SPATA6

Summary

SPATA6 (spermatogenesis associated 6, HGNC:18309) is a protein-coding gene on chromosome 1p33, encoding Spermatogenesis-associated protein 6 (Q9NWH7). Required for formation of the sperm connecting piece during spermiogenesis.

Predicted to enable myosin light chain binding activity. Predicted to be involved in motile cilium assembly and spermatogenesis. Predicted to be located in extracellular region and motile cilium. Predicted to be active in sperm head-tail coupling apparatus.

Source: NCBI Gene 54558 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 90 total
• MANE Select transcript: NM_019073

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18309
Approved symbol	SPATA6
Name	spermatogenesis associated 6
Location	1p33
Locus type	gene with protein product
Status	Approved
Aliases	SRF1, FLJ10007, SRF-1
Ensembl gene	ENSG00000132122
Ensembl biotype	protein_coding
OMIM	613947
Entrez	54558

Gene structure

Transcript identifiers

Ensembl transcripts: 18 — 11 protein_coding, 5 protein_coding_CDS_not_defined, 2 nonsense_mediated_decay

ENST00000371841, ENST00000371843, ENST00000371847, ENST00000396199, ENST00000463938, ENST00000465990, ENST00000471975, ENST00000487543, ENST00000487629, ENST00000490850, ENST00000603831, ENST00000872885, ENST00000872886, ENST00000872887, ENST00000872888, ENST00000930127, ENST00000930128, ENST00000930129

RefSeq mRNA: 3 — MANE Select: NM_019073 NM_001286238, NM_001286239, NM_019073

CCDS: CCDS551, CCDS65535, CCDS72787

Canonical transcript exons

ENST00000371847 — 13 exons

Exon	Start	End
ENSE00001456309	48471958	48472204
ENSE00001879864	48295373	48298893
ENSE00003469234	48305787	48305878
ENSE00003475782	48411464	48411588
ENSE00003529978	48359586	48359770
ENSE00003539829	48399351	48399644
ENSE00003549610	48385309	48385349
ENSE00003554099	48355670	48355769
ENSE00003672133	48395267	48395354
ENSE00003673588	48451552	48451600
ENSE00003677392	48403802	48403882
ENSE00003690597	48413110	48413151
ENSE00003742261	48452994	48453131

Expression profiles

Bgee: expression breadth ubiquitous, 239 present calls, max score 99.65.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 10.6425 / max 297.7161, expressed in 1520 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
12256	8.8327	1491
12252	0.9732	479
12253	0.4248	231
12255	0.2019	77
12254	0.1690	82
12249	0.0334	5
12248	0.0074	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sperm	CL:0000019	99.65	gold quality
male germ cell	CL:0000015	98.27	gold quality
left testis	UBERON:0004533	97.76	gold quality
right testis	UBERON:0004534	97.32	gold quality
sural nerve	UBERON:0015488	95.30	gold quality
testis	UBERON:0000473	95.29	gold quality
adult organism	UBERON:0007023	95.23	gold quality
bronchial epithelial cell	CL:0002328	92.13	gold quality
calcaneal tendon	UBERON:0003701	91.98	gold quality
mucosa of paranasal sinus	UBERON:0005030	90.45	gold quality
right uterine tube	UBERON:0001302	88.13	gold quality
epithelium of bronchus	UBERON:0002031	86.99	gold quality
tendon	UBERON:0000043	86.81	gold quality
tibial nerve	UBERON:0001323	86.45	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	85.98	gold quality
bronchus	UBERON:0002185	85.97	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	85.97	gold quality
left ovary	UBERON:0002119	83.57	gold quality
colonic epithelium	UBERON:0000397	83.17	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	83.15	gold quality
right adrenal gland cortex	UBERON:0035827	82.80	gold quality
caput epididymis	UBERON:0004358	82.33	gold quality
adrenal tissue	UBERON:0018303	82.02	gold quality
corpus callosum	UBERON:0002336	81.84	gold quality
tibia	UBERON:0000979	81.65	gold quality
right adrenal gland	UBERON:0001233	81.49	gold quality
right ovary	UBERON:0002118	81.49	gold quality
epithelium of nasopharynx	UBERON:0001951	81.37	gold quality
left adrenal gland cortex	UBERON:0035825	81.34	gold quality
left adrenal gland	UBERON:0001234	81.30	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-GEOD-134144	yes	31.51
E-ANND-3	yes	12.40

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

174 targeting SPATA6, 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-6867-5P	100.00	82.21	3464
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-3134	100.00	66.43	777
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-518D-5P	100.00	67.51	979
HSA-MIR-518E-5P	100.00	67.66	954
HSA-MIR-518F-5P	100.00	67.51	979
HSA-MIR-519A-5P	100.00	67.66	954
HSA-MIR-519B-5P	100.00	67.66	954
HSA-MIR-519C-5P	100.00	67.66	954
HSA-MIR-520C-5P	100.00	67.51	979
HSA-MIR-522-5P	100.00	67.66	954
HSA-MIR-523-5P	100.00	67.66	954
HSA-MIR-526A-5P	100.00	67.51	979
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-9-3P	99.96	70.88	2068
HSA-MIR-570-3P	99.96	72.41	4910
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-559	99.95	72.28	3609

Literature-anchored findings (GeneRIF, showing 3)

• SPATA6 may play an important role in testicular germ cell tumors, and down-regulation of SPATA6 could lead to apoptosis of testicular germ cell tumors. (PMID:26464655)
• Increased DNA methylation in the spermatogenesis-associated (SPATA) genes correlates with infertility. (PMID:31838782)
• Identification of nonfunctional SPATA20 causing acephalic spermatozoa syndrome in humans. (PMID:36415156)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
mus_musculus	Spata6	ENSMUSG00000034401
rattus_norvegicus	Spata6	ENSRNOG00000007568
drosophila_melanogaster	CG14079	FBGN0036849

Paralogs (1): SPATA6L (ENSG00000106686)

Protein

Protein identifiers

Spermatogenesis-associated protein 6 — Q9NWH7 (reviewed: Q9NWH7)

All UniProt accessions (6): Q9NWH7, A0A140VJV1, A8MU33, B1AN51, S4R3R3, S4R3X9

UniProt curated annotations — full annotation on UniProt →

Function. Required for formation of the sperm connecting piece during spermiogenesis. Sperm connecting piece is essential for linking the developing flagellum to the head during late spermiogenesis. May be involved in myosin-based microfilament transport through interaction with myosin subunits.

Subunit / interactions. Interacts with MYL6.

Subcellular location. Secreted. Cell projection. Cilium. Flagellum.

Similarity. Belongs to the SPATA6 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9NWH7-1	1	yes
Q9NWH7-2	2

RefSeq proteins (3): NP_001273167, NP_001273168, NP_061946* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR032732	SPATA6_N	Domain
IPR042769	SPATA6_fam	Family

Pfam: PF14909

UniProt features (24 total): modified residue 11, sequence variant 4, region of interest 2, sequence conflict 2, signal peptide 1, chain 1, glycosylation site 1, cross-link 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NWH7-F1	65.12	0.23

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 (12): 346, 354, 424, 465, 487, 248, 217, 219, 265, 274, 325, 343

Glycosylation sites (1): 181

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 202 (showing top): AP2_Q3, GOBP_MALE_GAMETE_GENERATION, CAGCTG_AP4_Q5, GOBP_CILIUM_ORGANIZATION, GOBP_ORGANELLE_ASSEMBLY, GNF2_CCNA1, PU1_Q6, LASTOWSKA_NEUROBLASTOMA_COPY_NUMBER_DN, GOBP_DEVELOPMENTAL_PROCESS_INVOLVED_IN_REPRODUCTION, GOBP_MOTILE_CILIUM_ASSEMBLY, GOBP_CELL_PROJECTION_ORGANIZATION, RGAGGAARY_PU1_Q6, RASHI_RESPONSE_TO_IONIZING_RADIATION_5, AP2_Q6_01, AP2GAMMA_01

GO Biological Process (3): spermatogenesis (GO:0007283), cell differentiation (GO:0030154), motile cilium assembly (GO:0044458)

GO Molecular Function (2): myosin light chain binding (GO:0032027), protein binding (GO:0005515)

GO Cellular Component (5): extracellular region (GO:0005576), motile cilium (GO:0031514), sperm head-tail coupling apparatus (GO:0120212), cilium (GO:0005929), cell projection (GO:0042995)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
developmental process involved in reproduction	1
male gamete generation	1
cellular developmental process	1
cilium assembly	1
myosin binding	1
binding	1
cilium	1
intraciliary transport particle	1
membrane-bounded organelle	1
plasma membrane bounded cell projection	1

Protein interactions and networks

STRING

664 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SPATA6	SUN5	Q8TC36	749
SPATA6	SWI5	Q1ZZU3	717
SPATA6	ODF1	Q14990	707
SPATA6	OAZ3	Q9UMX2	678
SPATA6	PMFBP1	Q8TBY8	656
SPATA6	MEGF10	Q96KG7	631
SPATA6	TSSK4	Q6SA08	607
SPATA6	SPATA20	Q8TB22	595
SPATA6	SPATC1L	Q9H0A9	594
SPATA6	HOOK1	Q9UJC3	587
SPATA6	SCARF1	Q14162	576
SPATA6	SPATA18	Q8TC71	563
SPATA6	DNAH1	Q9P2D7	561
SPATA6	ROPN1	Q9HAT0	552
SPATA6	CABYR	O75952	526

IntAct

4 interactions, top by confidence:

A	B	Type	Score
SPATA6	DDB2	psi-mi:“MI:0915”(physical association)	0.500
SPATA6	SNX17	psi-mi:“MI:0914”(association)	0.350
FTL		psi-mi:“MI:0914”(association)	0.350

BioGRID (17): SPATA6 (Affinity Capture-MS), NEDD8-MDP1 (Affinity Capture-MS), DDB2 (Affinity Capture-MS), SPATA6 (Affinity Capture-RNA), SPATA6 (Affinity Capture-MS), SPATA6 (Synthetic Lethality), SPATA6 (Two-hybrid), SPATA6 (Two-hybrid), SPATA6 (Two-hybrid), GEM (Two-hybrid), SPATA6 (Affinity Capture-RNA), C2orf44 (Affinity Capture-MS), IP6K1 (Affinity Capture-MS), WDR83 (Affinity Capture-MS), SNX17 (Affinity Capture-MS)

ESM2 similar proteins: A0JNF3, A3KMW7, A6NFA0, B2RQL2, B2RV46, D3Z8E6, D3ZAP3, D3ZJ47, E9Q309, E9Q793, F5H4B4, O14513, O60303, Q0P5X5, Q1RMQ5, Q2KIP3, Q2KJG1, Q2T9M9, Q32LN6, Q3URK1, Q3V0J4, Q3V0M2, Q53FD0, Q5PQL8, Q5T5Y3, Q642A3, Q68FV5, Q6AYJ3, Q6AYP4, Q6ZVD7, Q7PCK7, Q8BJS7, Q8CB14, Q8CCC3, Q8CCG1, Q8CDL9, Q8K3V1, Q8K3V7, Q8N4H0, Q95LL2

Diamond homologs: B2RV46, Q2KJG1, Q3U6K5, Q6AYJ3, Q8N4H0, Q99MU5, Q9NWH7

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	78
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

3179 predictions. Top by Δscore:

Variant	Effect	Δscore
1:48307216:T:TA	donor_gain	1.0000
1:48403782:TTTA:T	donor_gain	1.0000
1:48403783:TTAT:T	donor_gain	1.0000
1:48403828:T:C	donor_gain	1.0000
1:48411462:A:AC	donor_gain	1.0000
1:48411463:C:CC	donor_gain	1.0000
1:48411463:CT:C	donor_gain	1.0000
1:48411585:CCCA:C	acceptor_gain	1.0000
1:48411586:CCAC:C	acceptor_gain	1.0000
1:48411589:C:CC	acceptor_gain	1.0000
1:48451551:CATT:C	donor_gain	1.0000
1:48452989:CTCA:C	donor_loss	1.0000
1:48452990:TCA:T	donor_loss	1.0000
1:48452991:CA:C	donor_loss	1.0000
1:48452992:A:AC	donor_gain	1.0000
1:48452992:ACCTT:A	donor_loss	1.0000
1:48452993:C:CC	donor_gain	1.0000
1:48453127:GTTAC:G	acceptor_gain	1.0000
1:48453128:TTAC:T	acceptor_gain	1.0000
1:48453129:TAC:T	acceptor_gain	1.0000
1:48453129:TACC:T	acceptor_loss	1.0000
1:48453130:AC:A	acceptor_gain	1.0000
1:48453131:CC:C	acceptor_gain	1.0000
1:48453132:C:CC	acceptor_gain	1.0000
1:48471956:A:AC	donor_gain	1.0000
1:48471957:C:CC	donor_gain	1.0000
1:48471957:CTGAG:C	donor_gain	1.0000
1:48305781:TCATA:T	donor_loss	0.9900
1:48305782:CATA:C	donor_loss	0.9900
1:48305783:ATAC:A	donor_loss	0.9900

AlphaMissense

3200 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:48403860:A:G	F143S	1.000
1:48355719:C:G	R382P	0.999
1:48403859:A:C	F143L	0.999
1:48403859:A:T	F143L	0.999
1:48403861:A:G	F143L	0.999
1:48411546:A:G	F108S	0.999
1:48413130:A:G	L87S	0.999
1:48453000:A:C	F61L	0.999
1:48453000:A:T	F61L	0.999
1:48453001:A:G	F61S	0.999
1:48453002:A:G	F61L	0.999
1:48399363:A:C	F256L	0.998
1:48399363:A:T	F256L	0.998
1:48399365:A:G	F256L	0.998
1:48411539:A:C	F110L	0.998
1:48411539:A:T	F110L	0.998
1:48411541:A:G	F110L	0.998
1:48451557:A:G	L78P	0.998
1:48453019:A:G	F55S	0.998
1:48453085:A:G	L33P	0.998
1:48399390:G:C	F247L	0.997
1:48399390:G:T	F247L	0.997
1:48399392:A:G	F247L	0.997
1:48399454:A:G	M226T	0.997
1:48399457:C:G	R225P	0.997
1:48399459:T:A	R224S	0.997
1:48399459:T:G	R224S	0.997
1:48403842:A:C	I149S	0.997
1:48403866:A:G	L141P	0.997
1:48411552:C:G	R106P	0.997

dbSNP variants (sampled 300 via entrez): RS1000004079 (1:48286037 C>T), RS1000035303 (1:48286351 T>A), RS1000038163 (1:48368956 G>T), RS1000038505 (1:48440758 A>T), RS1000041328 (1:48360200 G>GA), RS1000044276 (1:48397219 G>A), RS1000050794 (1:48324960 A>G), RS1000105000 (1:48422794 G>A), RS1000106072 (1:48369083 A>T), RS1000111233 (1:48378319 A>G), RS1000111746 (1:48331755 C>T), RS1000115638 (1:48314200 A>C,T), RS1000130964 (1:48394270 A>G), RS1000137398 (1:48300313 G>A,C), RS1000158053 (1:48469670 T>A,C)

Disease associations

OMIM: gene MIM:613947 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST008753_1	Early spontaneous preterm birth	4.000000e-07
GCST009391_1153	Metabolite levels	3.000000e-07
GCST009391_772	Metabolite levels	5.000000e-06

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0006917	spontaneous preterm birth
EFO:0010459	aminoadipic acid measurement
EFO:0010393	sphingomyelin 18:0 measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

27 total (human), top 27 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression, increases expression	3
sodium arsenite	decreases expression, affects cotreatment, increases abundance	2
Nickel	decreases expression	2
Cadmium Chloride	decreases expression	2
aristolochic acid I	decreases expression	1
FR900359	increases phosphorylation	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
trichostatin A	decreases expression	1
arsenite	increases methylation	1
manganese chloride	affects cotreatment, decreases expression, increases abundance	1
di-n-butylphosphoric acid	affects expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
Sunitinib	decreases expression	1
Arsenic Trioxide	decreases expression	1
Air Pollutants	increases abundance, increases expression	1
Arsenic	affects cotreatment, decreases expression, increases abundance	1
Benzo(a)pyrene	increases methylation	1
Manganese	affects cotreatment, decreases expression, increases abundance	1
Phthalic Acids	increases methylation	1
Smoke	increases abundance, increases expression	1
Tobacco Smoke Pollution	decreases expression	1
Aflatoxin B1	decreases methylation	1
Asbestos, Crocidolite	decreases expression	1
Acrylamide	decreases expression	1

Clinical trials (associated diseases)

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