RBM8A

Summary

RBM8A (RNA binding motif protein 8A, HGNC:9905) is a protein-coding gene on chromosome 1q21.1, encoding RNA-binding protein 8A (Q9Y5S9). Required for pre-mRNA splicing as component of the spliceosome. It is a common-essential gene (DepMap: required in 99.6% of cancer cell lines).

This gene encodes a protein with a conserved RNA-binding motif. The protein is found predominantly in the nucleus, although it is also present in the cytoplasm. It is preferentially associated with mRNAs produced by splicing, including both nuclear mRNAs and newly exported cytoplasmic mRNAs. It is thought that the protein remains associated with spliced mRNAs as a tag to indicate where introns had been present, thus coupling pre- and post-mRNA splicing events. Previously, it was thought that two genes encode this protein, RBM8A and RBM8B; it is now thought that the RBM8B locus is a pseudogene. There are two alternate translation start codons with this gene, which result in two forms of the protein. An allele mutation and a low-frequency noncoding single-nucleotide polymorphism (SNP) in this gene cause thrombocytopenia-absent radius (TAR) syndrome.

Source: NCBI Gene 9939 — RefSeq curated summary.

At a glance

• Gene–disease (curated): thrombocytopenia-absent radius syndrome (Definitive, ClinGen)
• Clinical variants (ClinVar): 43 total — 6 pathogenic
• Phenotypes (HPO): 95
• Cancer dependency (DepMap): dependent in 99.6% of screened cell lines (common-essential)
• MANE Select transcript: NM_005105

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9905
Approved symbol	RBM8A
Name	RNA binding motif protein 8A
Location	1q21.1
Locus type	gene with protein product
Status	Approved
Aliases	ZNRP, BOV-1A, BOV-1B, BOV-1C, Y14
Ensembl gene	ENSG00000265241
Ensembl biotype	protein_coding
OMIM	605313
Entrez	9939

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 7 protein_coding, 4 retained_intron

ENST00000369307, ENST00000484825, ENST00000498663, ENST00000583313, ENST00000632555, ENST00000634161, ENST00000691760, ENST00000692065, ENST00000890492, ENST00000930503, ENST00000930504

RefSeq mRNA: 1 — MANE Select: NM_005105 NM_005105

CCDS: CCDS72872

Canonical transcript exons

ENST00000583313 — 6 exons

Exon	Start	End
ENSE00002693594	145921556	145925927
ENSE00002713211	145926809	145926886
ENSE00003536387	145927360	145927484
ENSE00003745117	145927018	145927077
ENSE00004475429	145926041	145926177
ENSE00004475431	145926482	145926618

Expression profiles

Bgee: expression breadth ubiquitous, 294 present calls, max score 98.55.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 6.4819 / max 155.1186, expressed in 1704 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
14155	6.4819	1704

Top tissues by expression

295 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
ganglionic eminence	UBERON:0004023	98.55	gold quality
lower esophagus mucosa	UBERON:0035834	98.53	gold quality
ventricular zone	UBERON:0003053	98.42	gold quality
calcaneal tendon	UBERON:0003701	98.22	gold quality
esophagus mucosa	UBERON:0002469	98.05	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	97.94	gold quality
gastrocnemius	UBERON:0001388	97.49	gold quality
cortical plate	UBERON:0005343	97.30	gold quality
islet of Langerhans	UBERON:0000006	97.29	gold quality
muscle of leg	UBERON:0001383	97.29	gold quality
monocyte	CL:0000576	97.22	gold quality
skin of abdomen	UBERON:0001416	97.22	gold quality
right testis	UBERON:0004534	97.18	gold quality
left testis	UBERON:0004533	97.17	gold quality
granulocyte	CL:0000094	97.14	gold quality
skin of leg	UBERON:0001511	97.02	gold quality
lymph node	UBERON:0000029	96.96	gold quality
leukocyte	CL:0000738	96.94	gold quality
mononuclear cell	CL:0000842	96.91	gold quality
omental fat pad	UBERON:0010414	96.91	gold quality
peritoneum	UBERON:0002358	96.89	gold quality
esophagus	UBERON:0001043	96.88	gold quality
left ovary	UBERON:0002119	96.77	gold quality
vermiform appendix	UBERON:0001154	96.75	gold quality
minor salivary gland	UBERON:0001830	96.71	gold quality
ectocervix	UBERON:0012249	96.71	gold quality
gall bladder	UBERON:0002110	96.65	gold quality
left uterine tube	UBERON:0001303	96.64	gold quality
adenohypophysis	UBERON:0002196	96.63	gold quality
mucosa of stomach	UBERON:0001199	96.51	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-MTAB-10042	yes	9.71
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): IRF6, MYC, NFKB, PURA

miRNA regulators (miRDB)

146 targeting RBM8A, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-196A-5P	100.00	68.16	684
HSA-MIR-196B-5P	100.00	68.16	681
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-144-3P	99.94	73.98	2698
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-3143	99.93	71.96	3104
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-5680	99.91	69.83	3421
HSA-MIR-4302	99.89	67.94	1187
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 99.6% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 29)

• conserved physical linkage in medaka and human genomes (PMID:12054603)
• Tethered function analysis shows that the Y14/hUpf3b interaction is essential for nonsense-mediated decay, while surprisingly the interaction between hUpf3b and hUpf2 is not. (PMID:12718880)
• antagonistic post-translational modifications of Y14 may be involved in the remodeling of Y14-containing mRNPs (PMID:16100109)
• The stable association of multiprotein exon junction complex core with RNA is maintained by inhibition of eIF4AIII ATPase activity by MAGOH-Y14. (PMID:16170325)
• crystal structure of a tetrameric exon junction core complex containing the DEAD-box adenosine triphosphatase eukaryotic initiation factor 4AIII bound to an ATP analog, MAGOH, Y14, a fragment of MLN51, and a polyuracil mRNA mimic (PMID:16931718)
• Increased TAP binding correlates with increased SF2/ASF binding, but not increased REF/Aly or Y14 binding. (PMID:18243119)
• Y14 interacts with STAT3 and regulates the transcriptional activation of STAT3 by influencing the tyrosine-phosphorylation of STAT3. (PMID:18503751)
• These results indicate that MAGOH regulates the transcriptional activation of STAT3 by interfering complex formation between STAT3 and Y14. (PMID:19254694)
• Y14 provides a regulatory link between pre-mRNA splicing and snRNP biogenesis. (PMID:21209085)
• Y14 mutants, which are deficient in binding to Magoh, could still be localized to the nucleus, suggesting the existence of both the nuclear import pathway and function for Y14 unaccompanied by Magoh (PMID:22355610)
• findings show that the two regulatory SNPs result in diminished RBM8A transcription in vitro and that Y14 expression is reduced in platelets from individuals with thrombocytopenia with absent radii (TAR) (PMID:22366785)
• Data show that Y14 interacts directly with the decapping factor Dcp2 and the 5’ cap structure of mRNAs via different but overlapping domains. (PMID:23115303)
• Y14 positively regulates signals for TNF-alpha-induced IL-6 production at multiple steps beyond an exon junction complex protein. (PMID:23817415)
• Depletion of RNA-binding protein RBM8A (Y14) causes cell cycle deficiency and apoptosis in human tumor cells. (PMID:23970407)
• Mutations of RBM8A and TBX6 are associated with disorders of the mullerian ducts. (PMID:25813282)
• It was demonstrated that Rbm8a is an essential neurogenesis regulator in embryonic cortical development. (PMID:25948253)
• this data suggests a novel role of RBM8a in the regulation of neurodevelopment. (PMID:26094033)
• Y14 may selectively and differentially modulate protein biosynthesis. (PMID:26887951)
• Results demonstrated that RBM8A is highly expressed in hepatocellular carcinoma (HCC), and patients with lower RBM8A expression level had longer overall survival and progression free survival. Also, results indicate that RBM8A promotes invasion and metastasis via epithelial-mesenchymal transition signaling pathway. (PMID:28259942)
• A direct link between Y14 and p53 expression and suggests a function for Y14 in DNA damage signaling. (PMID:28361991)
• Findings demonstrate that Y14 nucleoplasmic localization is regulated not only by the previously reported N-terminal localization signal but also by the C-terminal serine/arginine repeat-containing region through phosphorylation and MAGOH binding to Y14. (PMID:29330450)
• These results demonstrate that data mining efficiently reveals information about RBM8A expression and potential regulatory networks in HCC, laying a foundation for further study of the role of RBM8A in carcinogenesis. (PMID:30670676)
• These results reveal that the stability of Magoh and Y14 is not only dependent on the heterodimer structure, but also dependent on nuclear localization. (PMID:30826064)
• Identification of molecular correlations of RBM8A with autophagy in Alzheimer’s disease. (PMID:31816601)
• TAR syndrome: Clinical and molecular characterization of a cohort of 26 patients and description of novel noncoding variants of RBM8A. (PMID:32227665)
• Double-Stranded RNA Structural Elements Holding the Key to Translational Regulation in Cancer: The Case of Editing in RNA-Binding Motif Protein 8A. (PMID:34944051)
• Thrombocytopenia-Absent Radius Syndrome: Descriptions of Three New Cases and a Novel Splicing Variant in RBM8A That Expands the Spectrum of Null Alleles. (PMID:36077017)
• RBM8A Depletion Decreases the Cisplatin Resistance and Represses the Proliferation and Metastasis of Breast Cancer Cells via AKT/mTOR Pathway. (PMID:36105365)
• RBM8A, a new target of TEAD4, promotes breast cancer progression by regulating IGF1R and IRS-2. (PMID:39232805)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	rbm8a	ENSDARG00000016516
mus_musculus	Rbm8a	ENSMUSG00000038374
mus_musculus	Rbm8a2	ENSMUSG00000078184
rattus_norvegicus	Rbm8a	ENSRNOG00000021215
drosophila_melanogaster	tsu	FBGN0033378
caenorhabditis_elegans		WBGENE00004387

Protein

Protein identifiers

RNA-binding protein 8A — Q9Y5S9 (reviewed: Q9Y5S9)

Alternative names: Binder of OVCA1-1, RNA-binding motif protein 8A, RNA-binding protein Y14, Ribonucleoprotein RBM8A

All UniProt accessions (2): A0A023T787, Q9Y5S9

UniProt curated annotations — full annotation on UniProt →

Function. Required for pre-mRNA splicing as component of the spliceosome. 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.

Subunit / interactions. Heterodimer with either MAGOH or MAGOHB. Part of the mRNA splicing-dependent exon junction complex (EJC) complex; the core complex contains CASC3, EIF4A3, MAGOH or MAGOHB, and RBM8A. Component of the ALYREF/THOC4-EJC-RNA complex; in the complex interacts with EIF4A3 and MAGOH; these interactions are likely specific to RNA-bound EJC. Interacts with PYM1; the interaction is direct and dissociates the EJC from spliced mRNAs. Part of a complex that contains the EJC core components CASC3, EIF4A3, MAGOH and RBM8A plus proteins involved in nonsense-mediated mRNA decay, such as UPF1, UPF2, UPF3A and UPF3B. Found in a post-splicing complex with NXF1, MAGOH, UPF1, UPF2, UPF3A, UPF3B and RNPS1. Interacts with DDX39B, MAGOH, DPH1, UPF3B, RNPS1, SRRM1 and ALYREF/THOC4. Interacts with IPO13; the interaction mediates the nuclear import of the MAGOH-RBM8A heterodimer. Identified in the spliceosome C complex. Associates with polysomes.

Subcellular location. Nucleus. Nucleus speckle. Cytoplasm.

Tissue specificity. Ubiquitous.

Disease relevance. Thrombocytopenia-absent radius syndrome (TAR) [MIM:274000] An autosomal recessive disorder characterized by bilateral absence of the radii with the presence of both thumbs, thrombocytopenia, low numbers of megakaryocytes, and bleeding episodes in the first year of life. Thrombocytopenic episodes decrease with age. Skeletal anomalies range from absence of radii to virtual absence of upper limbs, with or without lower limb defects such as malformations of the hip and knee. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the RBM8A family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9Y5S9-1	1, BOV-1a	yes
Q9Y5S9-2	2, BOV-1b

RefSeq proteins (1): NP_005096* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000504	RRM_dom	Domain
IPR008111	RNA-bd_8	Family
IPR012677	Nucleotide-bd_a/b_plait_sf	Homologous_superfamily
IPR033744	RRM_RBM8	Domain
IPR035979	RBD_domain_sf	Homologous_superfamily

Pfam: PF00076

UniProt features (29 total): strand 5, modified residue 4, mutagenesis site 4, compositionally biased region 4, helix 3, region of interest 2, initiator methionine 1, chain 1, cross-link 1, splice variant 1, sequence conflict 1, domain 1, turn 1

Structure

Experimental structures (PDB)

18 structures.

PDB	Method	Resolution (Å)
1P27	X-RAY DIFFRACTION	2
2J0S	X-RAY DIFFRACTION	2.21
2HYI	X-RAY DIFFRACTION	2.3
3EX7	X-RAY DIFFRACTION	2.3
7ZNJ	ELECTRON MICROSCOPY	2.4
8C6J	ELECTRON MICROSCOPY	2.8
6ICZ	ELECTRON MICROSCOPY	3
2J0Q	X-RAY DIFFRACTION	3.2
6QDV	ELECTRON MICROSCOPY	3.3
9FMD	ELECTRON MICROSCOPY	3.3
2XB2	X-RAY DIFFRACTION	3.4
8I0W	ELECTRON MICROSCOPY	3.4
5XJC	ELECTRON MICROSCOPY	3.6
7W59	ELECTRON MICROSCOPY	3.6
7W5A	ELECTRON MICROSCOPY	3.6
5YZG	ELECTRON MICROSCOPY	4.1
7W5B	ELECTRON MICROSCOPY	4.3
7A5P	ELECTRON MICROSCOPY	5

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9Y5S9-F1	80.24	0.50

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (5): 24, 42, 56, 27, 2

Mutagenesis-validated functional residues (4):

Position	Phenotype
82–83	impaired nonsense-mediated decay activity.
106–108	complete loss of nonsense-mediated decay activity.
118	complete loss of nonsense-mediated decay activity.
149–150	complete loss of nonsense-mediated decay activity.

Function

Pathways and Gene Ontology

Reactome pathways

6 pathways

ID	Pathway
R-HSA-159236	Transport of Mature mRNA derived from an Intron-Containing Transcript
R-HSA-72163	mRNA Splicing - Major Pathway
R-HSA-72187	mRNA 3’-end processing
R-HSA-9010553	Regulation of expression of SLITs and ROBOs
R-HSA-975957	Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC)
R-HSA-73856	RNA Polymerase II Transcription Termination

MSigDB gene sets: 485 (showing top): MORF_RAGE, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, GCM_GSPT1, GOBP_REGULATION_OF_MRNA_CATABOLIC_PROCESS, GOBP_ALTERNATIVE_MRNA_SPLICING_VIA_SPLICEOSOME, ASTON_MAJOR_DEPRESSIVE_DISORDER_DN, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, FERREIRA_EWINGS_SARCOMA_UNSTABLE_VS_STABLE_DN, GOBP_TRANSLATION, GOBP_NUCLEAR_TRANSPORT, GOBP_POST_TRANSCRIPTIONAL_REGULATION_OF_GENE_EXPRESSION, CREIGHTON_ENDOCRINE_THERAPY_RESISTANCE_1, GOBP_REGULATION_OF_CATABOLIC_PROCESS, BLALOCK_ALZHEIMERS_DISEASE_UP, REACTOME_MRNA_3_END_PROCESSING

GO Biological Process (11): nuclear-transcribed mRNA catabolic process, nonsense-mediated decay (GO:0000184), regulation of alternative mRNA splicing, via spliceosome (GO:0000381), mRNA splicing, via spliceosome (GO:0000398), mRNA export from nucleus (GO:0006406), regulation of translation (GO:0006417), RNA splicing (GO:0008380), regulation of mRNA processing (GO:0050684), regulation of nuclear-transcribed mRNA catabolic process, nonsense-mediated decay (GO:2000622), RNA processing (GO:0006396), mRNA processing (GO:0006397), mRNA transport (GO:0051028)

GO Molecular Function (4): RNA binding (GO:0003723), mRNA binding (GO:0003729), nucleic acid binding (GO:0003676), protein binding (GO:0005515)

GO Cellular Component (12): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), cytosol (GO:0005829), nuclear speck (GO:0016607), dendrite (GO:0030425), exon-exon junction complex (GO:0035145), neuronal cell body (GO:0043025), U2-type catalytic step 1 spliceosome (GO:0071006), catalytic step 2 spliceosome (GO:0071013), exon-exon junction subcomplex mago-y14 (GO:1990501), spliceosomal complex (GO:0005681)

Reactome top-level categories

Rollup of top-6 pathways:

Category	Pathways
Transport of Mature Transcript to Cytoplasm	1
mRNA Splicing	1
Processing of Capped Intron-Containing Pre-mRNA	1
Signaling by ROBO receptors	1
Nonsense-Mediated Decay (NMD)	1
RNA Polymerase II Transcription	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
mRNA processing	2
gene expression	2
RNA processing	2
binding	2
nuclear protein-containing complex	2
nuclear-transcribed mRNA catabolic process	1
alternative mRNA splicing, via spliceosome	1
regulation of mRNA splicing, via spliceosome	1
RNA splicing, via transesterification reactions with bulged adenosine as nucleophile	1
RNA export from nucleus	1
mRNA transport	1
translation	1
post-transcriptional regulation of gene expression	1
regulation of protein metabolic process	1
regulation of mRNA metabolic process	1
nuclear-transcribed mRNA catabolic process, nonsense-mediated decay	1
regulation of mRNA catabolic process	1
RNA biosynthetic process	1
primary metabolic process	1
mRNA metabolic process	1
RNA transport	1
nucleic acid binding	1
RNA binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
intracellular anatomical structure	1
cytoplasm	1
nuclear ribonucleoprotein granule	1
neuron projection	1
dendritic tree	1
somatodendritic compartment	1
cell body	1
U2-type spliceosomal complex	1
U2 snRNP	1
U6 snRNP	1
catalytic step 1 spliceosome	1
Prp19 complex	1
spliceosomal complex	1
U5 snRNP	1

Protein interactions and networks

STRING

2884 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RBM8A	MAGOHB	Q96A72	999
RBM8A	MAGOH	P50606	999
RBM8A	CASC3	O15234	998
RBM8A	EIF4A3	P38919	997
RBM8A	CCNT1	O60563	995
RBM8A	DICER1	Q9UPY3	994
RBM8A	AGO2	Q9UKV8	961
RBM8A	TARBP2	Q15633	956
RBM8A	UPF3B	Q9BZI7	931
RBM8A	UPF3A	Q9H1J1	924
RBM8A	UPF2	Q9HAU5	885
RBM8A	ALYREF	Q86V81	878
RBM8A	HEXIM1	O94992	873
RBM8A	CDK9	P50750	861
RBM8A	DPH1	Q9BZG8	848

IntAct

235 interactions, top by confidence:

A	B	Type	Score
CASC3	EIF4A3	psi-mi:“MI:0915”(physical association)	0.980
MAGOH	RBM8A	psi-mi:“MI:0915”(physical association)	0.980
RBM8A	MAGOH	psi-mi:“MI:0407”(direct interaction)	0.980
RBM8A	MAGOH	psi-mi:“MI:0915”(physical association)	0.980
MAGOH	RBM8A	psi-mi:“MI:0407”(direct interaction)	0.980
MAGOH	RBM8A	psi-mi:“MI:2364”(proximity)	0.980
EIF4A3	CASC3	psi-mi:“MI:0914”(association)	0.980
RBM8A	MAGOH	psi-mi:“MI:0914”(association)	0.980
MAGOH	CASC3	psi-mi:“MI:0914”(association)	0.970

BioGRID (584): RBM8A (Two-hybrid), MAGOHB (Two-hybrid), RBM8A (Protein-RNA), RBM8A (Protein-RNA), RBM8A (Affinity Capture-Western), RBM8A (Affinity Capture-Western), RBM8A (Affinity Capture-Western), RBM8A (Affinity Capture-MS), RBM8A (Affinity Capture-MS), RBM8A (Affinity Capture-MS), RBM8A (Affinity Capture-MS), RBM8A (Affinity Capture-MS), RBM8A (Two-hybrid), MAGOHB (Two-hybrid), RBM8A (Affinity Capture-Western)

ESM2 similar proteins: A1A4K8, A1Z9L3, A2A4P0, B5DGI7, E0X9N4, O01159, O23212, O48534, P17133, P90727, P90978, Q01081, Q08C72, Q09176, Q09217, Q14498, Q21832, Q27W01, Q28BZ1, Q2QKB3, Q2QKB4, Q2QZL4, Q2R0Q1, Q3T127, Q3ZCE8, Q52KN9, Q5D018, Q5RC80, Q5ZKA3, Q6AUG0, Q6IDS6, Q6P616, Q6PH90, Q7TP17, Q7ZXB5, Q8BGJ9, Q8L716, Q8VH51, Q8WU68, Q94535

Diamond homologs: A0A0D1C8Z4, A2SW84, A6PVI3, A8Y1R8, B0W939, B1WC40, B3LYP1, B3P0D7, B4GLK8, B4IBA4, B4JUT1, B4KCD5, B4LZ88, B4M205, B4NB54, B4PL68, B4QV17, B5DGI7, B5G279, B7P877, C0H859, C0HFE5, C1BY64, O35698, O89086, P19684, P27476, P33240, P52298, P52299, P60824, P60825, P60826, P62995, P62996, P62997, P78795, P98179, Q05AT9, Q08920

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
SRPK1	down-regulates	RBM8A	phosphorylation
RBM8A	“form complex”	“Exon junction complex”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 126 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Transport of Mature Transcript to Cytoplasm	8	30.1×	7e-09
mRNA 3’-end processing	15	29.2×	1e-16
RNA Polymerase II Transcription Termination	11	23.9×	3e-11
Transport of Mature mRNA derived from an Intron-Containing Transcript	15	22.6×	6e-15
FGFR2 alternative splicing	5	20.9×	8e-05
Nonsense-Mediated Decay (NMD)	9	20.8×	2e-08
mRNA Splicing	18	19.6×	1e-16
Processing of Capped Intron-Containing Pre-mRNA	24	19.5×	2e-22

GO biological processes:

GO term	Partners	Fold	FDR
nuclear-transcribed mRNA catabolic process, nonsense-mediated decay	13	52.5×	2e-17
mRNA export from nucleus	18	45.9×	3e-23
RNA export from nucleus	5	40.4×	1e-05
regulation of mRNA splicing, via spliceosome	5	38.2×	1e-05
regulation of mRNA processing	5	38.2×	1e-05
U2-type prespliceosome assembly	6	32.3×	3e-06
spliceosomal complex assembly	6	31.1×	4e-06
mRNA splicing, via spliceosome	28	22.1×	3e-27

