RAI1

retinoic acid induced 1

Basic information

Region (hg38): 17:17681457-17811453

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 (1441 variants)
• Inborn genetic diseases (309 variants)
• not specified (107 variants)
• Smith-Magenis syndrome (98 variants)
• RAI1-related condition (77 variants)
• Intellectual disability (6 variants)
• Developmental disorder (2 variants)
• See cases (2 variants)
• Smith-Magenis syndrome;Deafness;PMP22-RAI1 contiguous gene duplication syndrome (1 variants)
• Neurodevelopmental disorder (1 variants)
• History of neurodevelopmental disorder (1 variants)
• Autosomal recessive nonsyndromic hearing loss 9 (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.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			13	423	23	459
missense		4	586	122	88	800
nonsense	20	6				26
start loss						0
frameshift	50	15	1	1	3	70
inframe indel			21	22	5	48
splice donor/acceptor (+/-2bp)						0
splice region		1	1	1	1	4
non coding	1		1	21	9	32
Total	71	25	622	589	128

Highest pathogenic variant AF is 0.00000657

Variants in RAI1

This is a list of pathogenic ClinVar variants found in the RAI1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
17-17710075-CGGCCACGCTCATGTCAGGATTCTGAAGACCTCGAGCACACACAGACACGCACCTGGTCACGTGCACTTTCACACATACACTTGGCACCAGGGTGGCAGCAGCGGAGGTGACTGAGAAGCCTGCTTTTCACAGAGAATCAGAACCCAGCGGGGGCTTTAGCCACAAAAAAAGAGCATTTCAAGGAGAAGGGCTGCCTGCATGCCAAGCACACGCCCCTCACCTACCCAGGACCCCTTGTGGGAGCTGAGCCCCATGGAGACCCCGGGGTACCCATCCCACCCTCCAACATCCATCCCTACGTGGATATACGGCCACAGTTGCAGCTGCGGCCATGAGGAGGGGTTTTTGCTCCTTTTTAGCAGTGCTCCATCCCCCACCCCAGAGTACAGGGGGCTGCCCAGAGACCCTCCTGGCCCTGGGGGCCTGTGAGTCAGAGGCTGCCAGTGGTGGCCTTTCGGCTGTTGCTGGGGAAATGGCAGCACAGTGGCCACCAAGACTAGGACTCCCTGGGGAGGCCCTGCTGGCCCTGGCACTGGTGGCTTGGCCTCACCCAGCCCCACCTGGCAGATGTGCCCCTTGTGGCTACCCAAGGACTGGCCCCCTCCTCATTTCAGAGGTGGAGAAACTGAGGTAAAAAAGTGGAGACAGCCAGGGCACCCCTCCCACAAGGCCCTGCCTCATTTGAGACAGAGCCCTCTGGGAAGCCTGTGCATTCTGTAGGTGGGGACCTTTGGGGCCATTTTTTCCAGAGGCCCAGAGAGGGCCGTCTTCTTGCCCAAGGTCACACAGCAAGTTCATGGCATAAGCTAGCCAGCCTCGTACTCCAGAGCTCTCCTGAGGGCCCCCATGTGTCTGTGCGGGGGTGTTGATGGGGGGCAGGTGGGAGGGAGGAGGTAAGGCTGATTTGTTTCCCAGCCTCCTCCCCCTCCCCTGCTCCCTTCTCTCCCTCACACGGTTTGTTTGGAGAATGACTCACAGGAATGCAGCAAAATCCTGATGGATGGGAAGGCAGGGCCGCAGTACCCGGAAAACCTCTCCAGGGTAGGGAGGCGGGGCTGAGCCTTGGGGCCTGAGAGGCTGGTGATAGGGGAGCCCTGCATGCAGGTGGGGCGACTGAGGCCCTGGAAGAACTCTGGTCACGTCCTGGCTGGGGGTTGTCCCTCCTCGACAGAAACACACAGGCCCTGGCTGCCGCAGCACCCCTGGAGCACCCGTCCCCCATGATTTCCATCTTTGTGTCCCCGAGGCATCTGGTGCACTGTAGCTGACAAACACATGCATTTTGGCACTGAGTGTGACCCAAGTCAGACCCTCCTGTGTGTGCCCTGTCCCCCAGGTCCTCCCAGCTCCCCGGAGTTGGGGGGCGGGTGCTTGCCATTCAGTCCTTTCAGAGGCAGCCAAGGGCCTACGGCATGCTGGACACTGCCAGGGGCTGGGGAGGCTGGGATGGAGCTGGAGGGAAGTGGGAGGTGTACACGGGATGGACACCTCCTGTGTATGTTCCAAATGTGCTGGAGGCCTCAACAGGTCTTGGTACAAGGTGAGGCAAACCTTAGAGGACCTAGGATGAAGTTTCACGTAAAGGAACAGTGGCTGTAAGGGCTCCCAGAAAGTGTAGGGACCCTGGGAAGGTCCCAGTCTTTGAATAAAGGTGGGTGGGACCTTATTGGTAGCTTGGGGCATTAGGGCCCAGATATCAGGCAGCAGCATGAGGTGAGGCCCGGGCTCTGTCCCAGGGCAAGCCCTCCTCCTGCGCACCACATCTGGGGCCTCCGAGGAGGGACAAAGCATTCAACTCCCGGGACCTGTGGGTGGGAATGTCCCCAGGCCCAGCCCTTTAGTGCCTGCTGATGGCTGTCACGCGGTGTCCGGCCCTGATGACCAGATATGTGTTTTCAAGAGAAGCTGGAATTTGGATTTTTATGTGAACTCTCCTGATTCTCAAATGCTGGCTCCGTTAACAAAAGGCACAGTGTGGTTTAAACCACACATGTCCGCAGGCAGAGGACCACCAGTTTCTAATGTCTGCGCTGTGGGGCGCTTGGGTTTTTGCATTTGGTTCTTTTACATTCCTTATTTTATTGGAAACAGCCCAAATAGTCACTGAGCTGCAACTCTGTGCTAGGTGCCGGGGCTCTATCAGCGAATAAAACAACATGTGACGGAGCTGCCATTTTAGTGGGAGAAGACAGTGAATAAACATATATCAGGTGATATGTGTTAGGAAGCAAATGGAAGCAGGGCTCCAGAACAGAGAGCGGCTGCAAGGCCAAGCCCACATTTGGGTGGAAGGGGCAGCTAGTGCAAAGGCCCTGAGGTGGGGCTATGCTAGGTGTGTTAGAGGCCTGTGTGGCTGCAGCGGGAGTGGGTGGGGAAGTGGGAGGAGGTGAGGTCAGAAGGTAGCATAGGTCAAATGGCATAGGAGACTGTGGGCTGTGGTATAAGCTTGGTTTTAAGTCTTATGTGAGGTGGGAGCCATGGAGGATTCCTAGGGAGGGAGGGTCAGGATCAGACTTGGTTTAACAGGCTCTGTCTGGGTGTTGTAATGGCTGAGTGGGGCAAGGATGGGCCTAGGAGGCCCAGAAGGGGCTATTGCACTTGTCTGGCTGAGTGATGATGCGGCCTGAACAGGAAGGGGGTAGTCACCAGAGGGTGACCTGAGGAAACTGTGGTCAAGCCTCTCCATGGTGTAAACAGTAAACACGATACTGATTCTAAGGACTTGGTAGTAACATGGAAATGGTGACTGTGTATAATGCTATGTGAAAATAGGATTAGAAAATTGTACATTAAAAACACACCAGCCCAGATGCAAAAGGCTGCAGATCATATGATTCCATTCATACGAAATGCCCAGGACAGGCGAATCCAGAGAGACAGACAGGAGGTGAGCAATTGCCAGGGGCTGGGGGTGGGGAAATGGGGGGTGACTGCCTATGGGAACAGGTTTCTTTTTGGGAGGGGGATGAAAATGTTCTGAAATTAGGTAGCAGTGATAGTTGCACAACTTCATGAATATACCAAAACCCTGAGTTGTCCCCTTTAAAAGGGTGAATTTTATAGTGAGTGAATTATACCTCAAAAAAAAAATTTTTTTTAAGGCATGTCCAGATTTCTAACCAAAATTGGATGCACATAGAAAACATTGCAAGGAGCTGGGCGTGATGGTGCCTGTGGTCCCCACTGCTTGGGAGGCCAAGGCAGGTGAATCACCTAAGCCCAGGAGTTCAAGACTAGAGCCTGGGTGATATAGTGAGATCCTGTCTCTAAATAATAATAATAGGCCAGCTGCAGTGGCTCATGCCTGTAATCCCAGTACTTTGGGAGGCCGAGGTGCACGGATCACCTGAGGTCAGGGGTTCGAGACCAG-C		Smith-Magenis syndrome	Pathogenic (Oct 01, 2021)
17-17724126-G-A			Likely benign (Sep 18, 2021)
17-17724233-G-T			Likely benign (Aug 23, 2021)
17-17791447-G-A			Benign (Apr 09, 2019)
17-17792945-A-T			Uncertain significance (Jun 02, 2022)
17-17792953-A-G			Likely benign (Nov 02, 2023)
17-17792955-T-G			Uncertain significance (Nov 02, 2023)
17-17792960-T-C		not specified	Conflicting classifications of pathogenicity (Oct 26, 2023)
17-17792961-C-T		Smith-Magenis syndrome	Likely pathogenic (Aug 01, 2021)
17-17792962-G-A		Inborn genetic diseases	Uncertain significance (Jan 12, 2024)
17-17792963-A-C			Likely benign (Mar 07, 2021)
17-17792963-A-G			Likely benign (Nov 22, 2021)
17-17792969-G-A			Likely benign (Nov 26, 2022)
17-17792971-G-A			Uncertain significance (Jul 26, 2022)
17-17792979-C-T			Uncertain significance (Aug 21, 2022)
17-17792982-G-T			Uncertain significance (Oct 18, 2023)
17-17792983-G-A			Likely benign (Jan 15, 2024)
17-17792984-C-T			Uncertain significance (Apr 15, 2022)
17-17793010-C-T			Uncertain significance (Apr 12, 2023)
17-17793011-G-A		Inborn genetic diseases	Likely benign (Nov 18, 2023)
17-17793011-G-T			Likely benign (Sep 22, 2023)
17-17793012-C-A			Uncertain significance (Mar 24, 2022)
17-17793021-T-A		RAI1-related disorder	Conflicting classifications of pathogenicity (Jan 29, 2024)
17-17793023-A-G			Likely benign (Dec 02, 2022)
17-17793024-C-T		not specified • RAI1-related disorder	Conflicting classifications of pathogenicity (Dec 21, 2023)

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