SPAG16

protein-coding

sperm associated antigen 16, the group of WD repeat domain containing|MicroRNA protein coding host genes

Gene summary

Cilia and flagella are comprised of a microtubular backbone, the axoneme, which is organized by the basal body and surrounded by plasma membrane. SPAG16 encodes 2 major proteins that associate with the axoneme of sperm tail and the nucleus of postmeiotic germ cells, respectively (Zhang et al., 2007 [PubMed 17699735]).[supplied by OMIM, Jul 2008]

MANE transcript

NM_024532.5

Inheritance

—

ClinVar variants

P:2U:101B:9

Top phenotype

Fetal akinesia deformation sequence 1

gnomAD constraint

pLI —, LoF o/e 1.34

Max pathogenic AF

—

Genomic locus

chr2:213,284,389-214,410,501

External References & Databases

Ensembl (ENSG00000144451)

Transcript & Mutation Effects

hg38 • Region Span ~1,126.1 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 SPAG16 variants in ClinVar

6 Conditions Cataloged

not specifiedTotal: 103

not providedTotal: 4

Fetal akinesia deformation sequence 1Total: 2

Primary ciliary dyskinesiaTotal: 2

Arthrogryposis multiplex congenitaTotal: 2

SPAG16-related disorderTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_024532.5. 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			2 clinvar			2
missense			98 clinvar	7 clinvar	2 clinvar	107
nonsense		1 clinvar				1
start loss						0
frameshift		1 clinvar				1
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	2	101	7	2	112

Highest pathogenic variant AF is 0.0028344993

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 52 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_024532.5	RefSeq	NP_078808.3	16	MANE Select
ENST00000331683.10	Ensembl	ENSP00000332592.5	16	MANE Select
NM_001025436.3	RefSeq	NP_001020607.1	5	Standard
ENST00000406979.6	Ensembl	ENSP00000385496.2	3	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

sperm axoneme assembly
axoneme assembly
cilium assembly

Cellular Component

axoneme
sperm flagellum
axonemal central apparatus

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000331683
Coding exons: 16
Length: 1126113
Individuals with no LoFs: 125153
Homozygous LoFs: 0
Heterozygous LoFs: 595
Defined: 125748
p: 0.00237

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.869	374	330	1.13	0.0000164	4161
Missense (PolyPhen)		100	92.124	1.0855		1181
Synonymous	-0.669	128	119	1.08	0.00000626	1148
Loss of Function	-1.81	45	33.7	1.34	0.00000171	424

Population LoF Frequency

Population	CAF	p-value	Status
African	0.0011	0.0010	notable
Latino/Admixed American	0.00057	0.00055	rare
Ashkenazi Jewish	0.0022	0.0022	notable
East Asian	0.00016	0.00016	rare
Finnish	0.00079	0.00079	rare
European (Non-Finnish)	0.0038	0.0038	notable
South Asian	0.0022	0.0022	notable
Other	0.0027	0.0026	notable

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Necessary for sperm flagellar function. Plays a role in motile ciliogenesis. May help to recruit STK36 to the cilium or apical surface of the cell to initiate subsequent steps of construction of the central pair apparatus of motile cilia (By similarity). {ECO:0000250}.;

Recessive Scores

pRec: 0.109

Intolerance Scores

LoFtool: 0.541
RVIS EVS: 0.18
RVIS percentile EVS: 66.13

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.417

Gene Damage Prediction

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