TNPO2

Chr 19AD

transportin 2

Also known as: IDDHISD, IPO3, KPNB2B, TRN2

TNPO2 encodes transportin-2, a nuclear import receptor that transports proteins containing nuclear localization signals from the cytoplasm into the nucleus through nuclear pores. Mutations cause intellectual developmental disorder with hypotonia, impaired speech, and dysmorphic facies with autosomal dominant inheritance. The gene is highly constrained against loss-of-function variants (pLI 1.0, LOEUF 0.129), indicating that functional copies are critical for normal development.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismADLOEUF 0.131 OMIM phenotype
Clinical SummaryTNPO2
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Dual constrained — LoF & missense intolerant
LoF Constraint
0.13LOEUF
pLI 1.000
Z-score 6.20
OE 0.04 (0.020.13)
Highly constrained

Among the most LoF-intolerant genes (~top 3%)

Missense Constraint
5.88Z-score
OE missense 0.28 (0.250.33)
152 obs / 534.3 exp
Constrained

Extremely missense-constrained (top ~0.01%)

Observed / Expected Ratios
LoF OE0.04 (0.020.13)
00.351.4
Missense OE0.28 (0.250.33)
00.61.4
Synonymous OE1.01
01.21.6
LoF obs/exp: 2 / 48.6Missense obs/exp: 152 / 534.3Syn Z: -0.15
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
limitedTNPO2-related intellectual disabilityOTHERAD
DN
0.3395th %ile
GOF
0.3689th %ile
LOF
0.68top 10%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · 1 literature citation · LOEUF 0.13

Literature Evidence

LOFStudies of another variant (W727C) suggested a loss-of-function effect.PMID:34314705

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

TNPO2 · 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

No active trials found for this gene.

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Clinical Literature
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