TRA2B

Chr 3AD

transformer 2 beta homolog

Also known as: Htra2-beta, PPP1R156, RAMELN, SFRS10, SRFS10, TRA2-BETA, TRAN2B

NCBI Gene: 6434ENSG00000136527UniProt: P62995

This gene encodes a nuclear protein which functions as sequence-specific serine/arginine splicing factor which plays a role in mRNA processing, splicing patterns, and gene expression. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2011]

Primary Disease Associations & Inheritance

Ramond-Elliott neurodevelopmental syndromeMIM #621421
AD
72
ClinVar variants
47
Pathogenic / LP
0.99
pLI score· haploinsufficient
0
Active trials
Clinical Summary— TRA2B
⚡
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
47 Pathogenic / Likely Pathogenic· 25 VUS of 72 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Dual constrained — LoF & missense intolerant
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.
0.25LOEUF
pLI 0.993
Z-score 3.86
OE 0.05 (0.02–0.25)
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.
3.50Z-score
OE missense 0.30 (0.24–0.37)
60 obs / 198.7 exp
Constrained

Highly missense-constrained (top ~0.1%)

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.0.05 (0.02–0.25)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.30 (0.24–0.37)
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.0.99
0≤1.21.6
LoF obs/exp: 1 / 19.3Missense obs/exp: 60 / 198.7Syn Z: 0.04

ClinVar Variant Classifications

72 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic41
Likely Pathogenic6
VUS25
41
Pathogenic
6
Likely Pathogenic
25
VUS

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
2
2
37
0
41
Likely Pathogenic
0
0
6
0
6
VUS
5
15
5
0
25
Likely Benign
0
0
0
0
0
Benign
0
0
0
0
0
Total71748072

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

View in ClinVar →

Protein Context — Lollipop Plot

TRA2B · protein map & ClinVar variants

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

Gene2Phenotype Curations

TRA2B-related neurodevelopmental syndrome

moderate
ADUndeterminedAltered Gene Product Structure
Dev. Disorders
G2P ↗
splice acceptor variantsplice donor variantstart loststop gained NMD triggering

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Ramond-Elliott neurodevelopmental syndrome

MIM #621421

Molecular basis of disorder known

Autosomal dominant
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
TRA2B Gene Splice Variant Linked to Seizures and Neurodevelopmental Delay: A Second Case Study.
Shatokhina O et al.·Int J Mol Sci
2023Case report
PRPF40A induces inclusion of exons in GC-rich regions important for human myeloid cell differentiation.
Tan CW et al.·Nucleic Acids Res
2024
Epigenetic-focused CRISPR/Cas9 screen identifies (absent, small, or homeotic)2-like protein (ASH2L) as a regulator of glioblastoma cell survival.
Ozyerli-Goknar E et al.·Cell Commun Signal
2023
Overexpression of the transcribed ultraconserved region Uc.138 accelerates colon cancer progression.
Kuwano Y et al.·Sci Rep
2021
Transformer 2β regulates the alternative splicing of cell cycle regulatory genes to promote the malignant phenotype of ovarian cancer.
Zhou T et al.·Oncol Res
2023
TRA2A Promoted Paclitaxel Resistance and Tumor Progression in Triple-Negative Breast Cancers via Regulating Alternative Splicing.
Liu T et al.·Mol Cancer Ther
2017
The cardiotonic steroid digitoxin regulates alternative splicing through depletion of the splicing factors SRSF3 and TRA2B.
Anderson ES et al.·RNA
2012
Regulation of Human Sortilin Alternative Splicing by Glucagon-like Peptide-1 (GLP1) in Adipocytes.
Lui A et al.·Int J Mol Sci
2023
CHK1-S, a splicing variant of CHK1, suppresses chronic myeloid leukemia.
Lei H et al.·Leuk Res
2025
Differential transcriptional and posttranslational transcription factor 7-like regulation among nondiabetic individuals and type 2 diabetic patients.
Pradas-Juni M et al.·Mol Endocrinol
2014Cohort
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