CEP104

centrosomal protein 104, the group of Cilia and flagella associated|TOG domain containing

Basic information

Region (hg38): 1:3812086-3857396

Previous symbols: [ "KIAA0562" ]

Links

ENSG00000116198 ∙ NCBI:9731 ∙ OMIM:616690 ∙ HGNC:24866 ∙ Uniprot:O60308 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Joubert syndrome 17 (Definitive), mode of inheritance: AR
• Joubert syndrome 25 (Moderate), mode of inheritance: AR
• Joubert syndrome 25 (Strong), mode of inheritance: AR
• Joubert syndrome (Supportive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Intellectual developmental disorder, autosomal recessive 77	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	Neurologic	34196201; 35359234

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CEP104 gene.

• Joubert syndrome 25 (6 variants)
• not provided (2 variants)
• Joubert syndrome and related disorders (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CEP104 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				55	5	60
missense			130	14	3	147
nonsense	2	6				8
start loss						0
frameshift	5	7				12
inframe indel						0
splice donor/acceptor (+/-2bp)	1	1	1	1		4
splice region			6	5	2	13
non coding				74	116	190
Total	8	14	131	144	124

Highest pathogenic variant AF is 0.00000658

Variants in CEP104

This is a list of pathogenic ClinVar variants found in the CEP104 region.

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

Position	Type	Phenotype	Significance	ClinVar
1-3815090-C-CT			Benign (Jul 06, 2018)
1-3815093-C-T			Benign (Jul 15, 2018)
1-3815262-C-T			Likely benign (Jul 01, 2022)
1-3815364-T-G			Likely benign (Oct 01, 2024)
1-3815395-C-T			Benign (Aug 03, 2018)
1-3815401-G-A			Benign (Jul 15, 2018)
1-3815405-G-A		Joubert syndrome 25	Likely benign (Jan 04, 2024)
1-3815414-G-A		Joubert syndrome 25	Likely benign (Jun 24, 2023)
1-3815415-T-A		not specified	Uncertain significance (Feb 18, 2022)
1-3815418-G-A		Inborn genetic diseases	Uncertain significance (Jun 17, 2022)
1-3815425-T-C		Joubert syndrome 25	Likely benign (Jan 19, 2024)
1-3815429-G-A		Joubert syndrome 25	Likely benign (Jun 20, 2019)
1-3815431-T-C		Inborn genetic diseases	Uncertain significance (Nov 09, 2023)
1-3815443-C-T		Joubert syndrome 25 • Inborn genetic diseases	Uncertain significance (Oct 24, 2022)
1-3815444-G-A		Joubert syndrome 25	Benign/Likely benign (Oct 13, 2023)
1-3815450-C-T		Joubert syndrome 25 • CEP104-related disorder	Likely benign (Nov 08, 2022)
1-3815451-G-A		Inborn genetic diseases	Uncertain significance (Nov 05, 2021)
1-3815467-T-C		Inborn genetic diseases	Uncertain significance (Oct 07, 2024)
1-3815470-C-T		Inborn genetic diseases	Uncertain significance (Apr 09, 2024)
1-3815471-G-A		Joubert syndrome 25	Likely benign (Nov 23, 2022)
1-3815477-T-C		Joubert syndrome 25	Likely benign (Dec 31, 2019)
1-3815496-G-A		Joubert syndrome 25	Uncertain significance (Jan 27, 2021)
1-3815496-G-T		Joubert syndrome 25	Uncertain significance (Sep 01, 2021)
1-3815497-C-G		Inborn genetic diseases	Uncertain significance (Aug 10, 2024)
1-3815497-C-T			Uncertain significance (Sep 19, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CEP104	protein_coding	protein_coding	ENST00000378230	21	45134

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.23e-12	0.999	125617	0	131	125748	0.000521

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.444	503	532	0.946	0.0000312	6046
Missense in Polyphen		144	176.07	0.81784		2011
Synonymous	1.65	171	201	0.852	0.0000126	1737
Loss of Function	3.05	28	51.7	0.542	0.00000291	604

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000765	0.000764
Ashkenazi Jewish	0.000200	0.000198
East Asian	0.000163	0.000163
Finnish	0.000508	0.000508
European (Non-Finnish)	0.000785	0.000783
Middle Eastern	0.000163	0.000163
South Asian	0.000229	0.000229
Other	0.000327	0.000326

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Required for ciliogenesis and for structural integrity at the ciliary tip. {ECO:0000269|PubMed:23970417}.
• Disease: DISEASE: Joubert syndrome 25 (JBTS25) [MIM:616781]: A form of Joubert syndrome, 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, renal disease, liver fibrosis, and polydactyly. JBTS25 clinical manifestations appear to be confined to the neurologic system. JBTS25 inheritance is autosomal recessive. {ECO:0000269|PubMed:26477546}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Intolerance Scores

• rvis_EVS: -0.15
• rvis_percentile_EVS: 42.34

Haploinsufficiency Scores

• pHI: 0.124
• hipred: N
• hipred_score: 0.443
• ghis: 0.531

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• 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: Cep104

Gene ontology

• Cellular component: spindle pole;centriole;cilium
• Molecular function: protein binding;glycine binding;glutamate binding;thienylcyclohexylpiperidine binding