RBM20

Summary

RBM20 (RNA binding motif protein 20, HGNC:27424) is a protein-coding gene on chromosome 10q25.2, encoding RNA-binding protein 20 (Q5T481). RNA-binding protein that acts as a regulator of mRNA splicing of a subset of genes encoding key structural proteins involved in cardiac development, such as TTN (Titin), CACNA1C, CAMK2D or PDLIM5/ENH.

This gene encodes a protein that binds RNA and regulates splicing. Mutations in this gene have been associated with familial dilated cardiomyopathy.

Source: NCBI Gene 282996 — RefSeq curated summary.

At a glance

• Gene–disease (curated): dilated cardiomyopathy (Definitive, ClinGen) — +3 more curated relationships
• GWAS associations: 15
• Clinical variants (ClinVar): 2,390 total — 71 pathogenic, 31 likely-pathogenic
• Phenotypes (HPO): 16
• Dosage sensitivity (ClinGen): haploinsufficiency little evidence, triplosensitivity no evidence
• MANE Select transcript: NM_001134363

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:27424
Approved symbol	RBM20
Name	RNA binding motif protein 20
Location	10q25.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000203867
Ensembl biotype	protein_coding
OMIM	613171
Entrez	282996

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 3 protein_coding, 2 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000369519, ENST00000465774, ENST00000471172, ENST00000480343, ENST00000718239, ENST00000961386

RefSeq mRNA: 1 — MANE Select: NM_001134363 NM_001134363

CCDS: CCDS44477

Canonical transcript exons

ENST00000369519 — 14 exons

Exon	Start	End
ENSE00001450225	110821275	110821935
ENSE00001450226	110820072	110820176
ENSE00001450227	110812278	110812947
ENSE00001450228	110810383	110810462
ENSE00001450229	110799787	110799918
ENSE00001450230	110797508	110797648
ENSE00001450234	110644336	110644645
ENSE00001603282	110780801	110781884
ENSE00001753365	110784341	110784432
ENSE00001756724	110784792	110784889
ENSE00002370382	110783366	110783427
ENSE00002449242	110823480	110823614
ENSE00002534175	110835868	110839468
ENSE00003678602	110831061	110831182

Expression profiles

Bgee: expression breadth ubiquitous, 191 present calls, max score 98.57.

FANTOM5 (CAGE): breadth broad, TPM avg 3.1140 / max 358.2505, expressed in 519 samples.

FANTOM5 promoters (9 alternative TSS)

Promoter ID	TPM avg	Samples expressed
106989	0.9548	342
106993	0.6565	180
106990	0.5642	192
106991	0.4438	146
106992	0.3081	159
106988	0.0744	39
107005	0.0556	26
107004	0.0357	14
106987	0.0209	7

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
left ventricle myocardium	UBERON:0006566	98.57	gold quality
cardiac muscle of right atrium	UBERON:0003379	98.34	gold quality
myocardium	UBERON:0002349	96.87	gold quality
apex of heart	UBERON:0002098	95.26	gold quality
heart right ventricle	UBERON:0002080	94.65	gold quality
cardiac ventricle	UBERON:0002082	93.71	gold quality
heart left ventricle	UBERON:0002084	93.63	gold quality
oviduct epithelium	UBERON:0004804	92.68	gold quality
cardiac atrium	UBERON:0002081	92.23	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	91.87	gold quality
right atrium auricular region	UBERON:0006631	91.76	gold quality
biceps brachii	UBERON:0001507	91.68	gold quality
heart	UBERON:0000948	91.65	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	91.37	gold quality
skeletal muscle tissue	UBERON:0001134	89.75	gold quality
bronchial epithelial cell	CL:0002328	89.73	gold quality
deltoid	UBERON:0001476	89.03	gold quality
muscle tissue	UBERON:0002385	88.92	gold quality
bronchus	UBERON:0002185	88.03	gold quality
body of pancreas	UBERON:0001150	87.28	gold quality
right uterine tube	UBERON:0001302	87.22	gold quality
hindlimb stylopod muscle	UBERON:0004252	85.94	gold quality
quadriceps femoris	UBERON:0001377	85.75	silver quality
vastus lateralis	UBERON:0001379	85.37	gold quality
tibialis anterior	UBERON:0001385	84.42	gold quality
gastrocnemius	UBERON:0001388	83.91	gold quality
muscle of leg	UBERON:0001383	83.33	gold quality
lower esophagus mucosa	UBERON:0035834	82.34	gold quality
ascending aorta	UBERON:0001496	80.74	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	80.58	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-2	yes	3180.50
E-ANND-3	yes	5.44

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

238 targeting RBM20, 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-3163	100.00	77.23	8605
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-518D-5P	100.00	67.51	979
HSA-MIR-518E-5P	100.00	67.66	954
HSA-MIR-518F-5P	100.00	67.51	979
HSA-MIR-519A-5P	100.00	67.66	954
HSA-MIR-519B-5P	100.00	67.66	954
HSA-MIR-519C-5P	100.00	67.66	954
HSA-MIR-520C-5P	100.00	67.51	979
HSA-MIR-522-5P	100.00	67.66	954
HSA-MIR-523-5P	100.00	67.66	954
HSA-MIR-526A-5P	100.00	67.51	979
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-4673	100.00	66.64	1490
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-223-3P	99.99	70.14	1140
HSA-MIR-3667-3P	99.99	67.17	1636
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-568	99.98	69.86	2084
HSA-MIR-5696	99.98	72.36	4487
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593

Functional genomics

ClinGen dosage: haploinsufficiency 1 (little evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 34)

