RBM8A

RNA binding motif protein 8A, the group of RNA binding motif containing|Spliceosomal P complex|Exon junction complex

Basic information

Region (hg38): 1:145921555-145927678

Previous symbols: [ "RBM8" ]

Links

ENSG00000265241 ∙ NCBI:9939 ∙ OMIM:605313 ∙ HGNC:9905 ∙ Uniprot:Q9Y5S9 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• thrombocytopenia-absent radius syndrome (Definitive), mode of inheritance: AR
• thrombocytopenia-absent radius syndrome (Strong), mode of inheritance: AR
• thrombocytopenia-absent radius syndrome (Definitive), mode of inheritance: AR
• thrombocytopenia-absent radius syndrome (Supportive), mode of inheritance: AR
• thrombocytopenia-absent radius syndrome (Strong), mode of inheritance: AR
• thrombocytopenia-absent radius syndrome (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Thrombocytopenia-absent radius syndrome	AR	Hematologic	The condition can involve severe thrombocytopenia and bleeding episodes, and awareness may enable measures to prevent and better manage hematologic sequelae	Hematologic; Musculoskeletal	17236129; 22366785
The cause typically involves compound heterozygosity for a null variant (including a mult-gene deletion) affecting one allele and a rare non-coding variant affecting the other RBM8A allele

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the RBM8A gene.

• Radial aplasia-thrombocytopenia syndrome (38 variants)
• not provided (14 variants)
• not specified (7 variants)
• RBM8A-related condition (3 variants)
• Inborn genetic diseases (3 variants)
• Global developmental delay;Clinodactyly of the 5th finger;Abnormal brain morphology (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the RBM8A 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			1	9		10
missense			6	1		7
nonsense						0
start loss						0
frameshift	1					1
inframe indel						0
splice donor/acceptor (+/-2bp)	1	1				2
splice region			1	4		5
non coding	3	2		16	4	25
Total	5	3	7	26	4

Highest pathogenic variant AF is 0.0419

Variants in RBM8A

This is a list of pathogenic ClinVar variants found in the RBM8A region.

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

Position	Type	Phenotype	Significance	ClinVar
1-145923296-C-C		not specified	Likely benign (Jul 29, 2015)
1-145925774-G-A			Likely benign (Feb 28, 2019)
1-145925876-G-A		Radial aplasia-thrombocytopenia syndrome	Pathogenic (-)
1-145925876-G-C		RBM8A-related disorder • Radial aplasia-thrombocytopenia syndrome	Conflicting classifications of pathogenicity (Jan 05, 2024)
1-145925920-G-A		Radial aplasia-thrombocytopenia syndrome	Pathogenic (Feb 26, 2012)
1-145925932-G-A		Radial aplasia-thrombocytopenia syndrome	Likely benign (May 20, 2023)
1-145925935-A-C		Radial aplasia-thrombocytopenia syndrome	Likely benign (Sep 12, 2023)
1-145926026-C-T		Radial aplasia-thrombocytopenia syndrome	Benign (Jan 29, 2024)
1-145926029-T-C		Radial aplasia-thrombocytopenia syndrome	Likely benign (Nov 19, 2023)
1-145926041-C-T		Radial aplasia-thrombocytopenia syndrome	Uncertain significance (Dec 30, 2020)
1-145926065-C-A		Inborn genetic diseases	Uncertain significance (Feb 06, 2023)
1-145926098-C-T		Inborn genetic diseases	Uncertain significance (Jul 21, 2022)
1-145926116-T-C		Radial aplasia-thrombocytopenia syndrome	Uncertain significance (Jul 29, 2022)
1-145926117-T-G		not specified	Uncertain significance (Nov 26, 2018)
1-145926175-C-T		Radial aplasia-thrombocytopenia syndrome	Likely benign (Aug 22, 2022)
1-145926179-T-C		Radial aplasia-thrombocytopenia syndrome	Pathogenic (Sep 08, 2021)
1-145926190-A-G		Radial aplasia-thrombocytopenia syndrome	Likely benign (Feb 26, 2023)
1-145926194-G-A		Radial aplasia-thrombocytopenia syndrome	Likely benign (Jul 05, 2023)
1-145926196-C-G		Radial aplasia-thrombocytopenia syndrome	Likely benign (Dec 05, 2023)
1-145926463-A-G		Radial aplasia-thrombocytopenia syndrome	Likely benign (Jul 03, 2023)
1-145926470-CACTT-C		Radial aplasia-thrombocytopenia syndrome	Likely benign (Jan 06, 2023)
1-145926479-TACCTTCAGA-T		Radial aplasia-thrombocytopenia syndrome	Likely pathogenic (Apr 27, 2019)
1-145926506-G-A		not specified • Radial aplasia-thrombocytopenia syndrome	Benign/Likely benign (Jan 25, 2024)
1-145926545-G-A		Radial aplasia-thrombocytopenia syndrome	Likely benign (Dec 09, 2023)
1-145926548-T-C			Likely benign (Mar 01, 2022)

