PRM2

Chr 16

protamine 2

Also known as: CT94.2

NCBI Gene: 5620 ENSG00000122304 UniProt: P04554 OMIM: 182890

Protamine 2 substitutes for histones during spermatogenesis to compact sperm DNA into a highly condensed, stable complex. Mutations in PRM2 cause male infertility due to defective sperm chromatin condensation and are inherited in an autosomal recessive pattern. This gene shows tolerance to loss-of-function variants, consistent with its role in male fertility rather than essential developmental processes.

OMIM ResearchSummary from RefSeq, UniProt

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]

OMIM ResearchGenerating clinical summary…

DNmechanismLOEUF 1.39

Clinical Summary— PRM2

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Population Constraint (gnomAD)

Low constraint (pLI 0.02) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

27 VUS of 38 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?

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?

-0.98Z-score

OE missense 1.32 (1.12–1.57)

96 obs / 72.5 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.55 (0.25–1.39)

0≤0.351.4

Missense OE?1.32 (1.12–1.57)

0≤0.61.4

Synonymous OE?1.26

0≤1.21.6

LoF obs/exp: 3 / 5.5Missense obs/exp: 96 / 72.5Syn Z: -1.06

This gene — mechanism propensity

0.86top 5%

GOF

0.4184th %ile

LOF

0.1895th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction 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

38 submitted variants in ClinVar

ClinVar

Classification Summary

VUS27

Likely Benign4

Benign7

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	0	0	0
Likely Pathogenic	0	0	0	0	0
VUS	2	25	0	0	27
Likely Benign	0	3	0	1	4
Benign	0	2	5	0	7
Total	2	30	5	1	38

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

View in ClinVar →

17 pathogenic / likely-pathogenic (of 30) ClinVar copy-number / structural variants overlap PRM2 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →