RAI1

retinoic acid induced 1

Basic information

Region (hg38): 17:17681458-17811453

Previous symbols: [ "SMCR" ]

Links

ENSG00000108557

∙ NCBI:10743 ∙ OMIM:607642 ∙ HGNC:9834 ∙ Uniprot:Q7Z5J4 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

Smith-Magenis syndrome (Definitive), mode of inheritance: AD
Smith-Magenis syndrome (Supportive), mode of inheritance: AD
Potocki-Lupski syndrome (Moderate), mode of inheritance: AD
Smith-Magenis syndrome (Definitive), mode of inheritance: AD
Smith-Magenis syndrome (Strong), mode of inheritance: AD
Smith-Magenis syndrome (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Smith-Magenis syndrome	AD	Neurologic	The condition may involve sleep disturbances, and treatment with specific agents (eg, tasimelteon) may be beneficial	Craniofacial; Musculoskeletal; Neurologic; Ophthalmologic	12652298; 15788730; 16845274; 17539903; 21739587; 21897445; 22578325; 34316024

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the RAI1 gene.

not_provided (1966 variants)
RAI1-related_disorder (623 variants)
Inborn_genetic_diseases (482 variants)
Smith-Magenis_syndrome (150 variants)
not_specified (137 variants)
Intellectual_disability (11 variants)
See_cases (2 variants)
Developmental_disorder (2 variants)
Deafness (1 variants)
Neurodevelopmental_disorder (1 variants)
Syndromic_intellectual_disability (1 variants)
Vascular_disorder (1 variants)
Rare_genetic_intellectual_disability (1 variants)
Autosomal_recessive_nonsyndromic_hearing_loss_9 (1 variants)
PMP22-RAI1_contiguous_gene_duplication_syndrome (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the RAI1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000030665.4. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous			8 clinvar	670 clinvar	20 clinvar	698
missense	5 clinvar	8 clinvar	853 clinvar	360 clinvar	135 clinvar	1361
nonsense	30 clinvar	8 clinvar				38
start loss			1			1
frameshift	72 clinvar	32 clinvar	1 clinvar	2 clinvar	1 clinvar	108
splice donor/acceptor (+/-2bp)						0
Total	107	48	863	1032	156

Highest pathogenic variant AF is 0.00000657134

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
RAI1	protein_coding	protein_coding	ENST00000353383	4	129981

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	7.14e-8	125693	0	5	125698	0.0000199

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.12	1029	1.13e+3	0.907	0.0000747	12193
Missense in Polyphen		227	323.88	0.70087		3566
Synonymous	-3.04	610	522	1.17	0.0000376	4106
Loss of Function	6.58	2	54.4	0.0368	0.00000306	629

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000677	0.0000616
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000555	0.0000544
Finnish	0.0000465	0.0000462
European (Non-Finnish)	0.0000178	0.0000176
Middle Eastern	0.0000555	0.0000544
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

Function: FUNCTION: Transcriptional regulator of the circadian clock components: CLOCK, ARNTL/BMAL1, ARNTL2/BMAL2, PER1/3, CRY1/2, NR1D1/2 and RORA/C. Positively regulates the transcriptional activity of CLOCK a core component of the circadian clock. Regulates transcription through chromatin remodeling by interacting with other proteins in chromatin as well as proteins in the basic transcriptional machinery. May be important for embryonic and postnatal development. May be involved in neuronal differentiation. {ECO:0000269|PubMed:22578325}.;
Disease: DISEASE: Smith-Magenis syndrome (SMS) [MIM:182290]: Characterized by congenital mental retardation associated with development and growth delays. Affected persons have characteristic behavioral abnormalities, including self-injurious behaviors and sleep disturbance, and distinct craniofacial and skeletal anomalies. {ECO:0000269|PubMed:11404004, ECO:0000269|PubMed:12652298, ECO:0000269|PubMed:24863970}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Recessive Scores

pRec: 0.117

Intolerance Scores

loftool: 0.202
rvis_EVS: -3.68
rvis_percentile_EVS: 0.25

Haploinsufficiency Scores

pHI: 0.137
hipred: Y
hipred_score: 0.572
ghis: 0.668

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: N
essential_gene_gene_trap: N
gene_indispensability_pred: E
gene_indispensability_score: 0.753

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

Gene name: Rai1
Phenotype: homeostasis/metabolism phenotype; craniofacial phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); endocrine/exocrine gland phenotype; growth/size/body region phenotype; respiratory system phenotype; skeleton phenotype; limbs/digits/tail phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); normal phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan);

Gene ontology

Biological process: skeletal system development;circadian regulation of gene expression;negative regulation of multicellular organism growth;positive regulation of transcription, DNA-templated;positive regulation of transcription by RNA polymerase II
Cellular component: nucleus;nucleoplasm;mitochondrion
Molecular function: DNA-binding transcription factor activity;protein binding;enhancer binding;transcription regulatory region DNA binding;metal ion binding