GnomAD

Source: gnomAD

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Core component of the splicing-dependent multiprotein exon junction complex (EJC) deposited at splice junctions on mRNAs. The EJC is a dynamic structure consisting of core proteins and several peripheral nuclear and cytoplasmic associated factors that join the complex only transiently either during EJC assembly or during subsequent mRNA metabolism. The EJC marks the position of the exon-exon junction in the mature mRNA for the gene expression machinery and the core components remain bound to spliced mRNAs throughout all stages of mRNA metabolism thereby influencing downstream processes including nuclear mRNA export, subcellular mRNA localization, translation efficiency and nonsense-mediated mRNA decay (NMD). The MAGOH-RBM8A heterodimer inhibits the ATPase activity of EIF4A3, thereby trapping the ATP- bound EJC core onto spliced mRNA in a stable conformation. The MAGOH-RBM8A heterodimer interacts with the EJC key regulator PYM1 leading to EJC disassembly in the cytoplasm and translation enhancement of EJC-bearing spliced mRNAs by recruiting them to the ribosomal 48S preinitiation complex. Its removal from cytoplasmic mRNAs requires translation initiation from EJC-bearing spliced mRNAs. Associates preferentially with mRNAs produced by splicing. Does not interact with pre-mRNAs, introns, or mRNAs produced from intronless cDNAs. Associates with both nuclear mRNAs and newly exported cytoplasmic mRNAs. The MAGOH-RBM8A heterodimer is a component of the nonsense mediated decay (NMD) pathway. Involved in the splicing modulation of BCL2L1/Bcl-X (and probably other apoptotic genes); specifically inhibits formation of proapoptotic isoforms such as Bcl-X(S); the function is different from the established EJC assembly. {ECO:0000269|PubMed:12121612, ECO:0000269|PubMed:12718880, ECO:0000269|PubMed:12730685, ECO:0000269|PubMed:16209946, ECO:0000269|PubMed:19409878, ECO:0000269|PubMed:22203037}.
• Pathway: mRNA surveillance pathway - Homo sapiens (human);RNA transport - Homo sapiens (human);Spliceosome - Homo sapiens (human);Gene expression (Transcription);RNA Polymerase II Transcription;Metabolism of RNA;Cleavage of Growing Transcript in the Termination Region ;RNA Polymerase II Transcription Termination;mRNA Splicing - Major Pathway;Nonsense-Mediated Decay (NMD);Transport of Mature mRNA derived from an Intron-Containing Transcript;Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC);mRNA Splicing;mRNA 3,-end processing;Transport of Mature Transcript to Cytoplasm;Processing of Capped Intron-Containing Pre-mRNA (Consensus)

Recessive Scores

• pRec: 0.149

Intolerance Scores

• rvis_EVS: -0.08
• rvis_percentile_EVS: 47.79

Haploinsufficiency Scores

• pHI: 0.365
• hipred: Y
• hipred_score: 0.562
• ghis: 0.468

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.895

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Rbm8a
• 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); growth/size/body region phenotype; cellular phenotype

Gene ontology

• Biological process: nuclear-transcribed mRNA catabolic process, nonsense-mediated decay;regulation of alternative mRNA splicing, via spliceosome;mRNA splicing, via spliceosome;RNA export from nucleus;mRNA export from nucleus;regulation of translation;mRNA 3'-end processing
• Cellular component: nucleus;nucleoplasm;cytoplasm;cytosol;nuclear speck;dendrite;exon-exon junction complex;neuronal cell body;catalytic step 2 spliceosome
• Molecular function: RNA binding;mRNA binding;protein binding