KNTC1

protein-coding

kinetochore associated 1, the group of RZZ complex

Gene summary

This gene encodes a protein that is one of many involved in mechanisms to ensure proper chromosome segregation during cell division. Experimental evidence indicated that the encoded protein functioned in a similar manner to that of the Drosophila rough deal protein. [provided by RefSeq, Jul 2008]

MANE transcript

NM_014708.6

Inheritance

—

ClinVar variants

U:260B:10

Top phenotype

Prostate cancer

gnomAD constraint

pLI —, LoF o/e 0.69

Max pathogenic AF

—

Genomic locus

chr12:122,527,246-122,626,396

External References & Databases

Ensembl (ENSG00000184445)

Transcript & Mutation Effects

hg38 • Region Span ~99.2 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to KNTC1 variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 229

not providedTotal: 3

Prostate cancerTotal: 1

MicrocephalyTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_014708.6. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			6 clinvar	3 clinvar		9
missense			233 clinvar	7 clinvar		240
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			20 clinvar			20
Total	0	0	260	10	0	270

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 21 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_014708.6	RefSeq	NP_055523.1	63	MANE Select
ENST00000333479.12	Ensembl	ENSP00000328236.6	63	MANE Select
ENST00000423927.2	Ensembl	ENSP00000397140.2	3	Standard
ENST00000436959.7	Ensembl	ENSP00000408760.2	5	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

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

Biological Process

mitotic cell cycle checkpoint
regulation of exit from mitosis
cell division
protein-containing complex assembly

Molecular Function

protein binding

Cellular Component

condensed chromosome kinetochore
spindle pole
nucleus
kinetochore microtubule
cytosol

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000333479
Coding exons: 63
Length: 99151
Individuals with no LoFs: 124407
Homozygous LoFs: 0
Heterozygous LoFs: 251
Defined: 124658
p: 0.00101

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.913	968	1.05e+3	0.921	0.0000526	14424
Missense (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

Population LoF Frequency

Population	CAF	p-value	Status
African	0.0013	0.0012	notable
Latino/Admixed American	0.0013	0.0012	notable
Ashkenazi Jewish	0.00030	0.00030	rare
East Asian	0.0017	0.0017	notable
Finnish	0.00035	0.00032	rare
European (Non-Finnish)	0.0011	0.0011	notable
South Asian	0.00090	0.00088	rare
Other	0.00055	0.00050	rare

dbNSFP Gene Annotations

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}.;

Recessive Scores

pRec: 0.145

Intolerance Scores

LoFtool: 0.998
RVIS EVS: 0.49
RVIS percentile EVS: 79.48

Essentials

Essential (CRISPR): E
Essential (CRISPR2): E
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.765

Gene Damage Prediction

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