Disease & clinical

Clinical variants and AI predictions

ClinVar

43 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	6
Likely pathogenic	0
Uncertain significance	16
Likely benign	18
Benign	1

Top pathogenic / likely-pathogenic (6)

Variant ID	HGVS	Classification
1232306	NM_005105.5(RBM8A):c.343-2A>G	Pathogenic
1333010	NC_000001.10:g.145505732_145513588del	Pathogenic
2502301	NM_005105.5(RBM8A):c.*6C>T	Pathogenic
30467	NM_005105.5(RBM8A):c.487C>T (p.Arg163Ter)	Pathogenic
40975	NC_000001.10:g.(?145413072)(145592772_145596903)del	Pathogenic
528377	NC_000001.10:g.(?145507647)(145509231_?)del	Pathogenic

SpliceAI

941 predictions. Top by Δscore:

Variant	Effect	Δscore
1:145925813:G:GT	donor_gain	1.0000
1:145925926:G:GG	acceptor_gain	1.0000
1:145925926:GA:G	acceptor_gain	1.0000
1:145925926:GAGGT:G	acceptor_gain	1.0000
1:145925927:A:AG	acceptor_gain	1.0000
1:145926041:G:GT	donor_gain	1.0000
1:145926176:G:GG	acceptor_gain	1.0000
1:145926176:GG:G	acceptor_gain	1.0000
1:145926176:GGG:G	acceptor_gain	1.0000
1:145926176:GGGG:G	acceptor_gain	1.0000
1:145926176:GGGGT:G	acceptor_gain	1.0000
1:145926177:A:AG	acceptor_gain	1.0000
1:145926177:AG:A	acceptor_gain	1.0000
1:145926177:AGG:A	acceptor_gain	1.0000
1:145926177:AGGG:A	acceptor_gain	1.0000
1:145926178:CA:C	acceptor_loss	1.0000
1:145926478:T:G	donor_loss	1.0000
1:145926479:GT:G	donor_loss	1.0000
1:145926480:GGT:G	donor_loss	1.0000
1:145926481:AGGT:A	donor_loss	1.0000
1:145926482:A:T	donor_gain	1.0000
1:145926483:GAAG:G	donor_gain	1.0000
1:145926490:G:GT	donor_gain	1.0000
1:145926617:G:GA	acceptor_gain	1.0000
1:145926617:GC:G	acceptor_gain	1.0000
1:145926617:GCT:G	acceptor_gain	1.0000
1:145926617:GCTG:G	acceptor_gain	1.0000
1:145926617:GCTGT:G	acceptor_gain	1.0000
1:145926618:A:AG	acceptor_gain	1.0000
1:145926618:AGCT:A	acceptor_gain	1.0000

AlphaMissense

1148 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:145926070:A:C	F150L	1.000
1:145926070:A:T	F150L	1.000
1:145926071:A:C	F150C	1.000
1:145926071:A:G	F150S	1.000
1:145926072:A:G	F150L	1.000
1:145926073:A:C	C149W	1.000
1:145926076:C:A	W148C	1.000
1:145926076:C:G	W148C	1.000
1:145926078:A:G	W148R	1.000
1:145926078:A:T	W148R	1.000
1:145926083:A:T	V146D	1.000
1:145926131:G:T	A130D	1.000
1:145926140:G:T	A127D	1.000
1:145926141:C:G	A127P	1.000
1:145926164:A:T	V119D	1.000
1:145926167:A:G	L118P	1.000
1:145926176:C:A	G115V	1.000
1:145926176:C:T	G115E	1.000
1:145926177:C:A	G115W	1.000
1:145926177:C:G	G115R	1.000
1:145926177:C:T	G115R	1.000
1:145926482:C:A	K114N	1.000
1:145926482:C:G	K114N	1.000
1:145926484:T:C	K114E	1.000
1:145926492:C:A	G111V	1.000
1:145926492:C:T	G111E	1.000
1:145926493:C:G	G111R	1.000
1:145926493:C:T	G111R	1.000
1:145926495:G:A	T110I	1.000
1:145926500:C:A	R108S	1.000

dbSNP variants (sampled 300 via entrez): RS1001365402 (1:145922233 G>A,C,T), RS1003201633 (1:145928648 T>G), RS1003222951 (1:145929256 C>G,T), RS1003254370 (1:145928858 A>C), RS1004765500 (1:145921867 T>A), RS1008125247 (1:145928329 A>T), RS1008156533 (1:145928023 C>G), RS1011546982 (1:145928883 C>A), RS1012104016 (1:145928818 A>G), RS1014116120 (1:145922582 G>C,T), RS1014201635 (1:145927737 G>A), RS1014397259 (1:145922263 T>C), RS1015867554 (1:145923293 A>C), RS1016072388 (1:145921597 A>C), RS1016209859 (1:145921913 A>C)

Disease associations

OMIM: gene MIM:605313 | disease phenotypes: MIM:274000

GenCC curated gene-disease

Disease	Classification	Inheritance
thrombocytopenia-absent radius syndrome	Definitive	Autosomal recessive

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
thrombocytopenia-absent radius syndrome	Definitive	AR

Mondo (1): thrombocytopenia-absent radius syndrome (MONDO:0010121)

Orphanet (1): Thrombocytopenia-absent radius syndrome (Orphanet:3320)

HPO phenotypes

95 total (30 of 95 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000073	Ureteral duplication
HP:0000076	Vesicoureteral reflux
HP:0000077	Abnormality of the kidney
HP:0000085	Horseshoe kidney
HP:0000119	Abnormality of the genitourinary system
HP:0000151	Aplasia of the uterus
HP:0000175	Cleft palate
HP:0000248	Brachycephaly
HP:0000272	Malar flattening
HP:0000337	Broad forehead
HP:0000347	Micrognathia
HP:0000348	High forehead
HP:0000358	Posteriorly rotated ears
HP:0000407	Sensorineural hearing impairment
HP:0000463	Anteverted nares
HP:0000486	Strabismus
HP:0000508	Ptosis
HP:0000518	Cataract
HP:0000891	Cervical ribs
HP:0000895	Lateral clavicle hook
HP:0000996	Facial capillary hemangioma
HP:0001051	Seborrheic dermatitis
HP:0001181	Adducted thumb
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001263	Global developmental delay
HP:0001270	Motor delay
HP:0001320	Cerebellar vermis hypoplasia
HP:0001321	Cerebellar hypoplasia

GWAS associations

0 associations (top):

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C536940	Absent radii and thrombocytopenia (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

50 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression	5
trichostatin A	affects cotreatment, decreases expression	3
Hydrogen Peroxide	affects expression, affects cotreatment, decreases expression	2
aristolochic acid I	increases expression	1
GSK-J4	decreases expression	1
FR900359	affects phosphorylation	1
TAK-243	decreases sumoylation	1
dicrotophos	decreases expression	1
2,4,6-tribromophenol	decreases expression	1
methylmercuric chloride	decreases expression	1
uranyl acetate	affects expression	1
bisphenol A	decreases expression	1
sodium arsenate	decreases expression	1
decabromobiphenyl ether	decreases expression	1
methylparaben	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
tetrabromobisphenol A	decreases expression	1
coumarin	affects phosphorylation	1
di-n-butylphosphoric acid	affects expression	1
yessotoxin	decreases expression	1
4-phenylbutyric acid	decreases expression	1
CGP 52608	increases reaction, affects binding	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
2-amino-14,16-dimethyloctadecan-3-ol	decreases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
bromovanin	increases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
pentabrominated diphenyl ether 100	decreases expression	1
hexabrominated diphenyl ether 153	decreases expression	1
NSC 689534	affects binding, decreases expression	1

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.