SPATA4

Summary

SPATA4 (spermatogenesis associated 4, HGNC:17333) is a protein-coding gene on chromosome 4q34.2, encoding Spermatogenesis-associated protein 4 (Q8NEY3). May play a role in apoptosis regulation.

Predicted to enable microtubule binding activity. Predicted to be involved in regulation of cytoskeleton organization. Located in cytosol and nucleoplasm.

Source: NCBI Gene 132851 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 54 total
• MANE Select transcript: NM_144644

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17333
Approved symbol	SPATA4
Name	spermatogenesis associated 4
Location	4q34.2
Locus type	gene with protein product
Status	Approved
Aliases	TSARG2, SPEF1B, FAP178, CFAP178
Ensembl gene	ENSG00000150628
Ensembl biotype	protein_coding
OMIM	609879
Entrez	132851

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 2 protein_coding, 1 nonsense_mediated_decay

ENST00000280191, ENST00000508699, ENST00000515234

RefSeq mRNA: 1 — MANE Select: NM_144644 NM_144644

CCDS: CCDS3826

Canonical transcript exons

ENST00000280191 — 6 exons

Exon	Start	End
ENSE00000995660	176188119	176188235
ENSE00001130718	176193453	176193582
ENSE00001254627	176184579	176184892
ENSE00001254631	176195345	176195585
ENSE00003578066	176192627	176192847
ENSE00003581422	176192958	176193076

Expression profiles

Bgee: expression breadth ubiquitous, 151 present calls, max score 96.95.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.6854 / max 322.9768, expressed in 122 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
55023	0.5940	101
55026	0.0450	7
55025	0.0244	3
55024	0.0219	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sperm	CL:0000019	96.95	gold quality
left testis	UBERON:0004533	96.93	gold quality
right testis	UBERON:0004534	96.45	gold quality
adult organism	UBERON:0007023	96.15	gold quality
testis	UBERON:0000473	94.31	gold quality
bronchial epithelial cell	CL:0002328	91.31	gold quality
bronchus	UBERON:0002185	89.05	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	87.91	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	86.24	gold quality
right uterine tube	UBERON:0001302	83.33	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	81.09	gold quality
tibialis anterior	UBERON:0001385	77.25	silver quality
mucosa of paranasal sinus	UBERON:0005030	76.73	silver quality
fallopian tube	UBERON:0003889	64.98	gold quality
oviduct epithelium	UBERON:0004804	63.64	gold quality
hindlimb stylopod muscle	UBERON:0004252	63.19	gold quality
nasal cavity mucosa	UBERON:0001826	62.93	gold quality
deltoid	UBERON:0001476	61.16	gold quality
islet of Langerhans	UBERON:0000006	61.02	gold quality
prefrontal cortex	UBERON:0000451	60.07	gold quality
adult mammalian kidney	UBERON:0000082	59.89	gold quality
muscle of leg	UBERON:0001383	59.70	gold quality
right lung	UBERON:0002167	59.70	gold quality
hypothalamus	UBERON:0001898	59.59	gold quality
pancreatic ductal cell	CL:0002079	59.50	silver quality
nucleus accumbens	UBERON:0001882	59.27	gold quality
adenohypophysis	UBERON:0002196	59.02	gold quality
gastrocnemius	UBERON:0001388	58.96	gold quality
pituitary gland	UBERON:0000007	58.59	gold quality
calcaneal tendon	UBERON:0003701	58.52	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.27

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): RFX1

miRNA regulators (miRDB)

20 targeting SPATA4, 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-4795-3P	100.00	74.62	4024
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-4778-3P	99.93	70.40	1818
HSA-MIR-1305	99.91	71.43	3443
HSA-MIR-6124	99.87	69.78	3551
HSA-MIR-221-5P	99.86	65.45	1052
HSA-MIR-8073	99.86	65.21	1118
HSA-MIR-4677-5P	99.70	70.09	1940
HSA-MIR-302B-5P	99.50	69.49	1857
HSA-MIR-302D-5P	99.50	69.34	1863
HSA-MIR-323B-3P	99.14	68.89	725
HSA-MIR-661	99.09	65.94	2062
HSA-MIR-4433B-3P	97.22	63.62	663
HSA-MIR-3116	97.07	65.78	1324
HSA-MIR-4790-3P	96.63	67.08	806
HSA-MIR-6777-3P	95.35	64.30	699
HSA-MIR-8074	90.61	65.46	165

Literature-anchored findings (GeneRIF, showing 7)

