SPAG5

protein-coding

sperm associated antigen 5

Gene summary

This gene encodes a protein associated with the mitotic spindle apparatus. The encoded protein may be involved in the functional and dynamic regulation of mitotic spindles. [provided by RefSeq, Jul 2008]

MANE transcript

NM_006461.4

Inheritance

—

ClinVar variants

U:149B:25

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.54

Max pathogenic AF

—

Genomic locus

chr17:28,577,565-28,599,025

External References & Databases

Ensembl (ENSG00000076382)

Transcript & Mutation Effects

hg38 • Region Span ~21.5 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 SPAG5 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 157

not providedTotal: 8

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_006461.4. 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			4 clinvar	3 clinvar	1 clinvar	8
missense			142 clinvar	21 clinvar		163
nonsense						0
start loss			1 clinvar			1
frameshift						0
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	149	24	1	174

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 37 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_006461.4	RefSeq	NP_006452.3	24	MANE Select
ENST00000321765.10	Ensembl	ENSP00000323300.5	24	MANE Select
ENST00000378976.5	Ensembl	ENSP00000466021.1	6	Standard
ENST00000536674.2	Ensembl	ENSP00000444223.2	3	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

mitotic sister chromatid segregation
spindle organization
chromosome segregation
positive regulation of intracellular transport
cell division

Molecular Function

protein binding
microtubule binding

Cellular Component

kinetochore
condensed chromosome kinetochore
cytoplasm
midbody
centriolar satellite

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000321765
Coding exons: 24
Length: 21710
Individuals with no LoFs: 125357
Homozygous LoFs: 6
Heterozygous LoFs: 385
Defined: 125748
p: 0.00156

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.18	533	616	0.866	0.0000327	7795
Missense (PolyPhen)		168	186.25	0.90203		2583
Synonymous	0.466	225	234	0.961	0.0000115	2341
Loss of Function	3.40	35	64.4	0.543	0.00000323	736

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00012	0.00012	rare
Latino/Admixed American	0.00023	0.00023	rare
Ashkenazi Jewish	0.00050	0.00050	rare
East Asian	0.00033	0.00033	rare
Finnish	0.000093	0.000092	rare
European (Non-Finnish)	0.00042	0.00042	rare
South Asian	0.011	0.010	notable
Other	0.00033	0.00033	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Essential component of the mitotic spindle required for normal chromosome segregation and progression into anaphase (PubMed:11724960, PubMed:12356910, PubMed:27462074). Required for chromosome alignment, normal timing of sister chromatid segregation, and maintenance of spindle pole architecture (PubMed:17664331, PubMed:27462074). In complex with SKAP, promotes stable microtubule-kinetochore attachments. May contribute to the regulation of separase activity. May regulate AURKA localization to mitotic spindle, but not to centrosomes and CCNB1 localization to both mitotic spindle and centrosomes (PubMed:18361916, PubMed:21402792). Involved in centriole duplication. Required for CDK5RAP2, CEP152, WDR62 and CEP63 centrosomal localization and promotes the centrosomal localization of CDK2 (PubMed:26297806). In non-mitotic cells, upon stress induction, inhibits mammalian target of rapamycin complex 1 (mTORC1) association and recruits the mTORC1 component RPTOR to stress granules (SGs), thereby preventing mTORC1 hyperactivation-induced apoptosis (PubMed:23953116). May enhance GSK3B-mediated phosphorylation of other substrates, such as MAPT/TAU (PubMed:18055457). {ECO:0000269|PubMed:12356910, ECO:0000269|PubMed:17664331, ECO:0000269|PubMed:18055457, ECO:0000269|PubMed:18361916, ECO:0000269|PubMed:21402792, ECO:0000269|PubMed:23953116, ECO:0000269|PubMed:26297806, ECO:0000269|PubMed:27462074, ECO:0000305|PubMed:11724960}.;

Recessive Scores

pRec: 0.135

Intolerance Scores

LoFtool: 0.246
RVIS EVS: -0.39
RVIS percentile EVS: 27.08

Essentials

Essential (CRISPR): E
Essential (CRISPR2): S
Essential (gene trap): E
Indispensability pred.: N
Indispensability score: 0.233

Gene Damage Prediction

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