KNSTRN

kinetochore localized astrin (SPAG5) binding protein

Basic information

Region (hg38): 15:40382721-40394288

Previous symbols: [ "C15orf23" ]

Links

ENSG00000128944 ∙ NCBI:90417 ∙ OMIM:614718 ∙ HGNC:30767 ∙ Uniprot:Q9Y448 ∙ 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 KNSTRN gene.

• not_specified (57 variants)
• not_provided (4 variants)
• Combined_immunodeficiency_with_faciooculoskeletal_anomalies (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the KNSTRN gene is commonly pathogenic or not. These statistics are base on transcript: NM_000033286.4. 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			50	8		58
nonsense						0
start loss						0
frameshift	1					1
splice donor/acceptor (+/-2bp)						0
Total	1	0	50	9	0

Highest pathogenic variant AF is 0.00014373282

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
KNSTRN	protein_coding	protein_coding	ENST00000249776	9	11526

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00000213	0.903	124725	0	69	124794	0.000276

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.463	184	167	1.10	0.00000800	2037
Missense in Polyphen		37	47.393	0.78071		695
Synonymous	-1.10	78	66.6	1.17	0.00000314	604
Loss of Function	1.63	12	19.8	0.605	0.00000112	218

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000320	0.000320
Ashkenazi Jewish	0.0000995	0.0000993
East Asian	0.000343	0.000334
Finnish	0.000374	0.000371
European (Non-Finnish)	0.000283	0.000282
Middle Eastern	0.000343	0.000334
South Asian	0.000232	0.000229
Other	0.000662	0.000660

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Essential component of the mitotic spindle required for faithful chromosome segregation and progression into anaphase (PubMed:19667759). Promotes the metaphase-to-anaphase transition and is required for chromosome alignment, normal timing of sister chromatid segregation, and maintenance of spindle pole architecture (PubMed:19667759, PubMed:22110139). The astrin (SPAG5)-kinastrin (SKAP) complex promotes stable microtubule- kinetochore attachments (PubMed:21402792). Required for kinetochore oscillations and dynamics of microtubule plus-ends during live cell mitosis, possibly by forming a link between spindle microtubule plus-ends and mitotic chromosomes to achieve faithful cell division (PubMed:23035123). May be involved in UV- induced apoptosis via its interaction with PRPF19; however, these results need additional evidences (PubMed:24718257). {ECO:0000269|PubMed:19667759, ECO:0000269|PubMed:21402792, ECO:0000269|PubMed:22110139, ECO:0000269|PubMed:23035123, ECO:0000305|PubMed:24718257}.
• Disease: DISEASE: Note=Cutaneous squamous cell carcinomas (SCC): A malignancy of the skin. The hallmark of cutaneous SCC is malignant transformation of normal epidermal keratinocytes. Disease susceptibility is associated with variations affecting the gene represented in this entry. Variant Phe-24 appears specific for UV- associated malignancies (PubMed:25194279). {ECO:0000269|PubMed:25194279}.

Recessive Scores

• pRec: 0.0943

Intolerance Scores

• rvis_EVS: 1.31
• rvis_percentile_EVS: 94

Haploinsufficiency Scores

• pHI: 0.173
• hipred: N
• hipred_score: 0.123
• ghis: 0.553

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: H

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Knstrn
• Phenotype: cellular phenotype; endocrine/exocrine gland phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); hematopoietic system phenotype; reproductive system phenotype

Gene ontology

• Biological process: mitotic sister chromatid segregation;spindle organization;chromosome segregation;cell division;regulation of attachment of spindle microtubules to kinetochore
• Cellular component: kinetochore;condensed chromosome kinetochore;spindle pole;nucleus;cytosol;microtubule cytoskeleton;microtubule plus-end;mitotic spindle
• Molecular function: protein binding