TMEM126A (transmembrane protein 126A)

Gene

• Entrez ID: 84233
• Gene name: Transmembrane protein 126A
• Gene symbol: TMEM126A
• Synonyms (NCBI Gene): OPA7
• Chromosome: 11
• Chromosome location: 11q14.1
• Summary: The protein encoded by this gene is a mitochondrial membrane protein of unknown function. Defects in this gene are a cause of optic atrophy type 7 (OPA7). Two transcript variants encoding different isoforms have been found for this gene. [provided by RefS

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs36100288	T>G	Benign, uncertain-significance, conflicting-interpretations-of-pathogenicity	Coding sequence variant, 5 prime UTR variant, synonymous variant
rs121434508	C>T	Pathogenic	Coding sequence variant, stop gained, 5 prime UTR variant
rs146573578	G>A	Likely-benign, conflicting-interpretations-of-pathogenicity	Coding sequence variant, missense variant
rs1555208375	T>C	Likely-pathogenic	Splice donor variant, intron variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT031436	hsa-miR-16-5p	Proteomics	18668040

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0005739	Component	Mitochondrion	HTP	34800366
GO:0005739	Component	Mitochondrion	IBA
GO:0005739	Component	Mitochondrion	IDA	19327736
GO:0005739	Component	Mitochondrion	IEA
GO:0005743	Component	Mitochondrial inner membrane	IDA	38199007
GO:0005743	Component	Mitochondrial inner membrane	IEA
GO:0005743	Component	Mitochondrial inner membrane	TAS
GO:0005886	Component	Plasma membrane	IEA
GO:0016020	Component	Membrane	IEA
GO:0021554	Process	Optic nerve development	IMP	19327736
GO:0032979	Process	Protein insertion into mitochondrial inner membrane from matrix	IDA	38199007
GO:0032981	Process	Mitochondrial respiratory chain complex I assembly	IBA
GO:0032981	Process	Mitochondrial respiratory chain complex I assembly	IMP	33879611, 33882309, 38199007
GO:0034142	Process	Toll-like receptor 4 signaling pathway	IEA
GO:0141164	Process	Mitochondrial protein quality control	IDA	38199007

Other IDs

• MIM: 612988
• HGNC: 25382
• e!Ensembl: ENSG00000171202

Protein

• UniProt ID: Q9H061
• Protein name: Transmembrane protein 126A
• Protein function: Protein required for the cotranslational protein quality control in the inner membrane of the mitochondria (PubMed:38199007). Associates with newly synthesized polypeptides and may act as a chaperone that cooperates with OXA1L for the insertion
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF07114	TMEM126	11 → 190	Transmembrane protein 126	Family

• Tissue specificity: TISSUE SPECIFICITY: Strongly expressed in brain, cerebellum, skeletal muscle, testis. High expression also found in fetal brain, fetal retinal pigmentary epithelium, and fetal retina. Highly expressed in retinal ganglion cells. {ECO:0000269|PubMed:1932773
• Sequence:

  MENHKSNNKENITIVDISRKINQLPEAERNLLENGSVYVGLNAALCGLIANSLFRRILNV
  TKARIAAGLPMAGIPFLTTDLTYRCFVSFPLNTGDLDCETCTITRSGLTGLVIGGLYPVF
  LAIPVNGGLAARYQSALLPHKGNILSYWIRTSKPVFRKMLFPILLQTMFSAYLGSEQYKL
  LIKALQLSEPGKEIH

• Sequence length: 195

Associated diseases

Evidence Score:

• ★☆☆☆☆  Gene-disease association found in Text Mining only
• ★★☆☆☆  Found in Text Mining and Unknown/Other Associations
• ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources
• ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants)
• ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Causal
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession	Evidence Score
Autosomal recessive optic atrophy, OPA7 type	Pathogenic	rs121434508	RCV000000438	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
TMEM126A-related disorder	Pathogenic	rs121434508	RCV003914788	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
Acute myeloid leukemia	Benign; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
AUTOSOMAL RECESSIVE OPTIC ATROPHY TYPE 7	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Cholangiocarcinoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Clear cell carcinoma of kidney	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Colon adenocarcinoma	Benign; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Familial cancer of breast	Benign; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Gastric cancer	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Malignant lymphoma, large B-cell, diffuse	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Melanoma	Uncertain significance	ClinVar GWAS catalog	★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
MITOCHONDRIAL DISEASE	—	ClinGen, GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MITOCHONDRIAL DISEASES	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
OPTIC ATROPHY	—	Disgenet, GenCC Disgenet, GenCC	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
OPTIC ATROPHY 7	—	CTD, Disgenet CTD, Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
OPTIC ATROPHY 7 WITH OR WITHOUT AUDITORY NEUROPATHY	—	HPO	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Optic Atrophy, Recessive	Benign; Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
RETINITIS PIGMENTOSA 1	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Uterine carcinosarcoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Uterine corpus endometrial carcinoma	Benign; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Auditory neuropathy	Auditory Neuropathy	BEFREE	20405026		★☆☆☆☆ Found in Text Mining only
Auditory neuropathy	Auditory neuropathy	Pubtator	20405026	Associate	★☆☆☆☆ Found in Text Mining only
Auditory neuropathy spectrum disorder	Auditory neuropathy	BEFREE	20405026		★☆☆☆☆ Found in Text Mining only
Autosomal recessive optic atrophy, OPA7 type	Optic Atrophy	Orphanet			★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Breast Carcinoma	Breast Carcinoma	BEFREE	30393159		★☆☆☆☆ Found in Text Mining only
Disorder of eye	Disorder Of Eye	GENOMICS_ENGLAND_DG			★☆☆☆☆ Found in Text Mining only
Dyschromatopsia	Dyschromatopsia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Hereditary Motor And Sensory Neuropathy VI	Hereditary motor and sensory neuropathies	Pubtator	22815638	Associate	★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of breast	Breast Cancer	BEFREE	30393159		★☆☆☆☆ Found in Text Mining only
Mitochondrial complex I deficiency	Mitochondrial complex deficiency	Pubtator	33879611	Associate	★☆☆☆☆ Found in Text Mining only
Mitochondrial Diseases	Mitochondrial disease	Pubtator	33879611	Associate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Optic Atrophy	Optic Atrophy	BEFREE	19327736, 20405026, 22776096, 22815638, 26593267, 30961538		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Optic Atrophy	Optic atrophy	Pubtator	20405026, 22815638, 30961538, 33879611	Associate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Optic Atrophy	Optic Atrophy	HPO_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
OPTIC ATROPHY 7 (disorder)	Optic Atrophy	ORPHANET_DG	19327736, 22815638		★☆☆☆☆ Found in Text Mining only
OPTIC ATROPHY 7 (disorder)	Optic Atrophy	GENOMICS_ENGLAND_DG	31119195		★☆☆☆☆ Found in Text Mining only
OPTIC ATROPHY 7 (disorder)	Optic Atrophy	CTD_human_DG			★☆☆☆☆ Found in Text Mining only
OPTIC ATROPHY 7 (disorder)	Optic Atrophy	CLINVAR_DG			★☆☆☆☆ Found in Text Mining only
Optic Atrophy Autosomal Dominant	Optic atrophy	Pubtator	32855858	Associate	★☆☆☆☆ Found in Text Mining only
Optic Atrophy Hereditary Leber	Leber hereditary optic neuropathy	Pubtator	32855858	Associate	★☆☆☆☆ Found in Text Mining only