• expressed in many tissues and mapped to chromosome 4q33-34.1 by database analyses (PMID:12019456)
• TSARG2 may play an important role in the development of cryptorchid testis and be a testis-specific apoptosis candidate oncogene (PMID:15158438)
• analysis of SPATA4 expression and variation in promotor sequences (PMID:16336790)
• Results suggest a role for SPATA4 in membrane traffic and a specialized function for TRAPP in spermatocytes. (PMID:21827752)
• SPATA4 protects HeLa cells against etoposide-induced apoptosis through the mitochondrial apoptotic pathway, providing further evidence that SPATA4 plays a role in regulating apoptosis (PMID:26424010)
• Increased DNA methylation in the spermatogenesis-associated (SPATA) genes correlates with infertility. (PMID:31838782)
• SPATA4 improves aging-induced metabolic dysfunction through promotion of preadipocyte differentiation and adipose tissue expansion. (PMID:33314576)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	spata4	ENSDARG00000036189
mus_musculus	Spata4	ENSMUSG00000031518
rattus_norvegicus	Spata4	ENSRNOG00000048035

Paralogs (1): SPEF1 (ENSG00000101222)

Protein

Protein identifiers

Spermatogenesis-associated protein 4 — Q8NEY3 (reviewed: Q8NEY3)

Alternative names: Testis and spermatogenesis cell-related protein 2, Testis spermatocyte apoptosis-related gene 2 protein

All UniProt accessions (3): Q8NEY3, G5E9Y6, H0YA30

UniProt curated annotations — full annotation on UniProt →

Function. May play a role in apoptosis regulation.

Subunit / interactions. Interacts with CFAP65.

Subcellular location. Nucleus.

Tissue specificity. Highly expressed in testis, the expression is observed precisely in seminiferous tubules.

RefSeq proteins (1): NP_653245* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001715	CH_dom	Domain
IPR010441	CH_2	Domain
IPR036872	CH_dom_sf	Homologous_superfamily
IPR052111	Spermatogenesis_Ciliary_MAP	Family

Pfam: PF06294

UniProt features (4 total): chain 1, domain 1, sequence variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8NEY3-F1	75.66	0.46

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 52 (showing top): chr4q34, GOBP_REGULATION_OF_CYTOSKELETON_ORGANIZATION, GOCC_CYTOPLASMIC_REGION, GOCC_CILIUM, WEBER_METHYLATED_HCP_IN_SPERM_DN, GOMF_CYTOSKELETAL_PROTEIN_BINDING, DODD_NASOPHARYNGEAL_CARCINOMA_DN, WEBER_METHYLATED_HCP_IN_FIBROBLAST_UP, FOXN3_TARGET_GENES, HMGA1_TARGET_GENES, ID1_TARGET_GENES, IRF5_TARGET_GENES, SKIL_TARGET_GENES, SNRNP70_TARGET_GENES, ZNF597_TARGET_GENES

GO Biological Process (1): regulation of cytoskeleton organization (GO:0051493)

GO Molecular Function (2): microtubule binding (GO:0008017), protein binding (GO:0005515)

GO Cellular Component (5): nucleoplasm (GO:0005654), cytosol (GO:0005829), axoneme (GO:0005930), nucleus (GO:0005634), cytoplasm (GO:0005737)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
cytoskeleton organization	1
regulation of organelle organization	1
tubulin binding	1
binding	1
nuclear lumen	1
cytoplasm	1
cytoskeleton	1
microtubule	1
ciliary plasm	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

1083 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SPATA4	SPATA17	Q96L03	694
SPATA4	PLAAT5	Q96KN8	543
SPATA4	SPATA20	Q8TB22	532
SPATA4	ELMOD2	Q8IZ81	531
SPATA4	ASB5	Q8WWX0	520
SPATA4	SPATA22	Q8NHS9	496
SPATA4	MTUS1	Q9ULD2	491
SPATA4	SPATA6	Q9NWH7	491
SPATA4	WDR17	Q8IZU2	489
SPATA4	KLHDC3	Q9BQ90	471
SPATA4	FANK1	Q8TC84	466
SPATA4	GGNBP2	Q9H3C7	465
SPATA4	SPAG17	Q6Q759	463
SPATA4	PMFBP1	Q8TBY8	457
SPATA4	ZCCHC3	Q9NUD5	457

IntAct

8 interactions, top by confidence:

A	B	Type	Score
SIAH1	SPATA4	psi-mi:“MI:0915”(physical association)	0.560
SPATA4	FAT3	psi-mi:“MI:0915”(physical association)	0.400
SPATA4	LCN1	psi-mi:“MI:0915”(physical association)	0.400
Trappc2	SPATA4	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (7): SPATA4 (Two-hybrid), SPATA4 (Reconstituted Complex), SPATA4 (Biochemical Activity), FAT3 (Affinity Capture-MS), LCN1 (Affinity Capture-MS), APP (Reconstituted Complex), SPATA4 (Two-hybrid)

ESM2 similar proteins: A0A1L8HBI7, A0A1L8HJK9, A0A1L8HTT5, A6NP61, A7E2V4, B2RVL6, C0SPG1, C3VD30, K7SGN7, P56163, P56198, P62932, Q1XFL1, Q29RJ0, Q32L09, Q3UHH1, Q3V0J4, Q497M3, Q4R739, Q58D79, Q5EA86, Q5R8D5, Q5TKR9, Q5VWQ0, Q5XI33, Q6DMN8, Q768S4, Q7T3T8, Q7T3T9, Q7T3U0, Q80T69, Q8BV79, Q8BZ21, Q8CAK3, Q8CDN1, Q8HXK7, Q8K3Y6, Q8N2G6, Q8N9V6, Q8ND61

