TMEM126B

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

Basic information

Region (hg38): 11:85628573-85636539

Links

ENSG00000171204 ∙ NCBI:55863 ∙ OMIM:615533 ∙ HGNC:30883 ∙ Uniprot:Q8IUX1 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• mitochondrial complex I deficiency (Supportive), mode of inheritance: AR
• mitochondrial complex 1 deficiency, nuclear type 29 (Moderate), mode of inheritance: AR
• mitochondrial complex 1 deficiency, nuclear type 29 (Strong), mode of inheritance: AR
• mitochondrial disease (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Mitochondrial complex I deficiency, nuclear type 29	AR	Cardiovascular	Among other findings, individuals have been described with hypertrophic cardiomyopathy, and awareness may allow prompt diagnosis and management	Biochemical; Cardiovascular; Musculoskeletal; Neurologic	27374773; 27374774

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the TMEM126B gene.

• not provided (6 variants)
• Mitochondrial complex 1 deficiency, nuclear type 29 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TMEM126B 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				10		10
missense		1	29	6	2	38
nonsense	1					1
start loss						0
frameshift	5	3				8
inframe indel			1			1
splice donor/acceptor (+/-2bp)		1				1
splice region			1	3		4
non coding			2	12	5	19
Total	6	5	32	28	7

Highest pathogenic variant AF is 0.00000657

Variants in TMEM126B

This is a list of pathogenic ClinVar variants found in the TMEM126B region.

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

Position	Type	Phenotype	Significance	ClinVar
11-85628617-T-G		Inborn genetic diseases	Uncertain significance (Jun 17, 2024)
11-85628622-G-T			Likely benign (Jul 17, 2023)
11-85628626-G-C			Uncertain significance (Nov 06, 2021)
11-85628639-A-C			Uncertain significance (May 13, 2024)
11-85628641-C-T			Uncertain significance (Nov 11, 2021)
11-85628665-G-C			Uncertain significance (May 25, 2022)
11-85628672-C-T		Inborn genetic diseases	Uncertain significance (Apr 27, 2022)
11-85628677-G-A			Uncertain significance (Aug 12, 2022)
11-85628683-CCCAAG-C			Pathogenic (Nov 08, 2022)
11-85628706-G-A			Likely benign (Jan 17, 2024)
11-85629419-G-A			Likely benign (Jul 07, 2018)
11-85629547-C-T			Benign (Jun 16, 2018)
11-85631673-AT-A		TMEM126B-related disorder	Benign (Oct 05, 2023)
11-85631688-T-C			Benign/Likely benign (Jan 11, 2024)
11-85631689-T-A			Likely benign (Jul 08, 2022)
11-85631703-C-G			Uncertain significance (Oct 31, 2022)
11-85631730-C-T		TMEM126B-related disorder	Likely benign (Feb 21, 2024)
11-85631738-G-C			Uncertain significance (Feb 24, 2022)
11-85631741-GC-G		Mitochondrial complex 1 deficiency, nuclear type 29	Pathogenic (Apr 17, 2023)
11-85631766-T-C			Uncertain significance (Dec 10, 2021)
11-85631773-C-T			Likely benign (Nov 23, 2022)
11-85631774-A-C			Uncertain significance (Dec 01, 2022)
11-85631786-T-G		Inborn genetic diseases	Uncertain significance (Aug 13, 2021)
11-85631791-CT-C			Pathogenic (Jul 15, 2022)
11-85631793-A-G			Uncertain significance (Sep 07, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TMEM126B	protein_coding	protein_coding	ENST00000358867	5	7952

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.000186	0.486	124797	0	41	124838	0.000164

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.179	128	122	1.05	0.00000585	1502
Missense in Polyphen		22	29.521	0.74524		406
Synonymous	0.224	40	41.8	0.956	0.00000209	440
Loss of Function	0.338	6	6.96	0.862	2.87e-7	110

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00123	0.00115
Ashkenazi Jewish	0.000106	0.0000994
East Asian	0.00	0.00
Finnish	0.0000466	0.0000462
European (Non-Finnish)	0.0000282	0.0000265
Middle Eastern	0.00	0.00
South Asian	0.000649	0.000501
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Chaperone protein involved in the assembly of the mitochondrial NADH:ubiquinone oxidoreductase complex (complex I). Participates in constructing the membrane arm of complex I. {ECO:0000269|PubMed:24191001}.
• Pathway: Respiratory electron transport;The citric acid (TCA) cycle and respiratory electron transport;Metabolism;Complex I biogenesis;Respiratory electron transport, ATP synthesis by chemiosmotic coupling, and heat production by uncoupling proteins. (Consensus)

Recessive Scores

• pRec: 0.0730

Intolerance Scores

• loftool: 0.918
• rvis_EVS: 0.39
• rvis_percentile_EVS: 76.05

Haploinsufficiency Scores

• pHI: 0.0652
• hipred: N
• hipred_score: 0.112
• ghis: 0.529

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.0656

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Tmem126b

Gene ontology

• Biological process: biological_process;mitochondrial respiratory chain complex I assembly
• Cellular component: cellular_component;mitochondrion;mitochondrial inner membrane;integral component of membrane
• Molecular function: molecular_function;protein binding