• RBM20 as a dilated cardiomyopathy gene and reveal a mutation hotspot in the RS domain. Individuals in each family revealed distinct heterozygous missense mutations in exon 9 of RBM20, encoding ribonucleic acid (RNA) binding motif protein 20. (PMID:19712804)
• RBM20 missense mutation is a novel gene underlying one form of dilated cardiomyopathy (PMID:19712805)
• Dilated cardiomyopathy in patients with RBM20 mutations is associated with advanced disease. (PMID:20590677)
• Mutations in RBM20 identified in approximately 3% of individuals with dilated cardiomyopathy. Mutations in RBM20 did not adversely affect survival or ventricular arrhythmias in subjects with dilated cardiomyopathy. (PMID:22004663)
• Deep sequencing of the human and rat cardiac transcriptome revealed an RBM20-dependent regulation of alternative splicing (PMID:22466703)
• The RBM20 c.1907 G>A (p.Arg636His) was confirmed in all 3 affected subjects who underwent exome sequencing. (PMID:23861363)
• Nuclear retention domains have been identified in RBM20 which is a nuclear protein regulating alternative splicing of expressed genes. (PMID:23886709)
• Study demonstrates that Rbm20 is expressed in early cardiogenesis and functions in the patterning of cardiac gene expression. (PMID:24584570)
• In failing hearts, reduced expression of RBM20 affected alternative splicing of several direct targets, indicating that differences in RBM20 expression may affect cardiac function. (PMID:24960161)
• RBM20 familial dilated cardiomyopathy is a developmental disorder initiated by molecular defects that pattern maladaptive cellular mechanisms of pathological cardiac remodeling. (PMID:26604136)
• Mutations in RBM20 cause dilated cardiomyopathy along with dysregulated isoform switch. (PMID:27396593)
• Heterozygous loss of RBM20 suffices to profoundly impair myocyte biomechanics by its disturbance of TTN splicing causing dilated cardiomyopathy. (PMID:27496873)
• RBM20 is crucial for the formation of a subset of circular RNAs that originate from the I-band of the titin gene. (PMID:27531932)
• The first light on molecular mechanisms of RBM20-dependent pathological cardiac remodeling leading to DCM. (PMID:28941705)
• The carboxy-terminal region of RBM20 is necessary for exon repression.RBM20 binds the cluster containing most RBM20 binding motifs through its RNA recognition motif domain and represses the upstream and downstream introns.Repressor activity of RBM20 is counteracted by PTB4. (PMID:29518215)
• RBM20 mutations/loss disturbs Ca(2+) handling and leads to more proarrhythmic Ca(2+) releases from the sarcoplasmic reticulum. (PMID:29650543)
• Phosphorylation of the RSRSP stretch is critical for splicing regulation by RNA-Binding Motif Protein 20 (RBM20) through nuclear localization. (PMID:29895960)
• These results indicate that RBM20 and PTBP1 play a role in the actin filament functional organization mediated by FHOD3 isoforms and suggest their possible involvement in heart diseases. (PMID:30468920)
• The study showed that genotypic and phenotypic characterization of a family displaying dilated cardiomyopathy (DCM). 6 members of a family carrying the RBM20 mutation NM_001134363.2:c.1900C>T. The findings are the first report of co-segregation of the mutation in 6 family members, supporting its pathogenic role. (PMID:30557877)
• Our data establish RBM20 cardiomyopathy as a highly penetrant and arrhythmogenic cardiomyopathy (PMID:30871351)
• Whole exome sequencing in a large pedigree with DCM identifies a novel mutation in RBM20. (PMID:31583969)
• The Emerging Role of the RBM20 and PTBP1 Ribonucleoproteins in Heart Development and Cardiovascular Diseases. (PMID:32276354)
• Cardiomyopathy-associated mutations in the RS domain affect nuclear localization of RBM20. (PMID:32840935)
• Dysregulated ribonucleoprotein granules promote cardiomyopathy in RBM20 gene-edited pigs. (PMID:33188278)
• RBM20-Associated Ventricular Arrhythmias in a Patient with Structurally Normal Heart. (PMID:33450993)
• Phenotype and progression among patients with dilated cardiomyopathy and RBM20 mutations. (PMID:34174465)
• The Combined Human Genotype of Truncating TTN and RBM20 Mutations Is Associated with Severe and Early Onset of Dilated Cardiomyopathy. (PMID:34201072)
• RBM20 Is a Candidate Gene for Hypertrophic Cardiomyopathy. (PMID:34333030)
• Gain-of-function cardiomyopathic mutations in RBM20 rewire splicing regulation and re-distribute ribonucleoprotein granules within processing bodies. (PMID:34732726)
• RBM20(S639G) mutation is a high genetic risk factor for premature death through RNA-protein condensates. (PMID:35041844)
• SR Protein Kinases Regulate the Splicing of Cardiomyopathy-Relevant Genes via Phosphorylation of the RSRSP Stretch in RBM20. (PMID:36140694)
• I536T variant of RBM20 affects splicing of cardiac structural proteins that are causative for developing dilated cardiomyopathy. (PMID:36198914)
• Risks of Ventricular Arrhythmia and Heart Failure in Carriers of RBM20 Variants. (PMID:37593875)
• [Research progress on the expression of the RBM20 gene in dilated cardiomyopathy]. (PMID:37905768)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
mus_musculus	Rbm20	ENSMUSG00000043639
rattus_norvegicus	Rbm20	ENSRNOG00000014705
drosophila_melanogaster	sm	FBGN0003435
caenorhabditis_elegans		WBGENE00016624

Paralogs (5): PTBP1 (ENSG00000011304), HNRNPL (ENSG00000104824), PTBP2 (ENSG00000117569), PTBP3 (ENSG00000119314), HNRNPLL (ENSG00000143889)

