PRMT2

Chr 21

protein arginine methyltransferase 2

Also known as: HRMT1L1

NCBI Gene: 3275ENSG00000160310UniProt: P55345

The protein is an arginine methyltransferase that modifies histones and other proteins including STAT3, and acts as a coactivator for several nuclear receptors including androgen and estrogen receptors. PRMT2 is highly constrained against loss-of-function variants (LOEUF 0.653), but no definitive human disease has been established from mutations in this gene. While the gene has important cellular functions in transcriptional regulation and apoptosis, pathogenic variants causing pediatric neurological conditions have not been reliably documented.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
5
Pubs (1 yr)
93
P/LP submissions
0%
P/LP missense
0.65
LOEUF
GOF
Mechanism· predicted
Clinical Summary— PRMT2
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
87 unique Pathogenic / Likely Pathogenic· 65 VUS of 189 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
0.65LOEUF
pLI 0.002
Z-score 2.84
OE 0.37 (0.23–0.65)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
1.79Z-score
OE missense 0.68 (0.60–0.78)
174 obs / 254.3 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.37 (0.23–0.65)
0≤0.351.4
Missense OE0.68 (0.60–0.78)
0≤0.61.4
Synonymous OE1.00
0≤1.21.6
LoF obs/exp: 9 / 24.1Missense obs/exp: 174 / 254.3Syn Z: -0.02
DN
0.5967th %ile
GOF
0.6735th %ile
LOF
0.3163th %ile

The highest-scoring mechanism for this gene is gain-of-function.

GOFprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

189 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic79
Likely Pathogenic8
VUS65
Likely Benign8
Benign5
79
Pathogenic
8
Likely Pathogenic
65
VUS
8
Likely Benign
5
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
79
0
79
Likely Pathogenic
0
0
8
0
8
VUS
0
49
16
0
65
Likely Benign
0
4
2
2
8
Benign
0
1
3
1
5
Total0541083165

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

View in ClinVar →

Protein Context — Lollipop Plot

PRMT2 · protein map & ClinVar variants

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients