CSPP1

Chr 8AR

centrosome and spindle pole associated protein 1

Also known as: CSPP, CSPP-L, JBTS21

NCBI Gene: 79848 ENSG00000104218 UniProt: Q1MSJ5 OMIM: 611654

The encoded protein is a centrosome and spindle pole associated protein required for cilia formation, cell-cycle progression, and spindle organization. Mutations cause Joubert syndrome 21, a ciliopathy characterized by cerebellar vermis hypoplasia, developmental delay, and distinctive brainstem malformation. This condition follows autosomal recessive inheritance and has a GeneReviews entry available for detailed clinical guidance.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a centrosome and spindle pole associated protein. The encoded protein plays a role in cell-cycle progression and spindle organization, regulates cytokinesis, interacts with Nephrocystin 8 and is required for cilia formation. Mutations in this gene result in primary cilia abnormalities and classical Joubert syndrome. Alternatively spliced transcript variants encoding distinct isoforms have been found for this gene. [provided by RefSeq, Apr 2014]

GeneReviews OMIM ResearchGenerating clinical summary…

LOFmechanismARLOEUF 0.931 OMIM phenotype

Clinical Summary— CSPP1

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Gene-Disease Validity (ClinGen)

Joubert syndrome 21 · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

126 unique Pathogenic / Likely Pathogenic· 611 VUS of 1329 total submissions

Explore recent and relevant literature in Research Assistant →

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GeneReview available — CSPP1

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?

0.93LOEUF

pLI 0.000

Z-score 2.04

OE 0.74 (0.60–0.93)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.65Z-score

OE missense 0.93 (0.87–0.99)

601 obs / 647.8 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.74 (0.60–0.93)

0≤0.351.4

Missense OE?0.93 (0.87–0.99)

0≤0.61.4

Synonymous OE?1.00

0≤1.21.6

LoF obs/exp: 55 / 73.9Missense obs/exp: 601 / 647.8Syn Z: -0.02

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

definitiveCSPP1-related Joubert syndrome with or without Jeune asphyxiating thoracic dystrophyLOFAR

This gene — mechanism propensity

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

0.6552th %ile

GOF

0.4579th %ile

LOF

0.3939th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

1329 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic97

Likely Pathogenic29

VUS611

Likely Benign484

Benign57

Conflicting21

Pathogenic

Likely Pathogenic

611

VUS

484

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	91	1	5	0	97
Likely Pathogenic	25	0	4	0	29
VUS	16	542	48	5	611
Likely Benign	2	15	226	241	484
Benign	0	2	52	3	57
Conflicting	—				21
Total	134	560	335	249	1,299

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

27 pathogenic / likely-pathogenic (of 40) ClinVar copy-number / structural variants overlap CSPP1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →