TMEM108

protein-coding

transmembrane protein 108

Gene summary

Predicted to be involved in several processes, including cellular response to brain-derived neurotrophic factor stimulus; nervous system development; and regulation of signal transduction. Predicted to be located in somatodendritic compartment. Predicted to be active in axon; endosome; and postsynaptic density. [provided by Alliance of Genome Resources, Jun 2026]

MANE transcript

NM_023943.4

Inheritance

—

ClinVar variants

U:99B:11

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0

Max pathogenic AF

—

Genomic locus

chr3:133,038,391-133,397,775

External References & Databases

Ensembl (ENSG00000144868)

Transcript & Mutation Effects

hg38 • Region Span ~359.4 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to TMEM108 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 103

not providedTotal: 3

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_023943.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			1 clinvar		2 clinvar	3
missense			94 clinvar	9 clinvar		103
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			3 clinvar			3
Total	0	0	99	9	2	110

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 45 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_023943.4	RefSeq	NP_076432.1	4	MANE Select
ENST00000321871.11	Ensembl	ENSP00000324651.6	4	MANE Select
NM_001136469.3	RefSeq	NP_001129941.1	4	Standard
NM_001282865.2	RefSeq	NP_001269794.1	3	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

receptor-mediated endocytosis
retrograde axonal transport
biological_process
dentate gyrus development
neuron projection development

Molecular Function

molecular_function

Cellular Component

cellular_component
early endosome
endosome membrane
postsynaptic density
integral component of membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000321871
Coding exons: 4
Length: 359402
Individuals with no LoFs: 125706
Homozygous LoFs: 0
Heterozygous LoFs: 23
Defined: 125729
p: 0.0000915

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.667	313	348	0.899	0.0000201	3646
Missense (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

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00028	0.00025	rare
Latino/Admixed American	0.000059	0.000058	rare
Ashkenazi Jewish	0.00010	0.000099	rare
East Asian	0	0.0	absent
Finnish	0.000048	0.000046	rare
European (Non-Finnish)	0.00014	0.00013	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

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

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.412

Gene Damage Prediction

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