SPATA16

Summary

SPATA16 (spermatogenesis associated 16, HGNC:29935) is a protein-coding gene on chromosome 3q26.31, encoding Spermatogenesis-associated protein 16 (Q9BXB7). Essential for spermiogenesis and male fertility.

This gene encodes a testis-specific protein that belongs to the tetratricopeptide repeat-like superfamily. The encoded protein localizes to the Golgi apparatus and may play a role in spermatogenesis.

Source: NCBI Gene 83893 — RefSeq curated summary.

At a glance

• Gene–disease (curated): spermatogenic failure 6 (Moderate, GenCC) — +1 more curated relationship
• GWAS associations: 8
• Clinical variants (ClinVar): 117 total
• Phenotypes (HPO): 4
• MANE Select transcript: NM_031955

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29935
Approved symbol	SPATA16
Name	spermatogenesis associated 16
Location	3q26.31
Locus type	gene with protein product
Status	Approved
Aliases	NYD-SP12
Ensembl gene	ENSG00000144962
Ensembl biotype	protein_coding
OMIM	609856
Entrez	83893

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 1 protein_coding, 1 nonsense_mediated_decay

ENST00000351008, ENST00000652082

RefSeq mRNA: 1 — MANE Select: NM_031955 NM_031955

CCDS: CCDS3221

Canonical transcript exons

ENST00000351008 — 11 exons

Exon	Start	End
ENSE00001015460	172924208	172924317
ENSE00001076259	173019486	173019575
ENSE00001076262	172976968	172977052
ENSE00001076264	172956677	172956824
ENSE00001076266	172925346	172925492
ENSE00001151816	172913661	172913744
ENSE00001151821	172916317	172916481
ENSE00001151848	173048949	173049094
ENSE00001203361	173141103	173141235
ENSE00001203364	172889357	172889692
ENSE00001396615	173117120	173117749

Expression profiles

Bgee: expression breadth broad, 30 present calls, max score 94.51.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.1256 / max 100.6081, expressed in 6 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
45648	0.0708	4
45649	0.0350	3
45647	0.0175	4
203031	0.0023	2

Top tissues by expression

216 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
sperm	CL:0000019	94.51	gold quality
left testis	UBERON:0004533	91.38	gold quality
right testis	UBERON:0004534	90.14	gold quality
testis	UBERON:0000473	89.08	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	85.76	gold quality
adult organism	UBERON:0007023	81.05	gold quality
kidney epithelium	UBERON:0004819	78.96	gold quality
nasal cavity epithelium	UBERON:0005384	77.61	gold quality
upper arm skin	UBERON:0004263	75.82	gold quality
cardiac muscle of right atrium	UBERON:0003379	75.74	gold quality
left ventricle myocardium	UBERON:0006566	75.37	gold quality
oocyte	CL:0000023	73.51	gold quality
vastus lateralis	UBERON:0001379	71.39	gold quality
quadriceps femoris	UBERON:0001377	70.82	gold quality
heart right ventricle	UBERON:0002080	70.80	gold quality
secondary oocyte	CL:0000655	70.79	silver quality
myocardium	UBERON:0002349	69.46	gold quality
buccal mucosa cell	CL:0002336	69.13	gold quality
amniotic fluid	UBERON:0000173	66.45	gold quality
oral cavity	UBERON:0000167	63.82	gold quality
epithelial cell of pancreas	CL:0000083	63.79	gold quality
esophagus squamous epithelium	UBERON:0006920	63.76	gold quality
biceps brachii	UBERON:0001507	62.78	gold quality
superficial temporal artery	UBERON:0001614	61.95	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	60.80	gold quality
mucosa of paranasal sinus	UBERON:0005030	60.38	gold quality
deltoid	UBERON:0001476	60.26	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	60.19	gold quality
gingival epithelium	UBERON:0001949	59.77	gold quality
skin of hip	UBERON:0001554	59.27	silver quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.08

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

18 targeting SPATA16, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-4778-3P	99.93	70.40	1818
HSA-MIR-137-3P	99.87	74.74	2401
HSA-MIR-200A-5P	99.76	69.10	949
HSA-MIR-494-3P	99.70	71.45	2795
HSA-MIR-4663	99.62	65.33	957
HSA-MIR-8077	99.17	66.67	862
HSA-MIR-7160-5P	99.11	67.17	2207
HSA-MIR-6506-5P	99.04	65.66	1386
HSA-MIR-619-5P	98.57	64.97	1988
HSA-MIR-5586-5P	96.29	68.02	685
HSA-MIR-541-3P	96.07	66.11	1271
HSA-MIR-654-5P	96.07	66.18	1280
HSA-MIR-5586-3P	95.51	67.00	805

Literature-anchored findings (GeneRIF, showing 10)

• results suggest that NYD-SP12 is involved in spermatogenesis, and that NYD-SP12-encoded protein might function in the Golgi apparatus (PMID:12529416)
• study demonstrated NYD-SP12 protein was involved in the formation of the acrosome during spermatogenesis (PMID:16372119)
• Results indicate that NYD-SP12 evolves rapidly in both the human and the chimpanzee lineages, which is likely caused by Darwinian positive selection and/or sexual selection. (PMID:17665087)
• consanguineous family with three affected brothers, in whom we have identified a homozygous mutation in the spermatogenesis-specific gene SPATA16. This is the first example of a nonsyndromic male infertility condition caused by an autosomal gene defect. (PMID:17847006)
• Case Report: report of a pregnancy obtained in a man with homozygous SPATA16 mutated globozoospermia. (PMID:24825417)
• Mutation of SPATA16 is associated with globozoospermia. (PMID:27086357)
• This study demonstrates that Spata16 is indispensable for male fertility in mice, as well as in humans. (PMID:29065458)
• Study showed that SPATA16 defects could be associated with an abnormal meiosis leading to a particular morphological sperm defect of double/multiple round-headed and multi-flagella and a higher sperm aneuploidy rate than in case of DPY19L2-defects in classic globozoospermia. (PMID:30912172)
• Association of CATSPER1, SPATA16 and TEX11 genes polymorphism with idiopathic azoospermia and oligospermia risk in Iranian population. (PMID:35248021)
• SPATA16 promoter hypermethylation and downregulation in male infertility. (PMID:36177775)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
mus_musculus	Spata16	ENSMUSG00000039335
rattus_norvegicus	Spata16	ENSRNOG00000024521
drosophila_melanogaster	Sgt	FBGN0032640
drosophila_melanogaster	unc-45	FBGN0288846
caenorhabditis_elegans		WBGENE00006781

Paralogs (18): RPAP3 (ENSG00000005175), TOMM34 (ENSG00000025772), ST13 (ENSG00000100380), STUB1 (ENSG00000103266), SPAG1 (ENSG00000104450), SGTA (ENSG00000104969), TTC1 (ENSG00000113312), TTC31 (ENSG00000115282), UNC45A (ENSG00000140553), UNC45B (ENSG00000141161), TTC12 (ENSG00000149292), TOMM70 (ENSG00000154174), SUGT1 (ENSG00000165416), STIP1 (ENSG00000168439), TTC32 (ENSG00000183891), SGTB (ENSG00000197860), TTC4 (ENSG00000243725), DNAAF4 (ENSG00000256061)

Protein

Protein identifiers

Spermatogenesis-associated protein 16 — Q9BXB7 (reviewed: Q9BXB7)

Alternative names: Testis development protein NYD-SP12

All UniProt accessions (3): Q9BXB7, A0A140VJV8, A0A494BZR9

UniProt curated annotations — full annotation on UniProt →

Function. Essential for spermiogenesis and male fertility. Involved in the formation of sperm acrosome during spermatogenesis.

Subcellular location. Golgi apparatus. Cytoplasmic vesicle. Secretory vesicle. Acrosome.

Tissue specificity. Expressed in testis.

Disease relevance. Spermatogenic failure 6 (SPGF6) [MIM:102530] An infertility disorder caused by spermatogenesis defects. The most prominent feature is the malformation of the acrosome, which can be totally absent in most severe cases. Additional features are an abnormal nuclear shape and abnormal arrangement of the mitochondria of the spermatozoon. The disease is caused by variants affecting the gene represented in this entry. An autosomal recessive variation of SPATA16 has been shown to be responsible for the disease in a consanguineous family with members homozygous for the variation.

Miscellaneous. Association analysis reveals significant frequency of a synonymous (Ser-225) sequence polymorphism among clinical groups with different sperm traits: the donor group, which has the highest sperm count and motility level, has a significant higher polymorphism frequency compared to normal and asthenozoopermia groups.

Similarity. Belongs to the SPATA16 family.

RefSeq proteins (1): NP_114161* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR011990	TPR-like_helical_dom_sf	Homologous_superfamily
IPR029161	SPATA16	Family

Pfam: PF15015

UniProt features (14 total): sequence variant 11, chain 1, region of interest 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BXB7-F1	72.84	0.42

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 43 (showing top): GOCC_SECRETORY_GRANULE, ROVERSI_GLIOMA_COPY_NUMBER_UP, GOBP_MALE_GAMETE_GENERATION, chr3q26, AP1_Q4_01, TGANTCA_AP1_C, GOBP_CELLULAR_PROCESS_INVOLVED_IN_REPRODUCTION_IN_MULTICELLULAR_ORGANISM, GOBP_DEVELOPMENTAL_PROCESS_INVOLVED_IN_REPRODUCTION, GOCC_SECRETORY_VESICLE, GOCC_ACROSOMAL_VESICLE, AP1_Q6_01, HMGA1_TARGET_GENES, MIR137_3P, MIR494_3P, MIR9_5P

GO Biological Process (3): spermatogenesis (GO:0007283), spermatid development (GO:0007286), cell differentiation (GO:0030154)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (3): acrosomal vesicle (GO:0001669), Golgi apparatus (GO:0005794), cytoplasmic vesicle (GO:0031410)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cytoplasm	2
developmental process involved in reproduction	1
male gamete generation	1
germ cell development	1
spermatid differentiation	1
cellular developmental process	1
binding	1
secretory granule	1
endomembrane system	1
intracellular membrane-bounded organelle	1
intracellular vesicle	1

Protein interactions and networks

STRING

894 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SPATA16	DPY19L2	Q6NUT2	899
SPATA16	GOLGA3	Q08378	847
SPATA16	MEA1	Q16626	830
SPATA16	GOPC	Q9HD26	813
SPATA16	ZPBP	Q9BS86	789
SPATA16	PICK1	Q9NRD5	742
SPATA16	ACR	P10323	729
SPATA16	SPACA1	Q9HBV2	686
SPATA16	SPACDR	Q8IZ16	679
SPATA16	AURKC	Q9UQB9	673
SPATA16	FAM209A	Q5JX71	627
SPATA16	PLCZ1	Q86YW0	612
SPATA16	SPATA46	Q5T0L3	612
SPATA16	DNAH1	Q9P2D7	611
SPATA16	SPATA31G1	Q5VYM1	598

IntAct

3 interactions, top by confidence:

A	B	Type	Score
SPATA16	Dlg4	psi-mi:“MI:0407”(direct interaction)	0.440
SPATA16	MYH9	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (2): SPATA16 (Proximity Label-MS), SPATA16 (Cross-Linking-MS (XL-MS))

ESM2 similar proteins: A1A5R8, A6H694, A6PVS8, B8A5Y1, D3Z6S9, F1MCA7, P62283, P62285, P62287, P62288, P62289, P62290, P62291, P62292, P62293, P62294, P62296, P62297, P62932, P70587, Q05C16, Q14DL3, Q3U3V8, Q3V0J4, Q497N7, Q4R3V2, Q4R739, Q4V8G0, Q53TS8, Q5CZC0, Q5RA75, Q6AXY2, Q6AYL8, Q6P2D8, Q6PUR7, Q7PCK7, Q7T3T8, Q7Z7J5, Q80TE7, Q86WZ0

Diamond homologs: Q4R3V2, Q8C636, Q9BXB7

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

117 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	92
Likely benign	9
Benign	9

Top pathogenic / likely-pathogenic (0)

SpliceAI

3648 predictions. Top by Δscore:

Variant	Effect	Δscore
3:172913745:C:CC	acceptor_gain	1.0000
3:172913754:C:CT	acceptor_gain	1.0000
3:172916311:ACTT:A	donor_loss	1.0000
3:172916313:TTA:T	donor_loss	1.0000
3:172916314:TAC:T	donor_loss	1.0000
3:172916315:A:AC	donor_gain	1.0000
3:172916315:AC:A	donor_gain	1.0000
3:172916316:C:CT	donor_gain	1.0000
3:172916316:C:G	donor_loss	1.0000
3:172916316:CC:C	donor_gain	1.0000
3:172916316:CCA:C	donor_gain	1.0000
3:172916316:CCAA:C	donor_gain	1.0000
3:172916316:CCAAT:C	donor_gain	1.0000
3:172956671:TCTTA:T	donor_loss	1.0000
3:172956672:CTTAC:C	donor_loss	1.0000
3:172956673:TTAC:T	donor_loss	1.0000
3:172956674:TAC:T	donor_loss	1.0000
3:172956675:ACCTG:A	donor_loss	1.0000
3:172956676:C:T	donor_loss	1.0000
3:172956820:ATGGC:A	acceptor_gain	1.0000
3:172956821:TGGC:T	acceptor_gain	1.0000
3:172956822:GGCCT:G	acceptor_loss	1.0000
3:172956823:GCC:G	acceptor_loss	1.0000
3:172956825:C:CC	acceptor_gain	1.0000
3:173019571:TGCTC:T	acceptor_gain	1.0000
3:173019573:CTC:C	acceptor_gain	1.0000
3:173019574:TC:T	acceptor_gain	1.0000
3:173019574:TCCTG:T	acceptor_loss	1.0000
3:173019575:CC:C	acceptor_gain	1.0000
3:173019576:C:CC	acceptor_gain	1.0000

