TNP2

Chr 16

transition protein 2

Also known as: TP2

NCBI Gene: 7142 ENSG00000178279 UniProt: Q05952 OMIM: 190232

TNP2 encodes transition nuclear protein 2, which facilitates the replacement of histones with protamines during sperm DNA condensation in developing spermatids. Mutations in TNP2 cause male infertility due to defective sperm production and function, inherited in an autosomal recessive pattern. The gene shows tolerance to loss-of-function variants (low constraint), consistent with its specialized role in male reproductive function.

OMIM ResearchSummary from RefSeq, UniProt

Predicted to enable zinc ion binding activity. Predicted to be involved in several processes, including penetration of zona pellucida; positive regulation of protein processing; and sperm DNA condensation. Predicted to act upstream of or within binding activity of sperm to zona pellucida and flagellated sperm motility. Predicted to be located in male germ cell nucleus. Predicted to be part of nucleosome. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

DNmechanismLOEUF 1.78

Clinical Summary— TNP2

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Population Constraint (gnomAD)

Low constraint (pLI 0.01) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

27 VUS of 32 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?

1.78LOEUF

pLI 0.009

Z-score 0.29

OE 0.84 (0.37–1.78)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.54Z-score

OE missense 1.17 (0.99–1.38)

99 obs / 84.9 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.84 (0.37–1.78)

0≤0.351.4

Missense OE?1.17 (0.99–1.38)

0≤0.61.4

Synonymous OE?1.49

0≤1.21.6

LoF obs/exp: 3 / 3.6Missense obs/exp: 99 / 84.9Syn Z: -2.07

This gene — mechanism propensity

0.76top 25%

GOF

0.4481th %ile

LOF

0.3260th %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

32 submitted variants in ClinVar

ClinVar

Classification Summary

VUS27

Likely Benign4

Benign1

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Synonymous	Total
Pathogenic	0	0	0
Likely Pathogenic	0	0	0
VUS	27	0	27
Likely Benign	3	1	4
Benign	0	1	1
Total	30	2	32

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

View in ClinVar →

17 pathogenic / likely-pathogenic (of 29) ClinVar copy-number / structural variants overlap TNP2 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →