ZWILCH

zwilch kinetochore protein, the group of RZZ complex

Basic information

Region (hg38): 15:66504959-66550130

Links

ENSG00000174442 ∙ NCBI:55055 ∙ OMIM:609984 ∙ HGNC:25468 ∙ Uniprot:Q9H900 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• autism spectrum disorder (Limited), mode of inheritance: AD

ClinVar

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

• not_specified (71 variants)
• not_provided (6 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ZWILCH gene is commonly pathogenic or not. These statistics are base on transcript: NM_000017975.5. Only rare variants are included in the table.

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.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				1		1
missense			69	3	1	73
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	69	4	1

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ZWILCH	protein_coding	protein_coding	ENST00000307897	18	44819

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.20e-13	0.482	125688	0	60	125748	0.000239

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.387	317	298	1.06	0.0000142	3911
Missense in Polyphen		107	95.743	1.1176		1348
Synonymous	-0.626	110	102	1.08	0.00000501	1055
Loss of Function	1.46	25	34.2	0.731	0.00000145	449

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000318	0.000311
Ashkenazi Jewish	0.00	0.00
East Asian	0.000220	0.000217
Finnish	0.0000930	0.0000924
European (Non-Finnish)	0.000259	0.000255
Middle Eastern	0.000220	0.000217
South Asian	0.000474	0.000457
Other	0.000522	0.000489

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. Its function related to the spindle assembly machinery is proposed to depend on its association in the mitotic RZZ complex (PubMed:15824131). {ECO:0000269|PubMed:15824131}.
• 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: 0.0773

Intolerance Scores

• loftool: 0.914
• rvis_EVS: 0.04
• rvis_percentile_EVS: 57.41

Haploinsufficiency Scores

• pHI: 0.363
• hipred: N
• hipred_score: 0.321
• ghis: 0.643

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.434

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Zwilch
• Phenotype: growth/size/body region 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); cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); embryo phenotype

Gene ontology

• Biological process: mitotic cell cycle checkpoint;cell division
• Cellular component: kinetochore;condensed chromosome kinetochore;cytosol;RZZ complex
• Molecular function: protein binding