TMEM218

Chr 11AR

transmembrane protein 218

Also known as: JBTS39

NCBI Gene: 219854 ENSG00000150433 UniProt: A2RU14 OMIM: 619285

The TMEM218 protein is predicted to localize to cilia and cellular membranes and may be involved in ciliary biogenesis or function. Mutations cause Joubert syndrome 39, a ciliopathy characterized by cerebellar vermis hypoplasia, developmental delay, and brainstem malformation that typically presents in infancy. This condition follows autosomal recessive inheritance.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

Predicted to be located in cilium and membrane. Implicated in Joubert syndrome. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Joubert syndrome 39MIM #619562

Clinical highlights

Gene–disease validity

Not independently assessedOMIM lists Joubert syndrome 39; no ClinGen or GenCC tier

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.83

LOEUF

Multiple*

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.83LOEUF

pLI 0.002

Z-score 0.03

OE 0.99 (0.47–1.83)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.74Z-score

OE missense 0.74 (0.58–0.94)

47 obs / 63.7 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.99 (0.47–1.83)

0≤0.351.4

Missense OE?0.74 (0.58–0.94)

0≤0.61.4

Synonymous OE?1.03

0≤1.21.6

LoF obs/exp: 4 / 4.1Missense obs/exp: 47 / 63.7Syn Z: -0.14

Background carrier burden — how many people carry a rare variant somewhere in TMEM218?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 380

147 rare PASS variants

Rare truncating (LoF)

1 in 6,200

26 rare PASS variants

Rare synonymous (reference)

1 in 1,100

74 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for TMEM218. 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 510	1 in 12,000
South Asian	~43k	1 in 160	1 in 7,000
Remaining (unassigned)	~30k	1 in 210	none seen
European (Finnish)	~27k	1 in 720	≈ 1 in 18,000
Admixed American	~22k	1 in 330	1 in 2,100
African / African American	~21k	1 in 260	≈ 1 in 4,400
East Asian	~20k	1 in 280	1 in 730
Ashkenazi Jewish	~13k	1 in 620	none seen
Middle Eastern	~2,884	1 in 270	≈ 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 ↓