CSPP1

Summary

CSPP1 (centrosome and spindle pole associated protein 1, HGNC:26193) is a protein-coding gene on chromosome 8q13.1-q13.2, encoding Centrosome and spindle pole-associated protein 1 (Q1MSJ5). May play a role in cell-cycle-dependent microtubule organization.

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.

Source: NCBI Gene 79848 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Joubert syndrome 21 (Definitive, ClinGen) — +3 more curated relationships
• GWAS associations: 1
• Clinical variants (ClinVar): 1,062 total — 89 pathogenic, 19 likely-pathogenic
• Phenotypes (HPO): 157
• Druggable target: yes
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity no evidence
• MANE Select transcript: NM_001382391

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:26193
Approved symbol	CSPP1
Name	centrosome and spindle pole associated protein 1
Location	8q13.1-q13.2
Locus type	gene with protein product
Status	Approved
Aliases	FLJ22490, CSPP, JBTS21, CSPP-L
Ensembl gene	ENSG00000104218
Ensembl biotype	protein_coding
OMIM	611654
Entrez	79848

Gene structure

Transcript identifiers

Ensembl transcripts: 89 — 34 protein_coding, 27 nonsense_mediated_decay, 20 retained_intron, 8 protein_coding_CDS_not_defined

ENST00000262210, ENST00000519163, ENST00000519668, ENST00000519701, ENST00000521168, ENST00000521324, ENST00000521919, ENST00000674647, ENST00000674993, ENST00000675306, ENST00000675820, ENST00000675869, ENST00000675955, ENST00000675990, ENST00000676113, ENST00000676317, ENST00000676471, ENST00000676534, ENST00000676567, ENST00000676573, ENST00000676605, ENST00000676656, ENST00000676695, ENST00000676697, ENST00000676804, ENST00000676847, ENST00000676858, ENST00000676882, ENST00000676968, ENST00000676980, ENST00000677009, ENST00000677052, ENST00000677070, ENST00000677071, ENST00000677131, ENST00000677256, ENST00000677276, ENST00000677430, ENST00000677455, ENST00000677473, ENST00000677538, ENST00000677592, ENST00000677619, ENST00000677697, ENST00000677836, ENST00000677845, ENST00000677855, ENST00000677938, ENST00000677964, ENST00000678017, ENST00000678138, ENST00000678156, ENST00000678204, ENST00000678216, ENST00000678318, ENST00000678345, ENST00000678362, ENST00000678444, ENST00000678542, ENST00000678553, ENST00000678616, ENST00000678635, ENST00000678645, ENST00000678685, ENST00000678723, ENST00000678728, ENST00000678744, ENST00000678747, ENST00000678807, ENST00000678821, ENST00000678834, ENST00000678895, ENST00000678927, ENST00000679042, ENST00000679060, ENST00000679112, ENST00000679226, ENST00000679274, ENST00000679295, ENST00000679322, ENST00000853676, ENST00000914794, ENST00000914795, ENST00000914796, ENST00000914797, ENST00000914798, ENST00000914799, ENST00000953971, ENST00000953972

RefSeq mRNA: 8 — MANE Select: NM_001382391 NM_001291339, NM_001363131, NM_001363132, NM_001363133, NM_001364869, NM_001364870, NM_001382391, NM_024790

CCDS: CCDS43744, CCDS78344, CCDS94301, CCDS94304, CCDS94307, CCDS94308, CCDS94309, CCDS94310

Canonical transcript exons

ENST00000678616 — 31 exons

Exon	Start	End
ENSE00000980659	67193464	67193602
ENSE00001284096	67111972	67112065
ENSE00001284101	67105905	67105975
ENSE00001284106	67103037	67103135
ENSE00001433564	67113805	67113862
ENSE00003459087	67164391	67164508
ENSE00003462419	67093543	67093641
ENSE00003464565	67131951	67132080
ENSE00003477401	67115914	67116122
ENSE00003504128	67091803	67091883
ENSE00003519934	67137456	67137603
ENSE00003519951	67074243	67074351
ENSE00003521312	67158991	67159137
ENSE00003523398	67179863	67179926
ENSE00003534260	67175296	67175436
ENSE00003538410	67095293	67095732
ENSE00003540914	67076482	67076581
ENSE00003561734	67161811	67161915
ENSE00003563720	67118248	67118369
ENSE00003565574	67149783	67149935
ENSE00003568686	67158447	67158596
ENSE00003587642	67118743	67118821
ENSE00003616533	67172416	67172555
ENSE00003630925	67190650	67190759
ENSE00003637350	67163732	67163798
ENSE00003671959	67154024	67154136
ENSE00003672325	67177680	67177726
ENSE00003682829	67086007	67086110
ENSE00003902564	67114329	67114370
ENSE00003907885	67195382	67196614
ENSE00003909647	67064392	67064538

Expression profiles

Bgee: expression breadth ubiquitous, 275 present calls, max score 98.59.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 12.9140 / max 183.3407, expressed in 1742 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
89226	10.3243	1723
89227	2.5896	1036

Top tissues by expression

284 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
bronchial epithelial cell	CL:0002328	98.59	gold quality
sperm	CL:0000019	97.81	gold quality
right uterine tube	UBERON:0001302	96.79	gold quality
epithelium of bronchus	UBERON:0002031	95.96	gold quality
mucosa of paranasal sinus	UBERON:0005030	95.78	gold quality
sural nerve	UBERON:0015488	95.70	gold quality
bronchus	UBERON:0002185	95.47	gold quality
male germ cell	CL:0000015	94.73	gold quality
calcaneal tendon	UBERON:0003701	92.77	gold quality
tibia	UBERON:0000979	92.59	gold quality
right testis	UBERON:0004534	92.30	gold quality
left testis	UBERON:0004533	92.17	gold quality
secondary oocyte	CL:0000655	91.54	gold quality
testis	UBERON:0000473	91.23	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	91.10	gold quality
visceral pleura	UBERON:0002401	90.85	gold quality
colonic epithelium	UBERON:0000397	90.72	gold quality
Brodmann (1909) area 23	UBERON:0013554	90.39	gold quality
choroid plexus epithelium	UBERON:0003911	90.30	gold quality
caput epididymis	UBERON:0004358	90.27	gold quality
cortical plate	UBERON:0005343	89.64	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	89.37	gold quality
germinal epithelium of ovary	UBERON:0001304	89.29	gold quality
epithelium of nasopharynx	UBERON:0001951	88.96	gold quality
tendon	UBERON:0000043	88.88	gold quality
corpus callosum	UBERON:0002336	88.59	gold quality
ventricular zone	UBERON:0003053	88.51	gold quality
right lung	UBERON:0002167	88.43	gold quality
primary visual cortex	UBERON:0002436	88.24	gold quality
parietal pleura	UBERON:0002400	88.13	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-GEOD-130473	yes	367.27
E-MTAB-8498	yes	177.26
E-ANND-3	yes	9.75

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

70 targeting CSPP1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-433-3P	99.98	69.37	1203
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-493-5P	99.96	72.47	2382
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-6508-5P	99.92	70.67	2465
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-10395-5P	99.86	67.35	676
HSA-MIR-8067	99.86	69.59	2260
HSA-MIR-3121-3P	99.82	71.96	3630
HSA-MIR-548AJ-5P	99.78	71.12	3085

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 14)

• Novel centrosome/microtubule-associated coiled-coil protein (CSPP)is associated with centrosomes and microtubules and may play a role in the regulation of G(1)/S-phase progression and spindle assembly [CSPP]. (PMID:15580290)
• Taken together, CSPP and CSPP-L interact with centrosomes and microtubules and can differently affect microtubule organization. (PMID:16826565)
• CSPP interacts with and recruits MyoGEF to the central spindle, where MyoGEF contributes to the spatiotemporal regulation of cytokinesis. (PMID:19129481)
• CSPP isoforms require their common C-terminal domain to interact with Nephrocystin 8 (NPHP8/RPGRIP1L) and to form a ternary complex with NPHP8 and NPHP4. (PMID:20519441)
• mutations in CSPP1 were associated with variable ciliopathy phenotypes ranging from Joubert syndrome to the more severe Meckel-Gruber syndrome with perinatal lethality and occipital encephalocele (PMID:24360803)
• Our data suggest that CSPP1 is required for proper primary cilium formation or stability and that CSPP1 mutations result in abnormal mid-hindbrain development. (PMID:24360807)
• CSPP1 mutations are a major cause of the Joubert-Jeune phenotype in humans. (PMID:24360808)
• Differential expression of a nuclear CSPP1 isoform identified biologically and clinically distinct subgroups of basal-like breast carcinoma. (PMID:24901235)
• Microtubule-independent but desmoplakin-dependent localization of CSPP-L to desmosomes occurs in apical-basal polarized epithelial cells. CSPP-L depletion promoted multi-lumen spheroid formation in Caco-2 cells. (PMID:26241740)
• propose that CSPP1 cooperates with CENP-H on kinetochores to serve as a novel regulator of kinetochore microtubule dynamics for accurate chromosome segregation (PMID:26378239)
• Tumor-promoting effect was inhibited after we transfected miR-1236-3p into circ-CSPP1 overexpressing OC cells. (PMID:30965236)
• Roles of circ-CSPP1 on the proliferation and metastasis of glioma cancer. (PMID:32495924)
• Circle RNA circCSPP1 promotes human osteosarcoma cell proliferation and increases glucose metabolism by suppressing miR-200c maturation. (PMID:35713481)
• CSPP1 stabilizes growing microtubule ends and damaged lattices from the luminal side. (PMID:36752787)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	cspp1b	ENSDARG00000091628
danio_rerio	cspp1a	ENSDARG00000100236
mus_musculus	Cspp1	ENSMUSG00000056763
rattus_norvegicus	Cspp1	ENSRNOG00000021718

Protein

Protein identifiers

Centrosome and spindle pole-associated protein 1 — Q1MSJ5 (reviewed: Q1MSJ5)

All UniProt accessions (48): A0A6Q8PF61, A0A6Q8PF96, A0A6Q8PGI0, A0A6Q8PGS3, A0A6Q8PHN8, A0A7I2PHE7, A0A7I2V2I3, A0A7I2V2P7, A0A7I2V2X5, A0A7I2V372, A0A7I2V398, A0A7I2V3F0, A0A7I2V3F6, A0A7I2V3G6, Q1MSJ5, A0A7I2V3M9, A0A7I2V3Q0, A0A7I2V3V5, A0A7I2V3W2, A0A7I2V3Z9, A0A7I2V425, A0A7I2V450, A0A7I2V4C3, A0A7I2V4I1, A0A7I2V4L2, A0A7I2V4M7, A0A7I2V4R5, A0A7I2V4U4, A0A7I2V519, A0A7I2V571, A0A7I2V5A7, A0A7I2V5F2, A0A7I2V5G7, A0A7I2V5J7, A0A7I2V5J9, A0A7I2V5L8, A0A7I2V5N5, A0A7I2V5P5, A0A7I2V5U6, A0A7I2V5W3, A0A7I2V5Y8, A0A7I2V6B7, A0A7I2YQE8, A0A7I2YQH9, A0A7I2YQX1, E5RGA5, E5RI67, F2Z2M5

UniProt curated annotations — full annotation on UniProt →

Function. May play a role in cell-cycle-dependent microtubule organization.

Subunit / interactions. Interacts with PLEKHG6. Interacts with ARMC9, TOGARAM1, CCDC66, CEP104 and CEP290.

Subcellular location. Cytoplasm. Cytoskeleton. Microtubule organizing center. Centrosome. Spindle. Spindle pole. Cell projection. Cilium.

Tissue specificity. Expressed in adult and fetal brain with enrichment in the cerebellum. Detected in testis.

Post-translational modifications. Phosphorylated. Phosphorylation increases in colcemide-treated cells.

Disease relevance. 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. The disease is caused by variants affecting the gene represented in this entry.

Isoforms (3)

UniProt ID	Names	Canonical?
Q1MSJ5-3	3	yes
Q1MSJ5-1	1, CSPP-L
Q1MSJ5-2	2, CSPP, CSPP-S

RefSeq proteins (8): NP_001278268, NP_001350060, NP_001350061, NP_001350062, NP_001351798, NP_001351799, NP_001369320, NP_079066 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR026708	CSPP1	Family
IPR058191	CSPP1_C	Domain

Pfam: PF24578

UniProt features (33 total): region of interest 7, coiled-coil region 6, modified residue 6, compositionally biased region 4, sequence conflict 4, splice variant 3, sequence variant 2, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q1MSJ5-F1	57.34	0.08

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (6): 244, 459, 527, 901, 920, 966

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 471 (showing top): DARWICHE_SKIN_TUMOR_PROMOTER_DN, DARWICHE_PAPILLOMA_RISK_LOW_DN, DARWICHE_PAPILLOMA_RISK_HIGH_UP, DARWICHE_SQUAMOUS_CELL_CARCINOMA_DN, GOCC_MICROTUBULE_ORGANIZING_CENTER, ONKEN_UVEAL_MELANOMA_UP, GOBP_CYTOKINESIS, GOBP_POSITIVE_REGULATION_OF_CELL_DIVISION, GOBP_REGULATION_OF_CELL_CYCLE, GOCC_CENTROSOME, GOBP_POSITIVE_REGULATION_OF_CELL_CYCLE_PROCESS, GOBP_REGULATION_OF_CYTOKINESIS, GOBP_POSITIVE_REGULATION_OF_CYTOKINESIS, GOBP_REGULATION_OF_CELL_DIVISION, TGACATY_UNKNOWN

