TMEM126A

transmembrane protein 126A, the group of Mitochondrial complex I assembly complex

Basic information

Region (hg38): 11:85647967-85656547

Links

ENSG00000171202 ∙ NCBI:84233 ∙ OMIM:612988 ∙ HGNC:25382 ∙ Uniprot:Q9H061 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• autosomal recessive optic atrophy, OPA7 type (Strong), mode of inheritance: AR
• autosomal recessive optic atrophy, OPA7 type (Supportive), mode of inheritance: AR
• autosomal recessive optic atrophy, OPA7 type (Limited), mode of inheritance: AR
• optic atrophy (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Optic atrophy 7 with or without auditory neuropathy	AR	General	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	Audiologic/Otolaryngologic; Neurologic; Ophthalmologic	19327736; 20301500; 20405026; 22815638
One patient has been described as presenting with moderate hypertrophic cardiomyopathy; A heterozygote has been described as manifesting with transient loss of vision following exercise (Uhthoff's sign of optic neuropathy)

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the TMEM126A gene.

• not provided (4 variants)
• Autosomal recessive optic atrophy, OPA7 type (1 variants)
• TMEM126A-related disorder (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TMEM126A 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	23		25
missense			67	4	1	72
nonsense	1					1
start loss						0
frameshift	3		6			9
inframe indel			2			2
splice donor/acceptor (+/-2bp)		2				2
splice region			2	5		7
non coding			3	22	9	34
Total	4	2	80	49	10

Highest pathogenic variant AF is 0.0000197

Variants in TMEM126A

This is a list of pathogenic ClinVar variants found in the TMEM126A region.

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

Position	Type	Phenotype	Significance	ClinVar
11-85647999-C-G		Autosomal recessive optic atrophy, OPA7 type	Uncertain significance (Jan 13, 2018)
11-85648028-T-A		Autosomal recessive optic atrophy, OPA7 type	Benign (Jul 02, 2019)
11-85648050-A-AGACC		not specified • Optic Atrophy, Recessive	Benign (Apr 10, 2018)
11-85648081-G-C		Autosomal recessive optic atrophy, OPA7 type	Uncertain significance (Jan 12, 2018)
11-85648085-A-G		not specified	Likely benign (Mar 28, 2017)
11-85648109-G-C		not specified	Likely benign (Dec 01, 2017)
11-85648169-A-C			Benign (Jul 02, 2019)
11-85648210-A-G			Benign (Jun 23, 2018)
11-85650225-AATG-A		not specified	Likely benign (Jul 27, 2017)
11-85650239-GT-G		not specified	Likely benign (Jan 22, 2018)
11-85650268-A-G			Uncertain significance (Dec 03, 2021)
11-85650273-CAAT-C			Uncertain significance (Jan 16, 2025)
11-85650275-A-G		Autosomal recessive optic atrophy, OPA7 type • not specified	Uncertain significance (May 07, 2024)
11-85650275-A-T		not specified	Uncertain significance (Jul 21, 2023)
11-85650291-A-G			Uncertain significance (Oct 15, 2024)
11-85650298-G-A			Uncertain significance (Nov 13, 2023)
11-85650300-T-A			Uncertain significance (Mar 16, 2022)
11-85650307-T-C			Uncertain significance (Nov 27, 2023)
11-85650308-C-A			Uncertain significance (Jan 06, 2025)
11-85650309-C-T		not specified	Likely benign (Dec 17, 2015)
11-85650317-T-G			Uncertain significance (Jul 25, 2022)
11-85650318-T-C			Likely benign (Oct 07, 2020)
11-85650322-C-G			Uncertain significance (Dec 19, 2021)
11-85650324-G-A			Likely benign (Feb 17, 2024)
11-85650328-C-G			Uncertain significance (Oct 11, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TMEM126A	protein_coding	protein_coding	ENST00000304511	4	8581

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00216	0.768	125709	0	38	125747	0.000151

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.567	118	102	1.16	0.00000484	1256
Missense in Polyphen		38	40.005	0.94989		487
Synonymous	0.0796	34	34.6	0.983	0.00000157	394
Loss of Function	0.953	5	7.89	0.634	3.97e-7	102

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000605	0.000604
Ashkenazi Jewish	0.00	0.00
East Asian	0.000435	0.000435
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.000106	0.000105
Middle Eastern	0.000435	0.000435
South Asian	0.0000980	0.0000980
Other	0.000164	0.000163

dbNSFP

Source: dbNSFP

• Pathway: Validated targets of C-MYC transcriptional repression (Consensus)

Intolerance Scores

• loftool: 0.830
• rvis_EVS: 0.46
• rvis_percentile_EVS: 78.46

Haploinsufficiency Scores

• pHI: 0.0421
• hipred: N
• hipred_score: 0.112
• ghis: 0.505

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.307

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Tmem126a

Gene ontology

• Biological process: optic nerve development
• Cellular component: mitochondrion;mitochondrial inner membrane;integral component of membrane
• Molecular function: molecular_function