PRMT2

Chr 21

protein arginine methyltransferase 2

Also known as: HRMT1L1

NCBI Gene: 3275 ENSG00000160310 UniProt: P55345 OMIM: 601961

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.

OMIM ResearchSummary from RefSeq, UniProt

Enables several functions, including nuclear receptor binding activity; peroxisome proliferator activated receptor binding activity; and protein homodimerization activity. Involved in negative regulation of inflammatory response; positive regulation of DNA-templated transcription; and regulation of intracellular signal transduction. Located in cytosol and nucleoplasm. [provided by Alliance of Genome Resources, Jun 2026]

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.65

LOEUF

GOF

Mechanism· predicted

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 OE?0.37 (0.23–0.65)

0≤0.351.4

Missense OE?0.68 (0.60–0.78)

0≤0.61.4

Synonymous OE?1.00

0≤1.21.6

LoF obs/exp: 9 / 24.1Missense obs/exp: 174 / 254.3Syn Z: -0.02

Background carrier burden — how many people carry a rare variant somewhere in PRMT2?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 93

740 rare PASS variants

Rare truncating (LoF)

1 in 1,500

117 rare PASS variants

Rare synonymous (reference)

1 in 89

277 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for PRMT2. 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 120	1 in 1,800
South Asian	~43k	1 in 54	1 in 2,100
Remaining (unassigned)	~30k	1 in 76	1 in 1,400
European (Finnish)	~27k	1 in 320	1 in 910
Admixed American	~22k	1 in 100	1 in 1,400
African / African American	~21k	1 in 70	1 in 1,100
East Asian	~20k	1 in 71	1 in 940
Ashkenazi Jewish	~13k	1 in 280	≈ 1 in 13,000
Middle Eastern	~2,884	1 in 59	≈ 1 in 670

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): 9 of 10 coding exons well covered in gnomAD exomes; exon 10 marginal. Genomes: 9 of 10 (exon 10 below).? see exons ↓