RBM10

protein-coding

RNA binding motif protein 10, the group of Zinc fingers RANBP2-type |RNA binding motif containing|G-patch domain containing|Spliceosomal A complex

Gene summary

This gene encodes a nuclear protein that belongs to a family proteins that contain an RNA-binding motif. The encoded protein associates with hnRNP proteins and may be involved in regulating alternative splicing. Defects in this gene are the cause of the X-linked recessive disorder, TARP syndrome. Alternate splicing results in multiple transcript variants.[provided by RefSeq, Mar 2011]

MANE transcript

NM_005676.5

Inheritance

ClinVar variants

P:39U:217B:119

Top phenotype

TARP syndrome

gnomAD constraint

pLI —, LoF o/e 0.02

Max pathogenic AF

—

Genomic locus

chrX:47,145,221-47,186,813

External References & Databases

Ensembl (ENSG00000182872)

UniProt (P0DW28, P98175)

Transcript & Mutation Effects

hg38 • Region Span ~41.6 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

TARP syndromeDEFINITIVE

Inheritance Pattern: XL

Disease ID:MONDO:0010711

Submitter: ClinGen

*RBM10* was first reported in relation to X-linked recessive TARP syndrome in 2010 (Johnston et al., PMID: 20451169). Nine variants (nonsense, frameshift, splice site, and missense) that have been reported in 9 probands in 6 publications (PMIDs: 20451169, 24259342, 28577551, 30189253, 25186178, 21910224) are included in this curation. More evidence is available in the literature, but the maximum score for genetic evidence (12 pts.) has been reached. The mechanism of pathogenicity is loss of function. This gene-disease relationship is also supported by a study in mouse embryos that demonstrated an expression pattern that correlates well with the human malformations observed in TARP syndrome (PMID: 20451169). Additionally, a functional alteration study in a mouse embryonic mandibular cell line demonstrated a role for *RBM10* in the regulation of alternative splicing in mouse early development (PMID: 27763814). In summary, there is definitive evidence supporting the relationship between *RBM10* and X-linked recessive TARP syndrome. This has been repeatedly demonstrated in both the research and clinical diagnostic settings, and has been upheld over time. This classification was approved by the ClinGen Congenital Heart Disease GCEP on the meeting date October 7, 2025 (SOP Version 11).

TARP syndromeSTRONG

Inheritance Pattern: XL

Disease ID:MONDO:0010711

Submitter: PanelApp Australia

TARP syndromeSTRONG

Inheritance Pattern: XL

Disease ID:MONDO:0010711

Submitter: G2P

TARP syndromeSTRONG

Inheritance Pattern: XL

Disease ID:MONDO:0010711

Submitter: Labcorp Genetics (formerly Invitae)

Clinical Genomic Database (CGD)

TARP syndromeXL

Manifestation: Cardiovascular; Craniofacial; Musculoskeletal

Intervention: Cardiovascular

Rationale: The condition can include congenital cardiac anomalies, and awareness may allow early identification and management

Refs: 5410571; 20451169; 21910224; 24259342; 30189253

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to RBM10 variants in ClinVar

8 Conditions Cataloged

not providedTotal: 307

Inborn genetic diseasesTotal: 62

not specifiedTotal: 34

TARP syndromeTotal: 31

RBM10-related disorderTotal: 17

Neurodevelopmental delayTotal: 1

Hearing impairmentTotal: 1

Intellectual disabilityTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_005676.5. 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			12 clinvar	74 clinvar	20 clinvar	106
missense		4 clinvar	155 clinvar	20 clinvar	5 clinvar	184
nonsense	6 clinvar	4 clinvar	6 clinvar			16
start loss						0
frameshift	12 clinvar	4 clinvar	4 clinvar			20
splice donor/acceptor (+/-2bp)	3 clinvar	6 clinvar	40 clinvar			49
Total	21	18	217	94	25	375

Highest pathogenic variant AF is 9.1065806e-7

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 116 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_005676.5	RefSeq	NP_005667.2	23	MANE Select
ENST00000377604.8	Ensembl	ENSP00000366829.3	23	MANE Select
NM_001204466.2	RefSeq	NP_001191395.1	22	Standard
NM_001204467.2	RefSeq	NP_001191396.1	23	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

negative regulation of transcription by RNA polymerase II
regulation of alternative mRNA splicing, via spliceosome
mRNA processing
biological_process
negative regulation of cell population proliferation

Molecular Function

RNA binding
protein binding
miRNA binding
identical protein binding
metal ion binding

Cellular Component

nucleus
nuclear speck
protein-containing complex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000377604
Coding exons: 23
Length: 41945
Individuals with no LoFs: 123984
Homozygous LoFs: 0
Heterozygous LoFs: 1
Defined: 123985
p: 0.00000403

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	4.46	172	433	0.397	0.0000397	6004
Missense (PolyPhen)		46	141.72	0.32458		1901
Synonymous	0.242	176	180	0.977	0.0000171	1791
Loss of Function	5.94	1	43.1	0.0232	0.00000350	618

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.000012	0.0000089	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: May be involved in post-transcriptional processing, most probably in mRNA splicing. Binds to RNA homopolymers, with a preference for poly(G) and poly(U) and little for poly(A) (By similarity). May bind to specific miRNA hairpins (PubMed:28431233). {ECO:0000250|UniProtKB:P70501, ECO:0000269|PubMed:18315527, ECO:0000269|PubMed:28431233}.;
Disease: DISEASE: TARP syndrome (TARPS) [MIM:311900]: A disorder characterized by the Robin sequence (micrognathia, glossoptosis and cleft palate), talipes equinovarus and cardiac defects. {ECO:0000269|PubMed:20451169}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Recessive Scores

pRec: 0.157

Intolerance Scores

RVIS EVS: -0.67
RVIS percentile EVS: 15.76

Essentials

Essential (CRISPR): E
Essential (CRISPR2): S
Essential (gene trap): E
Indispensability pred.: E
Indispensability score: 0.687

Gene Damage Prediction

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