RBM33

Chr 7

RNA binding motif protein 33

Also known as: PRR8

NCBI Gene: 155435 ENSG00000184863 UniProt: Q96EV2 OMIM: 620833

The protein is an RNA reader that recognizes N6-methyladenosine-containing RNAs and regulates RNA export from the nucleus and mRNA stability by promoting demethylation and recruiting export machinery. RBM33 is extremely intolerant to loss-of-function variation (pLI ~1.0, LOEUF 0.082), but no specific human disease has been definitively associated with mutations in this gene. Additional research is needed to establish clear genotype-phenotype correlations.

OMIM ResearchSummary from RefSeq, UniProt

Enables N6-methyladenosine-containing RNA reader activity and lncRNA binding activity. Involved in RNA export from nucleus and regulation of mRNA stability. Located in cytoplasm. Is active in nucleus. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.08

LOEUF· LoF intol.

LOF

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.08LOEUF

pLI 1.000

Z-score 6.92

OE 0.02 (0.01–0.08)

Highly constrained

Among the most LoF-intolerant genes (~top 3%)

Missense Constraint?

1.80Z-score

OE missense 0.80 (0.75–0.86)

535 obs / 665.6 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.02 (0.01–0.08)

0≤0.351.4

Missense OE?0.80 (0.75–0.86)

0≤0.61.4

Synonymous OE?1.13

0≤1.21.6

LoF obs/exp: 1 / 57.7Missense obs/exp: 535 / 665.6Syn Z: -1.66

Background carrier burden — how many people carry a rare variant somewhere in RBM33?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 42

1,544 rare PASS variants

Rare truncating (LoF)

1 in 780

92 rare PASS variants

Rare synonymous (reference)

1 in 68

743 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for RBM33. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 64	1 in 810
South Asian	~43k	1 in 38	1 in 810
Remaining (unassigned)	~30k	1 in 44	1 in 760
European (Finnish)	~27k	1 in 110	1 in 1,700
Admixed American	~22k	1 in 44	1 in 290
African / African American	~21k	1 in 52	1 in 600
East Asian	~20k	1 in 46	1 in 2,300
Ashkenazi Jewish	~13k	1 in 280	≈ 1 in 6,300
Middle Eastern	~2,884	1 in 36	1 in 430

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 14 of 18 coding exons well covered in gnomAD exomes; exons 1, 3, 4, 12 marginal. Genomes: 17 of 18 (exon 12 below).? see exons ↓