TMEM106B

transmembrane protein 106B

Basic information

Region (hg38): 7:12211270-12243367

Links

ENSG00000106460 ∙ NCBI:54664 ∙ OMIM:613413 ∙ HGNC:22407 ∙ Uniprot:Q9NUM4 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• leukodystrophy, hypomyelinating, 16 (Limited), mode of inheritance: AD
• leukodystrophy, hypomyelinating, 16 (Strong), mode of inheritance: AD
• leukodystrophy, hypomyelinating, 16 (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Leukodystrophy, hypomyelinating 16	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	Neurologic	29186371; 29444210

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the TMEM106B gene.

• not_provided (72 variants)
• Inborn_genetic_diseases (27 variants)
• Leukodystrophy,_hypomyelinating,_16 (9 variants)
• TMEM106B-related_disorder (2 variants)
• Vascular_dementia (1 variants)
• See_cases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TMEM106B gene is commonly pathogenic or not. These statistics are base on transcript: NM_001134232.2. 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	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			2	12	3	17
missense	1	1	53	9	3	67
nonsense			1			1
start loss						0
frameshift			1			1
splice donor/acceptor (+/-2bp)			1			1
Total	1	1	58	21	6

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TMEM106B	protein_coding	protein_coding	ENST00000396667	7	32127

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.326	0.671	125722	0	7	125729	0.0000278

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.917	115	146	0.787	0.00000720	1794
Missense in Polyphen		31	60.649	0.51114		754
Synonymous	-0.617	57	51.4	1.11	0.00000259	517
Loss of Function	2.55	3	12.8	0.234	6.31e-7	175

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000914	0.0000906
Ashkenazi Jewish	0.0000992	0.0000992
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000353	0.0000352
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Involved in dendrite morphogenesis and maintenance by regulating lysosomal trafficking via its interaction with MAP6. May act by inhibiting retrograde transport of lysosomes along dendrites. Required for dendrite branching. {ECO:0000269|PubMed:23136129, ECO:0000269|PubMed:24357581}.
• Disease: DISEASE: Frontotemporal dementia and/or amyotrophic lateral sclerosis 1 (FTDALS1) [MIM:105550]: An autosomal dominant neurodegenerative disorder characterized by adult onset of frontotemporal dementia and/or amyotrophic lateral sclerosis in an affected individual. There is high intrafamilial variation. Frontotemporal dementia is characterized by frontal and temporal lobe atrophy associated with neuronal loss, gliosis, and dementia. Patients exhibit progressive changes in social, behavioral, and/or language function. Amyotrophic lateral sclerosis is characterized by the death of motor neurons in the brain, brainstem, and spinal cord, resulting in fatal paralysis. {ECO:0000269|PubMed:24385136, ECO:0000269|PubMed:24442578, ECO:0000303|PubMed:24488309}. Note=The gene represented in this entry acts as a disease modifier.

Recessive Scores

• pRec: 0.107

Intolerance Scores

• loftool: 0.519
• rvis_EVS: 0.33
• rvis_percentile_EVS: 73.27

Haploinsufficiency Scores

• pHI: 0.152
• hipred: Y
• hipred_score: 0.520
• ghis: 0.491

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.148

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Tmem106b
• Phenotype: skeleton phenotype; reproductive system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); homeostasis/metabolism phenotype; growth/size/body region phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan)

Gene ontology

• Biological process: lysosome organization;lysosomal transport;lysosome localization;dendrite morphogenesis;positive regulation of dendrite development
• Cellular component: lysosome;lysosomal membrane;endosome;integral component of membrane;late endosome membrane
• Molecular function: molecular_function;protein binding