Protein

Protein identifiers

RNA-binding protein 20 — Q5T481 (reviewed: Q5T481)

Alternative names: RNA-binding motif protein 20

All UniProt accessions (1): Q5T481

UniProt curated annotations — full annotation on UniProt →

Function. RNA-binding protein that acts as a regulator of mRNA splicing of a subset of genes encoding key structural proteins involved in cardiac development, such as TTN (Titin), CACNA1C, CAMK2D or PDLIM5/ENH. Acts as a repressor of mRNA splicing: specifically binds the 5’UCUU-3’ motif that is predominantly found within intronic sequences of pre-mRNAs, leading to the exclusion of specific exons in target transcripts. RBM20-mediated exon skipping is hormone-dependent and is essential for TTN isoform transition in both cardiac and skeletal muscles. RBM20-mediated exon skipping of TTN provides substrates for the formation of circular RNA (circRNAs) from the TTN transcripts. Together with RBM24, promotes the expression of short isoforms of PDLIM5/ENH in cardiomyocytes.

Subunit / interactions. Associates with components of the U1 and U2 U1 small nuclear ribonucleoprotein complexes.

Subcellular location. Nucleus. Cytoplasm. Cytoplasmic ribonucleoprotein granule.

Tissue specificity. Mainly expressed in the heart. Also expressed in skeletal muscle tissues, ovary, small intestine and colon.

Post-translational modifications. Phosphorylation regulates the subcellular localization. Phosphorylation of Ser-635 and Ser-637 in the RS (arginine/serine-rich) region promotes nuclear localization of the protein. In contrast, phosphorylation of the C-terminal disordered region promotes localization to cytoplasmic ribonucleoprotein granules.

Disease relevance. Cardiomyopathy, dilated, 1DD (CMD1DD) [MIM:613172] A disorder characterized by ventricular dilation and impaired systolic function, resulting in congestive heart failure and arrhythmia. Patients are at risk of premature death. The disease is caused by variants affecting the gene represented in this entry. Left ventricular non-compaction (LVNCX): A form of left ventricular non-compaction, a cardiomyopathy due to myocardial morphogenesis arrest and characterized by a hypertrophic left ventricle, a severely thickened 2-layered myocardium, numerous prominent trabeculations, deep intertrabecular recesses, and poor systolic function. Clinical manifestations are variable. Some affected individuals experience no symptoms at all, others develop heart failure. In some cases, left ventricular non-compaction is associated with other congenital heart anomalies. The disease is caused by variants affecting the gene represented in this entry.

RefSeq proteins (1): NP_001127835* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000504	RRM_dom	Domain
IPR000690	Matrin/U1-C_Znf_C2H2	Domain
IPR003604	Matrin/U1-like-C_Znf_C2H2	Domain
IPR012677	Nucleotide-bd_a/b_plait_sf	Homologous_superfamily
IPR034790	RBM20_RRM	Domain
IPR035979	RBD_domain_sf	Homologous_superfamily

UniProt features (97 total): sequence variant 31, modified residue 22, mutagenesis site 20, compositionally biased region 14, region of interest 6, zinc finger region 2, chain 1, domain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q5T481-F1	48.52	0.08

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 (22): 498, 635, 637, 640, 642, 660, 679, 742, 801, 865, 876, 891, 893, 977, 980, 1013, 1048, 1060, 1080, 1115 …

Mutagenesis-validated functional residues (20):

Position	Phenotype
660	in a10 mutant; does not affect nuclear localization; when associated with a-679; a-685; a-742; a-876; a-980; a-1060; a-1
660	in d10 mutant; mimics phosphorylation; does not prevent nuclear localization but induces increased localization to cytop
679	in a10 mutant; does not affect nuclear localization; when associated with a-660; a-685; a-742; a-876; a-980; a-1060; a-1
679	in d10 mutant; mimics phosphorylation; does not prevent nuclear localization but induces increased localization to cytop
685	in a10 mutant; does not affect nuclear localization; when associated with a-660; a-679; a-742; a-876; a-980; a-1060; a-1
685	in d10 mutant; mimics phosphorylation; does not prevent nuclear localization but induces increased localization to cytop
742	in a10 mutant; does not affect nuclear localization; when associated with a-660; a-679; a-685; a-876; a-980; a-1060; a-1
742	in d10 mutant; mimics phosphorylation; does not prevent nuclear localization but induces increased localization to cytop
876	in a10 mutant; does not affect nuclear localization; when associated with a-660; a-679; a-685; a-742; a-980; a-1060; a-1
876	in d10 mutant; mimics phosphorylation; does not prevent nuclear localization but induces increased localization to cytop
980	in a10 mutant; does not affect nuclear localization; when associated with a-660; a-679; a-685; a-742; a-876; a-1060; a-1
980	in d10 mutant; mimics phosphorylation; does not prevent nuclear localization but induces increased localization to cytop
1060	in a10 mutant; does not affect nuclear localization; when associated with a-660; a-679; a-685; a-742; a-876; a-980; a-10
1060	in d10 mutant; mimics phosphorylation; does not prevent nuclear localization but induces increased localization to cytop
1080	in a10 mutant; does not affect nuclear localization; when associated with a-660; a-679; a-685; a-742; a-876; a-980; a-10
1080	in d10 mutant; mimics phosphorylation; does not prevent nuclear localization but induces increased localization to cytop
1120	in a10 mutant; does not affect nuclear localization; when associated with a-660; a-679; a-685; a-742; a-876; a-980; a-10
1120	in d10 mutant; mimics phosphorylation; does not prevent nuclear localization but induces increased localization to cytop
1210	in a10 mutant; does not affect nuclear localization; when associated with a-660; a-679; a-685; a-742; a-876; a-980; a-10
1210	in d10 mutant; mimics phosphorylation; does not prevent nuclear localization but induces increased localization to cytop

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 160 (showing top): GOBP_POSITIVE_REGULATION_OF_RNA_SPLICING, GOBP_ALTERNATIVE_MRNA_SPLICING_VIA_SPLICEOSOME, GOBP_NEGATIVE_REGULATION_OF_RNA_SPLICING, GOBP_ANIMAL_ORGAN_MORPHOGENESIS, GOBP_HEART_MORPHOGENESIS, GOBP_RNA_SPLICING, GOBP_HEART_FORMATION, GOBP_REGULATION_OF_MRNA_SPLICING_VIA_SPLICEOSOME, GRYDER_PAX3FOXO1_ENHANCERS_IN_TADS, GOBP_CIRCULATORY_SYSTEM_DEVELOPMENT, GOBP_REGULATION_OF_RNA_SPLICING, GRYDER_PAX3FOXO1_TOP_ENHANCERS, chr10q25, GOCC_RIBONUCLEOPROTEIN_GRANULE, GOMF_MRNA_BINDING

GO Biological Process (9): regulation of alternative mRNA splicing, via spliceosome (GO:0000381), positive regulation of RNA splicing (GO:0033120), regulation of RNA splicing (GO:0043484), regulation of mRNA splicing, via spliceosome (GO:0048024), negative regulation of mRNA splicing, via spliceosome (GO:0048025), heart formation (GO:0060914), spliceosome-depend formation of circular RNA (GO:0160091), mRNA processing (GO:0006397), RNA splicing (GO:0008380)

GO Molecular Function (8): RNA binding (GO:0003723), mRNA binding (GO:0003729), zinc ion binding (GO:0008270), pre-mRNA intronic binding (GO:0097157), splicing factor binding (GO:1990935), nucleic acid binding (GO:0003676), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (3): nucleus (GO:0005634), cytoplasmic ribonucleoprotein granule (GO:0036464), cytoplasm (GO:0005737)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
mRNA splicing, via spliceosome	3
regulation of mRNA splicing, via spliceosome	2
RNA splicing	2
regulation of RNA splicing	2
RNA processing	2
binding	2
alternative mRNA splicing, via spliceosome	1
positive regulation of gene expression	1
regulation of gene expression	1
regulation of primary metabolic process	1
regulation of mRNA processing	1
negative regulation of RNA splicing	1
negative regulation of mRNA processing	1
heart morphogenesis	1
animal organ formation	1
mRNA metabolic process	1
nucleic acid binding	1
RNA binding	1
transition metal ion binding	1
pre-mRNA binding	1
protein binding	1
cation binding	1
intracellular membrane-bounded organelle	1
cytoplasm	1
ribonucleoprotein granule	1
intracellular anatomical structure	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1162 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RBM20	TTN	Q8WZ42	911
RBM20	MYBPC3	Q14896	825
RBM20	LDB3	O75112	813
RBM20	ABCC9	O60706	805
RBM20	TNNT2	P45379	795
RBM20	MYH7	P12883	791
RBM20	SCN5A	Q14524	788
RBM20	CSRP3	P50461	777
RBM20	TCAP	O15273	768
RBM20	NEXN	Q0ZGT2	767
RBM20	TNNI3	P19429	762
RBM20	DSG2	Q14126	756
RBM20	ACTC1	P04270	750
RBM20	TPM1	P09493	743
RBM20	EYA4	O95677	739

IntAct

16 interactions, top by confidence:

A	B	Type	Score
RBM20	NTAQ1	psi-mi:“MI:0915”(physical association)	0.560
RBM20	LNX1	psi-mi:“MI:0915”(physical association)	0.560
EGLN3	FAM168B	psi-mi:“MI:0914”(association)	0.350
B9D2	RGPD3	psi-mi:“MI:2364”(proximity)	0.270
EYA2	CNOT1	psi-mi:“MI:2364”(proximity)	0.270
SOX7	NFIB	psi-mi:“MI:2364”(proximity)	0.270
GATA1	BCL9	psi-mi:“MI:2364”(proximity)	0.270
GATA3	BCL9	psi-mi:“MI:2364”(proximity)	0.270
KLF5	BCL9	psi-mi:“MI:2364”(proximity)	0.270
SP7	IGF2BP3	psi-mi:“MI:2364”(proximity)	0.270
FHIP1B	MED19	psi-mi:“MI:2364”(proximity)	0.270
NTAQ1	RBM20	psi-mi:“MI:0915”(physical association)	0.000
LNX1	RBM20	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (47): RBM20 (Proximity Label-MS), RBM20 (Proximity Label-MS), RBM20 (Affinity Capture-MS), RBM20 (Affinity Capture-RNA), RBM20 (Synthetic Lethality), RBM20 (Two-hybrid), RBM20 (Two-hybrid), RBM20 (Proximity Label-MS), RBM20 (Proximity Label-MS), RBM20 (Proximity Label-MS), RBM20 (Proximity Label-MS), RBM20 (Proximity Label-MS), RBM20 (Proximity Label-MS), RBM20 (Proximity Label-MS), RBM20 (Proximity Label-MS)

ESM2 similar proteins: A0A1I8MUL8, A0A1L8H8C0, A0A1L8HFX9, A2AG58, A2AJT9, B9UYK6, C5IY45, E9Q309, E9Q4F7, O94687, P0DW16, P31629, P61129, P78332, P97868, Q01613, Q08D57, Q09JY9, Q17QQ9, Q27IV2, Q2T9M9, Q498L0, Q4R731, Q53FD0, Q5F3P8, Q5JSZ5, Q5LJZ2, Q5PPL1, Q5R6I3, Q5SW79, Q5T481, Q5VT06, Q62504, Q66J90, Q6IMN6, Q6P9P0, Q6UB99, Q7Z6E9, Q865B7, Q8BYK8

Diamond homologs: E9PT37, O95758, P0DW16, P17225, P26599, Q00438, Q14966, Q29099, Q3UQS8, Q5T481, Q61464, Q66H20, Q8BHD7, Q8WN55, Q91Z31, Q9FGL9, Q9UKA9, Q9ULV3, Q9Z118, P40567, P43243, P43244, Q15233, Q5FVM4, Q5RFL9, Q6ICX4, Q8K310, Q99K48, Q9MAC5, O74452, F1LQ48, P14866, P25299, Q8R081, Q8WVV9, Q921F4

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

2390 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	71
Likely pathogenic	31
Uncertain significance	1052
Likely benign	762
Benign	63

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1345980	NM_001134363.3(RBM20):c.522del (p.Ser175fs)	Pathogenic
1399883	NM_001134363.3(RBM20):c.1990_2000del (p.Gly663_Pro664insTer)	Pathogenic
1493612	NM_001134363.3(RBM20):c.1590C>A (p.Cys530Ter)	Pathogenic
1703676	GRCh37/hg19 10q25.2(chr10:112516278-112591134)	Pathogenic
1934853	NM_001134363.3(RBM20):c.2566C>T (p.Gln856Ter)	Pathogenic
1965699	NM_001134363.3(RBM20):c.277C>T (p.Gln93Ter)	Pathogenic
1973169	NM_001134363.3(RBM20):c.1070C>A (p.Ser357Ter)	Pathogenic
1990792	NM_001134363.3(RBM20):c.514dup (p.Ser172fs)	Pathogenic
202056	NM_001134363.3(RBM20):c.1183C>T (p.Gln395Ter)	Pathogenic
2032341	NM_001134363.3(RBM20):c.1075_1076del (p.Arg359fs)	Pathogenic
2191372	NM_001134363.3(RBM20):c.1292_1293del (p.Val431fs)	Pathogenic
268	NM_001134363.3(RBM20):c.1913C>T (p.Pro638Leu)	Pathogenic
2691235	NM_001134363.3(RBM20):c.1907_1909delinsTTG (p.Arg636_Ser637delinsLeuGly)	Pathogenic
2693203	NM_001134363.3(RBM20):c.127C>T (p.Gln43Ter)	Pathogenic
2703181	NM_001134363.3(RBM20):c.1792C>T (p.Gln598Ter)	Pathogenic
2710290	NM_001134363.3(RBM20):c.1280G>A (p.Trp427Ter)	Pathogenic
2743573	NM_001134363.3(RBM20):c.956G>A (p.Trp319Ter)	Pathogenic
2751096	NM_001134363.3(RBM20):c.2060del (p.Glu687fs)	Pathogenic
2755881	NM_001134363.3(RBM20):c.1723C>T (p.Gln575Ter)	Pathogenic
2758114	NM_001134363.3(RBM20):c.3383dup (p.Lys1129fs)	Pathogenic
2759658	NM_001134363.3(RBM20):c.191del (p.Asn64fs)	Pathogenic
2815172	NM_001134363.3(RBM20):c.3244del (p.Leu1082fs)	Pathogenic
2815372	NM_001134363.3(RBM20):c.2042del (p.Tyr681fs)	Pathogenic
2859153	NM_001134363.3(RBM20):c.1401del (p.Ala468fs)	Pathogenic
2985989	NM_001134363.3(RBM20):c.2374dup (p.Glu792fs)	Pathogenic
3637496	NM_001134363.3(RBM20):c.2337del (p.Arg781fs)	Pathogenic
3640093	NM_001134363.3(RBM20):c.1294A>T (p.Lys432Ter)	Pathogenic
3641066	NM_001134363.3(RBM20):c.779_797dup (p.His266delinsGlnCysAspLeuTer)	Pathogenic
3654251	NM_001134363.3(RBM20):c.2287G>T (p.Glu763Ter)	Pathogenic
3654781	NM_001134363.3(RBM20):c.952C>T (p.Gln318Ter)	Pathogenic

SpliceAI

3770 predictions. Top by Δscore:

Variant	Effect	Δscore
10:110644646:G:GG	donor_gain	1.0000
10:110797506:A:AG	acceptor_gain	1.0000
10:110797507:G:GG	acceptor_gain	1.0000
10:110797507:GT:G	acceptor_gain	1.0000
10:110797507:GTTT:G	acceptor_gain	1.0000
10:110797646:CAGG:C	donor_loss	1.0000
10:110797649:G:GG	donor_gain	1.0000
10:110799782:CTTA:C	acceptor_loss	1.0000
10:110799783:TTA:T	acceptor_loss	1.0000
10:110799785:A:AG	acceptor_gain	1.0000
10:110799785:A:AT	acceptor_loss	1.0000
10:110799786:G:GG	acceptor_gain	1.0000
10:110799786:GGC:G	acceptor_gain	1.0000
10:110799786:GGCC:G	acceptor_gain	1.0000
10:110799914:TCAAG:T	donor_loss	1.0000
10:110799915:CAAG:C	donor_loss	1.0000
10:110799916:AAGG:A	donor_loss	1.0000
10:110799917:AGGTA:A	donor_loss	1.0000
10:110799919:G:GA	donor_loss	1.0000
10:110799920:T:G	donor_loss	1.0000
10:110820065:T:A	acceptor_gain	1.0000
10:110820069:A:AG	acceptor_gain	1.0000
10:110820069:AAG:A	acceptor_gain	1.0000
10:110820070:A:G	acceptor_gain	1.0000
10:110820174:AAGGT:A	donor_loss	1.0000
10:110820175:AGGTA:A	donor_loss	1.0000
10:110820178:T:G	donor_loss	1.0000
10:110821920:G:GT	donor_gain	1.0000
10:110821932:CCGGG:C	donor_loss	1.0000
10:110821934:GG:G	donor_gain	1.0000

