TMEM43

transmembrane protein 43

Basic information

Region (hg38): 3:14125015-14143680

Previous symbols: [ "ARVD5" ]

Links

ENSG00000170876

∙ NCBI:79188 ∙ OMIM:612048 ∙ HGNC:28472 ∙ Uniprot:Q9BTV4 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

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

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Arrhythmogenic right ventricular dysplasia 5; Emery-Dreifuss muscular dystrophy 7, autosomal dominant	AD	Cardiovascular	Individuals 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 transplantation	Audiologic/Otolaryngologic; Cardiovascular; Musculoskeletal	18313022; 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.

Effect	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
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

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TMEM43	protein_coding	protein_coding	ENST00000306077	12	18740

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.16e-12	0.0873	125638	1	109	125748	0.000437

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.422	262	243	1.08	0.0000150	2586
Missense in Polyphen		69	76.751	0.89902		835
Synonymous	-0.565	108	101	1.07	0.00000649	818
Loss of Function	0.539	20	22.8	0.878	0.00000125	249

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00211	0.00211
Ashkenazi Jewish	0.00	0.00
East Asian	0.000381	0.000381
Finnish	0.000185	0.000185
European (Non-Finnish)	0.000238	0.000229
Middle Eastern	0.000381	0.000381
South Asian	0.000196	0.000196
Other	0.000326	0.000326

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

	All	Recessive	Dominant
Mendelian	High	High	High
Primary Immunodeficiency	High	High	High
Cancer	High	High	High

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