SPC24

SPC24 component of NDC80 kinetochore complex, the group of NDC80 kinetochore complex

Basic information

Region (hg38): 19:11131519-11155807

Previous symbols: [ "SPBC24" ]

Links

ENSG00000161888 ∙ NCBI:147841 ∙ OMIM:609394 ∙ HGNC:26913 ∙ Uniprot:Q8NBT2 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SPC24 gene.

• Inborn genetic diseases (6 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SPC24 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						0
missense			6			6
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	6	0	0

Variants in SPC24

This is a list of pathogenic ClinVar variants found in the SPC24 region.

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

Position	Type	Phenotype	Significance	ClinVar
19-11131539-G-A		Hypercholesterolemia, familial, 1	Likely benign (Jan 13, 2018)
19-11131603-C-A		Hypercholesterolemia, familial, 1	Uncertain significance (Jan 13, 2018)
19-11131631-G-C		Hypercholesterolemia, familial, 1 • Familial hypercholesterolemia	Benign/Likely benign (Jan 22, 2024)
19-11131654-G-A		Hypercholesterolemia, familial, 1	Likely benign (Jan 13, 2018)
19-11131688-C-A		Hypercholesterolemia, familial, 1	Uncertain significance (Jun 14, 2016)
19-11131692-C-A		Hypercholesterolemia, familial, 1	Uncertain significance (Jan 13, 2018)
19-11131736-C-A		Hypercholesterolemia, familial, 1	Uncertain significance (Jan 12, 2018)
19-11131819-C-T		Hypercholesterolemia, familial, 1	Uncertain significance (Jun 14, 2016)
19-11131820-G-A		Hypercholesterolemia, familial, 1	Benign/Likely benign (Jan 13, 2018)
19-11131833-C-A		Hypercholesterolemia, familial, 1	Likely benign (Jan 12, 2018)
19-11131839-G-T		Hypercholesterolemia, familial, 1	Uncertain significance (Jun 14, 2016)
19-11131849-G-T		Hypercholesterolemia, familial, 1	Uncertain significance (Jan 13, 2018)
19-11131879-G-T		Hypercholesterolemia, familial, 1	Uncertain significance (Jun 14, 2016)
19-11131895-G-T		Hypercholesterolemia, familial, 1	Uncertain significance (Jun 14, 2016)
19-11131900-G-T		Hypercholesterolemia, familial, 1	Uncertain significance (Jan 12, 2018)
19-11131969-G-C		Hypercholesterolemia, familial, 1	Uncertain significance (Jan 13, 2018)
19-11131982-T-C		Hypercholesterolemia, familial, 1	Benign/Likely benign (Jan 13, 2018)
19-11132020-G-A		Hypercholesterolemia, familial, 1	Uncertain significance (Mar 23, 2018)
19-11132032-C-T		Hypercholesterolemia, familial, 1	Uncertain significance (Jan 13, 2018)
19-11132083-G-C		Hypercholesterolemia, familial, 1	Uncertain significance (Jan 12, 2018)
19-11132089-A-G		Hypercholesterolemia, familial, 1	Benign/Likely benign (Feb 08, 2019)
19-11132100-C-T		Hypercholesterolemia, familial, 1	Uncertain significance (Jun 14, 2016)
19-11132119-C-T		Hypercholesterolemia, familial, 1	Likely benign (Feb 11, 2019)
19-11132120-G-A		Hypercholesterolemia, familial, 1	Uncertain significance (Jan 13, 2018)
19-11132124-T-G		Hypercholesterolemia, familial, 1	Uncertain significance (Jan 12, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SPC24	protein_coding	protein_coding	ENST00000592540	5	24289

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.000143	0.670	124612	0	8	124620	0.0000321

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.709	78	97.7	0.798	0.00000517	1251
Missense in Polyphen		21	29.314	0.71639		389
Synonymous	1.18	33	42.9	0.770	0.00000261	359
Loss of Function	0.834	7	9.82	0.713	5.03e-7	108

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000936	0.0000935
Ashkenazi Jewish	0.0000994	0.0000994
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000357	0.0000354
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.000165	0.000165

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Acts as a component of the essential kinetochore- associated NDC80 complex, which is required for chromosome segregation and spindle checkpoint activity (PubMed:14738735). Required for kinetochore integrity and the organization of stable microtubule binding sites in the outer plate of the kinetochore (PubMed:14738735). The NDC80 complex synergistically enhances the affinity of the SKA1 complex for microtubules and may allow the NDC80 complex to track depolymerizing microtubules (PubMed:23085020). {ECO:0000269|PubMed:14738735, ECO:0000269|PubMed:23085020}.
• Pathway: Signal Transduction;Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal;Amplification of signal from the kinetochores;Mitotic Spindle Checkpoint;Cell Cycle Checkpoints;RHO GTPases Activate Formins;RHO GTPase Effectors;Signaling by Rho GTPases;Mitotic Prometaphase;Separation of Sister Chromatids;Mitotic Anaphase;Mitotic Metaphase and Anaphase;M Phase;Cell Cycle;Resolution of Sister Chromatid Cohesion;Cell Cycle, Mitotic;PLK1 signaling events (Consensus)

Recessive Scores

• pRec: 0.119

Intolerance Scores

• loftool: 0.522
• rvis_EVS: 0.41
• rvis_percentile_EVS: 76.67

Haploinsufficiency Scores

• pHI: 0.0861
• hipred: Y
• hipred_score: 0.551
• ghis: 0.555

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.945

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Spc24

Gene ontology

• Biological process: cell cycle;cell division
• Cellular component: condensed chromosome kinetochore;nucleus;nucleolus;cytosol;Ndc80 complex
• Molecular function: protein binding