AlphaMissense

8060 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:110780902:T:C	L98P	1.000
10:110780917:T:C	L103P	1.000
10:110797584:T:A	V535D	1.000
10:110797595:G:T	G539W	1.000
10:110797596:G:A	G539E	1.000
10:110797604:T:C	F542L	1.000
10:110797606:T:A	F542L	1.000
10:110797606:T:G	F542L	1.000
10:110797608:G:A	G543E	1.000
10:110797608:G:T	G543V	1.000
10:110797614:T:A	V545D	1.000
10:110797626:T:A	I549N	1.000
10:110797626:T:C	I549T	1.000
10:110797632:T:C	M551T	1.000
10:110799790:T:C	F558L	1.000
10:110799791:T:C	F558S	1.000
10:110799791:T:G	F558C	1.000
10:110799792:T:A	F558L	1.000
10:110799792:T:G	F558L	1.000
10:110799800:T:G	M561R	1.000
10:110799908:T:C	L597S	1.000
10:110780890:T:C	L94P	0.999
10:110780895:G:C	A96P	0.999
10:110781849:T:C	C414R	0.999
10:110797539:T:A	V520E	0.999
10:110797541:C:G	H521D	0.999
10:110797545:T:A	I522N	0.999
10:110797545:T:C	I522T	0.999
10:110797545:T:G	I522S	0.999
10:110797593:T:C	L538P	0.999

dbSNP variants (sampled 300 via entrez): RS1000003277 (10:110768031 C>T), RS1000017125 (10:110829084 T>C), RS1000028208 (10:110644082 T>C), RS1000036078 (10:110669337 A>G), RS1000081816 (10:110795217 A>G), RS1000096036 (10:110685181 T>C), RS1000101432 (10:110644209 A>C), RS1000120533 (10:110752611 T>A,C), RS1000137076 (10:110822745 G>A), RS1000148479 (10:110692914 TATC>T), RS1000148550 (10:110711028 C>G), RS1000150418 (10:110676451 T>A), RS1000159913 (10:110837432 C>T), RS1000196384 (10:110748215 T>C), RS1000206467 (10:110805998 C>T)

Disease associations

OMIM: gene MIM:613171 | disease phenotypes: MIM:613172, MIM:115200, MIM:192600, MIM:603829, MIM:115080, MIM:613426, MIM:194200

GenCC curated gene-disease

Disease	Classification	Inheritance
dilated cardiomyopathy 1DD	Definitive	Autosomal dominant
dilated cardiomyopathy	Definitive	Autosomal dominant
familial isolated dilated cardiomyopathy	Supportive	Autosomal dominant
hypertrophic cardiomyopathy	Limited	Autosomal dominant

ClinGen Gene-Disease Validity (2)

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

Disease	Classification	Inheritance
hypertrophic cardiomyopathy	Limited	AD
dilated cardiomyopathy	Definitive	AD

Mondo (17): dilated cardiomyopathy 1DD (MONDO:0013168), dilated cardiomyopathy (MONDO:0005021), cardiomyopathy (MONDO:0004994), familial dilated cardiomyopathy (MONDO:0016333), familial hypertrophic cardiomyopathy (MONDO:0024573), hypertrophic cardiomyopathy (MONDO:0005045), ventricular tachycardia (MONDO:0005477), ventricular fibrillation, paroxysmal familial, type 1 (MONDO:0011376), dilated cardiomyopathy 1A (MONDO:0007269), arrhythmogenic right ventricular cardiomyopathy (MONDO:0016587), cardiac conduction defect (MONDO:0100042), long QT syndrome (MONDO:0002442), dilated cardiomyopathy 1S (MONDO:0013262), cardiac arrest (MONDO:0000745), heart failure (MONDO:0005252)

Orphanet (13): Familial isolated dilated cardiomyopathy (Orphanet:154), Dilated cardiomyopathy (Orphanet:217604), Rare cardiomyopathy (Orphanet:167848), Familial dilated cardiomyopathy (Orphanet:217607), Rare familial disorder with hypertrophic cardiomyopathy (Orphanet:99739), Rare hypertrophic cardiomyopathy (Orphanet:217569), Idiopathic ventricular fibrillation (Orphanet:228140), Familial dilated cardiomyopathy with conduction defect due to LMNA mutation (Orphanet:300751), Inherited arrhythmogenic cardiomyopathy (Orphanet:247), Hereditary progressive cardiac conduction defect (Orphanet:871), Left ventricular noncompaction (Orphanet:54260), NON RARE IN EUROPE: Familial isolated hypertrophic cardiomyopathy (Orphanet:155), NON RARE IN EUROPE: Wolff-Parkinson-White syndrome (Orphanet:907)

HPO phenotypes

16 total (18 of 16 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000407	Sensorineural hearing impairment
HP:0000969	Edema
HP:0001635	Congestive heart failure
HP:0001644	Dilated cardiomyopathy
HP:0001645	Sudden cardiac death
HP:0001727	Thromboembolic stroke
HP:0002875	Exertional dyspnea
HP:0003198	Myopathy
HP:0003457	EMG abnormality
HP:0011462	Young adult onset
HP:0011675	Arrhythmia
HP:0012378	Fatigue
HP:0012764	Orthopnea
HP:0025169	Left ventricular systolic dysfunction
HP:0100578	Lipoatrophy
HP:0001639	Hypertrophic cardiomyopathy
HP:0001716	Wolff-Parkinson-White syndrome

GWAS associations

15 associations (top):

Study	Trait	p-value
GCST006061_111	Atrial fibrillation	2.000000e-07
GCST006414_4	Atrial fibrillation	1.000000e-08
GCST010105_177	Nicotine dependence symptom count	3.000000e-06
GCST010105_26	Nicotine dependence symptom count	3.000000e-06
GCST010680_2	Acute respiratory distress syndrome in sepsis	4.000000e-08
GCST010796_345	Electrocardiogram morphology (amplitude at temporal datapoints)	2.000000e-18
GCST010796_346	Electrocardiogram morphology (amplitude at temporal datapoints)	4.000000e-21
GCST010796_347	Electrocardiogram morphology (amplitude at temporal datapoints)	4.000000e-21
GCST010796_348	Electrocardiogram morphology (amplitude at temporal datapoints)	2.000000e-17
GCST010796_349	Electrocardiogram morphology (amplitude at temporal datapoints)	3.000000e-12
GCST010796_350	Electrocardiogram morphology (amplitude at temporal datapoints)	5.000000e-23
GCST010796_5271	Electrocardiogram morphology (amplitude at temporal datapoints)	5.000000e-09
GCST010796_5272	Electrocardiogram morphology (amplitude at temporal datapoints)	8.000000e-10
GCST010796_5273	Electrocardiogram morphology (amplitude at temporal datapoints)	4.000000e-11
GCST012488_3	L1-L4 bone mineral density x serum urate levels interaction	1.000000e-06

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0009262	nicotine dependence symptom count
EFO:0004327	electrocardiography
EFO:0004531	urate measurement
EFO:0007701	spine bone mineral density

MeSH disease descriptors (14)

Descriptor	Name	Tree numbers
D019571	Arrhythmogenic Right Ventricular Dysplasia	C14.240.400.145; C14.280.238.028; C14.280.400.145; C16.131.240.400.145
D009202	Cardiomyopathies	C14.280.238
D002311	Cardiomyopathy, Dilated	C14.280.195.160; C14.280.238.070; C16.320.488.750
D002312	Cardiomyopathy, Hypertrophic	C14.280.238.100; C14.280.484.048.750.070.160
D024741	Cardiomyopathy, Hypertrophic, Familial	C14.280.238.100.500; C14.280.484.048.750.070.160.500; C16.320.160
D006323	Heart Arrest	C14.280.383
D006333	Heart Failure	C14.280.434
D008133	Long QT Syndrome	C14.280.067.565; C14.280.123.625; C16.131.240.400.715; C23.550.073.547
D017180	Tachycardia, Ventricular	C14.280.067.845.940; C14.280.123.875.940; C23.550.073.845.940
D014927	Wolff-Parkinson-White Syndrome	C14.280.067.780.977; C14.280.123.750.977; C16.131.240.400.980
C567725	Cardiomyopathy, Dilated, 1DD (supp.)
C563538	Cardiomyopathy, Dilated, 1s (supp.)
C567851	Ventricular Fibrillation, Paroxysmal Familial, 1 (supp.)
C536231	familial dilated cardiomyopathy (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, increases expression	6
mercuric bromide	increases expression, affects cotreatment	2
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	increases expression, affects cotreatment	2
Nickel	decreases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Tretinoin	increases expression	2
FR900359	increases phosphorylation	1
methylmercuric chloride	increases expression	1
bisphenol A	increases methylation, affects cotreatment	1
ascorbate-2-phosphate	affects binding, affects cotreatment, increases expression	1
butyraldehyde	decreases expression	1
tobacco tar	decreases expression	1
benzo(e)pyrene	decreases methylation	1
aflatoxin B2	decreases methylation	1
4-(2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)-1-propenyl)benzoic acid	increases expression, affects cotreatment	1
CGP 52608	affects binding, increases reaction	1
entinostat	increases expression	1
Chir 99021	affects cotreatment, increases expression, affects binding	1
2-methyl-2H-pyrazole-3-carboxylic acid (2-methyl-4-o-tolylazophenyl)amide	increases expression, affects cotreatment	1
dorsomorphin	affects cotreatment, increases expression	1
XAV939	affects binding, affects cotreatment, increases expression	1
LDN 193189	affects cotreatment, increases expression	1
3-(4-pyridyl)-1H-indole	affects cotreatment, increases expression	1
Temozolomide	increases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Vorinostat	increases expression	1
Arsenicals	decreases expression	1
Ascorbic Acid	affects binding, affects cotreatment, increases expression	1
Benzo(a)pyrene	decreases methylation, increases methylation	1
Doxorubicin	decreases expression	1

Cellosaurus cell lines

5 cell lines: 5 induced pluripotent stem cell

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_A9YQ	UMGi144-A	Induced pluripotent stem cell	Male
CVCL_A9YR	UMGi144-A-1	Induced pluripotent stem cell	Male
CVCL_C1XK	UCSFi001-A-64	Induced pluripotent stem cell	Male
CVCL_C1XL	UCSFi001-A-65	Induced pluripotent stem cell	Male
CVCL_D6MD	UMGi255-A	Induced pluripotent stem cell	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00374465	PHASE4	UNKNOWN	Therapy With Verapamil or Carvedilol in Chronic Heart Failure
NCT01293903	PHASE4	COMPLETED	Study of Qiliqiangxin Capsule to Treat Dilated Cardiomyopathy
NCT01557140	PHASE4	COMPLETED	A Randomized Trial of Carvedilol in Chronic Chagas Cardiomyopathy
NCT01917149	PHASE4	COMPLETED	Supramaximal Titrated Inhibition of RAAS in Dilated Cardiomyopathy
NCT02115581	PHASE4	COMPLETED	Coenzyme Q10 Supplementation in Children With Idiopathic Dilated Cardiomyopathy
NCT06236022	PHASE4	RECRUITING	The Effects of Sirolimus in Patients With Dilated Cardiomyopathy Infected With Kaposi Sarcoma-associated Virus
NCT00879060	PHASE4	COMPLETED	Clinical and Therapeutic Implications of Fibrosis in Hypertrophic Cardiomyopathy
NCT01721967	PHASE4	COMPLETED	Ranolazine for the Treatment of Chest Pain in HCM Patients
NCT02948998	PHASE4	UNKNOWN	Evaluating the Effect of Spironolactone on Hypertrophic Cardiomyopathy
NCT03249272	PHASE4	TERMINATED	Microvascular Dysfunction in Nonischemic Cardiomyopathy: Insights From CMR Assessment of Coronary Flow Reserve
NCT04133532	PHASE4	COMPLETED	Effect of Metoprolol in Post Alcohol Septal Ablation Patients With Hypertrophic Cardiomyopathy
NCT06401343	PHASE4	RECRUITING	Use of SGLT2i in noHCM With HFpEF
NCT07103655	PHASE4	NOT_YET_RECRUITING	The Therapeutic Value of Mavacamten in Hypertrophic Cardiomyopathy With Mid-to-Apical Left Ventricular Obstruction
NCT07600177	PHASE4	RECRUITING	Mavacamten to Aficamten Transition in Patients With Obstructive Hypertrophic Cardiomyopathy
NCT00348530	PHASE4	UNKNOWN	Carvedilol Versus Verapamil in Chronic Heart Failure Secondary to Non-Ischemic Cardiomyopathy
NCT00371891	PHASE4	COMPLETED	Ontario Multidetector Computed Tomographic (MDCT) Coronary Angiography Study (OMCAS)
NCT00401856	PHASE4	COMPLETED	CMR to Assess Fibrosis in Cardiomyopathy Using Eplerenone
NCT00559338	PHASE4	COMPLETED	Impact of Nesiritide Infusion for Decompensated Heart Failure in the Emergency Department
NCT00606775	PHASE4	UNKNOWN	The Preventive Efficacy of Carvedilol on Cardiac Dysfunction in Duchenne Muscular Dystrophy
NCT00658203	PHASE4	COMPLETED	Clinical Evaluation on Advanced Resynchronization
NCT00701220	PHASE4	COMPLETED	Statin Therapy for Ischemic and Nonischemic Cardiomyopathy
NCT00800761	PHASE4	COMPLETED	Intensive Combined Chelation Therapy for Iron-Induced Cardiac Disease in Patients With Thalassemia Major
NCT00806390	PHASE4	TERMINATED	Prevention of Anthracycline or Trastuzumab Induced Cardiomyopathy by Metoprolol
NCT01006473	PHASE4	COMPLETED	Exercise Training in Chagas Cardiomyopathy
NCT01261065	PHASE4	COMPLETED	Mechanisms of Improvement With Beta-Blocker Treatment in Heart Failure
NCT01345188	PHASE4	COMPLETED	Ranolazine in Ischemic Cardiomyopathy
NCT01868841	PHASE4	COMPLETED	123-I mIBG (AdreView) Heart-to-Mediastinal (H/M) Ratio and SPECT Imaging on a Small Field of View-High Efficiency Cardiac SPECT System
NCT02640846	PHASE4	UNKNOWN	Effects of Levosimendan, Milrinone and Norepinephrine on Left and Right Ventricular Function in Septic Shock
NCT03228823	PHASE4	UNKNOWN	Prospective Assessment of Premature Ventricular Contractions Suppression in Cardiomyopathy(PAPS)
NCT04323852	PHASE4	COMPLETED	Can Vitamin D Reduce Heart Muscle Damage After Bypass Surgery?
NCT05034432	PHASE4	RECRUITING	The PIVATAL Study -Study of Ventricular Arrhythmia (VTA) Ablation in Left Ventricular Assist Device (LVAD) Patients
NCT05718128	PHASE4	RECRUITING	Clinical Study of Endocardial Myocardial Biopsy
NCT06964464	PHASE4	RECRUITING	Comparative Effectiveness of Carvedilol Versus Metoprolol Succinate in Heart Failure Patients With an Implantable Cardioverter Defibrillator
NCT00333827	PHASE3	COMPLETED	Cell Therapy In Dilated Cardiomyopathy
NCT00505154	PHASE3	COMPLETED	Effect of Rosuvastatin on Left Ventricular Remodeling
NCT01223703	PHASE3	COMPLETED	PUFAs and Left Ventricular Function in Heart Failure
NCT01583114	PHASE3	TERMINATED	PREclinical Mutation CARriers From Families With DIlated Cardiomyopathy and ACE Inhibitors
NCT01914081	PHASE3	UNKNOWN	Resveratrol: A Potential Anti- Remodeling Agent in Heart Failure, From Bench to Bedside
NCT02989181	PHASE3	UNKNOWN	Continues Positive Airway Pressure Treatment for Patients With Dilated Cardiomyopathy and Obstructive Sleep Apnea
NCT03439514	PHASE3	TERMINATED	A Study of ARRY-371797 (PF-07265803) in Patients With Symptomatic Dilated Cardiomyopathy Due to a Lamin A/C Gene Mutation