CPLANE1

ciliogenesis and planar polarity effector complex subunit 1, the group of Ciliogenesis and planar polarity effector complex subunits

Basic information

Region (hg38): 5:37106227-37249376

Previous symbols: [ "C5orf42" ]

Links

ENSG00000197603 ∙ NCBI:65250 ∙ OMIM:614571 ∙ HGNC:25801 ∙ Uniprot:Q9H799 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Joubert syndrome (Supportive), mode of inheritance: AR
• orofaciodigital syndrome type 6 (Supportive), mode of inheritance: AR
• Joubert syndrome 17 (Definitive), mode of inheritance: AR
• Joubert syndrome 17 (Definitive), mode of inheritance: AR
• Joubert syndrome 17 (Definitive), mode of inheritance: AR
• orofaciodigital syndrome type 6 (Definitive), mode of inheritance: Mitochondrial
• Joubert syndrome 17 (Strong), mode of inheritance: AR
• orofaciodigital syndrome type 6 (Strong), mode of inheritance: AR
• Joubert syndrome 17 (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Joubert syndrome 17; Orofaciodigital syndrome VI	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Craniofacial; Genitourinary; Musculoskeletal; Neurologic	5816874; 20301500; 22425360; 23169490; 24178751
The condition may involve multi-systemic manifestations, and surveillance and avoidance of certain medications (eg, nephrotoxic agents) may be beneficial

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CPLANE1 gene.

• not provided (1779 variants)
• Joubert syndrome 17 (282 variants)
• Orofaciodigital syndrome type 6;Joubert syndrome 17 (123 variants)
• not specified (107 variants)
• Joubert syndrome 17;Orofaciodigital syndrome type 6 (101 variants)
• Orofaciodigital syndrome type 6 (21 variants)
• Joubert syndrome and related disorders (17 variants)
• CPLANE1-related condition (13 variants)
• Familial aplasia of the vermis (13 variants)
• Joubert syndrome 1 (7 variants)
• See cases (7 variants)
• Inborn genetic diseases (4 variants)
• Jaundice;Global developmental delay (3 variants)
• Nephronophthisis (2 variants)
• - (2 variants)
• Median cleft lip and palate;Encephalocele;Dysgenesis of the cerebellar vermis;Polydactyly (2 variants)
• Global developmental delay;Typical Joubert syndrome MRI findings (1 variants)
• Joubert-orofaciodigital syndrome (1 variants)
• Cleft lip;Cleft palate;Astrocytoma (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CPLANE1 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			19	297	13	329
missense	6	15	781	35	10	847
nonsense	49	17	1	1		68
start loss	1					1
frameshift	64	25	5			94
inframe indel			14			14
splice donor/acceptor (+/-2bp)	11	27	3			41
splice region	1	6	48	50	6	111
non coding	2		34	211	83	330
Total	133	84	857	544	106

Highest pathogenic variant AF is 0.0000723

Variants in CPLANE1

This is a list of pathogenic ClinVar variants found in the CPLANE1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
5-37106233-G-T		Joubert syndrome 17	Uncertain significance (Jan 13, 2018)
5-37106284-T-C		Joubert syndrome 17	Uncertain significance (Jan 12, 2018)
5-37106705-G-A		Joubert syndrome 17	Uncertain significance (Jan 13, 2018)
5-37106713-T-C		Joubert syndrome 17	Benign (Jan 13, 2018)
5-37106730-T-G		Joubert syndrome 17	Uncertain significance (Jan 12, 2018)
5-37106769-A-G		Joubert syndrome 17	Uncertain significance (Jan 13, 2018)
5-37106789-T-C		Joubert syndrome 17	Uncertain significance (Jan 13, 2018)
5-37106795-T-C		Joubert syndrome 17	Likely benign (Jan 12, 2018)
5-37106888-A-T		Joubert syndrome 17	Uncertain significance (Jan 12, 2018)
5-37106941-A-C		Joubert syndrome 17	Uncertain significance (Jan 13, 2018)
5-37106960-C-T		Joubert syndrome 17	Uncertain significance (Jan 13, 2018)
5-37106961-G-A		Joubert syndrome 17	Benign (Jan 13, 2018)
5-37107084-A-G		Joubert syndrome 17	Conflicting classifications of pathogenicity (Jan 01, 2023)
5-37107131-T-A		Joubert syndrome 17	Uncertain significance (Jan 12, 2018)
5-37107137-C-T		Joubert syndrome 17	Uncertain significance (Jan 13, 2018)
5-37107161-T-G		Joubert syndrome 17	Benign (Jan 12, 2018)
5-37107175-C-T		Joubert syndrome 17	Uncertain significance (Mar 23, 2018)
5-37107179-G-C		Joubert syndrome 17	Likely benign (Jan 13, 2018)
5-37107194-C-T		Joubert syndrome 17	Uncertain significance (Jan 13, 2018)
5-37107206-A-G		Joubert syndrome 17	Likely benign (Jan 12, 2018)
5-37107508-C-A		Joubert syndrome 17	Uncertain significance (Jan 13, 2018)
5-37107562-G-A		Joubert syndrome 17	Uncertain significance (Jan 12, 2018)
5-37107584-C-A		not specified • Joubert syndrome 17	Conflicting classifications of pathogenicity (Jan 13, 2018)
5-37107588-A-G		not specified	Likely benign (-)
5-37107604-A-C			Uncertain significance (Feb 10, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CPLANE1	protein_coding	protein_coding	ENST00000425232	51	143201

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
5.88e-36	1.00	125501	0	246	125747	0.000979

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.93	1307	1.52e+3	0.860	0.0000750	20974
Missense in Polyphen		308	406.02	0.75859		5940
Synonymous	1.27	505	543	0.931	0.0000282	5974
Loss of Function	4.92	82	146	0.561	0.00000708	2047

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00163	0.00161
Ashkenazi Jewish	0.000401	0.000397
East Asian	0.000708	0.000707
Finnish	0.000520	0.000508
European (Non-Finnish)	0.00136	0.00128
Middle Eastern	0.000708	0.000707
South Asian	0.000821	0.000784
Other	0.00183	0.00163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Involved in ciliogenesis (PubMed:25877302). Involved in the establishment of cell polarity required for directional cell migration. Proposed to act in association with the CPLANE (ciliogenesis and planar polarity effectors) complex. Involved in recruitment of peripheral IFT-A proteins to basal bodies (By similarity). {ECO:0000250|UniProtKB:Q8CE72, ECO:0000305|PubMed:25877302}.
• Disease: DISEASE: Joubert syndrome 17 (JBTS17) [MIM:614615]: A disorder presenting with cerebellar ataxia, oculomotor apraxia, hypotonia, neonatal breathing abnormalities and psychomotor delay. Neuroradiologically, it is characterized by cerebellar vermian hypoplasia/aplasia, thickened and reoriented superior cerebellar peduncles, and an abnormally large interpeduncular fossa, giving the appearance of a molar tooth on transaxial slices (molar tooth sign). Additional variable features include retinal dystrophy and renal disease. {ECO:0000269|PubMed:22425360, ECO:0000269|PubMed:23012439, ECO:0000269|PubMed:26477546}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Orofaciodigital syndrome 6 (OFD6) [MIM:277170]: A form of orofaciodigital syndrome, a group of heterogeneous disorders characterized by malformations of the oral cavity, face and digits, and associated phenotypic abnormalities that lead to the delineation of various subtypes. OFD6 is characterized by metacarpal abnormalities with central polydactyly, cerebellar abnormalities including the molar tooth sign, tongue hamartomas, additional frenula, and upper lip notch. {ECO:0000269|PubMed:24178751, ECO:0000269|PubMed:25846457, ECO:0000269|PubMed:27081551}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Intolerance Scores

• rvis_EVS: -0.55
• rvis_percentile_EVS: 19.94

Haploinsufficiency Scores

• pHI: 0.110
• hipred: N
• hipred_score: 0.233
• ghis: 0.544

Mouse Genome Informatics

• Gene name: Cplane1
• Phenotype: homeostasis/metabolism phenotype; cellular phenotype; craniofacial phenotype; growth/size/body region phenotype; respiratory system phenotype; embryo phenotype; skeleton phenotype; renal/urinary system phenotype; digestive/alimentary phenotype; limbs/digits/tail phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span)

Gene ontology

• Biological process: establishment of planar polarity;kidney development;ventricular septum development;heart development;cerebellum development;embryonic digit morphogenesis;roof of mouth development;cilium assembly;coronary vasculature development;protein localization to ciliary transition zone
• Cellular component: integral component of membrane;ciliary transition zone