TMEM108

Chr 3

transmembrane protein 108

Also known as: CT124, RTLN

NCBI Gene: 66000 ENSG00000144868 UniProt: Q6UXF1 OMIM: 617361

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]

OMIM Research

OMIM ResearchGenerating clinical summary…

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.19

LOEUF· LoF intol.

LOF

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.19LOEUF

pLI 0.996

Z-score 3.71

OE 0.00 (0.00–0.19)

Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?

0.67Z-score

OE missense 0.90 (0.82–0.99)

313 obs / 348.0 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.00 (0.00–0.19)

0≤0.351.4

Missense OE?0.90 (0.82–0.99)

0≤0.61.4

Synonymous OE?1.01

0≤1.21.6

LoF obs/exp: 0 / 16.0Missense obs/exp: 313 / 348.0Syn Z: -0.08

Background carrier burden — how many people carry a rare variant somewhere in TMEM108?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 67

723 rare PASS variants

Rare truncating (LoF)

1 in 6,800

38 rare PASS variants

Rare synonymous (reference)

1 in 200

309 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for TMEM108. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 84	1 in 11,000
South Asian	~43k	1 in 83	1 in 8,200
Remaining (unassigned)	~30k	1 in 54	≈ 1 in 15,000
European (Finnish)	~27k	1 in 570	1 in 680
Admixed American	~22k	1 in 54	1 in 2,700
African / African American	~21k	1 in 82	≈ 1 in 17,000
East Asian	~20k	1 in 89	≈ 1 in 20,000
Ashkenazi Jewish	~13k	1 in 160	none seen
Middle Eastern	~2,884	1 in 85	≈ 1 in 2,900

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 4 coding exons well covered in gnomAD exomes and genomes.? see exons ↓