CPLANE1

Chr 5AR

ciliogenesis and planar polarity effector complex subunit 1

Also known as: C5orf42, Hug, JBTS17, OFD6

NCBI Gene: 65250ENSG00000197603UniProt: Q9H799

The protein encoded by this gene has putative coiled-coil domains and may be a transmembrane protein. Defects in this gene are a cause of Joubert syndrome (JBTS). [provided by RefSeq, May 2012]

Primary Disease Associations & Inheritance

Joubert syndrome 17MIM #614615
AR
Orofaciodigital syndrome VIMIM #277170
AR
558
ClinVar variants
101
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— CPLANE1
🧬
Gene-Disease Validity (ClinGen)
Joubert syndrome 17 · 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.
📋
ClinVar Variants
101 Pathogenic / Likely Pathogenic· 235 VUS of 558 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.67LOEUF
pLI 0.000
Z-score 4.92
OE 0.56 (0.47–0.67)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
1.93Z-score
OE missense 0.86 (0.82–0.90)
1307 obs / 1518.9 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.56 (0.47–0.67)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.86 (0.82–0.90)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.93
0≤1.21.6
LoF obs/exp: 82 / 146.2Missense obs/exp: 1307 / 1518.9Syn Z: 1.27

ClinVar Variant Classifications

558 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic51
Likely Pathogenic50
VUS235
Likely Benign214
Benign4
Conflicting4
51
Pathogenic
50
Likely Pathogenic
235
VUS
214
Likely Benign
4
Benign
4
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
27
1
23
0
51
Likely Pathogenic
33
1
16
0
50
VUS
2
199
30
4
235
Likely Benign
0
5
79
130
214
Benign
0
0
4
0
4
Conflicting
—4
Total62206152134558

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

View in ClinVar →

Protein Context — Lollipop Plot

CPLANE1 · protein map & ClinVar variants

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

Gene2Phenotype Curations

CPLANE1-related Joubert syndrome

definitive
ARLoss Of FunctionAbsent Gene Product, Altered Gene Product Structure
Dev. DisordersEye
G2P ↗
splice acceptor variantframeshift variantstop gainedmissense variantwhole partial gene deletion

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Joubert syndrome 17

MIM #614615

Molecular basis of disorder known

Autosomal recessive

Orofaciodigital syndrome VI

MIM #277170

Molecular basis of disorder known

Autosomal recessive
📖
GeneReview available — CPLANE1
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Prenatal whole-exome sequencing for fetal structural anomalies: a retrospective analysis of 145 Chinese cases.
Qin Y et al.·BMC Med Genomics
2023Cohort
Clinical and genetic spectrum from a prototype of ciliopathy: Joubert syndrome.
Aksu Uzunhan T et al.·Clin Neurol Neurosurg
2023
Genetic Heterogeneity Underlying Phenotypes with Early-Onset Cerebellar Atrophy.
Martínez-Rubio D et al.·Int J Mol Sci
2023
Unveiling the Pathogenic Role of Novel CPLANE1 Compound Heterozygous Variants in Joubert Syndrome: Insights Into mRNA Stability and NMD Pathway.
Hong Z et al.·J Cell Mol Med
2025
Clinical heterogeneity and intrafamilial variability of Joubert syndrome in two siblings with CPLANE1 variants.
Zhang X et al.·Mol Genet Genomic Med
2021Case report
Exome sequencing and RNA analysis identify two novel CPLANE1 variants causing Joubert syndrome.
Fei H et al.·Mol Genet Genomic Med
2022
Biallelic intragenic tandem duplication of CPLANE1 in Joubert syndrome: A case report.
Martínez-Granero F et al.·Clin Genet
2023Case report
High Incidence of CPLANE1-Related Joubert Syndrome in the Products of Conceptions from Early Pregnancy Losses.
Bozhinovski G et al.·Balkan Med J
2024
Uncertain significance and molecular insights of CPLANE1 variants in prenatal diagnosis of Joubert syndrome: a case report.
Li SX et al.·BMC Pregnancy Childbirth
2024Case report
Novel compound heterozygous CPLANE1 variants identified in a Chinese family with Joubert syndrome.
Zhang C et al.·Int J Dev Neurosci
2021
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools