TNPO2

protein-coding

transportin 2, the group of Armadillo like helical domain containing|Importins|Small nucleolar RNA protein coding host genes

Gene summary

Predicted to enable nuclear import signal receptor activity and nuclear localization sequence binding activity. Predicted to be involved in protein import into nucleus. Predicted to act upstream of or within negative regulation of muscle cell differentiation. Predicted to be located in nuclear lumen. Predicted to be active in cytoplasm and nucleus. Implicated in intellectual developmental disorder with hypotonia, impaired speech, and dysmorphic facies. [provided by Alliance of Genome Resources, Jun 2026]

MANE transcript

NM_001382241.1

Inheritance

ClinVar variants

P:20U:114B:41

Top phenotype

Intellectual developmental disorder with hypotonia, impaired speech, and dysmorphic facies

gnomAD constraint

pLI —, LoF o/e 0.04

Max pathogenic AF

—

Genomic locus

chr19:12,699,201-12,724,011

External References & Databases

Ensembl (ENSG00000105576)

Transcript & Mutation Effects

hg38 • Region Span ~24.8 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

intellectual developmental disorder with hypotonia, impaired speech, and dysmorphic faciesLIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0859197

Submitter: G2P

intellectual developmental disorder with hypotonia, impaired speech, and dysmorphic faciesSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0859197

Submitter: PanelApp Australia

intellectual developmental disorder with hypotonia, impaired speech, and dysmorphic faciesSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0859197

Submitter: Labcorp Genetics (formerly Invitae)

Clinical Genomic Database (CGD)

Intellectual developmental disorder with hypotonia, impaired speech, and dysmorphic faciesAD

Manifestation: Cardiovascular; Craniofacial; Musculoskeletal; Neurologic; Ophthalmologic; Renal

Intervention: Cardiovascular

Rationale: The condition can involve congenital cardiac anomalies, and awareness may allow early management

Refs: 34314705

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to TNPO2 variants in ClinVar

6 Conditions Cataloged

not providedTotal: 86

Inborn genetic diseasesTotal: 40

Intellectual developmental disorder with hypotonia, impaired speech, and dysmorphic faciesTotal: 31

not specifiedTotal: 23

TNPO2-related disorderTotal: 20

Neurodevelopmental disorderTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001382241.1. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			2 clinvar	28 clinvar	4 clinvar	34
missense	4 clinvar	14 clinvar	98 clinvar	8 clinvar	1 clinvar	125
nonsense			2 clinvar			2
start loss						0
frameshift			4 clinvar			4
splice donor/acceptor (+/-2bp)		2 clinvar	8 clinvar			10
Total	4	16	114	36	5	175

Highest pathogenic variant AF is 6.887451e-7

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 55 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001382241.1	RefSeq	NP_001369170.1	23	MANE Select
ENST00000425528.6	Ensembl	ENSP00000407182.1	23	MANE Select
NM_001136195.2	RefSeq	NP_001129667.1	23	Standard
NM_001136196.2	RefSeq	NP_001129668.1	23	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

NLS-bearing protein import into nucleus
ribosomal protein import into nucleus

Molecular Function

protein binding
nuclear localization sequence binding
Ran GTPase binding
protein transporter activity

Cellular Component

nucleus
cytoplasm
nuclear membrane
nuclear periphery

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000425528
Coding exons: 23
Length: 24818
Individuals with no LoFs: 124634
Homozygous LoFs: 0
Heterozygous LoFs: 5
Defined: 124639
p: 0.0000201

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	5.88	152	534	0.284	0.0000319	5910
Missense (PolyPhen)		11	100.52	0.10943		1193
Synonymous	-0.146	235	232	1.01	0.0000159	1714
Loss of Function	6.20	2	48.6	0.0411	0.00000226	545

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.000036	0.000035	rare
South Asian	0.000033	0.000033	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Probably functions in nuclear protein import as nuclear transport receptor. Serves as receptor for nuclear localization signals (NLS) in cargo substrates. Is thought to mediate docking of the importin/substrate complex to the nuclear pore complex (NPC) through binding to nucleoporin and the complex is subsequently translocated through the pore by an energy requiring, Ran-dependent mechanism. At the nucleoplasmic side of the NPC, Ran binds to the importin, the importin/substrate complex dissociates and importin is re-exported from the nucleus to the cytoplasm where GTP hydrolysis releases Ran. The directionality of nuclear import is thought to be conferred by an asymmetric distribution of the GTP- and GDP-bound forms of Ran between the cytoplasm and nucleus (By similarity). {ECO:0000250}.;

Recessive Scores

pRec: 0.113

Intolerance Scores

RVIS EVS: -0.93
RVIS percentile EVS: 9.55

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.747

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium