TNNI2 (Troponin I2, Fast Skeletal Type)
Gene encoding the fast-twitch skeletal muscle troponin I isoform, critical for muscle contraction and implicated in distal arthrogryposis and nemaline myopathy.
Gene Information Card
| Symbol | TNNI2 |
|---|---|
| Full Name | Troponin I2, Fast Skeletal Type |
| Gene Type | Protein coding |
| Chromosomal Location | 11p15.5 |
| NCBI Gene ID | 7136 ncbi.nlm.nih.gov/gene/7136 |
| Ensembl ID | ENSG00000105856 |
| UniProt ID | P48788 |
| OMIM ID | 191043 |
| HGNC ID | 11946 |
| Aliases | AMCD2B, DA2B, FSSV, fsTnI, TNNI2 |
Description
TNNI2 encodes the fast-twitch skeletal muscle troponin I isoform (fsTnI), a component of the troponin complex that regulates calcium-mediated muscle contraction. Mutations in TNNI2 are associated with distal arthrogryposis type 2B (DA2B) and nemaline myopathy. The gene is located on chromosome 11p15.5 and is expressed predominantly in fast skeletal muscle fibers.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Distal Arthrogryposis Type 2B (DA2B) | Dominant-negative or gain-of-function mutations in TNNI2 disrupt troponin function, impairing muscle relaxation and leading to joint contractures. | ClinVar, OMIM |
| Nemaline Myopathy | Recessive or dominant mutations in TNNI2 cause abnormal thin filament assembly, resulting in nemaline rods and muscle weakness. | ClinVar, OMIM |
| Arthrogryposis Multiplex Congenita | Mutations in TNNI2 can contribute to multiple congenital joint contractures via altered calcium sensitivity. | ClinVar |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Skeletal muscle (fast fibers) | High | High |
| Heart | Low | Low |
| Brain | Not detected | Not detected |
| Liver | Not detected | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Skeletal muscle myotubes | High | Differentiated myotubes |
| Fibroblasts | Low | Basal expression |
| HEK293 | Not detected | No endogenous expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.310C>T (p.Arg104Trp) | Missense | Rare | Dominant-negative; associated with DA2B |
| c.359G>A (p.Arg120His) | Missense | Rare | Gain-of-function; increased calcium sensitivity; DA2B |
| c.424G>A (p.Glu142Lys) | Missense | Rare | Dominant-negative; nemaline myopathy |
| c.1A>G (p.Met1Val) | Start loss | Rare | Loss-of-function; recessive nemaline myopathy |
Mutation functional classification
Loss of Function (LOF)
Start codon mutations (e.g., p.Met1Val) lead to absent or truncated protein, causing recessive nemaline myopathy.
Gain of Function (GOF)
Missense mutations (e.g., p.Arg120His) increase calcium sensitivity of the troponin complex, leading to impaired muscle relaxation in DA2B.
Dominant Negative (DN)
Mutations such as p.Arg104Trp disrupt troponin I function and interfere with wild-type protein, causing DA2B.
View complete mutation data：
Gene Ontology (GO)
| • protein binding (GO:0005515) | • troponin complex (GO:0005862) |
| • muscle contraction (GO:0006936) | • calmodulin binding (GO:0005516) |
| • carbohydrate binding (GO:0030246) |
Pathways
• Troponin-mediated regulation of muscle contraction (Reactome: R-HSA-390522)
• Striated muscle contraction (Reactome: R-HSA-397014)
Protein Summary
Troponin I2 (fsTnI) is a 182-amino acid protein that inhibits actin-myosin interaction in fast skeletal muscle. It binds to troponin C and troponin T, forming the troponin complex. Calcium binding to troponin C induces a conformational change that relieves fsTnI inhibition, allowing muscle contraction. Mutations in TNNI2 alter calcium sensitivity or protein stability, leading to muscle diseases.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| TNNI2 Knockout HEK293 Cell Line | EDJ-KQ5952 | Human | 7136 | Details Get a Quote |
| TNNI2 Knockout HeLa Cell Line | EDJ-KQ54679 | Human | 7136 | Details Get a Quote |
| TNNI2 Knockout A-549 Cell Line | EDJ-KQ63162 | Human | 7136 | Details Get a Quote |
| TNNI2 Knockout HCT 116 Cell Line | EDJ-KQ71636 | Human | 7136 | Details Get a Quote |
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