PRM1

Chr 16

protamine 1

Also known as: CT94.1, P1

NCBI Gene: 5619 ENSG00000175646 UniProt: P04553 OMIM: 182880

Protamine 1 substitutes for histones to compact sperm DNA into a highly condensed, stable complex during spermatogenesis. Mutations in PRM1 cause male infertility due to defective sperm chromatin condensation, inherited in an autosomal recessive pattern. The gene shows low constraint to loss-of-function variation, consistent with its tissue-specific expression limited to male reproductive cells.

OMIM ResearchSummary from RefSeq, UniProt

Predicted to enable DNA binding activity. Predicted to be involved in chromosome organization and spermatogenesis. Predicted to act upstream of or within nucleus organization and spermatid development. Located in cytosol and nucleoplasm. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

DNmechanismLOEUF 1.87

Clinical Summary— PRM1

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Population Constraint (gnomAD)

Low constraint (pLI 0.03) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

15 VUS of 17 total submissions

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Clinical Trials

1 active or recruiting trial — potential therapeutic options may be available

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?

1.87LOEUF

pLI 0.027

Z-score 0.07

OE 0.95 (0.35–1.87)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.54Z-score

OE missense 1.25 (0.98–1.60)

45 obs / 36.0 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.95 (0.35–1.87)

0≤0.351.4

Missense OE?1.25 (0.98–1.60)

0≤0.61.4

Synonymous OE?1.63

0≤1.21.6

LoF obs/exp: 2 / 2.1Missense obs/exp: 45 / 36.0Syn Z: -1.60

This gene — mechanism propensity

0.75top 25%

GOF

0.1699th %ile

LOF

0.1796th %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

17 submitted variants in ClinVar

ClinVar

Classification Summary

VUS15

Benign2

VUS

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	0	0
Likely Pathogenic	0	0	0	0
VUS	15	0	0	15
Likely Benign	0	0	0	0
Benign	0	1	1	2
Total	15	1	1	17

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 PRM1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →