TMEM218

Chr 11AR

transmembrane protein 218

Also known as: JBTS39

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.

Summary from RefSeq, OMIM, UniProt
Research Assistant →

Primary Disease Associations & Inheritance

Joubert syndrome 39MIM #619562
AR
0
Active trials
0
Pubs (1 yr)
68
P/LP submissions
6%
P/LP missense
1.83
LOEUF
Multiple*
Mechanism· predicted
Clinical SummaryTMEM218
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
64 unique Pathogenic / Likely Pathogenic· 23 VUS of 100 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.83LOEUF
pLI 0.002
Z-score 0.03
OE 0.99 (0.471.83)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.74Z-score
OE missense 0.74 (0.580.94)
47 obs / 63.7 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.99 (0.471.83)
00.351.4
Missense OE0.74 (0.580.94)
00.61.4
Synonymous OE1.03
01.21.6
LoF obs/exp: 4 / 4.1Missense obs/exp: 47 / 63.7Syn Z: -0.14
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
strongTMEM218-related ciliopathyOTHERAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.7327th %ile
GOF
0.93top 5%
LOF
0.2679th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

100 submitted variants in ClinVar

Classification Summary

Pathogenic60
Likely Pathogenic4
VUS23
Likely Benign3
60
Pathogenic
4
Likely Pathogenic
23
VUS
3
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
2
58
0
60
Likely Pathogenic
0
2
2
0
4
VUS
2
16
5
0
23
Likely Benign
0
1
0
2
3
Benign
0
0
0
0
0
Total22165290

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

TMEM218 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Key Publications
Landmark & review papers · by relevance
PubMed
Top 2 results · since 2015Search PubMed ↗