KNSTRN

protein-coding

kinetochore localized astrin (SPAG5) binding protein

Gene summary

Enables microtubule plus-end binding activity and protein homodimerization activity. Involved in several processes, including cellular response to epidermal growth factor stimulus; mitotic sister chromatid segregation; and regulation of attachment of spindle microtubules to kinetochore. Located in kinetochore; microtubule cytoskeleton; and ruffle. Implicated in actinic keratosis and skin squamous cell carcinoma. [provided by Alliance of Genome Resources, Jun 2026]

Previous symbols:

C15orf23

MANE transcript

NM_033286.4

Inheritance

—

ClinVar variants

P:1U:61B:10

Top phenotype

Combined immunodeficiency with faciooculoskeletal anomalies

gnomAD constraint

pLI —, LoF o/e 0.61

Max pathogenic AF

—

Genomic locus

chr15:40,382,721-40,394,288

External References & Databases

Ensembl (ENSG00000128944)

Transcript & Mutation Effects

hg38 • Region Span ~11.6 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 KNSTRN variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 64

not providedTotal: 5

Combined immunodeficiency with faciooculoskeletal anomaliesTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_033286.4. 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				1 clinvar		1
missense			57 clinvar	9 clinvar		66
nonsense						0
start loss						0
frameshift	1 clinvar					1
splice donor/acceptor (+/-2bp)			4 clinvar			4
Total	1	0	61	10	0	72

Highest pathogenic variant AF is 0.00014373282

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 16 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_033286.4	RefSeq	NP_150628.3	9	MANE Select
ENST00000249776.13	Ensembl	ENSP00000249776.8	9	MANE Select
NM_001142761.1	RefSeq	NP_001136233.1	9	Standard
NM_001142762.1	RefSeq	NP_001136234.1	7	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

mitotic sister chromatid segregation
spindle organization
chromosome segregation
cell division
regulation of attachment of spindle microtubules to kinetochore

Molecular Function

protein binding

Cellular Component

kinetochore
condensed chromosome kinetochore
spindle pole
nucleus
cytosol

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000249776
Coding exons: 9
Length: 11526
Individuals with no LoFs: 124725
Homozygous LoFs: 0
Heterozygous LoFs: 69
Defined: 124794
p: 0.000276

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.463	184	167	1.10	0.00000800	2037
Missense (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

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.00032	0.00032	rare
Ashkenazi Jewish	0.000099	0.000099	rare
East Asian	0.00034	0.00033	rare
Finnish	0.00037	0.00037	rare
European (Non-Finnish)	0.00028	0.00028	rare
South Asian	0.00023	0.00023	rare
Other	0.00066	0.00066	rare

dbNSFP Gene Annotations

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

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): H

Gene Damage Prediction

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