SPAG7

Summary

SPAG7 (sperm associated antigen 7, HGNC:11216) is a protein-coding gene on chromosome 17p13.2, encoding Sperm-associated antigen 7 (O75391).

Predicted to enable nucleic acid binding activity. Predicted to be located in nucleus.

Source: NCBI Gene 9552 — RefSeq curated summary.

At a glance

• Gene–disease (curated): PFAPA syndrome (Limited, GenCC)
• GWAS associations: 3
• Clinical variants (ClinVar): 36 total
• MANE Select transcript: NM_004890

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11216
Approved symbol	SPAG7
Name	sperm associated antigen 7
Location	17p13.2
Locus type	gene with protein product
Status	Approved
Aliases	FSA-1, ACRP, MGC20134
Ensembl gene	ENSG00000091640
Ensembl biotype	protein_coding
OMIM	610056
Entrez	9552

Gene structure

Transcript identifiers

Ensembl transcripts: 14 — 9 protein_coding, 2 protein_coding_CDS_not_defined, 2 retained_intron, 1 nonsense_mediated_decay

ENST00000206020, ENST00000570341, ENST00000571023, ENST00000572148, ENST00000573366, ENST00000573805, ENST00000575142, ENST00000575784, ENST00000859822, ENST00000918591, ENST00000918592, ENST00000918593, ENST00000949752, ENST00000949753

RefSeq mRNA: 1 — MANE Select: NM_004890 NM_004890

CCDS: CCDS42240

Canonical transcript exons

ENST00000206020 — 7 exons

Exon	Start	End
ENSE00000676413	4960234	4960318
ENSE00000676414	4960022	4960111
ENSE00000676418	4959226	4959643
ENSE00002633854	4967720	4967817
ENSE00003548125	4960786	4960853
ENSE00003586056	4959760	4959916
ENSE00003757135	4960459	4960547

Expression profiles

Bgee: expression breadth ubiquitous, 295 present calls, max score 98.69.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 66.3429 / max 500.9994, expressed in 1825 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
163989	66.3429	1825

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
apex of heart	UBERON:0002098	98.69	gold quality
hindlimb stylopod muscle	UBERON:0004252	98.13	gold quality
gastrocnemius	UBERON:0001388	98.11	gold quality
triceps brachii	UBERON:0001509	98.07	gold quality
muscle of leg	UBERON:0001383	98.03	gold quality
heart left ventricle	UBERON:0002084	97.99	gold quality
cardiac ventricle	UBERON:0002082	97.97	gold quality
muscle organ	UBERON:0001630	97.95	gold quality
vastus lateralis	UBERON:0001379	97.92	gold quality
quadriceps femoris	UBERON:0001377	97.91	gold quality
right atrium auricular region	UBERON:0006631	97.73	gold quality
deltoid	UBERON:0001476	97.68	gold quality
cardiac atrium	UBERON:0002081	97.59	gold quality
skeletal muscle tissue	UBERON:0001134	97.57	gold quality
diaphragm	UBERON:0001103	97.55	gold quality
body of tongue	UBERON:0011876	97.45	gold quality
left ventricle myocardium	UBERON:0006566	97.42	gold quality
heart	UBERON:0000948	97.41	gold quality
muscle tissue	UBERON:0002385	97.33	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	97.32	gold quality
heart right ventricle	UBERON:0002080	97.21	gold quality
biceps brachii	UBERON:0001507	97.00	gold quality
metanephros cortex	UBERON:0010533	96.95	gold quality
tibialis anterior	UBERON:0001385	96.93	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	96.93	gold quality
myocardium	UBERON:0002349	96.88	gold quality
gluteal muscle	UBERON:0002000	96.75	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	96.69	gold quality
right uterine tube	UBERON:0001302	96.64	gold quality
vena cava	UBERON:0004087	96.64	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

31 targeting SPAG7, 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-4283	100.00	66.42	2097
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-185-3P	99.95	67.01	1743
HSA-MIR-144-3P	99.94	73.98	2698
HSA-MIR-497-5P	99.92	71.83	2674
HSA-MIR-15A-5P	99.90	72.80	2787
HSA-MIR-15B-5P	99.90	72.78	2798
HSA-MIR-16-5P	99.90	72.80	2780
HSA-MIR-195-5P	99.90	72.81	2805
HSA-MIR-424-5P	99.89	71.90	2641
HSA-MIR-6838-5P	99.89	71.94	2690
HSA-MIR-4271	99.88	68.32	2244
HSA-MIR-369-3P	99.85	70.52	2264
HSA-MIR-374C-5P	99.80	72.06	2910
HSA-MIR-655-3P	99.80	72.19	2909
HSA-MIR-6752-3P	99.72	66.71	1587
HSA-MIR-4524A-5P	99.57	71.73	1193
HSA-MIR-4524B-5P	99.57	71.68	1195
HSA-MIR-4489	99.50	65.56	785
HSA-MIR-5683	99.36	68.59	2083
HSA-MIR-361-3P	99.19	66.45	1381
HSA-MIR-503-5P	97.87	66.83	575
HSA-MIR-3173-5P	97.35	65.82	1282
HSA-MIR-6799-3P	97.35	65.60	1302
HSA-MIR-1913	97.07	66.20	1417
HSA-MIR-3126-5P	96.87	65.83	912
HSA-MIR-6875-5P	96.87	65.49	958
HSA-MIR-342-3P	96.44	67.48	1344

Literature-anchored findings (GeneRIF, showing 1)

• SPAG7 is a candidate gene for the periodic fever, aphthous stomatitis, pharyngitis and adenopathy (PFAPA) syndrome. (PMID:24452265)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	spag7	ENSDARG00000011555
mus_musculus	Spag7	ENSMUSG00000018287
rattus_norvegicus	Spag7	ENSRNOG00000004246
drosophila_melanogaster	CG2608	FBGN0032870

Protein

Protein identifiers

Sperm-associated antigen 7 — O75391 (reviewed: O75391)

All UniProt accessions (4): O75391, I3L0Q5, I3L0X5, I3L4C3

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Nucleus.

Tissue specificity. Detected in fetal brain.

RefSeq proteins (1): NP_004881* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001374	R3H_dom	Domain
IPR017330	SPAG7	Family
IPR034068	R3H_sperm-antigen	Domain
IPR036867	R3H_dom_sf	Homologous_superfamily

Pfam: PF01424

UniProt features (20 total): modified residue 4, strand 4, helix 3, region of interest 2, short sequence motif 2, compositionally biased region 2, initiator methionine 1, chain 1, domain 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
2CPM	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O75391-F1	86.21	0.49

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 (4): 114, 158, 202, 2

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 142 (showing top): WWTAAGGC_UNKNOWN, SP3_Q3, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, SRF_C, GATA1_03, GFI1_01, NOUZOVA_TRETINOIN_AND_H4_ACETYLATION, YAGI_AML_WITH_11Q23_REARRANGED, GTATTAT_MIR3693P, DODD_NASOPHARYNGEAL_CARCINOMA_DN, MORF_NME2, KIM_ALL_DISORDERS_OLIGODENDROCYTE_NUMBER_CORR_UP, KIM_BIPOLAR_DISORDER_OLIGODENDROCYTE_DENSITY_CORR_UP, KIM_ALL_DISORDERS_CALB1_CORR_UP

GO Biological Process (0):

GO Molecular Function (2): nucleic acid binding (GO:0003676), protein binding (GO:0005515)

GO Cellular Component (1): nucleus (GO:0005634)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
binding	2
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

206 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SPAG7	FAM220A	Q7Z4H9	952
SPAG7	CD34	P28906	495
SPAG7	M0QYU9	M0QYU9	447
SPAG7	RPAP3	Q9H6T3	446
SPAG7	SMIM7	Q9BQ49	444
SPAG7	TEX261	Q6UWH6	439
SPAG7	SPAG5	Q96R06	394
SPAG7	AQP12B	A6NM10	392
SPAG7	SNU13	P55769	391
SPAG7	TMEM141	Q96I45	378
SPAG7	SPATA24	Q86W54	370
SPAG7	SPAG8	Q99932	370
SPAG7	ZNF232	Q9UNY5	368
SPAG7	UAP1	Q16222	360
SPAG7	ITPRID2	P28290	357