AlphaMissense

3803 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:173019572:G:C	S254R	0.996
3:173019572:G:T	S254R	0.996
3:173019574:T:G	S254R	0.996
3:173049023:A:C	S228R	0.996
3:173049023:A:T	S228R	0.996
3:173049025:T:G	S228R	0.996
3:173019529:C:G	A269P	0.994
3:172977049:A:C	S284R	0.993
3:172977049:A:T	S284R	0.993
3:172977051:T:G	S284R	0.993
3:172956809:C:G	A317P	0.992
3:173019537:A:G	L266P	0.992
3:173048967:G:T	A247D	0.992
3:173048998:A:G	C237R	0.992
3:173048991:A:G	L239P	0.991
3:173048996:A:C	C237W	0.991
3:173117127:G:T	A202E	0.991
3:172977038:G:T	A288D	0.990
3:173049006:A:G	L234P	0.990
3:173019493:C:G	A281P	0.989
3:172977039:C:G	A288P	0.988
3:173019492:G:T	A281D	0.988
3:173117128:C:G	A202P	0.988
3:173117184:G:T	A183D	0.988
3:173117205:A:G	L176P	0.987
3:173019518:A:C	F272L	0.986
3:173019518:A:T	F272L	0.986
3:173019520:A:G	F272L	0.986
3:173019542:A:C	N264K	0.986
3:173019542:A:T	N264K	0.986

dbSNP variants (sampled 300 via entrez): RS1000001963 (3:173012290 A>G), RS1000006351 (3:173129864 G>A,T), RS1000022465 (3:172937776 TA>T,TAA), RS1000060947 (3:173094788 A>G), RS1000069662 (3:173001259 T>G), RS1000074975 (3:173077067 C>T), RS1000077670 (3:172950697 G>A,T), RS1000089654 (3:172985218 T>C), RS1000091535 (3:172950141 T>C), RS1000112340 (3:173064251 T>TGAGCCGA), RS1000112758 (3:173079747 C>T), RS1000117056 (3:173139636 C>G), RS1000118553 (3:173095106 G>A), RS1000125641 (3:172899943 A>G), RS1000126298 (3:172941486 T>G)

Disease associations

OMIM: gene MIM:609856 | disease phenotypes: MIM:102530

GenCC curated gene-disease

Disease	Classification	Inheritance
spermatogenic failure 6	Moderate	Autosomal recessive
male infertility due to globozoospermia	Supportive	Autosomal recessive

Mondo (2): spermatogenic failure 6 (MONDO:0007060), male infertility due to globozoospermia (MONDO:0015746)

Orphanet (1): Male infertility due to globozoospermia (Orphanet:171709)

HPO phenotypes

4 total (4 of 4 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0003251	Male infertility
HP:0012205	Globozoospermia
HP:0031136	Decreased acrosin in sperm head

GWAS associations

8 associations (top):

Study	Trait	p-value
GCST009218_48	Lateral ventricle temporal horn volume	1.000000e-08
GCST009391_136	Metabolite levels	7.000000e-06
GCST009391_1492	Metabolite levels	2.000000e-06
GCST009391_1505	Metabolite levels	8.000000e-07
GCST009391_1874	Metabolite levels	4.000000e-06
GCST009391_287	Metabolite levels	8.000000e-06
GCST009391_312	Metabolite levels	5.000000e-06
GCST009391_323	Metabolite levels	6.000000e-06

EFO canonical traits (7, from GWAS)

EFO ID	Trait name
EFO:0010355	diacylglycerol 36:2 measurement
EFO:0010416	triacylglycerol 52:4 measurement
EFO:0010417	triacylglycerol 52:5 measurement
EFO:0010411	triacylglycerol 50:4 measurement
EFO:0010424	triacylglycerol 54:6 measurement
EFO:0010430	triacylglycerol 56:3 measurement
EFO:0010431	triacylglycerol 56:4 measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

5 total (human), top 5 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects cotreatment, decreases methylation	1
2-palmitoylglycerol	increases expression	1
Fulvestrant	affects cotreatment, decreases methylation	1
Benzo(a)pyrene	decreases methylation	1
Aflatoxin B1	increases methylation	1

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.