RBMX

RNA binding motif protein X-linked, the group of RNA binding motif containing|Small nucleolar RNA protein coding host genes|Heterogeneous nuclear ribonucleoproteins

Basic information

Region (hg38): X:136848004-136880764

Links

ENSG00000147274 ∙ NCBI:27316 ∙ OMIM:300199 ∙ HGNC:9910 ∙ Uniprot:P38159 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• syndromic X-linked intellectual disability Shashi type (Moderate), mode of inheritance: XL
• syndromic X-linked intellectual disability Shashi type (Limited), mode of inheritance: Unknown

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Intellectual developmental disorder, X-linked, syndromic 11 (Shashi type); Intellectual developmental disorder, X-linked syndromic, Gustavson type	XL	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Audiologic/Otolaryngologic; Craniofacial; Musculoskeletal; Neurologic	10677307; 25256757; 37277488

ClinVar

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

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the RBMX 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			2	3		5
missense		1	10			11
nonsense						0
start loss						0
frameshift						0
inframe indel			1			1
splice donor/acceptor (+/-2bp)			1			1
splice region			2	1		3
non coding			2		2	4
Total	0	1	16	3	2

Variants in RBMX

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

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

Position	Type	Phenotype	Significance	ClinVar
X-136872324-CATA-C		RBMX-related disorder	Benign (Dec 06, 2019)
X-136872325-A-AT		Severe X-linked intellectual disability, Gustavson type	Uncertain significance (Mar 29, 2024)
X-136874213-G-A		Inborn genetic diseases	Uncertain significance (Sep 17, 2021)
X-136874250-C-A			Likely benign (Apr 01, 2024)
X-136874258-CCATAGAAGGGGGAAGCCCTCTTT-C		Syndromic X-linked intellectual disability Shashi type	Pathogenic (Mar 13, 2024)
X-136874266-G-C			Uncertain significance (Jun 01, 2023)
X-136874287-C-T		Syndromic X-linked intellectual disability Shashi type	Uncertain significance (Jan 04, 2022)
X-136874321-C-A		Syndromic X-linked intellectual disability Shashi type	Uncertain significance (Jul 15, 2020)
X-136874381-AATC-A		RBMX-related disorder	Uncertain significance (Feb 14, 2024)
X-136874427-T-C		not specified	Likely benign (Mar 28, 2016)
X-136874429-T-C		Inborn genetic diseases	Uncertain significance (Mar 30, 2024)
X-136874453-C-CATAACTCTCATA		CIC-rearranged sarcoma	not provided (-)
X-136875144-A-C		Inborn genetic diseases	Uncertain significance (Jun 10, 2024)
X-136875254-T-G		not specified	Likely benign (Aug 15, 2017)
X-136875323-T-C		Inborn genetic diseases	Conflicting classifications of pathogenicity (Nov 14, 2024)
X-136875466-A-G			Uncertain significance (Mar 01, 2022)
X-136875536-T-C		Syndromic X-linked intellectual disability Shashi type	Uncertain significance (Feb 18, 2020)
X-136876506-T-C		not specified	Uncertain significance (Feb 08, 2024)
X-136876557-TAGG-T		Severe X-linked intellectual disability, Gustavson type	Pathogenic (Mar 13, 2024)
X-136876650-C-A		Inborn genetic diseases	Uncertain significance (May 04, 2023)
X-136876663-A-G		Syndromic X-linked intellectual disability Shashi type	Uncertain significance (May 03, 2020)
X-136876672-A-G		not specified	Uncertain significance (Jul 06, 2023)
X-136877915-C-A		Severe X-linked intellectual disability, Gustavson type	Likely pathogenic (Mar 25, 2024)
X-136877996-T-C		Inborn genetic diseases	Uncertain significance (Sep 08, 2024)
X-136878001-C-T		Inborn genetic diseases	Uncertain significance (Feb 05, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
RBMX	protein_coding	protein_coding	ENST00000320676	8	32761

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.829	0.171	124927	0	3	124930	0.0000120

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.90	62	168	0.369	0.0000139	2424
Missense in Polyphen		18	43.401	0.41474		733
Synonymous	-0.498	54	49.5	1.09	0.00000353	809
Loss of Function	3.05	2	14.6	0.137	0.00000127	258

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000367	0.0000367
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000263	0.0000177
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: RNA-binding protein that plays several role in the regulation of pre- and post-transcriptional processes. Implicated in tissue-specific regulation of gene transcription and alternative splicing of several pre-mRNAs. Binds to and stimulates transcription from the tumor suppressor TXNIP gene promoter; may thus be involved in tumor suppression. When associated with SAFB, binds to and stimulates transcription from the SREBF1 promoter. Associates with nascent mRNAs transcribed by RNA polymerase II. Component of the supraspliceosome complex that regulates pre-mRNA alternative splice site selection. Can either activate or suppress exon inclusion; acts additively with TRA2B to promote exon 7 inclusion of the survival motor neuron SMN2. Represses the splicing of MAPT/Tau exon 10. Binds preferentially to single- stranded 5'-CC[A/C]-rich RNA sequence motifs localized in a single-stranded conformation; probably binds RNA as a homodimer. Binds non-specifically to pre-mRNAs. Plays also a role in the cytoplasmic TNFR1 trafficking pathways; promotes both the IL-1- beta-mediated inducible proteolytic cleavage of TNFR1 ectodomains and the release of TNFR1 exosome-like vesicles to the extracellular compartment. {ECO:0000269|PubMed:12165565, ECO:0000269|PubMed:12761049, ECO:0000269|PubMed:16707624, ECO:0000269|PubMed:18445477, ECO:0000269|PubMed:18541147, ECO:0000269|PubMed:19282290, ECO:0000269|PubMed:21327109}.
• Disease: DISEASE: Mental retardation, X-linked, syndromic, 11 (MRXS11) [MIM:300238]: A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. MRXS11 patients manifest moderate intellectual disability and craniofacial dysmorphism. {ECO:0000269|PubMed:25256757}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Spliceosome - Homo sapiens (human);mRNA Processing;Metabolism of RNA;mRNA Splicing - Major Pathway;mRNA Splicing;Processing of Capped Intron-Containing Pre-mRNA (Consensus)

Intolerance Scores

• loftool: 0.132
• rvis_EVS: 0.33
• rvis_percentile_EVS: 73.11

Haploinsufficiency Scores

• pHI: 0.261
• hipred: Y
• hipred_score: 0.698
• ghis: 0.540

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.970

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Rbmx
• Phenotype: homeostasis/metabolism phenotype; growth/size/body region phenotype; immune system phenotype; hematopoietic system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan)

Gene ontology

• Biological process: regulation of alternative mRNA splicing, via spliceosome;mRNA splicing, via spliceosome;osteoblast differentiation;transcription by RNA polymerase II;mRNA splice site selection;membrane protein ectodomain proteolysis;RNA metabolic process;positive regulation of transcription by RNA polymerase II;negative regulation of mRNA splicing, via spliceosome;positive regulation of mRNA splicing, via spliceosome;protein complex oligomerization;protein homooligomerization;cellular response to interleukin-1
• Cellular component: extracellular space;nucleus;nucleoplasm;spliceosomal complex;nuclear euchromatin;membrane;supraspliceosomal complex;extracellular exosome;catalytic step 2 spliceosome;ribonucleoprotein complex
• Molecular function: RNA polymerase II proximal promoter sequence-specific DNA binding;chromatin binding;RNA binding;single-stranded RNA binding;mRNA binding;protein binding;protein domain specific binding;identical protein binding