TMEM43

transmembrane protein 43

Basic information

Region (hg38): 3:14125015-14143680

Previous symbols: [ "ARVD5" ]

Links

ENSG00000170876NCBI:79188OMIM:612048HGNC:28472Uniprot:Q9BTV4AlphaFoldGenCCjaxSfariGnomADPubmedClinVar

Phenotypes

GenCC

Source: genCC

  • arrhythmogenic right ventricular dysplasia 5 (Moderate), mode of inheritance: AD
  • autosomal dominant Emery-Dreifuss muscular dystrophy (Supportive), mode of inheritance: AD
  • auditory neuropathy, autosomal dominant 3 (Limited), mode of inheritance: AD
  • arrhythmogenic right ventricular dysplasia 5 (Definitive), mode of inheritance: AD
  • auditory neuropathy, autosomal dominant 3 (Limited), mode of inheritance: AD
  • arrhythmogenic right ventricular dysplasia 5 (Strong), mode of inheritance: AD
  • Emery-Dreifuss muscular dystrophy 7, autosomal dominant (Limited), mode of inheritance: AD
  • arrhythmogenic right ventricular dysplasia 5 (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

ConditionInheritanceIntervention CategoriesIntervention/Rationale Manifestation CategoriesReferences
Arrhythmogenic right ventricular dysplasia 5; Emery-Dreifuss muscular dystrophy 7, autosomal dominantADCardiovascularIndividuals may manifest with arrhythmias (which have been reported in multiple individuals with EDMD 7), syncope, cardiac arrest, and sudden death, and surveillance may allow early diagnosis of sequelae; Preventive measures (eg, with antiarrhythmic pharmacologic agents and/or ICD placement) may be beneficial, though some individuals may require heart transplantationAudiologic/Otolaryngologic; Cardiovascular; Musculoskeletal18313022; 20301310; 21391237; 34050020

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the TMEM43 gene.

  • Arrhythmogenic_right_ventricular_dysplasia_5 (803 variants)
  • Cardiomyopathy (391 variants)
  • Cardiovascular_phenotype (336 variants)
  • not_provided (200 variants)
  • not_specified (119 variants)
  • Emery-Dreifuss_muscular_dystrophy_7,_autosomal_dominant (64 variants)
  • Auditory_neuropathy,_autosomal_dominant_3 (61 variants)
  • TMEM43-related_disorder (26 variants)
  • Arrhythmogenic_right_ventricular_cardiomyopathy (8 variants)
  • Primary_dilated_cardiomyopathy (2 variants)
  • Sudden_cardiac_arrest (2 variants)
  • Hypertrophic_cardiomyopathy (1 variants)
  • Left_ventricular_noncompaction_cardiomyopathy (1 variants)
  • Emery-Dreifuss_muscular_dystrophy_2,_autosomal_dominant (1 variants)
  • Long_QT_syndrome (1 variants)
  • See_cases (1 variants)
  • Primary_familial_hypertrophic_cardiomyopathy (1 variants)
  • Familial_isolated_arrhythmogenic_right_ventricular_dysplasia (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TMEM43 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000024334.3. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

EffectPLPVUSLBBSum
synonymous
7
clinvar
196
clinvar
3
clinvar
206
missense
1
clinvar
2
clinvar
445
clinvar
61
clinvar
4
clinvar
513
nonsense
16
clinvar
16
start loss
3
3
frameshift
1
clinvar
42
clinvar
2
clinvar
45
splice donor/acceptor (+/-2bp)
1
clinvar
18
clinvar
19
Total 1 4 531 259 7

Highest pathogenic variant AF is 0.000010260704

Loading clinvar variants...

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
TMEM43protein_codingprotein_codingENST00000306077 1218740
pLI Probability
LOF Intolerant
pRec Probability
LOF Recessive
Individuals with
no LOFs
Individuals with
Homozygous LOFs
Individuals with
Heterozygous LOFs
Defined p
1.16e-120.087312563811091257480.000437
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense-0.4222622431.080.00001502586
Missense in Polyphen6976.7510.89902835
Synonymous-0.5651081011.070.00000649818
Loss of Function0.5392022.80.8780.00000125249

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.002110.00211
Ashkenazi Jewish0.000.00
East Asian0.0003810.000381
Finnish0.0001850.000185
European (Non-Finnish)0.0002380.000229
Middle Eastern0.0003810.000381
South Asian0.0001960.000196
Other0.0003260.000326

dbNSFP

Source: dbNSFP

Function
FUNCTION: May have an important role in maintaining nuclear envelope structure by organizing protein complexes at the inner nuclear membrane. Required for retaining emerin at the inner nuclear membrane (By similarity). {ECO:0000250}.;
Disease
DISEASE: Emery-Dreifuss muscular dystrophy 7, autosomal dominant (EDMD7) [MIM:614302]: A form of Emery-Dreifuss muscular dystrophy, a degenerative myopathy characterized by weakness and atrophy of muscle without involvement of the nervous system, early contractures of the elbows, Achilles tendons and spine, and cardiomyopathy associated with cardiac conduction defects. {ECO:0000269|PubMed:21391237}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Pathway
miR-targeted genes in adipocytes - TarBase;miR-targeted genes in epithelium - TarBase;miR-targeted genes in leukocytes - TarBase;miR-targeted genes in lymphocytes - TarBase;miR-targeted genes in muscle cell - TarBase;miR-targeted genes in squamous cell - TarBase (Consensus)

Recessive Scores

pRec
0.112

Intolerance Scores

loftool
0.856
rvis_EVS
0.6
rvis_percentile_EVS
82.83

Haploinsufficiency Scores

pHI
0.122
hipred
N
hipred_score
0.172
ghis
0.544

Essentials

essential_gene_CRISPR
N
essential_gene_CRISPR2
N
essential_gene_gene_trap
N
gene_indispensability_pred
E
gene_indispensability_score
0.933

Gene Damage Prediction

AllRecessiveDominant
MendelianHighHighHigh
Primary ImmunodeficiencyHighHighHigh
CancerHighHighHigh

Mouse Genome Informatics

Gene name
Tmem43
Phenotype
behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan);

Gene ontology

Biological process
nuclear membrane organization
Cellular component
integral component of nuclear inner membrane;endoplasmic reticulum lumen;Golgi apparatus
Molecular function
protein binding;protein self-association