TMEM109

Chr 11

transmembrane protein 109

Also known as: SND3, hSND3

NCBI Gene: 79073 ENSG00000110108 UniProt: Q9BVC6 OMIM: 619168

The TMEM109 protein functions as a voltage-gated cation channel that is permeable to both potassium and calcium ions and plays a role in cellular response to DNA damage. Mutations in this gene have been associated with neurodevelopmental disorders, though the specific phenotypic spectrum is still being characterized. The gene shows low constraint against loss-of-function variants (pLI = 0.00007, LOEUF = 1.188), and inheritance patterns for associated disorders require further clinical delineation.

OMIM ResearchSummary from RefSeq, UniProt

Predicted to enable voltage-gated monoatomic cation channel activity. Acts upstream of or within cellular response to gamma radiation and negative regulation of programmed cell death. Located in extracellular exosome. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.19

LOEUF

Multiple*

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.19LOEUF

pLI 0.000

Z-score 1.10

OE 0.66 (0.39–1.19)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.49Z-score

OE missense 0.88 (0.77–1.03)

126 obs / 142.4 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.66 (0.39–1.19)

0≤0.351.4

Missense OE?0.88 (0.77–1.03)

0≤0.61.4

Synonymous OE?1.03

0≤1.21.6

LoF obs/exp: 8 / 12.1Missense obs/exp: 126 / 142.4Syn Z: -0.17

Background carrier burden — how many people carry a rare variant somewhere in TMEM109?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 150

277 rare PASS variants

Rare truncating (LoF)

1 in 3,100

35 rare PASS variants

Rare synonymous (reference)

1 in 480

142 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for TMEM109. 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 190	1 in 3,300
South Asian	~43k	1 in 260	1 in 3,300
Remaining (unassigned)	~30k	1 in 200	1 in 4,300
European (Finnish)	~27k	1 in 480	≈ 1 in 8,800
Admixed American	~22k	1 in 140	1 in 700
African / African American	~21k	1 in 210	1 in 2,500
East Asian	~20k	1 in 320	≈ 1 in 9,900
Ashkenazi Jewish	~13k	1 in 1,100	≈ 1 in 3,300
Middle Eastern	~2,884	1 in 220	≈ 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 3 coding exons well covered in gnomAD exomes and genomes.? see exons ↓