several novel missense variants, including a de novo missense variant that failed to rescue defects in the positioning of cortical neurons in the embryonic mouse brain following RNAi-mediated knockdown of endogeneous Nr1d1 (Goto et al., 2017). However, NR1D1 variants identified in these two studies showed incomplete segregation with ASD. Nr1d1-knockout mice were shown to display hyperactivity, impaired response habituation in novel environments, deficiencies in contextual memories, and impaired nest-building activity, suggesting impaired hippocampal function (Jager et al., 2014).
Score Delta: Score remained at 2
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

Decreased from 3 to 2
Description
Screening of circadian-relevant genes in Japanese ASD patients with or without sleep disorders identified a missense variant in the NR1D1 gene (Yang et al., 2016). Additional screening of Caucasian ASD patients for NR1D1 variants identified several novel missense variants, including a de novo missense variant that failed to rescue defects in the positioning of cortical neurons in the embryonic mouse brain following RNAi-mediated knockdown of endogeneous Nr1d1 (Goto et al., 2017). However, NR1D1 variants identified in these two studies showed incomplete segregation with ASD. Nr1d1-knockout mice were shown to display hyperactivity, impaired response habituation in novel environments, deficiencies in contextual memories, and impaired nest-building activity, suggesting impaired hippocampal function (Jager et al., 2014).
10/1/2019

Decreased from 4 to 3
New Scoring Scheme
Description
Screening of circadian-relevant genes in Japanese ASD patients with or without sleep disorders identified a missense variant in the NR1D1 gene (Yang et al., 2016). Additional screening of Caucasian ASD patients for NR1D1 variants identified several novel missense variants, including a de novo missense variant that failed to rescue defects in the positioning of cortical neurons in the embryonic mouse brain following RNAi-mediated knockdown of endogeneous Nr1d1 (Goto et al., 2017). However, NR1D1 variants identified in these two studies showed incomplete segregation with ASD. Nr1d1-knockout mice were shown to display hyperactivity, impaired response habituation in novel environments, deficiencies in contextual memories, and impaired nest-building activity, suggesting impaired hippocampal function (Jager et al., 2014).
Reports Added
[New Scoring Scheme]4/1/2017

Increased from to 4
Description
Screening of circadian-relevant genes in Japanese ASD patients with or without sleep disorders identified a missense variant in the NR1D1 gene (Yang et al., 2016). Additional screening of Caucasian ASD patients for NR1D1 variants identified several novel missense variants, including a de novo missense variant that failed to rescue defects in the positioning of cortical neurons in the embryonic mouse brain following RNAi-mediated knockdown of endogeneous Nr1d1 (Goto et al., 2017). However, NR1D1 variants identified in these two studies showed incomplete segregation with ASD. Nr1d1-knockout mice were shown to display hyperactivity, impaired response habituation in novel environments, deficiencies in contextual memories, and impaired nest-building activity, suggesting impaired hippocampal function (Jager et al., 2014).
Krishnan Probability Score
Score 0.51276314846167
Ranking 1801/25841 scored genes
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ExAC Score
Score 0.9460854182801
Ranking 2755/18225 scored genes
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Sanders TADA Score
Score 0.93729120576235
Ranking 13476/18665 scored genes
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Zhang D Score
Score -0.060009392658952
Ranking 10788/20870 scored genes
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