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7 sources retrieved · Most recent: April 2026 · Index updated 15 days ago
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TMEM17
transmembrane protein 17
Chromosome 2 · 2p15
NCBI Gene: 200728Ensembl: ENSG00000186889.11HGNC: HGNC:26623UniProt: Q86X19
13PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
protein bindingnon-motile cilium assemblycilium assemblyciliary transition zoneprostate carcinomaprostate cancersmoking cessationsubstance-related disorder
✦AI Summary

TMEM17 is a transmembrane protein localized at the ciliary transition zone, serving as a critical structural component of the tectonic-like complex that acts as a diffusion barrier preventing inappropriate protein entry into primary cilia 1. The protein is essential for ciliogenesis and Sonic Hedgehog signaling, with loss-of-function variants causing disruption of TMEM17 stability, mislocalization, and compromised cilium composition 2. Biallelic TMEM17 variants are associated with a spectrum of ciliopathies ranging in severity from viable conditions—including orofaciodigital syndrome type 6 (OFD6) and Joubert syndrome (JS)—to fetal-lethal Meckel-Gruber syndrome (MGS) characterized by encephalocele, polycystic kidney dysplasia, and polydactyly 23. The gene was proposed as a ciliopathy candidate based on functional assays in patient-derived fibroblasts and C. elegans models demonstrating ciliogenesis defects 41. Notably, TMEM17 variants show potential genotype-phenotype correlation, with loss-of-function mutations underlying more severe manifestations 3. Beyond ciliary function, TMEM17 has been identified as a prostate cancer susceptibility locus in genome-wide association studies 5, and recent evidence suggests it promotes glioblastoma progression via PI3K/AKT pathway activation 6.

Sources cited
1
TMEM17 missense variants cause loss-of-function with destabilization, mislocalization, ciliary dysfunction, and abrogation of Sonic Hedgehog signaling; associated with OFD6, Joubert syndrome, and Meckel syndrome
PMID: 40841990
2
Biallelic TMEM17 variants cause Meckel-Gruber syndrome with severe prenatal phenotype; loss-of-function variants underlie most severe manifestations with genotype-phenotype correlation
PMID: 41054827
3
TMEM17 proposed as novel candidate ciliopathy gene supported by functional assays in patient-derived fibroblasts
PMID: 32055034
4
TMEM17 (Tmem17) is a CEP-290-dependent transition zone component essential for ciliary gate function; mutations cause OFD6 and ciliogenesis defects
PMID: 26982032
5
TMEM17 identified as prostate cancer susceptibility locus in Japanese population GWAS
PMID: 31562322
6
TMEM17 promotes glioblastoma progression by activating PI3K/AKT pathway and serves as independent prognostic factor
PMID: 39206901
Disease Associationsⓘ20
prostate carcinomaOpen Targets
0.53Moderate
prostate cancerOpen Targets
0.42Moderate
smoking cessationOpen Targets
0.41Moderate
substance-related disorderOpen Targets
0.40Weak
Urinary incontinenceOpen Targets
0.40Weak
nicotine dependenceOpen Targets
0.32Weak
type 2 diabetes mellitusOpen Targets
0.30Weak
neurodegenerative diseaseOpen Targets
0.29Weak
Abnormality of the skeletal systemOpen Targets
0.29Weak
mathematical abilityOpen Targets
0.27Weak
diabetic ketoacidosisOpen Targets
0.27Weak
amyotrophic lateral sclerosisOpen Targets
0.27Weak
Crohn's diseaseOpen Targets
0.27Weak
Meckel syndromeOpen Targets
0.26Weak
Abruptio PlacentaeOpen Targets
0.24Weak
schizophreniaOpen Targets
0.15Weak
pathological myopiaOpen Targets
0.13Weak
orofaciodigital syndrome IOpen Targets
0.12Weak
Joubert syndromeOpen Targets
0.11Weak
psoriasisOpen Targets
0.11Weak
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
CC2D2AProtein interaction97%NPHP1Protein interaction95%NPHP4Protein interaction88%B9D1Protein interaction88%TCTN2Protein interaction88%TCTN3Protein interaction82%
Tissue Expression6 tissues
Heart
100%
Ovary
86%
Brain
71%
Liver
61%
Bone Marrow
49%
Lung
36%
Gene Interaction Network
Click a node to explore
TMEM17CC2D2ANPHP1NPHP4B9D1TCTN2TCTN3
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted · UniProt Q86X19
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
1.29LoF Tolerant
pLIⓘ
0.01Tolerant
Observed/Expected LoF0.72 [0.42–1.29]
RankingsWhere TMEM17 stands among ~20K protein-coding genes
  • #16,335of 20,598
    Most Researched13
  • #13,644of 17,882
    Most Constrained (LOEUF)1.29
Genes detectedTMEM17
Sources retrieved7 papers
Response time—
📄 Sources
7▼
1
The morbid genome of ciliopathies: an update.
PMID: 32055034
Genet Med · 2020
1.00
2
Missense Variants in the Second Transmembrane Domain of TMEM17 Disrupt Its Stability and Function and Lead to a Wide Phenotypic Spectrum of Ciliopathies.
PMID: 40841990
Clin Genet · 2026
0.86
3
Biallelic Variants in TMEM17 Cause Meckel-Gruber Syndrome Within the Ciliopathy Spectrum.
PMID: 41054827
Clin Genet · 2025
0.71
4
12 new susceptibility loci for prostate cancer identified by genome-wide association study in Japanese population.
PMID: 31562322
Nat Commun · 2019
0.57
5
MKS5 and CEP290 Dependent Assembly Pathway of the Ciliary Transition Zone.
PMID: 26982032
PLoS Biol · 2016
0.43