TMEM43

transmembrane protein 43

Basic information

Region (hg38): 3:14125014-14143680

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 (539 variants)
• Cardiomyopathy (370 variants)
• Cardiovascular phenotype (221 variants)
• not provided (194 variants)
• not specified (110 variants)
• Arrhythmogenic right ventricular cardiomyopathy (34 variants)
• Arrhythmogenic right ventricular dysplasia 5;Auditory neuropathy, autosomal dominant 3;Emery-Dreifuss muscular dystrophy 7, autosomal dominant (16 variants)
• Emery-Dreifuss muscular dystrophy 7, autosomal dominant;Arrhythmogenic right ventricular dysplasia 5;Auditory neuropathy, autosomal dominant 3 (15 variants)
• Xeroderma pigmentosum (12 variants)
• Arrhythmogenic right ventricular dysplasia 5;Emery-Dreifuss muscular dystrophy 7, autosomal dominant;Auditory neuropathy, autosomal dominant 3 (12 variants)
• Auditory neuropathy, autosomal dominant 3;Emery-Dreifuss muscular dystrophy 7, autosomal dominant;Arrhythmogenic right ventricular dysplasia 5 (6 variants)
• Emery-Dreifuss muscular dystrophy 7, autosomal dominant;Auditory neuropathy, autosomal dominant 3;Arrhythmogenic right ventricular dysplasia 5 (5 variants)
• Emery-Dreifuss muscular dystrophy 7, autosomal dominant (5 variants)
• Inborn genetic diseases (3 variants)
• TMEM43-related condition (3 variants)
• Auditory neuropathy, autosomal dominant 3 (2 variants)
• Sudden cardiac arrest (2 variants)
• Primary dilated cardiomyopathy (2 variants)
• Hypertrophic cardiomyopathy (2 variants)
• Benign scapuloperoneal muscular dystrophy with cardiomyopathy (1 variants)
• See cases (1 variants)
• Auditory neuropathy, autosomal dominant 3;Arrhythmogenic right ventricular dysplasia 5;Emery-Dreifuss muscular dystrophy 7, autosomal dominant (1 variants)
• Long QT syndrome (1 variants)
• Familial isolated arrhythmogenic right ventricular dysplasia (1 variants)
• Primary familial hypertrophic cardiomyopathy (1 variants)
• Left ventricular noncompaction cardiomyopathy (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.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			2	141	3	146
missense	1		331	14	4	350
nonsense			10			10
start loss			2			2
frameshift			28			28
inframe indel			4			4
splice donor/acceptor (+/-2bp)		1	12			13
splice region			21	33	1	55
non coding			18	90	35	143
Total	1	1	407	245	42

Variants in TMEM43

This is a list of pathogenic ClinVar variants found in the TMEM43 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
3-14125052-G-A			Benign (Mar 03, 2015)
3-14125163-G-A			Benign (Mar 03, 2015)
3-14125179-G-A		Cardiomyopathy	Uncertain significance (Feb 01, 2021)
3-14125181-G-C		Arrhythmogenic right ventricular dysplasia 5	Uncertain significance (Aug 15, 2023)
3-14125182-C-T		Arrhythmogenic right ventricular dysplasia 5	Uncertain significance (Oct 02, 2023)
3-14125183-C-T		not specified	Likely benign (Nov 02, 2017)
3-14125184-G-C		Arrhythmogenic right ventricular dysplasia 5	Uncertain significance (Sep 04, 2023)
3-14125188-C-T		Hypertrophic cardiomyopathy • Arrhythmogenic right ventricular dysplasia 5	Conflicting classifications of pathogenicity (Mar 09, 2023)
3-14125190-C-T		Cardiovascular phenotype • Cardiomyopathy • not specified • Arrhythmogenic right ventricular dysplasia 5	Conflicting classifications of pathogenicity (Dec 13, 2023)
3-14125191-A-G		Cardiomyopathy • Cardiovascular phenotype	Uncertain significance (Jan 05, 2022)
3-14125191-A-T		Cardiomyopathy • Arrhythmogenic right ventricular dysplasia 5 • Cardiovascular phenotype	Benign/Likely benign (Feb 15, 2024)
3-14125192-C-T		not specified • Cardiovascular phenotype • Cardiomyopathy • Arrhythmogenic right ventricular dysplasia 5	Conflicting classifications of pathogenicity (Dec 13, 2023)
3-14125194-A-G		Cardiovascular phenotype • Arrhythmogenic right ventricular dysplasia 5;Emery-Dreifuss muscular dystrophy 7, autosomal dominant;Auditory neuropathy, autosomal dominant 3 • Arrhythmogenic right ventricular dysplasia 5	Uncertain significance (Aug 15, 2023)
3-14125195-T-A		Cardiomyopathy	Uncertain significance (Mar 05, 2021)
3-14125196-G-A		Arrhythmogenic right ventricular dysplasia 5	Uncertain significance (Dec 13, 2023)
3-14125197-G-C		Arrhythmogenic right ventricular dysplasia 5	Uncertain significance (Jan 14, 2020)
3-14125199-C-A		Cardiomyopathy • Cardiovascular phenotype	Likely benign (Nov 27, 2022)
3-14125200-G-A		Arrhythmogenic right ventricular dysplasia 5	Uncertain significance (Nov 16, 2022)
3-14125201-C-G		Arrhythmogenic right ventricular dysplasia 5	Uncertain significance (Mar 09, 2023)
3-14125204-A-T		Arrhythmogenic right ventricular dysplasia 5	Uncertain significance (Jun 02, 2023)
3-14125206-G-A		Cardiomyopathy	Uncertain significance (Mar 06, 2020)
3-14125207-T-C		Arrhythmogenic right ventricular dysplasia 5	Uncertain significance (Jun 23, 2023)
3-14125209-A-C		Arrhythmogenic right ventricular dysplasia 5	Uncertain significance (Oct 03, 2021)
3-14125221-C-T		Arrhythmogenic right ventricular dysplasia 5	Likely benign (May 05, 2023)
3-14125239-G-C			Likely benign (Jun 26, 2018)

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