RBMX

protein-coding

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

Gene summary

This gene belongs to the RBMY gene family which includes candidate Y chromosome spermatogenesis genes. This gene, an active X chromosome homolog of the Y chromosome RBMY gene, is widely expressed whereas the RBMY gene evolved a male-specific function in spermatogenesis. Pseudogenes of this gene, found on chromosomes 1, 4, 9, 11, and 6, were likely derived by retrotransposition from the original gene. Alternatively spliced transcript variants encoding different isoforms have been identified. A snoRNA gene (SNORD61) is found in one of its introns. [provided by RefSeq, Sep 2009]

MANE transcript

NM_002139.4

Inheritance

ClinVar variants

P:9U:86B:8

Top phenotype

Intellectual developmental disorder, X-linked, syndromic 11 (Shashi type); Intellectual developmental disorder, X-linked syndromic, Gustavson type

gnomAD constraint

pLI —, LoF o/e 0.14

Max pathogenic AF

—

Genomic locus

chrX:136,848,004-136,880,764

External References & Databases

Ensembl (ENSG00000147274)

Transcript & Mutation Effects

hg38 • Region Span ~32.8 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

intellectual developmental disorder, X-linked, syndromic, Shashi typeMODERATE

Inheritance Pattern: XL

Disease ID:MONDO:0010277

Submitter: Ambry Genetics

intellectual developmental disorder, X-linked, syndromic, Gustavson typeMODERATE

Inheritance Pattern: XL

Disease ID:MONDO:0010661

Submitter: PanelApp Australia

intellectual developmental disorder, X-linked, syndromic, Shashi typeMODERATE

Inheritance Pattern: XL

Disease ID:MONDO:0010277

Submitter: PanelApp Australia

intellectual developmental disorder, X-linked, syndromic, Shashi typeLIMITED

Inheritance Pattern: Unknown

Disease ID:MONDO:0010277

Submitter: Labcorp Genetics (formerly Invitae)

Clinical Genomic Database (CGD)

Intellectual developmental disorder, X-linked, syndromic 11 (Shashi type); Intellectual developmental disorder, X-linked syndromic, Gustavson typeXL

Manifestation: Audiologic/Otolaryngologic; Craniofacial; Musculoskeletal; Neurologic

Intervention: General

Rationale: 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

Refs: 10677307; 25256757; 37277488

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to RBMX variants in ClinVar

7 Conditions Cataloged

not specifiedTotal: 18

not providedTotal: 17

Inborn genetic diseasesTotal: 15

Syndromic X-linked intellectual disability Shashi typeTotal: 11

RBMX-related disorderTotal: 9

Severe X-linked intellectual disability, Gustavson typeTotal: 4

CIC-rearranged sarcomaTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_002139.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			3 clinvar	8 clinvar		11
missense		3 clinvar	44 clinvar			47
nonsense		2 clinvar	3 clinvar			5
start loss			1 clinvar			1
frameshift	1 clinvar	3 clinvar	1 clinvar			5
splice donor/acceptor (+/-2bp)			34 clinvar			34
Total	1	8	86	8	0	103

Highest pathogenic variant AF is 9.117133e-7

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 64 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_002139.4	RefSeq	NP_002130.2	8	MANE Select
ENST00000320676.11	Ensembl	ENSP00000359645.3	8	MANE Select
NM_001164803.2	RefSeq	NP_001158275.1	6	Standard
ENST00000419968.6	Ensembl	ENSP00000405117.2	8	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Spliceosome - Homo sapiens (human)
mRNA Processing
Metabolism of RNA
mRNA Splicing - Major Pathway
mRNA Splicing

Biological Process

regulation of alternative mRNA splicing, via spliceosome
mRNA splicing, via spliceosome
osteoblast differentiation
transcription by RNA polymerase II
mRNA splice site selection

Molecular Function

RNA polymerase II proximal promoter sequence-specific DNA binding
chromatin binding
RNA binding
single-stranded RNA binding
mRNA binding

Cellular Component

extracellular space
nucleus
nucleoplasm
spliceosomal complex
nuclear euchromatin

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000320676
Coding exons: 8
Length: 32761
Individuals with no LoFs: 124927
Homozygous LoFs: 0
Heterozygous LoFs: 3
Defined: 124930
p: 0.0000120

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.90	62	168	0.369	0.0000139	2424
Missense (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

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000037	0.000029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.000026	0.000018	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

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.;

Intolerance Scores

LoFtool: 0.132
RVIS EVS: 0.33
RVIS percentile EVS: 73.11

Essentials

Essential (CRISPR): E
Essential (CRISPR2): E
Essential (gene trap): E
Indispensability pred.: E
Indispensability score: 0.970

Gene Damage Prediction

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