RBM28

Chr 7AR

RNA binding motif protein 28

Also known as: ANES, NOP4

NCBI Gene: 55131ENSG00000106344UniProt: Q9NW13

The protein encoded by this gene is a specific nucleolar component of the spliceosomal small nuclear ribonucleoprotein (snRNP)complexes . It specifically associates with U1, U2, U4, U5, and U6 small nuclear RNAs (snRNAs), possibly coordinating their transition through the nucleolus. Mutation in this gene causes alopecia, progressive neurological defects, and endocrinopathy (ANE syndrome), a pleiotropic and clinically heterogeneous disorder. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2009]

Primary Disease Associations & Inheritance

?Alopecia, neurologic defects, and endocrinopathy syndromeMIM #612079
AR
168
ClinVar variants
28
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— RBM28
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
28 Pathogenic / Likely Pathogenic· 101 VUS of 168 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
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.
0.81LOEUF
pLI 0.000
Z-score 2.52
OE 0.58 (0.42–0.81)
Tolerant

Typical tolerance to LoF variation

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.
0.18Z-score
OE missense 0.97 (0.90–1.06)
388 obs / 398.1 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.0.58 (0.42–0.81)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.97 (0.90–1.06)
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.0.92
0≤1.21.6
LoF obs/exp: 25 / 42.8Missense obs/exp: 388 / 398.1Syn Z: 0.77

ClinVar Variant Classifications

168 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic26
Likely Pathogenic2
VUS101
Likely Benign30
Benign8
Conflicting1
26
Pathogenic
2
Likely Pathogenic
101
VUS
30
Likely Benign
8
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
2
1
23
0
26
Likely Pathogenic
1
1
0
0
2
VUS
2
93
5
1
101
Likely Benign
0
11
5
14
30
Benign
0
2
2
4
8
Conflicting
—1
Total51083519168

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

View in ClinVar →

Protein Context — Lollipop Plot

RBM28 · protein map & ClinVar variants

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

Gene2Phenotype Curations

RBM28-related alopecia, neurologic defects, and endocrinopathy syndrome

limited
ARUndeterminedUncertain
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

?Alopecia, neurologic defects, and endocrinopathy syndrome

MIM #612079

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
RNA-binding motif protein 28 enhances angiogenesis by improving STAT3 translation in hepatocellular carcinoma.
Han H et al.·Cancer Lett
2024
Biallelic splicing variants in the nucleolar 60S assembly factor RBM28 cause the ribosomopathy ANE syndrome.
Bryant CJ et al.·Proc Natl Acad Sci U S A
2021
Alopecia, neurological defects, and endocrinopathy syndrome caused by decreased expression of RBM28, a nucleolar protein associated with ribosome biogenesis.
Nousbeck J et al.·Am J Hum Genet
2008
ANE syndrome caused by mutated RBM28 gene: a novel etiology of combined pituitary hormone deficiency.
Spiegel R et al.·Eur J Endocrinol
2010
Comprehensive bioinformatics analysis of a RBM family-based prognostic signature with experiment validation in hepatocellular carcinoma.
Wu Z et al.·J Cancer Res Clin Oncol
2023
High throughput circRNA sequencing analysis reveals novel insights into the mechanism of nitidine chloride against hepatocellular carcinoma.
Xiong DD et al.·Cell Death Dis
2019Functional
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