GO Biological Process (2): positive regulation of cytokinesis (GO:0032467), positive regulation of cell division (GO:0051781)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (11): spindle pole (GO:0000922), nucleoplasm (GO:0005654), centrosome (GO:0005813), spindle (GO:0005819), microtubule (GO:0005874), cilium (GO:0005929), centriolar satellite (GO:0034451), ciliary basal body (GO:0036064), cytoplasm (GO:0005737), cytoskeleton (GO:0005856), cell projection (GO:0042995)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
microtubule organizing center	2
microtubule cytoskeleton	2
intracellular membraneless organelle	2
cytokinesis	1
regulation of cytokinesis	1
positive regulation of cell division	1
positive regulation of cell cycle process	1
positive regulation of cellular process	1
cell division	1
regulation of cell division	1
binding	1
spindle	1
nuclear lumen	1
centriole	1
polymeric cytoskeletal fiber	1
intraciliary transport particle	1
membrane-bounded organelle	1
plasma membrane bounded cell projection	1
centrosome	1
cilium	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

2096 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CSPP1	FAM110B	Q8TC76	948
CSPP1	FAM110A	Q9BQ89	947
CSPP1	FAM110C	Q1W6H9	942
CSPP1	PLEKHG6	Q3KR16	642
CSPP1	CC2D2A	Q9P2K1	601
CSPP1	TMEM138	Q9NPI0	596
CSPP1	CPLANE1	Q9H799	594
CSPP1	CEP41	Q9BYV8	589
CSPP1	TCTN3	Q6NUS6	579
CSPP1	CEP290	O15078	576
CSPP1	CEP104	O60308	572
CSPP1	TMEM237	Q96Q45	570
CSPP1	AHI1	Q8N157	565
CSPP1	ULK4	Q96C45	561
CSPP1	TMEM231	Q9H6L2	550
CSPP1	PDE6D	O43924	550

IntAct

67 interactions, top by confidence:

A	B	Type	Score
SPC25	NDC80	psi-mi:“MI:0914”(association)	0.940
MED4	MED19	psi-mi:“MI:2364”(proximity)	0.900
CEP290	CCP110	psi-mi:“MI:2364”(proximity)	0.890
YWHAG	BLTP3B	psi-mi:“MI:2364”(proximity)	0.640
YWHAH	BLTP3B	psi-mi:“MI:2364”(proximity)	0.570
CEP104	CCDC66	psi-mi:“MI:2364”(proximity)	0.540
CEP104	CSPP1	psi-mi:“MI:0915”(physical association)	0.540
GAR1	PRMT5	psi-mi:“MI:0914”(association)	0.530
PNMA2	CCDC85C	psi-mi:“MI:0914”(association)	0.530
KIAA0753	OFD1	psi-mi:“MI:2364”(proximity)	0.480
CEP162	CCP110	psi-mi:“MI:2364”(proximity)	0.420
CSPP1	ARMC9	psi-mi:“MI:0915”(physical association)	0.400
CSPP1	TOGARAM1	psi-mi:“MI:0915”(physical association)	0.400
CSPP1	CCDC66	psi-mi:“MI:0915”(physical association)	0.400
CSPP1	CSPP1	psi-mi:“MI:0915”(physical association)	0.400
TOGARAM1	CSPP1	psi-mi:“MI:0915”(physical association)	0.400
PCM1	SUPT5H	psi-mi:“MI:0914”(association)	0.350
CEP162	IPO5	psi-mi:“MI:0914”(association)	0.350
RPGRIP1L	KIF2A	psi-mi:“MI:0914”(association)	0.350
	ESYT2	psi-mi:“MI:0914”(association)	0.350
MYC	PDZD2	psi-mi:“MI:0914”(association)	0.350
MAPRE1	SCAMP1	psi-mi:“MI:0914”(association)	0.350
MIF	BLTP3B	psi-mi:“MI:0914”(association)	0.350
VPS35	KIF2A	psi-mi:“MI:0914”(association)	0.350
FIG4	YEATS4	psi-mi:“MI:0914”(association)	0.350
CEP290	ARPC3	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (137): CSPP1 (Two-hybrid), CSPP1 (Two-hybrid), CSPP1 (Two-hybrid), MRFAP1L1 (Two-hybrid), ACTR1B (Affinity Capture-MS), DCTN3 (Affinity Capture-MS), KLHL13 (Affinity Capture-MS), CPNE8 (Affinity Capture-MS), DCTN4 (Affinity Capture-MS), CAPZA2 (Affinity Capture-MS), DCTN2 (Affinity Capture-MS), GAN (Affinity Capture-MS), ACTR10 (Affinity Capture-MS), DCTN5 (Affinity Capture-MS), DCTN6 (Affinity Capture-MS)

ESM2 similar proteins: A0A087WRI3, A2BFC9, A2RRW4, A4QMS7, A6NJV1, A6NL82, A6QPC0, A6QQ68, A8E4X8, A8E5W8, A8QW39, A9JS51, D6REC4, F1P3Y5, G3X6E2, P0C875, Q0VB26, Q1MSJ5, Q2IA00, Q2T9Q3, Q2TA11, Q3UY96, Q494V2, Q497Q6, Q4KKZ1, Q4QR77, Q4R5Y0, Q4R8V8, Q5NC57, Q5ZIH9, Q6J272, Q6PII3, Q6ZQR2, Q6ZVS7, Q7Z4T9, Q8CFW7, Q8N1D5, Q8N6G2, Q8WW14, Q95LR0

Diamond homologs: B2RX88, Q1MSJ5

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 65 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Loss of Nlp from mitotic centrosomes	12	42.3×	4e-15
Loss of proteins required for interphase microtubule organization from the centrosome	12	42.3×	4e-15
AURKA Activation by TPX2	12	40.6×	5e-15
Anchoring of the basal body to the plasma membrane	16	40.2×	7e-20
Recruitment of mitotic centrosome proteins and complexes	12	36.2×	2e-14
Regulation of PLK1 Activity at G2/M Transition	12	33.8×	3e-14
Recruitment of NuMA to mitotic centrosomes	12	31.1×	8e-14
Cilium Assembly	6	14.5×	9e-05

GO biological processes:

GO term	Partners	Fold	FDR
centriole replication	5	58.1×	3e-06
non-motile cilium assembly	8	36.9×	1e-08
cilium assembly	13	15.2×	1e-09
intracellular protein localization	6	10.0×	2e-03
cell division	10	7.3×	1e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

1062 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	89
Likely pathogenic	19
Uncertain significance	480
Likely benign	369
Benign	44

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
100666	NM_001382391.1(CSPP1):c.2335C>T (p.Arg779Ter)	Pathogenic
100667	NM_001382391.1(CSPP1):c.2259_2260del (p.Glu755fs)	Pathogenic
100668	NM_001382391.1(CSPP1):c.2295del (p.Glu766fs)	Pathogenic
100670	NM_001382391.1(CSPP1):c.2968+1G>A	Pathogenic
100671	NM_001382391.1(CSPP1):c.2542_2543del (p.Met848fs)	Pathogenic
100672	NM_001382391.1(CSPP1):c.631C>T (p.Arg211Ter)	Pathogenic
100673	NM_001382391.1(CSPP1):c.255_256del (p.His85fs)	Pathogenic
100674	NM_001382391.1(CSPP1):c.2259_2262del (p.Glu755fs)	Pathogenic
100675	NM_001382391.1(CSPP1):c.625C>T (p.Gln209Ter)	Pathogenic
100676	NM_001382391.1(CSPP1):c.2788C>T (p.Arg930Ter)	Pathogenic
1030873	NM_001382391.1(CSPP1):c.132dup (p.Lys45Ter)	Pathogenic
1031405	NM_001382391.1(CSPP1):c.2521_2524del (p.Ile841fs)	Pathogenic
1070338	NM_001382391.1(CSPP1):c.1544_1547del (p.Asn515fs)	Pathogenic
1184140	NM_001382391.1(CSPP1):c.1698-1G>C	Pathogenic
1322166	NM_001382391.1(CSPP1):c.1822C>T (p.Gln608Ter)	Pathogenic
1322168	NM_001382391.1(CSPP1):c.2538+1G>T	Pathogenic
1359163	NM_001382391.1(CSPP1):c.1505del (p.Pro502fs)	Pathogenic
1451541	NM_001382391.1(CSPP1):c.1787_1790del (p.Lys596fs)	Pathogenic
1453060	NM_001382391.1(CSPP1):c.2285_2286del (p.Leu762fs)	Pathogenic
1453404	NM_001382391.1(CSPP1):c.419_422del (p.Asn140fs)	Pathogenic
1453492	NM_001382391.1(CSPP1):c.263_267del (p.Lys88fs)	Pathogenic
1458414	NC_000008.10:g.(?67998222)(67998365_?)del	Pathogenic
1458591	NM_001382391.1(CSPP1):c.1834G>T (p.Glu612Ter)	Pathogenic
1459004	NC_000008.10:g.(?68044166)(68044335_?)del	Pathogenic
1916387	NM_001382391.1(CSPP1):c.264del (p.Glu89fs)	Pathogenic
1935102	NM_001382391.1(CSPP1):c.239_240del (p.Asp79_Tyr80insTer)	Pathogenic
1964919	NM_001382391.1(CSPP1):c.-56del	Pathogenic
2008008	NM_001382391.1(CSPP1):c.2266G>T (p.Glu756Ter)	Pathogenic
2017085	NM_001382391.1(CSPP1):c.2669C>A (p.Ser890Ter)	Pathogenic
2017968	NM_001382391.1(CSPP1):c.2477_2478insT (p.Lys826fs)	Pathogenic

