CEP41

centrosomal protein 41

Basic information

Region (hg38): 7:130393770-130442433

Previous symbols: [ "TSGA14" ]

Links

ENSG00000106477 ∙ NCBI:95681 ∙ OMIM:610523 ∙ HGNC:12370 ∙ Uniprot:Q9BYV8 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Joubert syndrome 15 (Definitive), mode of inheritance: AR
• Joubert syndrome (Supportive), mode of inheritance: AR
• Joubert syndrome with ocular defect (Supportive), mode of inheritance: AR
• Joubert syndrome 15 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Joubert syndrome 15	AR/Digenic	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	Gastrointestinal; Neurologic; Ophthalmologic; Pulmonary; Renal	20301500; 22246503
The condition may involve multi-systemic manifestations, including sequelae affecting the renal and hepatic systems, and surveillance and avoidance of certain medications (eg, nephrotoxic agents) may be beneficial; Digenic inheritance has been reported

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CEP41 gene.

• Joubert syndrome 15 (357 variants)
• not provided (62 variants)
• Inborn genetic diseases (22 variants)
• Familial aplasia of the vermis (13 variants)
• not specified (11 variants)
• Familial Autism Spectrum Disorder (7 variants)
• Joubert syndrome 9/15, digenic (2 variants)
• Joubert syndrome 12/15, digenic (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CEP41 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		1	1	45		47
missense			122	4		126
nonsense	1	1	3			5
start loss						0
frameshift	3	1	1			5
inframe indel			1			1
splice donor/acceptor (+/-2bp)	3	2				5
splice region			9	14		23
non coding	1		89	56	30	176
Total	8	5	217	105	30

Highest pathogenic variant AF is 0.0000131

Variants in CEP41

This is a list of pathogenic ClinVar variants found in the CEP41 region.

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

Position	Type	Phenotype	Significance	ClinVar
7-130393789-C-T		Joubert syndrome 15	Benign (Jan 13, 2018)
7-130393823-C-T		Joubert syndrome 15	Uncertain significance (Jan 13, 2018)
7-130393897-A-G		Joubert syndrome 15	Uncertain significance (Jan 12, 2018)
7-130393918-G-A		Joubert syndrome 15	Uncertain significance (Jan 12, 2018)
7-130393983-C-T		Joubert syndrome 15	Uncertain significance (Jan 13, 2018)
7-130394025-G-A		Joubert syndrome 15	Uncertain significance (Jan 13, 2018)
7-130394122-G-A		Joubert syndrome 15	Uncertain significance (Jan 12, 2018)
7-130394177-A-G		Joubert syndrome 15	Uncertain significance (Jan 12, 2018)
7-130394232-G-C		Joubert syndrome 15	Uncertain significance (Jan 13, 2018)
7-130394292-T-C		Joubert syndrome 15	Uncertain significance (Jan 12, 2018)
7-130394296-C-T		Joubert syndrome 15	Benign (Apr 27, 2017)
7-130394297-G-A		Joubert syndrome 15	Likely benign (Jan 13, 2018)
7-130394352-G-A		Joubert syndrome 15	Uncertain significance (Jan 13, 2018)
7-130394386-C-A		Joubert syndrome 15	Uncertain significance (Jan 13, 2018)
7-130394427-A-G		Joubert syndrome 15	Uncertain significance (Jan 12, 2018)
7-130394474-C-T		Joubert syndrome 15	Uncertain significance (Jan 12, 2018)
7-130394500-C-T		Joubert syndrome 15	Uncertain significance (Jan 13, 2018)
7-130394506-G-A		Joubert syndrome 15	Uncertain significance (Jan 13, 2018)
7-130394526-C-T		Joubert syndrome 15	Uncertain significance (Jan 13, 2018)
7-130394548-G-C		Joubert syndrome 15	Uncertain significance (Jan 12, 2018)
7-130394569-C-T		Joubert syndrome 15	Uncertain significance (Jan 12, 2018)
7-130394577-A-G		Joubert syndrome 15	Likely benign (Jan 12, 2018)
7-130394596-C-G		Joubert syndrome 15	Benign (Jan 12, 2018)
7-130394647-G-C		Joubert syndrome 15	Uncertain significance (Jan 13, 2018)
7-130394675-G-A		Joubert syndrome 15	Uncertain significance (Jan 12, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CEP41	protein_coding	protein_coding	ENST00000223208	11	48663

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00000359	0.948	125704	0	44	125748	0.000175

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.347	188	202	0.931	0.0000109	2423
Missense in Polyphen		36	48.299	0.74536		558
Synonymous	0.329	75	78.7	0.953	0.00000461	731
Loss of Function	1.83	12	21.1	0.569	0.00000109	252

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000812	0.000807
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000544	0.0000544
Finnish	0.000140	0.000139
European (Non-Finnish)	0.000115	0.000114
Middle Eastern	0.0000544	0.0000544
South Asian	0.000131	0.000131
Other	0.000490	0.000489

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Required during ciliogenesis for tubulin glutamylation in cilium. Probably acts by participating in the transport of TTLL6, a tubulin polyglutamylase, between the basal body and the cilium. {ECO:0000269|PubMed:22246503}.
• Disease: DISEASE: Joubert syndrome 15 (JBTS15) [MIM:614464]: An autosomal recessive 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, renal disease, liver fibrosis and polydactyly. {ECO:0000269|PubMed:22246503}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Note=Genetic variations in CEP41 may be associated with susceptibility to autism (PubMed:21438139). {ECO:0000269|PubMed:21438139}.
• Pathway: Regulation of PLK1 Activity at G2/M Transition;Recruitment of mitotic centrosome proteins and complexes;Loss of Nlp from mitotic centrosomes;Loss of proteins required for interphase microtubule organization from the centrosome;Centrosome maturation;AURKA Activation by TPX2;G2/M Transition;Mitotic G2-G2/M phases;Recruitment of NuMA to mitotic centrosomes;Mitotic Prometaphase;M Phase;Cell Cycle;Cell Cycle, Mitotic;Anchoring of the basal body to the plasma membrane;Cilium Assembly;Organelle biogenesis and maintenance (Consensus)

Recessive Scores

• pRec: 0.123

Intolerance Scores

• rvis_EVS: 0.55
• rvis_percentile_EVS: 81.48

Haploinsufficiency Scores

• pHI: 0.354
• hipred: N
• hipred_score: 0.289
• ghis: 0.479

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: H
• gene_indispensability_pred: N
• gene_indispensability_score: 0.114

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Cep41
• Phenotype: 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); 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); embryo 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)

Zebrafish Information Network

• Gene name: cep41
• Affected structure: otolith
• Phenotype tag: abnormal
• Phenotype quality: position

Gene ontology

• Biological process: G2/M transition of mitotic cell cycle;regulation of G2/M transition of mitotic cell cycle;protein transport;protein polyglutamylation;cilium assembly;ciliary basal body-plasma membrane docking
• Cellular component: centrosome;centriole;cytosol;cilium;membrane;ciliary basal body
• Molecular function: protein binding