ZWINT

protein-coding

ZW10 interacting kinetochore protein, the group of KNL1 complex

Gene summary

This gene encodes a protein that is clearly involved in kinetochore function although an exact role is not known. It interacts with ZW10, another kinetochore protein, possibly regulating the association between ZW10 and kinetochores. The encoded protein localizes to prophase kinetochores before ZW10 does and it remains detectable on the kinetochore until late anaphase. It has a uniform distribution in the cytoplasm of interphase cells. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

MANE transcript

NM_007057.4

Inheritance

—

ClinVar variants

U:60B:3

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.88

Max pathogenic AF

—

Genomic locus

chr10:56,357,227-56,361,273

External References & Databases

Ensembl (ENSG00000122952)

Transcript & Mutation Effects

hg38 • Region Span ~4.0 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 ZWINT variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 53

not providedTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_007057.4. 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			2 clinvar		1 clinvar	3
missense			53 clinvar	2 clinvar		55
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			4 clinvar			4
Total	0	0	60	2	1	63

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 80 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_007057.4	RefSeq	NP_008988.2	8	MANE Select
ENST00000373944.8	Ensembl	ENSP00000363055.3	8	MANE Select
NM_001005413.1	RefSeq	NP_001005413.1	8	Standard
NM_032997.3	RefSeq	NP_127490.1	8	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 sister chromatid segregation
mitotic cell cycle checkpoint
cell division
establishment of localization in cell

Molecular Function

protein binding
protein N-terminus binding

Cellular Component

kinetochore
condensed chromosome kinetochore
nucleus
nucleoplasm
cytoplasm

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000373944
Coding exons: 8
Length: 4048
Individuals with no LoFs: 125723
Homozygous LoFs: 0
Heterozygous LoFs: 25
Defined: 125748
p: 0.0000994

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.502	166	149	1.12	0.00000772	1800
Missense (PolyPhen)		42	46.493	0.90337		630
Synonymous	0.291	55	57.8	0.951	0.00000294	532
Loss of Function	0.507	17	19.4	0.876	0.00000108	196

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0.000099	0.000099	rare
East Asian	0.00022	0.00022	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00011	0.00011	rare
South Asian	0.00020	0.00020	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Part of the MIS12 complex, which is required for kinetochore formation and spindle checkpoint activity. Required to target ZW10 to the kinetochore at prometaphase. {ECO:0000269|PubMed:15094189, ECO:0000269|PubMed:15485811, ECO:0000269|PubMed:15824131, ECO:0000269|PubMed:16732327}.;

Recessive Scores

pRec: 0.106

Intolerance Scores

LoFtool: 0.976
RVIS EVS: 0.82
RVIS percentile EVS: 87.95

Essentials

Essential (CRISPR): E
Essential (CRISPR2): N
Essential (gene trap): K
Indispensability pred.: E
Indispensability score: 0.620

Gene Damage Prediction

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