SpliceAI

6158 predictions. Top by Δscore:

Variant	Effect	Δscore
8:67064495:GA:G	donor_gain	1.0000
8:67064497:G:GG	donor_gain	1.0000
8:67064525:GC:G	donor_gain	1.0000
8:67074239:A:AG	acceptor_gain	1.0000
8:67074239:AAAG:A	acceptor_loss	1.0000
8:67074240:A:G	acceptor_gain	1.0000
8:67074240:AAGA:A	acceptor_loss	1.0000
8:67074241:A:G	acceptor_gain	1.0000
8:67074241:A:T	acceptor_loss	1.0000
8:67074242:G:A	acceptor_loss	1.0000
8:67074242:G:GA	acceptor_gain	1.0000
8:67074242:GA:G	acceptor_gain	1.0000
8:67074242:GAA:G	acceptor_gain	1.0000
8:67074242:GAAT:G	acceptor_gain	1.0000
8:67074242:GAATC:G	acceptor_gain	1.0000
8:67074348:GAAG:G	donor_gain	1.0000
8:67074348:GAAGG:G	donor_loss	1.0000
8:67074349:A:T	donor_gain	1.0000
8:67074349:AAGGT:A	donor_loss	1.0000
8:67074350:AGGT:A	donor_loss	1.0000
8:67074351:GGT:G	donor_loss	1.0000
8:67074352:G:T	donor_loss	1.0000
8:67074353:T:G	donor_loss	1.0000
8:67086001:TTCTA:T	acceptor_loss	1.0000
8:67086004:TA:T	acceptor_loss	1.0000
8:67086005:A:AG	acceptor_gain	1.0000
8:67086005:AG:A	acceptor_gain	1.0000
8:67086006:G:GT	acceptor_gain	1.0000
8:67086006:GG:G	acceptor_gain	1.0000
8:67086006:GGA:G	acceptor_gain	1.0000

AlphaMissense

8133 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000007786 (8:67096577 A>G), RS1000014111 (8:67140438 A>G), RS1000050220 (8:67196242 A>G), RS1000083426 (8:67099839 G>A), RS1000087629 (8:67148438 C>A), RS1000145335 (8:67180380 G>A), RS1000163355 (8:67137309 A>G), RS1000167527 (8:67169561 T>G), RS1000180633 (8:67070794 C>A), RS1000230049 (8:67120154 T>C), RS1000235913 (8:67148882 A>G), RS1000236583 (8:67100823 T>C,G), RS1000281282 (8:67133508 A>C), RS1000287031 (8:67127428 A>G), RS1000311442 (8:67085710 T>G)

Disease associations

OMIM: gene MIM:611654 | disease phenotypes: MIM:615636, MIM:249000, MIM:213300

GenCC curated gene-disease

Disease	Classification	Inheritance
Joubert syndrome 21	Definitive	Autosomal recessive
Joubert syndrome with Jeune asphyxiating thoracic dystrophy	Supportive	Autosomal recessive
Joubert syndrome	Supportive	Autosomal recessive
Meckel syndrome	Supportive	Autosomal recessive

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
Joubert syndrome 21	Definitive	AR

Mondo (7): Joubert syndrome 21 (MONDO:0014288), Meckel syndrome (MONDO:0018921), Joubert syndrome (MONDO:0018772), inherited retinal dystrophy (MONDO:0019118), optic atrophy (MONDO:0003608), microcephaly (MONDO:0001149), Joubert syndrome with Jeune asphyxiating thoracic dystrophy (MONDO:0018342)

Orphanet (3): Meckel syndrome (Orphanet:564), Isolated Joubert syndrome (Orphanet:475), OBSOLETE: Inherited retinal disorder (Orphanet:71862)

HPO phenotypes

157 total (30 of 157 shown, HPO-id order):

HPO	Term
HP:0000003	Multicystic kidney dysplasia
HP:0000007	Autosomal recessive inheritance
HP:0000028	Cryptorchidism
HP:0000037	Male pseudohermaphroditism
HP:0000047	Hypospadias
HP:0000062	Ambiguous genitalia
HP:0000068	Urethral atresia
HP:0000073	Ureteral duplication
HP:0000083	Renal insufficiency
HP:0000107	Renal cyst
HP:0000110	Renal dysplasia
HP:0000175	Cleft palate
HP:0000202	Orofacial cleft
HP:0000221	Furrowed tongue
HP:0000238	Hydrocephalus
HP:0000252	Microcephaly
HP:0000276	Long face
HP:0000286	Epicanthus
HP:0000293	Full cheeks
HP:0000316	Hypertelorism
HP:0000340	Sloping forehead
HP:0000347	Micrognathia
HP:0000358	Posteriorly rotated ears
HP:0000369	Low-set ears
HP:0000396	Overfolded helix
HP:0000407	Sensorineural hearing impairment
HP:0000426	Prominent nasal bridge
HP:0000457	Depressed nasal ridge
HP:0000463	Anteverted nares
HP:0000482	Microcornea

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST008156_54	Hip circumference adjusted for BMI	4.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0008039	BMI-adjusted hip circumference

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D008831	Microcephaly	C05.660.207.620; C10.500.507.400.500; C16.131.621.207.620; C16.131.666.507.400.500
D009896	Optic Atrophy	C10.292.700.225; C11.640.451
D058499	Retinal Dystrophies	C11.768.585.658

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6067222 (SINGLE PROTEIN)

PharmGKB: 1 entry (VIP=true, CPIC=false)

ChEMBL bioactivities

2 potent at pChembl≥5 of 2 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.09	Kd	810.8	nM	CHEMBL3752910
5.85	ED50	1406	nM	CHEMBL3752910

PubChem BioAssay actives

1 with measured affinity, of 2 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149847: Binding affinity to human CSPP1 incubated for 45 mins by Kinobead based pull down assay	kd	0.8108	uM

CTD chemical–gene interactions

40 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases expression, affects expression, affects cotreatment	4
Arsenic Trioxide	decreases expression	2
Cisplatin	affects cotreatment, decreases expression, increases response to substance	2
Formaldehyde	decreases expression	2
Tobacco Smoke Pollution	affects expression, decreases expression	2
aristolochic acid I	decreases expression	1
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
FR900359	affects phosphorylation	1
methylmercuric chloride	increases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	decreases methylation	1
trichostatin A	increases expression	1
methylparaben	decreases expression	1
benzo(e)pyrene	decreases methylation	1
coumarin	increases phosphorylation	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
jinfukang	affects cotreatment, decreases expression	1
Sunitinib	increases expression	1
Air Pollutants	increases expression, increases abundance	1
Benzo(a)pyrene	increases methylation	1
Caffeine	affects phosphorylation	1
Doxorubicin	decreases expression	1
Estradiol	increases expression	1
Hydrogen Peroxide	affects expression	1
Indomethacin	decreases expression	1
Lead	decreases expression	1
Methapyrilene	decreases methylation	1
Methyl Methanesulfonate	increases expression	1
Ozone	increases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5652889	Binding	Binding affinity to human CSPP1 incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Clinical trials (associated diseases)

69 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT04224207	PHASE3	COMPLETED	Management of Retinitis Pigmentosa by Mesenchymal Stem Cells by Wharton’s Jelly Derived Mesenchymal Stem Cells
NCT07082855	PHASE3	NOT_YET_RECRUITING	A Multicenter, Randomized, Double-Blind, Controlled Clinical Study of Minocycline for the Treatment of Retinitis Pigmentosa
NCT03763227	PHASE2	COMPLETED	Intravitreal Ranibizumab (Lucentis®) in the Treatment of Non-leaking Macular Cysts in Retinal Dystrophy
NCT04068207	PHASE2	COMPLETED	Minocycline Treatment in Retinitis Pigmentosa
NCT04945772	PHASE2	COMPLETED	Efficacy and Safety of MCO-010 Optogenetic Therapy in Adults With Retinitis Pigmentosa [RESTORE]
NCT05902962	PHASE1	COMPLETED	SAD of IVT VP-001 in PRPF31 Mutation-Associated Retinal Dystrophy Subjects
NCT06319872	PHASE1	RECRUITING	The Effects of Disulfiram (Antabuse®) on Visual Acuity in Patients With Retinal Degeneration
NCT06455826	PHASE1	COMPLETED	MAD of IVT VP-001 in PRPF31 Mutation-Associated Retinal Dystrophy Subjects (Wallaby)
NCT01064505	PHASE1	COMPLETED	Safety Study of a Single IVT Injection of QPI-1007 in Chronic Optic Nerve Atrophy and Recent Onset NAION Patients
NCT05147701	PHASE1	RECRUITING	Safety of Cultured Allogeneic Adult Umbilical Cord Derived Mesenchymal Stem Cells for NAION
NCT00873678	Not specified	COMPLETED	Assessment of the Prevalence of Genes AHI1, NPHP1 and CEP290 in Joubert Syndrome
NCT01401998	Not specified	RECRUITING	ARPKD Database Study
NCT04874909	Not specified	COMPLETED	Classification, Functional Stratification and Biomarkers in Ciliopathy (CILLICORIRCM)
NCT04855045	PHASE2/PHASE3	UNKNOWN	An Open-label, Dose Escalation and Double-masked, Randomized, Controlled Trial Evaluating Safety and Tolerability of Sepofarsen in Children (<8 Years of Age) With LCA10 Caused by Mutations in the CEP290 Gene.
NCT03872479	PHASE1/PHASE2	UNKNOWN	Single Ascending Dose Study in Participants With LCA10
NCT04123626	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	A Study to Evaluate the Safety and Tolerability of QR-1123 in Subjects With Autosomal Dominant Retinitis Pigmentosa Due to the P23H Mutation in the RHO Gene
NCT04545736	PHASE1/PHASE2	RECRUITING	Oral Metformin for Treatment of ABCA4 Retinopathy
NCT06212297	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Fellow-eye Study (FE) of LX101 in Subjects With Inherited Retinal Dystrophy
NCT06852963	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	A Repeat-Dose, Open-Label, Two Arm Safety and Efficacy Study of Two Doses of VP-001 Administered Intravitreally in Participants With Confirmed PRPF31 Mutation-Associated Retinal Dystrophy, Including Participants Previously Treated With VP001
NCT07177196	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Personalized Antisense Oligonucleotide Therapy for a Single Participant With PRPH2 Mutation Associated With Retinal Dystrophy
NCT07063030	EARLY_PHASE1	RECRUITING	A Study of LX107 Gene Therapy in AIPL1-IRD Patients
NCT01546181	Not specified	COMPLETED	Retinal Imaging by Adaptive Optics in Healthy Eyes and During Retinal and General Diseases
NCT01876147	Not specified	COMPLETED	Visual and Functional Assessment in Low Vision Patients
NCT01920867	Not specified	UNKNOWN	Stem Cell Ophthalmology Treatment Study
NCT02014389	Not specified	RECRUITING	Evaluation of Objective Perimetry Using Chromatic Multifocal Pupillometer
NCT02983305	Not specified	COMPLETED	Optical Head-Mounted Display Technology for Low Vision Rehabilitation
NCT03592017	Not specified	COMPLETED	Performance of Long-wavelength Autofluorescence Imaging
NCT03662386	Not specified	TERMINATED	Prospective Analysis of Genotype-phenotype Correlations Observed in a Large Cohort of Patients With Hereditary Retinal Dystrophies - GEPHIRD
NCT03691168	Not specified	UNKNOWN	Multi-center Observation of the Natural Course of Inherited Retinal Dystrophies
NCT03843840	Not specified	COMPLETED	Dual Wavelength OCT
NCT03853252	Not specified	COMPLETED	iPS Cells of Patients for Models of Retinal Dystrophies
NCT05130385	Not specified	UNKNOWN	High Resolution Optical Coherence Tomography
NCT05294978	Not specified	RECRUITING	EyeConic: Qualification for Cone-Optogenetics
NCT05573984	Not specified	ACTIVE_NOT_RECRUITING	Natural History of PRPF31 Mutation-Associated Retinal Dystrophy
NCT05793515	Not specified	COMPLETED	Mechanisms of Inherited Retinal Dystrophies Using Whole Genome Sequencing and in Vitro and in Vivo Models
NCT05820100	Not specified	COMPLETED	Observational Study to Assess the Reliability and Validity of the MLYMT and MLSDT
NCT05976139	Not specified	RECRUITING	Micropulsed Laser in Patients With Macular Oedema in Retinal Dystrophies
NCT06162585	Not specified	ACTIVE_NOT_RECRUITING	Non-Interventional Long Term Follow-up Study of Participants Previously Enrolled in the RESTORE Study
NCT06177977	Not specified	RECRUITING	SS-HH-OCT as a Novel Diagnostic Modality for Early-Onset Retinal Dystrophies (EORDs)
NCT06375239	Not specified	RECRUITING	Observational Study to Assess Endpoint Operational Feasibility & Measurement Properties in Patients with Retinal Degeneration