AURKC

protein-coding

aurora kinase C

Gene summary

This gene encodes a member of the Aurora subfamily of serine/threonine protein kinases. The encoded protein is a chromosomal passenger protein that forms complexes with Aurora-B and inner centromere proteins and may play a role in organizing microtubules in relation to centrosome/spindle function during mitosis. This gene is overexpressed in several cancer cell lines, suggesting an involvement in oncogenic signal transduction. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2008]

Previous symbols:

STK13

MANE transcript

NM_001015878.2

Inheritance

ClinVar variants

P:8U:46B:4

Top phenotype

Spermatogenic failure 5

gnomAD constraint

pLI —, LoF o/e 0.32

Max pathogenic AF

—

Genomic locus

chr19:57,231,009-57,235,548

External References & Databases

Ensembl (ENSG00000105146)

Transcript & Mutation Effects

hg38 • Region Span ~4.5 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

spermatogenic failure 5STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0009461

Submitter: Labcorp Genetics (formerly Invitae)

spermatogenic failure 5DEFINITIVE

Inheritance Pattern: AR

Disease ID:MONDO:0009461

Submitter: ClinGen

The Male Infertility GCEP’s preferred term for this curation is “macrozoospermia with multiflagellar polyploid spermatozoa,” which is an exact synonym for “spermatogenic failure 5" (MONDO:0009461). *AURKC* was first reported in relation to autosomal recessive macrozoospermia with multiflagellar polyploid spermatozoa in 2007 (Dieterich et al., PMID: 17435757). Macrozoospermia is a severe male infertility disorder characterized by large-headed, often multiflagellated spermatozoa with abnormal chromosomal content. Over 100 affected individuals have been reported in the literature carrying biallelic *AURKC* variants. The majority of reported cases harbor a recurrent frameshift variant, NM_001015878.2(AURKC):c.145del (p.Leu49TrpfsTer23), particularly in individuals of North African origin. Three variants (e.g. frameshift, nonsense, and splice site) that have been reported in fifteen probands in three publications (PMIDs: 17435757, 25755131, 21733974) are included in this curation. In all reported cases, affected men carry biallelic variants, while fertile parents are heterozygous carriers, consistent with an autosomal recessive mode of inheritance. More evidence is available in the literature, but the maximum score for genetic evidence (12 pts.) has been reached. The mechanism of pathogenicity is believed to be biallelic loss of function. This gene disease relationship is also supported by expression and protein localization studies, in vitro functional assays, and a mouse knockout model demonstrating impaired spermatogenesis and abnormal sperm morphology (PMIDs: 38577799, 16386730, 17192404). In summary, there is definitive evidence to support the relationship between *AURKC* and autosomal recessive macrozoospermia with multiflagellar polyploid spermatozoa. This has been repeatedly demonstrated in both the research and clinical diagnostic settings and has been upheld over time. This classification was approved by the ClinGen Male Infertility GCEP on January 7, 2026 (SOP v11).

spermatogenic failure 5SUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0009461

Submitter: Orphanet

spermatogenic failure 5STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0009461

Submitter: Laboratory for Molecular Medicine

This gene-disease relationship has undergone rapid assessment. Classifications are based on preliminary review of gene-disease validity during analysis of genomic sequencing results.

spermatogenic failure 5STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0009461

Submitter: PanelApp Australia

spermatogenic failure 5STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0009461

Submitter: Ambry Genetics

Clinical Genomic Database (CGD)

Spermatogenic failure 5AR

Manifestation: Genitourinary

Intervention: General

Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing

Refs: 17435757; 19147683; 21733974; 22888167

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to AURKC variants in ClinVar

7 Conditions Cataloged

Inborn genetic diseasesTotal: 33

Infertility associated with multi-tailed spermatozoa and excessive DNATotal: 23

not providedTotal: 12

AURKC-related disorderTotal: 5

not specifiedTotal: 2

MacrozoospermiaTotal: 1

Male infertility with spermatogenesis disorderTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001015878.2. 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			7 clinvar	2 clinvar		9
missense	1 clinvar		38 clinvar	1 clinvar	1 clinvar	41
nonsense	1 clinvar					1
start loss						0
frameshift		5 clinvar				5
splice donor/acceptor (+/-2bp)	1 clinvar		1 clinvar			2
Total	3	5	46	3	1	58

Highest pathogenic variant AF is 0.0006492549

Loading ClinVar variants...

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_001015878.2	RefSeq	NP_001015878.1	7	MANE Select
ENST00000302804.12	Ensembl	ENSP00000302898.6	7	MANE Select
NM_001015879.2	RefSeq	NP_001015879.1	7	Standard
NM_003160.3	RefSeq	NP_003151.2	6	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Aurora C signaling
Aurora B signaling

Biological Process

protein phosphorylation
mitotic spindle organization
spermatogenesis
attachment of spindle microtubules to kinetochore
histone modification

Molecular Function

protein kinase activity
protein serine/threonine/tyrosine kinase activity
protein binding
ATP binding
histone serine kinase activity

Cellular Component

condensed nuclear chromosome, centromeric region
condensed chromosome
cytoplasm
spindle
spindle microtubule

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000302804
Coding exons: 7
Length: 4540
Individuals with no LoFs: 125614
Homozygous LoFs: 0
Heterozygous LoFs: 133
Defined: 125747
p: 0.000529

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.502	153	172	0.892	0.0000105	1997
Missense (PolyPhen)		54	73.38	0.7359		888
Synonymous	-0.00864	67	66.9	1.00	0.00000350	623
Loss of Function	2.25	4	12.6	0.317	5.48e-7	169

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0.00087	0.00087	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.00086	0.00085	rare
South Asian	0.000098	0.000098	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Serine/threonine-protein kinase component of the chromosomal passenger complex (CPC), a complex that acts as a key regulator of mitosis. The CPC complex has essential functions at the centromere in ensuring correct chromosome alignment and segregation and is required for chromatin-induced microtubule stabilization and spindle assembly. Plays also a role in meiosis and more particularly in spermatogenesis. Has redundant cellular functions with AURKB and can rescue an AURKB knockdown. Like AURKB, AURKC phosphorylates histone H3 at 'Ser-10' and 'Ser-28'. AURKC phosphorylates the CPC complex subunits BIRC5/survivin and INCENP leading to increased AURKC activity. Phosphorylates TACC1, another protein involved in cell division, at 'Ser-228'. {ECO:0000269|PubMed:15316025, ECO:0000269|PubMed:15499654, ECO:0000269|PubMed:15670791, ECO:0000269|PubMed:15938719, ECO:0000269|PubMed:21493633, ECO:0000269|PubMed:21531210, ECO:0000269|PubMed:27332895}.;
Disease: DISEASE: Spermatogenic failure 5 (SPGF5) [MIM:243060]: An infertility disorder caused by spermatogenesis defects. Semen from affected men show close to 100% morphologically abnormal multiflagellar spermatozoa with low motility, oversized irregular heads, and abnormal midpiece and acrosome. {ECO:0000269|PubMed:17435757, ECO:0000269|PubMed:21733974}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Recessive Scores

pRec: 0.0955

Intolerance Scores

LoFtool: 0.907
RVIS EVS: -0.21
RVIS percentile EVS: 38.58

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.628

Gene Damage Prediction

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