SPATA33

Summary

SPATA33 (spermatogenesis associated 33, HGNC:26463) is a protein-coding gene on chromosome 16q24.3, encoding Spermatogenesis-associated protein 33 (Q96N06). Plays an important role in sperm motility and male fertility.

Predicted to be involved in mitophagy. Predicted to act upstream of or within fertilization; flagellated sperm motility; and protein localization. Predicted to be located in male germ cell nucleus and sperm mitochondrial sheath. Predicted to be active in cytoplasm and nucleus.

Source: NCBI Gene 124045 — RefSeq curated summary.

At a glance

• GWAS associations: 13
• Clinical variants (ClinVar): 44 total
• MANE Select transcript: NM_001271907

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:26463
Approved symbol	SPATA33
Name	spermatogenesis associated 33
Location	16q24.3
Locus type	gene with protein product
Status	Approved
Aliases	FLJ31606
Ensembl gene	ENSG00000167523
Ensembl biotype	protein_coding
OMIM	615409
Entrez	124045

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 6 protein_coding, 3 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000301031, ENST00000457689, ENST00000564238, ENST00000565890, ENST00000566204, ENST00000566857, ENST00000567827, ENST00000568929, ENST00000579310, ENST00000611218

RefSeq mRNA: 6 — MANE Select: NM_001271907 NM_001271907, NM_001271908, NM_001271909, NM_001271910, NM_001387226, NM_153025

CCDS: CCDS10983, CCDS62012, CCDS73929

Canonical transcript exons

ENST00000579310 — 3 exons

Exon	Start	End
ENSE00003489999	89657836	89657948
ENSE00003570283	89658248	89658421
ENSE00003920048	89669286	89670458

Expression profiles

Bgee: expression breadth ubiquitous, 183 present calls, max score 97.72.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 11.0485 / max 350.0419, expressed in 1775 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
155632	6.3232	1744
155630	4.6986	1384
155631	0.0267	5

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sperm	CL:0000019	97.72	gold quality
left testis	UBERON:0004533	97.13	gold quality
right testis	UBERON:0004534	97.11	gold quality
testis	UBERON:0000473	94.57	gold quality
adult organism	UBERON:0007023	93.37	gold quality
pancreatic ductal cell	CL:0002079	92.22	silver quality
bronchial epithelial cell	CL:0002328	90.19	gold quality
right uterine tube	UBERON:0001302	89.95	gold quality
bronchus	UBERON:0002185	88.76	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	86.89	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	84.27	gold quality
cortical plate	UBERON:0005343	82.65	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	82.21	gold quality
ventricular zone	UBERON:0003053	82.04	gold quality
prefrontal cortex	UBERON:0000451	80.67	gold quality
anterior cingulate cortex	UBERON:0009835	80.56	gold quality
right frontal lobe	UBERON:0002810	80.21	gold quality
ganglionic eminence	UBERON:0004023	79.99	gold quality
Brodmann (1909) area 9	UBERON:0013540	79.48	gold quality
adenohypophysis	UBERON:0002196	78.96	gold quality
hypothalamus	UBERON:0001898	78.91	gold quality
small intestine Peyer’s patch	UBERON:0003454	78.21	gold quality
pituitary gland	UBERON:0000007	77.77	gold quality
mucosa of transverse colon	UBERON:0004991	77.62	gold quality
amygdala	UBERON:0001876	77.58	gold quality
fallopian tube	UBERON:0003889	77.32	gold quality
neocortex	UBERON:0001950	77.14	gold quality
metanephros cortex	UBERON:0010533	77.08	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	77.00	gold quality
left lobe of thyroid gland	UBERON:0001120	76.90	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-GEOD-134144	yes	30.71
E-CURD-114	yes	11.43
E-ANND-3	yes	6.69

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

41 targeting SPATA33, 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-513A-5P	100.00	69.77	2465
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-1229-3P	99.97	66.49	906
HSA-MIR-185-3P	99.95	67.01	1743
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-6835-3P	99.93	70.49	2904
HSA-MIR-3151-5P	99.86	63.83	1069
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-92A-2-5P	99.75	67.01	2164
HSA-MIR-4729	99.69	72.18	4233
HSA-MIR-6766-5P	99.68	67.70	2325
HSA-MIR-5197-5P	99.64	69.08	1494
HSA-MIR-4516	99.61	67.78	3390
HSA-MIR-17-3P	99.55	66.77	1311
HSA-MIR-12123	99.52	71.79	2990
HSA-MIR-4735-5P	99.43	68.49	1780
HSA-MIR-664A-3P	99.22	71.08	2696
HSA-MIR-6815-3P	99.13	68.98	1530
HSA-MIR-4434	99.10	67.01	1984
HSA-MIR-5703	99.10	67.09	2053
HSA-MIR-6770-5P	98.97	66.76	1853
HSA-MIR-3196	98.96	63.91	326
HSA-MIR-3154	98.94	66.55	1455
HSA-MIR-6829-5P	98.86	65.12	1480
HSA-MIR-548Q	98.71	65.35	563
HSA-MIR-4700-5P	98.63	67.43	1915
HSA-MIR-3180	98.46	64.68	348
HSA-MIR-3180-3P	98.46	64.68	348
HSA-MIR-6816-5P	98.46	64.35	364
HSA-MIR-3179	98.22	65.90	1445

Literature-anchored findings (GeneRIF, showing 1)

• the current study illustrated that alterations in SPATA33 gene, at least those found in this study, may not impair spermatogenesis in patients with nonobstructive azoospermia. (PMID:30098056)

Cross-species orthologs

0 orthologs

Protein

Protein identifiers

Spermatogenesis-associated protein 33 — Q96N06 (reviewed: Q96N06)

All UniProt accessions (7): Q96N06, H3BQG0, H3BSG8, J3KRC8, J3KS00, J3KS58, J3KSB2

UniProt curated annotations — full annotation on UniProt →

Function. Plays an important role in sperm motility and male fertility. Required for sperm midpiece flexibility and for the localization of sperm calcineurin to the mitochondria. Promotes mitophagy as well as acts as an autophagy mediator in male germline cells. Links damaged mitochondria to autophagosomes via its binding to the outer mitochondrial membrane protein VDAC2, as well as to key autophagy machinery component ATG16L1.

Subunit / interactions. Interacts (via PQIIIT motif) with PPP3R1, PPP3R2, PPP3CA, PPP3CB and PPP3CC. Interacts with VDAC2. Interacts with ATG16L1 (via WD repeats).

Subcellular location. Cytoplasm. Cytosol. Nucleus. Mitochondrion.

Isoforms (2)

UniProt ID	Names	Canonical?
Q96N06-1	1	yes
Q96N06-2	2

RefSeq proteins (6): NP_001258836, NP_001258837, NP_001258838, NP_001258839, NP_001374155, NP_694570 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR027930	DUF4609	Family

Pfam: PF15382

UniProt features (12 total): region of interest 4, compositionally biased region 3, chain 1, splice variant 1, sequence variant 1, short sequence motif 1, modified residue 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96N06-F1	66.26	0.07

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (1): 94

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 65 (showing top): GSE45365_HEALTHY_VS_MCMV_INFECTION_CD8_TCELL_IFNAR_KO_DN, GOBP_MACROAUTOPHAGY, NIKOLSKY_BREAST_CANCER_16Q24_AMPLICON, SENGUPTA_NASOPHARYNGEAL_CARCINOMA_DN, GOCC_MOTILE_CILIUM, GOCC_SPERM_MIDPIECE, GOCC_CILIUM, DODD_NASOPHARYNGEAL_CARCINOMA_DN, GOBP_AUTOPHAGY_OF_MITOCHONDRION, GOBP_MITOPHAGY, BAKKER_FOXO3_TARGETS_DN, GOBP_PROCESS_UTILIZING_AUTOPHAGIC_MECHANISM, DELACROIX_RARG_BOUND_MEF, DELACROIX_RAR_BOUND_ES, GOCC_9PLUS2_MOTILE_CILIUM

GO Biological Process (2): mitophagy (GO:0000423), autophagy (GO:0006914)

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

GO Cellular Component (6): nucleus (GO:0005634), cytoplasm (GO:0005737), mitochondrion (GO:0005739), cytosol (GO:0005829), sperm midpiece (GO:0097225), sperm mitochondrial sheath (GO:0097226)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
intracellular membrane-bounded organelle	2
cytoplasm	2
autophagy of mitochondrion	1
macroautophagy	1
catabolic process	1
transmembrane transport	1
process utilizing autophagic mechanism	1
binding	1
intracellular anatomical structure	1
sperm flagellum	1
sperm midpiece	1

Protein interactions and networks

STRING

244 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SPATA33	DEF8	Q6ZN54	599
SPATA33	SPMIP10	Q6ZNM6	560
SPATA33	DBNDD1	Q9H9R9	557
SPATA33	CDK10	Q15131	528
SPATA33	SPIRE2	Q8WWL2	464
SPATA33	KBTBD2	Q8IY47	447
SPATA33	CENPBD1P	B2RD01	435
SPATA33	SPATA2L	Q8IUW3	430
SPATA33	CHMP1A	Q9HD42	399
SPATA33	SYPL2	Q5VXT5	393
SPATA33	VPS9D1	Q9Y2B5	386
SPATA33	DPEP1	P16444	385
SPATA33	SPESP1	Q6UW49	384
SPATA33	MC1R	Q01726	371
SPATA33	ZNF276	Q8N554	359

IntAct

21 interactions, top by confidence:

A	B	Type	Score
RUBCN	BECN1	psi-mi:“MI:0914”(association)	0.920
PPP3CC	SPATA33	psi-mi:“MI:0915”(physical association)	0.670
ACOT2	ACOT1	psi-mi:“MI:0914”(association)	0.530
KCNE3	RIOK3	psi-mi:“MI:0914”(association)	0.530
SPATA33	AP1G1	psi-mi:“MI:0914”(association)	0.350
LBX2	GGPS1	psi-mi:“MI:0914”(association)	0.350
ZNF492	HPR	psi-mi:“MI:0914”(association)	0.350
TCF15	TCF4	psi-mi:“MI:0914”(association)	0.350
DTWD1	ACTA2	psi-mi:“MI:0914”(association)	0.350
MTERF3	ACOT4	psi-mi:“MI:0914”(association)	0.350
PPP3CA	ZNF593	psi-mi:“MI:0914”(association)	0.350
MAPT	PITPNM1	psi-mi:“MI:2364”(proximity)	0.270
MAPT	DCTN6	psi-mi:“MI:2364”(proximity)	0.270
MAPT		psi-mi:“MI:2364”(proximity)	0.270
SPATA33	PPP3CC	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (25): SPATA33 (Affinity Capture-MS), SPATA33 (Two-hybrid), PPP3CB (Affinity Capture-MS), SPATA33 (Affinity Capture-MS), AP1S2 (Affinity Capture-MS), AP1M1 (Affinity Capture-MS), PPP3CA (Affinity Capture-MS), SPATA33 (Affinity Capture-MS), SPATA33 (Affinity Capture-MS), SPATA33 (Affinity Capture-MS), SPATA33 (Affinity Capture-MS), AP1B1 (Affinity Capture-MS), AP1S1 (Affinity Capture-MS), SPATA33 (Affinity Capture-MS), PPP3CC (Affinity Capture-MS)

ESM2 similar proteins: A0A1B0GUA9, A0JNH1, A1L170, A2TJV2, A6H7B4, A6NFA0, A6NGY1, A6X8Z5, A7YY35, B2RQL2, D3Z1D3, M0RD54, P43359, Q05860, Q0VF49, Q1RMX6, Q1RN00, Q2M1Z3, Q32LI3, Q3URK1, Q5EBJ4, Q5M831, Q5RJL0, Q62100, Q640N3, Q64256, Q642A3, Q66H53, Q66LM6, Q68D20, Q68DA7, Q68US1, Q6AXN6, Q6AYA8, Q6IR42, Q711Q0, Q80VY2, Q86UF4, Q8IY42, Q8TDR4

Diamond homologs: Q8C624, Q96N06

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	38
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

511 predictions. Top by Δscore:

Variant	Effect	Δscore
16:89669284:A:AG	acceptor_gain	0.9900
16:89669285:G:GG	acceptor_gain	0.9900
16:89669285:GA:G	acceptor_gain	0.9900
16:89669285:GAGA:G	acceptor_gain	0.9900
16:89669285:GAGAA:G	acceptor_gain	0.9900
16:89657836:G:GG	donor_gain	0.9700
16:89669280:CTCTA:C	acceptor_loss	0.9700
16:89669282:CTA:C	acceptor_loss	0.9700
16:89669283:TA:T	acceptor_loss	0.9700
16:89669284:A:AT	acceptor_loss	0.9700
16:89669285:G:GA	acceptor_loss	0.9700
16:89658419:AAGGT:A	donor_loss	0.9600
16:89658421:GGTAG:G	donor_loss	0.9600
16:89658423:T:G	donor_loss	0.9600
16:89658419:A:T	donor_gain	0.9500
16:89658209:GGTA:G	donor_loss	0.9400
16:89658210:G:A	donor_loss	0.9400
16:89658211:T:TC	donor_loss	0.9400
16:89658210:G:GG	donor_gain	0.9300
16:89663376:C:G	donor_gain	0.9200
16:89658213:AGT:A	donor_loss	0.9000
16:89661398:T:A	acceptor_gain	0.8900
16:89658242:TTTCA:T	acceptor_loss	0.8800
16:89658243:TTCA:T	acceptor_loss	0.8800
16:89658244:TCAGG:T	acceptor_loss	0.8800
16:89658245:CAGG:C	acceptor_loss	0.8800
16:89658246:A:T	acceptor_loss	0.8800
16:89658247:G:GA	acceptor_loss	0.8800
16:89658247:GGT:G	acceptor_gain	0.8800
16:89658241:ATTTC:A	acceptor_loss	0.8700

AlphaMissense

916 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:89669340:T:C	I88T	0.995
16:89669340:T:G	I88S	0.994
16:89669459:A:C	S128R	0.992
16:89669461:T:A	S128R	0.992
16:89669461:T:G	S128R	0.992
16:89669346:T:A	I90N	0.985
16:89669346:T:G	I90S	0.983
16:89669412:T:C	I112T	0.978
16:89669340:T:A	I88N	0.976
16:89669449:C:A	H124Q	0.973
16:89669449:C:G	H124Q	0.973
16:89669334:C:A	P86Q	0.972
16:89669447:C:G	H124D	0.972
16:89669412:T:A	I112N	0.971
16:89669346:T:C	I90T	0.970
16:89669456:C:T	P127S	0.966
16:89669412:T:G	I112S	0.965
16:89669457:C:A	P127H	0.964
16:89669471:G:C	A132P	0.964
16:89669333:C:A	P86T	0.962
16:89669333:C:T	P86S	0.962
16:89669448:A:G	H124R	0.960
16:89669334:C:G	P86R	0.958
16:89669460:G:T	S128I	0.953
16:89669474:T:G	Y133D	0.951
16:89669452:G:C	R125S	0.949
16:89669452:G:T	R125S	0.949
16:89669472:C:A	A132D	0.948
16:89669460:G:A	S128N	0.942
16:89669432:G:C	G119R	0.941

dbSNP variants (sampled 300 via entrez): RS1000034231 (16:89664295 G>A,C,T), RS1000251385 (16:89662835 C>G,T), RS1000335852 (16:89659132 C>G), RS1000388476 (16:89659228 G>A), RS1000680806 (16:89670391 A>G), RS1000876604 (16:89656743 G>C), RS1000887887 (16:89656207 G>A), RS1001135515 (16:89670244 C>T), RS1001600508 (16:89660470 G>T), RS1001806658 (16:89668198 G>C), RS1002005247 (16:89658177 C>A,G,T), RS1002060523 (16:89658332 A>G), RS1002319282 (16:89657314 G>C,T), RS1002373265 (16:89656890 G>C), RS1002488526 (16:89664058 G>A,T)

Disease associations

OMIM: gene MIM:615409 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

13 associations (top):

Study	Trait	p-value
GCST001885_11	Height	9.000000e-07
GCST002785_3	Facial pigmentation	9.000000e-15
GCST003327_11	Squamous cell carcinoma	1.000000e-20
GCST004067_174	Hip circumference adjusted for BMI	9.000000e-07
GCST004067_76	Hip circumference adjusted for BMI	7.000000e-10
GCST004604_27	Hematocrit	7.000000e-11
GCST004615_108	Hemoglobin concentration	1.000000e-09
GCST007488_10	Skin pigmentation traits	3.000000e-08
GCST007927_52	Medication use (beta blocking agents)	2.000000e-11
GCST010083_322	Hemoglobin levels	3.000000e-22
GCST010703_280	Brain morphology (MOSTest)	2.000000e-15
GCST012020_135	Serum metabolite levels	3.000000e-11
GCST90002403_692	Red blood cell count	1.000000e-12

EFO canonical traits (7, from GWAS)

EFO ID	Trait name
EFO:0008039	BMI-adjusted hip circumference
EFO:0004348	hematocrit
EFO:0004509	hemoglobin measurement
EFO:0003963	freckles
EFO:0009929	Beta blocking agent use measurement
EFO:0004346	neuroimaging measurement
EFO:0004305	erythrocyte count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

20 total (human), top 20 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases expression, affects expression	3
trichostatin A	affects expression	1
beta-lapachone	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
abrine	decreases expression	1
Sunitinib	decreases expression	1
Air Pollutants	increases abundance, increases expression	1
Benzo(a)pyrene	affects methylation	1
Cadmium	increases abundance, increases expression	1
Cisplatin	decreases expression	1
Diethylhexyl Phthalate	decreases expression	1
Methyl Methanesulfonate	increases expression	1
Phthalic Acids	increases methylation	1
Quercetin	increases expression	1
Smoke	increases abundance, increases expression	1
Tobacco Smoke Pollution	decreases expression	1
Triclosan	increases expression	1
Valproic Acid	increases methylation	1
Cadmium Chloride	increases abundance, increases expression	1

Clinical trials (associated diseases)

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