CPLANE1

Chr 5AR

ciliogenesis and planar polarity effector complex subunit 1

Also known as: C5orf42, Hug, JBTS17, OFD6

NCBI Gene: 65250 ENSG00000197603 UniProt: Q9H799 OMIM: 614571

This protein is involved in ciliogenesis and establishment of cell polarity required for directional cell migration, functioning as part of the CPLANE complex to recruit peripheral IFT-A proteins to basal bodies. Mutations cause Joubert syndrome 17 and orofaciodigital syndrome VI, both ciliopathies affecting the central nervous system and multiple organ systems. The inheritance pattern is autosomal recessive.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

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]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Joubert syndrome 17MIM #614615

Orofaciodigital syndrome VIMIM #277170

Clinical highlights

Gene–disease validity (ClinGen)

Definitive · Joubert syndrome 17 · AR · ClinGen 2022

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.67

LOEUF

LOF

Mechanism· G2P

📖

GeneReview available — CPLANE1

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.67LOEUF

pLI 0.000

Z-score 4.92

OE 0.56 (0.47–0.67)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

1.93Z-score

OE missense 0.86 (0.82–0.90)

1307 obs / 1518.9 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.56 (0.47–0.67)

0≤0.351.4

Missense OE?0.86 (0.82–0.90)

0≤0.61.4

Synonymous OE?0.93

0≤1.21.6

LoF obs/exp: 82 / 146.2Missense obs/exp: 1307 / 1518.9Syn Z: 1.27

Background carrier burden — how many people carry a rare variant somewhere in CPLANE1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 17

3,710 rare PASS variants

Rare truncating (LoF)

1 in 160

628 rare PASS variants

Rare synonymous (reference)

1 in 41

1,286 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for CPLANE1. 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 24	1 in 150
South Asian	~43k	1 in 14	1 in 210
Remaining (unassigned)	~30k	1 in 15	1 in 120
European (Finnish)	~27k	1 in 63	1 in 360
Admixed American	~22k	1 in 16	1 in 230
African / African American	~21k	1 in 17	1 in 130
East Asian	~20k	1 in 15	1 in 190
Ashkenazi Jewish	~13k	1 in 58	1 in 760
Middle Eastern	~2,884	1 in 17	1 in 310

Each group is summed over the variants that are rare in that group. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 28 of 52 coding exons well covered in gnomAD exomes; exon 45 poorly covered; exons 3, 4, 5, 6, 7 and 18 more marginal. Genomes: 51 of 52 (exon 40 below).? see exons ↓