SPAG8

sperm associated antigen 8

Basic information

Region (hg38): 9:35808045-35812272

Links

ENSG00000137098 ∙ NCBI:26206 ∙ OMIM:605731 ∙ HGNC:14105 ∙ Uniprot:Q99932 ∙ 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 SPAG8 gene.

• Acromesomelic dysplasia 1, Maroteaux type;Tall stature-scoliosis-macrodactyly of the great toes syndrome (3 variants)
• Acromesomelic dysplasia 1, Maroteaux type (2 variants)
• Tall stature-scoliosis-macrodactyly of the great toes syndrome;Acromesomelic dysplasia 1, Maroteaux type (1 variants)
• Epilepsy, familial focal, with variable foci 2 (1 variants)
• NPR2-related disorder (1 variants)
• not provided (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SPAG8 gene is commonly pathogenic or not.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			1	1	3	5
missense			56	1	4	61
nonsense					1	1
start loss						0
frameshift						0
inframe indel			1			1
splice donor/acceptor (+/-2bp)				1		1
splice region				1		1
non coding	6	7	35	18	3	69
Total	6	7	93	21	11

Highest pathogenic variant AF is 0.00000657

Variants in SPAG8

This is a list of pathogenic ClinVar variants found in the SPAG8 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
9-35808216-A-G		not specified	Uncertain significance (Oct 28, 2024)
9-35808237-T-C		not specified	Uncertain significance (Dec 06, 2022)
9-35808262-G-A		not specified	Uncertain significance (Mar 18, 2024)
9-35808266-T-A		not specified	Uncertain significance (Jul 30, 2024)
9-35808277-C-T			Benign (Jun 14, 2018)
9-35808294-T-C		not specified	Uncertain significance (Oct 25, 2023)
9-35808337-C-G			Benign (Nov 12, 2018)
9-35808498-C-T		Acromesomelic dysplasia 1, Maroteaux type;Tall stature-scoliosis-macrodactyly of the great toes syndrome	Likely benign (Oct 18, 2024)
9-35808507-A-T		Acromesomelic dysplasia 1, Maroteaux type;Tall stature-scoliosis-macrodactyly of the great toes syndrome	Likely pathogenic (Nov 02, 2021)
9-35808509-G-T		Acromesomelic dysplasia 1, Maroteaux type	Uncertain significance (Jan 01, 2019)
9-35808516-C-T		Acromesomelic dysplasia 1, Maroteaux type;Tall stature-scoliosis-macrodactyly of the great toes syndrome • Acromesomelic dysplasia 1, Maroteaux type • Short stature with nonspecific skeletal abnormalities	Pathogenic/Likely pathogenic (Sep 01, 2022)
9-35808517-G-A		Acromesomelic dysplasia 1, Maroteaux type • Acromesomelic dysplasia 1, Maroteaux type;Tall stature-scoliosis-macrodactyly of the great toes syndrome	Conflicting classifications of pathogenicity (Jul 01, 2024)
9-35808519-T-C		Acromesomelic dysplasia 1, Maroteaux type;Tall stature-scoliosis-macrodactyly of the great toes syndrome	Uncertain significance (Oct 29, 2024)
9-35808527-G-A		Acromesomelic dysplasia 1, Maroteaux type;Tall stature-scoliosis-macrodactyly of the great toes syndrome	Uncertain significance (Apr 18, 2024)
9-35808528-C-A		Acromesomelic dysplasia 1, Maroteaux type;Tall stature-scoliosis-macrodactyly of the great toes syndrome	Uncertain significance (Apr 10, 2022)
9-35808533-A-AT		Acromesomelic dysplasia 1, Maroteaux type;Tall stature-scoliosis-macrodactyly of the great toes syndrome	Pathogenic (Feb 14, 2023)
9-35808534-T-C		Acromesomelic dysplasia 1, Maroteaux type;Tall stature-scoliosis-macrodactyly of the great toes syndrome	Uncertain significance (Aug 31, 2021)
9-35808535-G-A		Acromesomelic dysplasia 1, Maroteaux type;Tall stature-scoliosis-macrodactyly of the great toes syndrome	Uncertain significance (Apr 23, 2024)
9-35808547-C-A		Acromesomelic dysplasia 1, Maroteaux type;Tall stature-scoliosis-macrodactyly of the great toes syndrome	Likely benign (Oct 30, 2023)
9-35808550-C-A		Acromesomelic dysplasia 1, Maroteaux type;Tall stature-scoliosis-macrodactyly of the great toes syndrome	Likely benign (Dec 20, 2023)
9-35808552-C-T		Acromesomelic dysplasia 1, Maroteaux type;Tall stature-scoliosis-macrodactyly of the great toes syndrome	Uncertain significance (Jan 19, 2022)
9-35808557-C-T		Acromesomelic dysplasia 1, Maroteaux type;Tall stature-scoliosis-macrodactyly of the great toes syndrome • NPR2-related disorder	Pathogenic (Dec 17, 2024)
9-35808558-G-A		Acromesomelic dysplasia 1, Maroteaux type;Tall stature-scoliosis-macrodactyly of the great toes syndrome	Uncertain significance (Jan 21, 2025)
9-35808560-A-C		Acromesomelic dysplasia 1, Maroteaux type;Tall stature-scoliosis-macrodactyly of the great toes syndrome	Uncertain significance (Oct 02, 2024)
9-35808569-C-T		Tall stature-scoliosis-macrodactyly of the great toes syndrome;Acromesomelic dysplasia 1, Maroteaux type	Uncertain significance (Aug 23, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SPAG8	protein_coding	protein_coding	ENST00000340291	8	4228

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.68e-12	0.108	122844	77	2827	125748	0.0116

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.568	253	280	0.905	0.0000145	3211
Missense in Polyphen		39	56.01	0.69631		686
Synonymous	0.128	106	108	0.984	0.00000583	1054
Loss of Function	0.617	20	23.2	0.862	0.00000126	235

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0197	0.0198
Ashkenazi Jewish	0.000497	0.000496
East Asian	0.0792	0.0788
Finnish	0.0430	0.0362
European (Non-Finnish)	0.00202	0.00201
Middle Eastern	0.0792	0.0788
South Asian	0.00183	0.00183
Other	0.00606	0.00588

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Plays a role in spermatogenesis by enhancing the binding of CREM isoform tau to its coactivator FHL5 and increasing the FHL5-regulated transcriptional activation of CREM isoform tau (By similarity). Involved in the acrosome reaction and in binding of sperm to the zona pellucida (By similarity). Plays a role in regulation of the cell cycle by controlling progression through the G2/M phase, possibly by delaying the activation of CDK1 which is required for entry into mitosis (PubMed:19548270). May play a role in fertility and microtubule formation through interaction with RANBP9 (PubMed:10500252). {ECO:0000250|UniProtKB:Q3V0Q6, ECO:0000269|PubMed:10500252, ECO:0000269|PubMed:19548270}.

Recessive Scores

• pRec: 0.105

Intolerance Scores

• loftool: 0.927
• rvis_EVS: 0.87
• rvis_percentile_EVS: 88.82

Haploinsufficiency Scores

• pHI: 0.118
• hipred: N
• hipred_score: 0.123
• ghis: 0.427

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.265

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Spag8

Gene ontology

• Biological process: cell cycle;spermatogenesis;single fertilization;biological_process;cell differentiation;positive regulation of transcription by RNA polymerase II
• Cellular component: acrosomal vesicle;nucleus;cytoplasm;spindle;membrane
• Molecular function: molecular_function;protein binding;microtubule binding