CSPP1

centrosome and spindle pole associated protein 1

Basic information

Region (hg38): 8:67062417-67196778

Links

ENSG00000104218 ∙ NCBI:79848 ∙ OMIM:611654 ∙ HGNC:26193 ∙ Uniprot:Q1MSJ5 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Meckel syndrome (Supportive), mode of inheritance: AR
• Joubert syndrome (Supportive), mode of inheritance: AR
• Joubert syndrome with Jeune asphyxiating thoracic dystrophy (Supportive), mode of inheritance: AR
• Joubert syndrome 21 (Strong), mode of inheritance: AR
• Joubert syndrome 21 (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Joubert syndrome 21	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	Allergy/Immunology/Infectious; Audiologic/Otolaryngologic; Gastrointestinal; Musculoskeletal; Neurologic; Ophthalmologic; Renal	24360803; 24360807; 24360808
Mild sensorineural hearing loss has been described in several individuals

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CSPP1 gene.

• Joubert syndrome 21 (76 variants)
• not provided (10 variants)
• CSPP1-related disorder (4 variants)
• Meckel-Gruber syndrome (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CSPP1 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			3	198	2	203
missense	1		480	14	2	497
nonsense	25	3	4			32
start loss			3			3
frameshift	41	4	7			52
inframe indel			7			7
splice donor/acceptor (+/-2bp)	8	16	2	2		28
splice region			31	40	4	75
non coding	1	1	27	154	49	232
Total	76	24	533	368	53

Highest pathogenic variant AF is 0.0000924

Variants in CSPP1

This is a list of pathogenic ClinVar variants found in the CSPP1 region.

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

Position	Type	Phenotype	Significance	ClinVar
8-67064144-C-G			Benign (Jun 26, 2018)
8-67064342-C-T			Likely benign (Nov 01, 2022)
8-67064343-G-A			Likely benign (Mar 20, 2020)
8-67064384-GCCCGGAGGTCTGTCA-G		Joubert syndrome 21	Uncertain significance (Jul 01, 2022)
8-67064387-C-T		not specified	Likely benign (Oct 13, 2017)
8-67064399-A-C		not specified	Uncertain significance (Sep 20, 2018)
8-67064399-A-T		Joubert syndrome 21	Uncertain significance (Jun 28, 2022)
8-67064400-T-A		Joubert syndrome 21	Uncertain significance (Mar 10, 2022)
8-67064400-T-G		Joubert syndrome 21	Uncertain significance (Feb 09, 2022)
8-67064402-C-G		Joubert syndrome 21	Uncertain significance (Jun 04, 2022)
8-67064403-T-A		Joubert syndrome 21	Uncertain significance (Mar 14, 2023)
8-67064406-T-A		Joubert syndrome 21	Uncertain significance (Aug 01, 2023)
8-67064407-C-A		Joubert syndrome 21	Uncertain significance (Jul 09, 2021)
8-67064409-C-G		Joubert syndrome 21	Uncertain significance (Nov 05, 2024)
8-67064410-G-C		Joubert syndrome 21	Likely benign (Aug 10, 2023)
8-67064411-C-A		Joubert syndrome 21	Uncertain significance (Aug 16, 2022)
8-67064411-C-T		Joubert syndrome 21	Uncertain significance (Apr 22, 2022)
8-67064421-C-T		Joubert syndrome 21 • CSPP1-related disorder	Uncertain significance (Jul 26, 2022)
8-67064422-C-G		Joubert syndrome 21	Likely benign (Oct 12, 2024)
8-67064423-G-C		Inborn genetic diseases	Uncertain significance (Mar 31, 2024)
8-67064424-C-A		Joubert syndrome 21	Uncertain significance (Jun 27, 2022)
8-67064425-T-C		Joubert syndrome 21	Likely benign (Apr 16, 2024)
8-67064428-A-C		Joubert syndrome 21	Likely benign (Dec 12, 2022)
8-67064428-A-G		Joubert syndrome 21 • not specified • CSPP1-related disorder	Benign/Likely benign (Jan 30, 2025)
8-67064433-C-T		Joubert syndrome 21 • Inborn genetic diseases	Conflicting classifications of pathogenicity (Jan 06, 2025)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CSPP1	protein_coding	protein_coding	ENST00000262210	29	133838

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
3.26e-29	0.140	124581	0	220	124801	0.000882

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.654	601	648	0.928	0.0000342	8060
Missense in Polyphen		171	206.79	0.82694		2662
Synonymous	-0.0213	218	218	1.00	0.0000109	2204
Loss of Function	2.04	55	73.9	0.744	0.00000430	878

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00169	0.00168
Ashkenazi Jewish	0.00	0.00
East Asian	0.00215	0.00212
Finnish	0.000188	0.000186
European (Non-Finnish)	0.000880	0.000865
Middle Eastern	0.00215	0.00212
South Asian	0.00105	0.00101
Other	0.000661	0.000660

dbNSFP

Source: dbNSFP

• Function: FUNCTION: May play a role in cell-cycle-dependent microtubule organization. {ECO:0000269|PubMed:16826565}.
• Disease: DISEASE: Joubert syndrome 21 (JBTS21) [MIM:615636]: 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. {ECO:0000269|PubMed:24360803, ECO:0000269|PubMed:24360807, ECO:0000269|PubMed:24360808}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Intolerance Scores

• loftool: 0.953
• rvis_EVS: -0.26
• rvis_percentile_EVS: 34.97

Haploinsufficiency Scores

• pHI: 0.0821
• hipred: N
• hipred_score: 0.327
• ghis: 0.521

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.204

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Cspp1

Zebrafish Information Network

• Gene name: cspp1a
• Affected structure: pronephros
• Phenotype tag: abnormal
• Phenotype quality: cystic

Gene ontology

• Biological process: positive regulation of cytokinesis;positive regulation of cell division
• Cellular component: spindle pole;cytoplasm;centrosome;spindle;microtubule