RBM5

protein-coding

RNA binding motif protein 5, the group of Spliceosomal A complex|RNA binding motif containing|G-patch domain containing|Zinc fingers RANBP2-type

Gene summary

This gene is a candidate tumor suppressor gene which encodes a nuclear RNA binding protein that is a component of the spliceosome A complex. The encoded protein plays a role in the induction of cell cycle arrest and apoptosis through pre-mRNA splicing of multiple target genes including the tumor suppressor protein p53. This gene is located within the tumor suppressor region 3p21.3, and may play a role in the inhibition of tumor transformation and progression of several malignancies including lung cancer. [provided by RefSeq, Oct 2011]

MANE transcript

NM_005778.4

Inheritance

—

ClinVar variants

P:1U:81

Top phenotype

Male infertility with azoospermia or oligozoospermia due to single gene mutation

gnomAD constraint

pLI —, LoF o/e 0.05

Max pathogenic AF

—

Genomic locus

chr3:50,088,919-50,119,021

External References & Databases

Ensembl (ENSG00000003756)

Transcript & Mutation Effects

hg38 • Region Span ~30.1 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to RBM5 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 69

Male infertility with azoospermia or oligozoospermia due to single gene mutationTotal: 1

See casesTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_005778.4. 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			4 clinvar			4
missense		1 clinvar	71 clinvar			72
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			6 clinvar			6
Total	0	1	81	0	0	82

Highest pathogenic variant AF is 0.0000012393632

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 80 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_005778.4	RefSeq	NP_005769.1	24	MANE Select
ENST00000347869.8	Ensembl	ENSP00000343054.3	24	MANE Select
ENST00000395174.6	Ensembl	ENSP00000378603.2	2	Standard
ENST00000404526.6	Ensembl	ENSP00000384872.2	6	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

mRNA Processing
Metabolism of RNA
mRNA Splicing - Major Pathway
mRNA Splicing
Processing of Capped Intron-Containing Pre-mRNA

Biological Process

spliceosomal complex assembly
regulation of alternative mRNA splicing, via spliceosome
mRNA splicing, via spliceosome
RNA processing
apoptotic process

Molecular Function

DNA binding
RNA binding
mRNA binding
protein binding
metal ion binding

Cellular Component

nucleus
nucleoplasm
spliceosomal complex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000347869
Coding exons: 24
Length: 30114
Individuals with no LoFs: 125734
Homozygous LoFs: 0
Heterozygous LoFs: 14
Defined: 125748
p: 0.0000557

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	4.17	224	481	0.465	0.0000278	5370
Missense (PolyPhen)		68	198.67	0.34228		2164
Synonymous	1.80	143	173	0.826	0.0000103	1503
Loss of Function	6.66	3	57.5	0.0522	0.00000320	625

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.00023	0.00023	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.000026	0.000026	rare
South Asian	0.000065	0.000065	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Component of the spliceosome A complex. Regulates alternative splicing of a number of mRNAs. May modulate splice site pairing after recruitment of the U1 and U2 snRNPs to the 5' and 3' splice sites of the intron. May both positively and negatively regulate apoptosis by regulating the alternative splicing of several genes involved in this process, including FAS and CASP2/caspase-2. In the case of FAS, promotes exclusion of exon 6 thereby producing a soluble form of FAS that inhibits apoptosis. In the case of CASP2/caspase-2, promotes exclusion of exon 9 thereby producing a catalytically active form of CASP2/Caspase-2 that induces apoptosis. {ECO:0000269|PubMed:10949932, ECO:0000269|PubMed:12207175, ECO:0000269|PubMed:12581154, ECO:0000269|PubMed:15192330, ECO:0000269|PubMed:16585163, ECO:0000269|PubMed:18840686, ECO:0000269|PubMed:18851835}.;

Recessive Scores

pRec: 0.117

Intolerance Scores

LoFtool: 0.287
RVIS EVS: -1.11
RVIS percentile EVS: 6.72

Essentials

Essential (CRISPR): E
Essential (CRISPR2): N
Essential (gene trap): H
Indispensability pred.: E
Indispensability score: 0.710

Gene Damage Prediction

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