SPC25

SPC25 component of NDC80 kinetochore complex, the group of NDC80 kinetochore complex

Basic information

Region (hg38): 2:168834131-168913371

Previous symbols: [ "SPBC25" ]

Links

ENSG00000152253 ∙ NCBI:57405 ∙ OMIM:609395 ∙ HGNC:24031 ∙ Uniprot:Q9HBM1 ∙ 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 SPC25 gene.

• Inborn genetic diseases (8 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SPC25 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			8			8
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	8	0	0

Variants in SPC25

This is a list of pathogenic ClinVar variants found in the SPC25 region.

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

Position	Type	Phenotype	Significance	ClinVar
2-168834321-G-A			Benign (Jul 06, 2018)
2-168851280-G-A		not specified	Uncertain significance (Feb 10, 2022)
2-168851286-C-T		not specified	Uncertain significance (Jul 05, 2022)
2-168851322-A-G		not specified	Uncertain significance (Jan 23, 2024)
2-168851328-A-T		not specified	Uncertain significance (Nov 08, 2022)
2-168851367-C-T		not specified	Uncertain significance (Dec 19, 2023)
2-168856702-T-C		not specified	Uncertain significance (Aug 10, 2021)
2-168856757-C-G		not specified	Uncertain significance (Sep 27, 2021)
2-168856770-A-G		not specified	Uncertain significance (Dec 21, 2023)
2-168859599-C-T		not specified	Uncertain significance (May 25, 2022)
2-168859617-A-G		not specified	Uncertain significance (Aug 23, 2021)
2-168860822-T-A		not specified	Uncertain significance (Mar 04, 2024)
2-168860825-C-T		not specified	Conflicting classifications of pathogenicity (Sep 16, 2021)
2-168860907-C-T			Benign (Mar 29, 2018)
2-168861971-G-A		not specified	Uncertain significance (Apr 12, 2022)
2-168861998-G-T		not specified	Uncertain significance (Sep 15, 2022)
2-168864854-G-A		not specified	Uncertain significance (Sep 15, 2021)
2-168871444-G-A		not specified	Likely benign (Nov 14, 2023)
2-168871505-C-T		not specified	Uncertain significance (Dec 31, 2023)
2-168871532-C-G		not specified	Uncertain significance (Sep 22, 2022)
2-168871550-C-G		not specified	Uncertain significance (Nov 07, 2022)
2-168873630-G-T		not specified	Uncertain significance (Nov 30, 2021)
2-168873631-G-T		not specified	Uncertain significance (Oct 26, 2021)
2-168873678-T-G		not specified	Uncertain significance (Jul 06, 2021)
2-168876135-T-C		not specified	Uncertain significance (Dec 15, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SPC25	protein_coding	protein_coding	ENST00000282074	6	79240

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0255	0.963	125693	0	39	125732	0.000155

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.679	90	110	0.818	0.00000540	1492
Missense in Polyphen		9	16.814	0.53526		252
Synonymous	0.870	35	42.2	0.830	0.00000230	383
Loss of Function	2.21	5	13.9	0.360	9.53e-7	153

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000102	0.000102
Ashkenazi Jewish	0.00	0.00
East Asian	0.000123	0.000109
Finnish	0.00	0.00
European (Non-Finnish)	0.000179	0.000176
Middle Eastern	0.000123	0.000109
South Asian	0.000442	0.000425
Other	0.000164	0.000163

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:14699129, PubMed:14738735). Required for kinetochore integrity and the organization of stable microtubule binding sites in the outer plate of the kinetochore (PubMed:14738735, PubMed:14699129). 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:14699129, 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 (Consensus)

Recessive Scores

• pRec: 0.118

Intolerance Scores

• loftool: 0.576
• rvis_EVS: 0.01
• rvis_percentile_EVS: 54.95

Haploinsufficiency Scores

• pHI: 0.493
• hipred: Y
• hipred_score: 0.746
• ghis: 0.689

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.643

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Spc25

Gene ontology

• Biological process: mitotic spindle organization;chromosome segregation;cell division
• Cellular component: condensed chromosome kinetochore;nucleus;cytosol;Ndc80 complex
• Molecular function: protein binding