RBM4

Chr 11

RNA binding motif protein 4

Also known as: LARK, RBM4A, ZCCHC21, ZCRB3A

NCBI Gene: 5936ENSG00000173933UniProt: Q9BWF3

Enables RNA binding activity and cyclin binding activity. Involved in several processes, including IRES-dependent translational initiation of linear mRNA; negative regulation of translation; and regulation of alternative mRNA splicing, via spliceosome. Located in cytoplasmic stress granule; cytosol; and nuclear lumen. [provided by Alliance of Genome Resources, Apr 2025]

31
ClinVar variants
10
Pathogenic / LP
0.99
pLI score· haploinsufficient
0
Active trials
Clinical Summary— RBM4
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.99). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
10 Pathogenic / Likely Pathogenic· 18 VUS of 31 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.22LOEUF
pLI 0.990
Z-score 3.45
OE 0.00 (0.00–0.22)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
1.98Z-score
OE missense 0.65 (0.57–0.74)
161 obs / 248.7 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.00 (0.00–0.22)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.65 (0.57–0.74)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.05
0≤1.21.6
LoF obs/exp: 0 / 13.9Missense obs/exp: 161 / 248.7Syn Z: -0.41

ClinVar Variant Classifications

31 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic8
Likely Pathogenic2
VUS18
Likely Benign1
8
Pathogenic
2
Likely Pathogenic
18
VUS
1
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
8
0
8
Likely Pathogenic
0
0
2
0
2
VUS
0
14
4
0
18
Likely Benign
0
0
0
1
1
Benign
0
0
0
0
0
Total01414129

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

RBM4 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
RBM4 dictates ESCC cell fate switch from cellular senescence to glutamine-addiction survival through inhibiting LKB1-AMPK-axis.
Chen L et al.·Signal Transduct Target Ther
2023
FUT8-mediated aberrant N-glycosylation of SEMA7A promotes head and neck squamous cell carcinoma progression.
Liu Z et al.·Int J Oral Sci
2024
The cryptic lncRNA-encoded microprotein TPM3P9 drives oncogenic RNA splicing and tumorigenesis.
Meng K et al.·Signal Transduct Target Ther
2025
RNA-binding motif 4 promotes angiogenesis in HCC by selectively activating VEGF-A expression.
Han H et al.·Pharmacol Res
2023
The splicing factor RBM4 controls apoptosis, proliferation, and migration to suppress tumor progression.
Wang Y et al.·Cancer Cell
2014
USP3 promotes proliferation of non-small cell lung cancer through regulating RBM4.
Liao XH et al.·Eur Rev Med Pharmacol Sci
2020
Functional pre- mRNA trans-splicing of coactivator CoAA and corepressor RBM4 during stem/progenitor cell differentiation.
Brooks YS et al.·J Biol Chem
2009Functional
MicroRNA-146a and RBM4 form a negative feed-forward loop that disrupts cytokine mRNA translation following TLR4 responses in human THP-1 monocytes.
Brudecki L et al.·Immunol Cell Biol
2013
Proteogenomic, Epigenetic, and Clinical Implications of Recurrent Aberrant Splice Variants in Clear Cell Renal Cell Carcinoma.
Chang A et al.·Eur Urol
2022
Alternative splicing of the human rhomboid family-1 gene RHBDF1 inhibits epidermal growth factor receptor activation.
Ji R et al.·J Biol Chem
2022
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools