TMEM216

Chr 11AR

transmembrane protein 216

The encoded transmembrane protein is essential for primary ciliogenesis and embryonic development, facilitating Hedgehog signaling pathway activation and ensuring proper photoreceptor outer segment development. Autosomal recessive mutations cause Joubert syndrome 2, Meckel syndrome 2, and retinitis pigmentosa 98, representing a spectrum of ciliopathy disorders affecting the brain, kidneys, and retina. These conditions typically present in infancy to early childhood with characteristic cerebellar malformation (molar tooth sign), cystic kidney disease, and progressive vision loss.

OMIMResearchSummary from RefSeq, OMIM, UniProt
MultiplemechanismARLOEUF 1.373 OMIM phenotypes
Clinical SummaryTMEM216
🧬
Gene-Disease Validity (ClinGen)
ciliopathy · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
Some data sources returned errors (1)

ncbi: Error: NCBI fetch failed: 429 https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esearch.fcgi

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.37LOEUF
pLI 0.002
Z-score 0.88
OE 0.66 (0.341.37)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.49Z-score
OE missense 0.84 (0.691.04)
66 obs / 78.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.66 (0.341.37)
00.351.4
Missense OE0.84 (0.691.04)
00.61.4
Synonymous OE0.78
01.21.6
LoF obs/exp: 5 / 7.6Missense obs/exp: 66 / 78.2Syn Z: 1.00
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
strongTMEM216-related Joubert syndromeOTHERAR

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

DN
0.75top 25%
GOF
0.81top 10%
LOF
0.2288th %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

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

TMEM216 · 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 →