Diamond homologs: Q0IH24, Q58DA1, Q6DMN8, Q8K3V1, Q8NEY3, Q99JL1, Q9Y4P9

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	45
Likely benign	4
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

935 predictions. Top by Δscore:

Variant	Effect	Δscore
4:176188112:AACTT:A	donor_loss	1.0000
4:176188113:ACT:A	donor_loss	1.0000
4:176188114:CTTAC:C	donor_loss	1.0000
4:176188115:T:TA	donor_loss	1.0000
4:176188116:TACGT:T	donor_loss	1.0000
4:176188117:A:AC	donor_gain	1.0000
4:176188117:A:T	donor_loss	1.0000
4:176188118:C:CC	donor_gain	1.0000
4:176188138:T:TA	donor_gain	1.0000
4:176188231:CCATT:C	acceptor_gain	1.0000
4:176188232:CATT:C	acceptor_gain	1.0000
4:176188232:CATTC:C	acceptor_gain	1.0000
4:176188233:ATT:A	acceptor_gain	1.0000
4:176188233:ATTC:A	acceptor_loss	1.0000
4:176188234:TT:T	acceptor_gain	1.0000
4:176188235:TC:T	acceptor_loss	1.0000
4:176188236:C:A	acceptor_loss	1.0000
4:176188236:C:CC	acceptor_gain	1.0000
4:176192846:TT:T	acceptor_gain	1.0000
4:176192846:TTC:T	acceptor_loss	1.0000
4:176192848:C:CC	acceptor_gain	1.0000
4:176192848:CT:C	acceptor_loss	1.0000
4:176192849:T:A	acceptor_loss	1.0000
4:176192956:A:AC	donor_gain	1.0000
4:176192957:C:CC	donor_gain	1.0000
4:176192957:CT:C	donor_gain	1.0000
4:176192957:CTCT:C	donor_gain	1.0000
4:176193594:CAAT:C	acceptor_gain	1.0000
4:176193595:A:T	acceptor_gain	1.0000
4:176193597:T:C	acceptor_gain	1.0000

AlphaMissense

1981 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:176193470:A:G	W111R	0.995
4:176193470:A:T	W111R	0.995
4:176193468:C:A	W111C	0.993
4:176193468:C:G	W111C	0.993
4:176193568:C:T	G78D	0.992
4:176195391:A:G	W58R	0.989
4:176195391:A:T	W58R	0.989
4:176193480:C:A	K107N	0.987
4:176193480:C:G	K107N	0.987
4:176193569:C:G	G78R	0.987
4:176193570:A:C	N77K	0.986
4:176193570:A:T	N77K	0.986
4:176193469:C:G	W111S	0.985
4:176193568:C:A	G78V	0.985
4:176193014:T:A	K137N	0.984
4:176193014:T:G	K137N	0.984
4:176193471:G:C	N110K	0.984
4:176193471:G:T	N110K	0.984
4:176193582:T:A	R73S	0.982
4:176193582:T:G	R73S	0.982
4:176193556:G:T	A82E	0.980
4:176195387:A:G	L59P	0.978
4:176193027:G:T	T133K	0.977
4:176188228:A:C	F232L	0.976
4:176188228:A:T	F232L	0.976
4:176188230:A:G	F232L	0.976
4:176193557:C:G	A82P	0.974
4:176193577:A:G	F75S	0.973
4:176193482:T:C	K107E	0.972
4:176195389:C:A	W58C	0.971

dbSNP variants (sampled 300 via entrez): RS10000168 (4:176189051 G>A), RS1000136954 (4:176190108 C>A,T), RS1000145716 (4:176194759 G>C,T), RS10004325 (4:176185138 G>A,C), RS1000495002 (4:176185055 T>G), RS1000684887 (4:176191548 G>A), RS1000740853 (4:176188795 T>C), RS1001089723 (4:176188553 T>G), RS1001861282 (4:176191101 T>A,G), RS1001892351 (4:176191292 C>T), RS1001930311 (4:176197233 G>A), RS1002086723 (4:176194527 G>C), RS1002429877 (4:176196998 A>G), RS10027520 (4:176185323 C>T), RS1003008767 (4:176184722 C>A,G)

Disease associations

OMIM: gene MIM:609879 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

9 total (human), top 9 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
2-methyl-4-isothiazolin-3-one	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
butyraldehyde	decreases expression	1
pentanal	decreases expression	1
Temozolomide	decreases expression	1
Air Pollutants	increases abundance, increases expression	1
Smoke	increases expression, increases abundance	1
Tobacco Smoke Pollution	decreases expression	1
Valproic Acid	decreases methylation	1

Clinical trials (associated diseases)

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