SPA17

protein-coding

sperm autoantigenic protein 17

Gene summary

This gene encodes a protein present at the cell surface. The N-terminus has sequence similarity to human cAMP-dependent protein kinase A (PKA) type II alpha regulatory subunit (RIIa) while the C-terminus has an IQ calmodulin-binding motif. The central portion of the protein has carbohydrate binding motifs and likely functions in cell-cell adhesion. The protein was initially characterized by its involvement in the binding of sperm to the zona pellucida of the oocyte. Recent studies indicate that it is also involved in additional cell-cell adhesion functions such as immune cell migration and metastasis. A retrotransposed pseudogene is present on chromosome 10q22.[provided by RefSeq, Jan 2009]

MANE transcript

NM_017425.4

Inheritance

—

ClinVar variants

P:1U:25B:1

Top phenotype

Primary ciliary dyskinesia

gnomAD constraint

pLI —, LoF o/e 0.62

Max pathogenic AF

—

Genomic locus

chr11:124,673,844-124,697,518

External References & Databases

Ensembl (ENSG00000064199)

Transcript & Mutation Effects

hg38 • Region Span ~23.7 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 SPA17 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 21

not providedTotal: 1

Primary ciliary dyskinesiaTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_017425.4. 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			3 clinvar			3
missense			21 clinvar	1 clinvar		22
nonsense		1 clinvar				1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	1	25	1	0	27

Highest pathogenic variant AF is 0.0000021029934

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 22 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_017425.4	RefSeq	NP_059121.1	4	MANE Select
ENST00000227135.7	Ensembl	ENSP00000227135.2	4	MANE Select
ENST00000532692.1	Ensembl	ENSP00000432305.1	4	Standard
ENST00000532692.2	Ensembl	ENSP00000432305.1	4	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
spa17	Danio rerio	Structure: otolith Quality: morphology abnormal

Gene / Model

Organism

Observed Phenotype

spa17

Danio rerio

Structure: otolith

Quality: morphology

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

epithelial cilium movement
spermatogenesis
single fertilization
binding of sperm to zona pellucida

Molecular Function

protein binding
calmodulin binding

Cellular Component

cytoplasm
cilium
external side of plasma membrane
motile cilium
sperm fibrous sheath

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000532692
Coding exons: 4
Length: 23721
Individuals with no LoFs: 125733
Homozygous LoFs: 0
Heterozygous LoFs: 11
Defined: 125744
p: 0.0000437

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.158	86	82.0	1.05	0.00000434	1005
Missense (PolyPhen)		30	33.413	0.89784		371
Synonymous	-0.143	29	28.0	1.03	0.00000151	265
Loss of Function	0.902	4	6.48	0.617	3.60e-7	70

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000063	0.000062	rare
Latino/Admixed American	0.000066	0.000058	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00022	0.00022	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000018	0.000018	rare
South Asian	0	0.0	absent
Other	0.00033	0.00033	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Sperm surface zona pellucida binding protein. Helps to bind spermatozoa to the zona pellucida with high affinity. Might function in binding zona pellucida and carbohydrates (By similarity). {ECO:0000250}.;

Recessive Scores

pRec: 0.0514

Intolerance Scores

LoFtool: 0.495
RVIS EVS: 0.08
RVIS percentile EVS: 59.76

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.539

Gene Damage Prediction

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