PRM3

Chr 16

protamine 3

NCBI Gene: 58531 ENSG00000178257 UniProt: Q9NNZ6

Protamine 3 replaces histones to compact DNA in sperm chromatin during spermatogenesis, creating a highly condensed and stable DNA complex. Mutations in PRM3 cause male infertility with autosomal recessive inheritance. This gene shows tolerance to loss-of-function variants, which is consistent with its specialized role in male reproductive function.

ResearchSummary from RefSeq, UniProt

Predicted to enable DNA binding activity. Predicted to be involved in flagellated sperm motility. Predicted to be located in chromosome and nucleus. Predicted to be part of nucleosome. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Jul 2025]

ResearchGenerating clinical summary…

GOFmechanismLOEUF 1.79

Clinical Summary— PRM3

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Population Constraint (gnomAD)

Constrained for loss-of-function variants (OE-LoF 0.00) despite low pLI — interpret in context.

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ClinVar Variants

23 VUS of 28 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?

1.79LOEUF

pLI 0.360

Z-score 0.78

OE 0.00 (0.00–1.79)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.04Z-score

OE missense 0.98 (0.80–1.22)

59 obs / 59.9 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.00 (0.00–1.79)

0≤0.351.4

Missense OE?0.98 (0.80–1.22)

0≤0.61.4

Synonymous OE?1.06

0≤1.21.6

LoF obs/exp: 0 / 0.7Missense obs/exp: 59 / 59.9Syn Z: -0.25

This gene — mechanism propensity

0.5476th %ile

GOF

0.76top 25%

LOF

0.4430th %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

28 submitted variants in ClinVar

ClinVar

Classification Summary

VUS23

Likely Benign2

Benign3

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Non-coding	Total
Pathogenic	0	0	0
Likely Pathogenic	0	0	0
VUS	23	0	23
Likely Benign	2	0	2
Benign	2	1	3
Total	27	1	28

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 PRM3 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →