KNTC1

kinetochore associated 1, the group of RZZ complex

Basic information

Region (hg38): 12:122527246-122626396

Links

ENSG00000184445 ∙ NCBI:9735 ∙ OMIM:607363 ∙ HGNC:17255 ∙ Uniprot:P50748 ∙ 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 KNTC1 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the KNTC1 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		3
missense			100	3		103
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	100	6	0

Variants in KNTC1

This is a list of pathogenic ClinVar variants found in the KNTC1 region.

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

Position	Type	Phenotype	Significance	ClinVar
12-122530071-A-G		not specified	Uncertain significance (Jan 03, 2024)
12-122530096-T-A		not specified	Uncertain significance (Mar 29, 2024)
12-122530103-G-A		not specified	Uncertain significance (Aug 12, 2021)
12-122530158-A-G		not specified	Uncertain significance (Dec 14, 2023)
12-122534707-G-A		not specified	Uncertain significance (Aug 19, 2024)
12-122534771-G-C		not specified	Uncertain significance (May 11, 2022)
12-122538384-T-C		not specified	Uncertain significance (May 09, 2023)
12-122538390-T-C		not specified	Uncertain significance (Jan 03, 2024)
12-122538395-G-A		not specified	Uncertain significance (Aug 10, 2021)
12-122538398-A-G		not specified	Uncertain significance (Jul 30, 2024)
12-122538431-T-A		not specified	Uncertain significance (Jun 18, 2021)
12-122539706-C-T		not specified	Uncertain significance (Dec 04, 2023)
12-122539740-A-G		not specified	Uncertain significance (Oct 03, 2022)
12-122542059-A-C		not specified	Uncertain significance (Jan 23, 2023)
12-122542059-A-G		not specified	Uncertain significance (Mar 31, 2024)
12-122542074-C-T		not specified	Uncertain significance (Jul 05, 2024)
12-122543624-C-G		not specified	Uncertain significance (Sep 27, 2022)
12-122546212-G-A		not specified	Uncertain significance (Apr 23, 2024)
12-122546223-G-T		not specified	Uncertain significance (Oct 12, 2024)
12-122546242-A-G		not specified	Uncertain significance (Nov 14, 2024)
12-122547470-C-T		not specified	Uncertain significance (Oct 10, 2023)
12-122547920-G-A		not specified	Uncertain significance (Dec 11, 2023)
12-122551502-C-A		not specified	Uncertain significance (Jun 29, 2022)
12-122551502-C-T		not specified	Uncertain significance (Mar 31, 2023)
12-122551508-C-T		not specified	Uncertain significance (Sep 08, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
KNTC1	protein_coding	protein_coding	ENST00000333479	63	99151

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
5.33e-43	0.779	124407	0	251	124658	0.00101

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.913	968	1.05e+3	0.921	0.0000526	14424
Missense in Polyphen		388	442.46	0.87692		6277
Synonymous	0.543	373	387	0.965	0.0000208	4016
Loss of Function	3.19	87	126	0.693	0.00000613	1720

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00251	0.00248
Ashkenazi Jewish	0.000298	0.000298
East Asian	0.00173	0.00167
Finnish	0.000345	0.000325
European (Non-Finnish)	0.00110	0.00106
Middle Eastern	0.00173	0.00167
South Asian	0.000899	0.000883
Other	0.000552	0.000495

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Essential component of the mitotic checkpoint, which prevents cells from prematurely exiting mitosis. Required for the assembly of the dynein-dynactin and MAD1-MAD2 complexes onto kinetochores (PubMed:11146660, PubMed:11590237, PubMed:15824131). Its function related to the spindle assembly machinery is proposed to depend on its association in the mitotic RZZ complex. {ECO:0000269|PubMed:11146660, ECO:0000269|PubMed:11590237, ECO:0000269|PubMed:15824131, ECO:0000305}.
• 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: 0.145

Intolerance Scores

• loftool: 0.998
• rvis_EVS: 0.49
• rvis_percentile_EVS: 79.48

Haploinsufficiency Scores

• pHI: 0.531
• hipred: N
• hipred_score: 0.319
• ghis: 0.603

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.765

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Kntc1
• Phenotype: mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); pigmentation phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); limbs/digits/tail phenotype; vision/eye phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); homeostasis/metabolism phenotype

Gene ontology

• Biological process: mitotic cell cycle checkpoint;regulation of exit from mitosis;cell division;protein-containing complex assembly
• Cellular component: condensed chromosome kinetochore;spindle pole;nucleus;kinetochore microtubule;cytosol;plasma membrane;actin cytoskeleton;RZZ complex
• Molecular function: protein binding