TNNI2
protein-codingtroponin I2, fast skeletal type, the group of Troponin complex subunits
Gene summary
This gene encodes a fast-twitch skeletal muscle protein, a member of the troponin I gene family, and a component of the troponin complex including troponin T, troponin C and troponin I subunits. The troponin complex, along with tropomyosin, is responsible for the calcium-dependent regulation of striated muscle contraction. Mouse studies show that this component is also present in vascular smooth muscle and may play a role in regulation of smooth muscle function. In addition to muscle tissues, this protein is found in corneal epithelium, cartilage where it is an inhibitor of angiogenesis to inhibit tumor growth and metastasis, and mammary gland where it functions as a co-activator of estrogen receptor-related receptor alpha. This protein also suppresses tumor growth in human ovarian carcinoma. Mutations in this gene cause myopathy and distal arthrogryposis type 2B. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Mar 2009]
- AMCD2B
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~2.7 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AD
Disease ID:MONDO:0020820
Submitter: Labcorp Genetics (formerly Invitae)
Inheritance Pattern: AD
Disease ID:MONDO:0011128
Submitter: Orphanet
Inheritance Pattern: AD
Disease ID:MONDO:0020820
Submitter: PanelApp Australia
Inheritance Pattern: AD
Disease ID:MONDO:0015240
Submitter: Orphanet
Inheritance Pattern: AR
Disease ID:MONDO:0020820
Submitter: Ambry Genetics
Clinical Genomic Database (CGD)
Manifestation: Craniofacial; Musculoskeletal
Intervention: General
Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to TNNI2 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_003282.4. 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 | 21 | 2 | 25 | ||
| missense | 2 | 7 | 42 | 2 | 53 | |
| nonsense | 1 | 2 | 1 | 4 | ||
| start loss | 1 | 1 | ||||
| frameshift | 2 | 2 | ||||
| splice donor/acceptor (+/-2bp) | 1 | 2 | 3 | |||
| Total | 3 | 10 | 50 | 23 | 2 | 88 |
Highest pathogenic variant AF is 0.0000020522361
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_003273.1 | 7 | MANE Select | |
| Ensembl | ENSP00000371336.1 | 7 | MANE Select | |
| RefSeq | NP_001139301.1 | 7 | Standard | |
| RefSeq | NP_001139313.1 | 6 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| tnni2a.4 | Danio rerio | Structure: fast muscle cell Quality: disorganized abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Disopyramide Action Pathway
- Procainamide (Antiarrhythmic) Action Pathway
- Phenytoin (Antiarrhythmic) Action Pathway
- Fosphenytoin (Antiarrhythmic) Action Pathway
- Bopindolol Action Pathway
Biological Process
- skeletal muscle contraction
- muscle contraction
- regulation of muscle contraction
- muscle filament sliding
- positive regulation of transcription, DNA-templated
Molecular Function
- actin binding
- protein binding
- troponin T binding
Cellular Component
- nucleus
- cytosol
- troponin complex
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000381906
- Coding exons
- 7
- Length
- 2692
- Individuals with no LoFs
- 125589
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 7
- Defined
- 125596
- p
- 0.0000279
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.618 | 101 | 120 | 0.841 | 0.00000846 | 1203 |
| Missense (PolyPhen) | 33 | 43.378 | 0.76075 | 421 | ||
| Synonymous | -3.34 | 77 | 47.7 | 1.61 | 0.00000354 | 324 |
| Loss of Function | 2.06 | 3 | 10.1 | 0.298 | 4.28e-7 | 127 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.000029 | 0.000029 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000054 | 0.000053 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Troponin I is the inhibitory subunit of troponin, the thin filament regulatory complex which confers calcium-sensitivity to striated muscle actomyosin ATPase activity.;
- Disease
- DISEASE: Arthrogryposis, distal, 2B (DA2B) [MIM:601680]: A form of distal arthrogryposis, a disease characterized by congenital joint contractures that mainly involve two or more distal parts of the limbs, in the absence of a primary neurological or muscle disease. DA2B is characterized by contractures of the hands and feet, and a distinctive face characterized by prominent nasolabial folds, small mouth and downslanting palpebral fissures. {ECO:0000269|PubMed:12592607}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Recessive Scores
- pRec
- 0.182
Intolerance Scores
- LoFtool
- 0.128
- RVIS EVS
- -0.3
- RVIS percentile EVS
- 32.62
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.868
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Low | Medium |
| Primary Immunodeficiency | Medium | Low | Medium |
| Cancer | Medium | Medium | Medium |