PRM2

Chr 16

protamine 2

Also known as: CT94.2

NCBI Gene: 5620ENSG00000122304UniProt: P04554

Protamines substitute for histones in the chromatin of sperm during the haploid phase of spermatogenesis, and are the major DNA-binding proteins in the nucleus of sperm in many vertebrates. They package the sperm DNA into a highly condensed complex in a volume less than 5% of a somatic cell nucleus. Many mammalian species have only one protamine (protamine 1); however, a few species, including human and mouse, have two. This gene encodes protamine 2, which is cleaved to give rise to a family of protamine 2 peptides. Alternatively spliced transcript variants have also been found for this gene. [provided by RefSeq, Sep 2015]

67
ClinVar variants
17
Pathogenic / LP
0.02
pLI score
0
Active trials
Clinical Summary— PRM2
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.02) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
17 Pathogenic / Likely Pathogenic· 38 VUS of 67 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.
1.39LOEUF
pLI 0.025
Z-score 0.99
OE 0.55 (0.25–1.39)
Tolerant

Highly tolerant — LoF variants common in population

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.
-0.98Z-score
OE missense 1.32 (1.12–1.57)
96 obs / 72.5 exp
Tolerant

Tolerant to missense variation

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.0.55 (0.25–1.39)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.32 (1.12–1.57)
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.1.26
0≤1.21.6
LoF obs/exp: 3 / 5.5Missense obs/exp: 96 / 72.5Syn Z: -1.06

ClinVar Variant Classifications

67 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic17
VUS38
Likely Benign5
Benign7
17
Pathogenic
38
VUS
5
Likely Benign
7
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
17
0
17
Likely Pathogenic
0
0
0
0
0
VUS
1
25
12
0
38
Likely Benign
0
3
1
1
5
Benign
0
2
5
0
7
Total13035167

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

View in ClinVar →

Protein Context — Lollipop Plot

PRM2 · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
SPERM PROTAMINE P2; PRM2
MIM #182890 · *
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Impact of tobacco smoking in association with H2BFWT, PRM1 and PRM2 genes variants on male infertility.
Amor H et al.·Andrologia
2022
Protamine expression in somatic cells condenses chromatin and disrupts transcription without altering DNA methylation.
Puri D et al.·Epigenetics Chromatin
2025
Loss of the cleaved-protamine 2 domain leads to incomplete histone-to-protamine exchange and infertility in mice.
Arévalo L et al.·PLoS Genet
2022
Evaluation of cell-free seminal mRNA for the diagnosis of obstruction as the cause of azoospermia in infertile men: A prospective cohort study.
Goel R et al.·Andrologia
2022Cohort
PRM1 variant rs35576928 (Arg>Ser) is associated with defective spermatogenesis in the Chinese Han population.
He XJ et al.·Reprod Biomed Online
2012
TXNDC2 joint molecular marker is associated with testis pathology and is an accurate predictor of sperm retrieval.
Javadirad SM et al.·Sci Rep
2021
Novel genetic variants of sperm chromatin compaction regulators are associated with non-obstructive azoospermia in Indian men.
Dutta S et al.·Eur J Obstet Gynecol Reprod Biol
2025
Genetic variants associated with vein graft stenosis after coronary artery bypass grafting.
Shah AA et al.·Heart Surg Forum
2015
Effect of cryopreservation on human sperm messenger RNAs crucial for fertilization and early embryo development.
Valcarce DG et al.·Cryobiology
2013
Exploration of genetic diversity of Plasmodium vivax circumsporozoite protein (Pvcsp) and Plasmodium vivax sexual stage antigen (Pvs25) among North Indian isolates.
Kaur H et al.·Malar J
2019
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