TNP2

Chr 16

transition protein 2

ENSG00000178279UniProt: Q05952OMIM: 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.

OMIMResearchSummary from RefSeq, UniProt
DNmechanismLOEUF 1.78
Clinical Summary— TNP2
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.01) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
17 unique Pathogenic / Likely Pathogenic· 38 VUS of 61 total submissions
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Some data sources returned errors (1)

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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 OE0.84 (0.37–1.78)
0≤0.351.4
Missense OE1.17 (0.99–1.38)
0≤0.61.4
Synonymous OE1.49
0≤1.21.6
LoF obs/exp: 3 / 3.6Missense obs/exp: 99 / 84.9Syn Z: -2.07
DN
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

61 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic17
VUS38
Likely Benign5
Benign1
17
Pathogenic
38
VUS
5
Likely Benign
1
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
0
27
11
0
38
Likely Benign
0
3
1
1
5
Benign
0
0
0
1
1
Total03029261

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

View in ClinVar →

Protein Context — Lollipop Plot

TNP2 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 4 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients