TMEM108

transmembrane protein 108

Basic information

Region (hg38): 3:133038391-133397775

Links

ENSG00000144868 ∙ NCBI:66000 ∙ OMIM:617361 ∙ HGNC:28451 ∙ Uniprot:Q6UXF1 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the TMEM108 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TMEM108 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	2
missense			34	5		39
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	34	5	2

Variants in TMEM108

This is a list of pathogenic ClinVar variants found in the TMEM108 region.

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

Position	Type	Phenotype	Significance	ClinVar
3-133379767-T-C		not specified	Uncertain significance (Feb 21, 2024)
3-133379770-C-A		not specified	Uncertain significance (Jun 06, 2023)
3-133379778-G-A		not specified	Uncertain significance (Aug 22, 2023)
3-133379782-C-T		not specified	Uncertain significance (Jan 16, 2024)
3-133379796-A-G		not specified	Likely benign (Nov 09, 2022)
3-133379845-C-T		not specified	Uncertain significance (May 17, 2023)
3-133379898-G-A		not specified	Uncertain significance (Oct 20, 2024)
3-133379928-C-A		not specified	Uncertain significance (Mar 12, 2024)
3-133379971-G-A		not specified	Likely benign (Jan 17, 2024)
3-133380019-C-T		not specified	Uncertain significance (Jun 07, 2023)
3-133380027-G-A		not specified	Likely benign (Jan 06, 2023)
3-133380031-C-G		not specified	Uncertain significance (Nov 28, 2024)
3-133380067-C-T		not specified	Uncertain significance (Sep 20, 2023)
3-133380085-C-T		not specified	Uncertain significance (Jan 26, 2023)
3-133380106-G-A		not specified	Likely benign (Sep 08, 2024)
3-133380129-A-C		not specified	Uncertain significance (Aug 02, 2021)
3-133380151-C-T		not specified	Uncertain significance (Apr 16, 2024)
3-133380152-G-A			Benign (Dec 31, 2019)
3-133380159-A-G		not specified	Uncertain significance (Apr 28, 2022)
3-133380166-G-A		not specified	Uncertain significance (Nov 13, 2024)
3-133380181-C-A		not specified	Uncertain significance (Jun 18, 2021)
3-133380184-C-G		not specified	Uncertain significance (Mar 18, 2024)
3-133380189-A-G		not specified	Likely benign (Aug 01, 2024)
3-133380199-G-A		not specified	Uncertain significance (Dec 11, 2023)
3-133380205-C-T		not specified	Uncertain significance (Aug 20, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TMEM108	protein_coding	protein_coding	ENST00000321871	4	359402

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.996	0.00445	125706	0	23	125729	0.0000915

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.667	313	348	0.899	0.0000201	3646
Missense in Polyphen		93	114.4	0.81292		1222
Synonymous	-0.0810	145	144	1.01	0.00000862	1346
Loss of Function	3.71	0	16.0	0.00	9.33e-7	165

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000342	0.000305
Ashkenazi Jewish	0.000103	0.0000992
East Asian	0.00	0.00
Finnish	0.0000483	0.0000462
European (Non-Finnish)	0.000142	0.000132
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Transmembrane protein required for proper cognitive functions. Involved in the development of dentate gyrus (DG) neuron circuitry, is neccessary for AMPA receptors surface expression and proper excitatory postsynaptic currents of DG granule neurons. Regulates the organization and stability of the microtubule network of sensory neurons to allow axonal transport. Through the interaction with DST, mediates the docking of the dynein/dynactin motor complex to vesicle cargos for retrograde axonal transport. In hippocampal neurons, required for BDNF- dependent dendrite outgrowth. Cooperates with SH3GL2 and recruits the WAVE1 complex to facilitate actin-dependent BDNF:NTRK2 early endocytic trafficking and mediate signaling from early endosomes. {ECO:0000250|UniProtKB:Q8BHE4}.

Intolerance Scores

• loftool: 0.289
• rvis_EVS: -1.4
• rvis_percentile_EVS: 4.22

Haploinsufficiency Scores

• pHI: 0.388
• hipred: N
• hipred_score: 0.376
• ghis: 0.625

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.412

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Tmem108
• Phenotype: muscle phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); 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)

Gene ontology

• Biological process: receptor-mediated endocytosis;retrograde axonal transport;biological_process;dentate gyrus development;neuron projection development;positive regulation of neurotrophin TRK receptor signaling pathway;postsynaptic density organization;dendrite extension;modulation of excitatory postsynaptic potential;cellular response to brain-derived neurotrophic factor stimulus
• Cellular component: cellular_component;early endosome;endosome membrane;postsynaptic density;integral component of membrane;cell junction;axon;dendrite;somatodendritic compartment;postsynaptic membrane;axon cytoplasm
• Molecular function: molecular_function