IntAct

21 interactions, top by confidence:

A	B	Type	Score
SPAG7	LXN	psi-mi:“MI:0915”(physical association)	0.560
H3C1	SMCHD1	psi-mi:“MI:2364”(proximity)	0.410
SPAG7	RAN	psi-mi:“MI:0915”(physical association)	0.400
KLHL20	KRBA1	psi-mi:“MI:0914”(association)	0.350
SLC25A32	NEDD8-MDP1	psi-mi:“MI:0914”(association)	0.350
KRT27	CCDC88B	psi-mi:“MI:0914”(association)	0.350
LMNA	SMCHD1	psi-mi:“MI:2364”(proximity)	0.270
H2BC10	SMCHD1	psi-mi:“MI:2364”(proximity)	0.270
HNRNPC	SBNO1	psi-mi:“MI:2364”(proximity)	0.270
PPIL4	ESYT2	psi-mi:“MI:2364”(proximity)	0.270
SMNDC1	SMCHD1	psi-mi:“MI:2364”(proximity)	0.270
SRSF7	ESYT2	psi-mi:“MI:2364”(proximity)	0.270
U2AF1	MED19	psi-mi:“MI:2364”(proximity)	0.270
ZRANB2	SBNO1	psi-mi:“MI:2364”(proximity)	0.270
TAF15	SBNO1	psi-mi:“MI:2364”(proximity)	0.270
NPM1	SBNO1	psi-mi:“MI:2364”(proximity)	0.270
LXN	SPAG7	psi-mi:“MI:0915”(physical association)	0.000
ABHD16A	SPAG7	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (38): SPAG7 (Affinity Capture-MS), SPAG7 (Two-hybrid), SPAG7 (Co-fractionation), SPAG7 (Proximity Label-MS), SPAG7 (Proximity Label-MS), SPAG7 (Affinity Capture-MS), SPAG7 (Affinity Capture-MS), SPAG7 (Affinity Capture-MS), SPAG7 (Negative Genetic), SPAG7 (Negative Genetic), UBA2 (Positive Genetic), SPAG7 (Proximity Label-MS), SPAG7 (Proximity Label-MS), SPAG7 (Affinity Capture-MS), SPAG7 (Two-hybrid)

ESM2 similar proteins: A0JPM9, A2AQ19, O43395, O75391, O75822, P04973, P09496, P29084, P29540, Q02614, Q0VCU8, Q13123, Q15650, Q2HJ41, Q2KIA6, Q2KJF9, Q3MHJ0, Q3UGC7, Q5BK07, Q5I0B5, Q5NVI3, Q5R5F1, Q5R8D1, Q5RAD5, Q5RE03, Q5ZJ85, Q5ZJ97, Q5ZK25, Q5ZKA4, Q66HG8, Q66JS6, Q6GMH0, Q6INR1, Q6P320, Q7SXU0, Q7SYJ9, Q7TNE3, Q8BM39, Q91WE2, Q922U1

Diamond homologs: O75391, Q7SYJ9, Q7TNE3

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 24 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Dengue Virus-Host Interactions	7	20.0×	3e-06
mRNA Splicing - Major Pathway	5	17.1×	5e-04

GO biological processes:

GO term	Partners	Fold	FDR
RNA splicing	5	21.0×	4e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	24
Likely benign	1
Benign	3

Top pathogenic / likely-pathogenic (0)

SpliceAI

962 predictions. Top by Δscore:

Variant	Effect	Δscore
17:4959753:GCCT:G	donor_loss	1.0000
17:4959754:CCTCA:C	donor_loss	1.0000
17:4959755:CTC:C	donor_loss	1.0000
17:4959756:TCACC:T	donor_loss	1.0000
17:4959757:CA:C	donor_loss	1.0000
17:4959759:C:A	donor_loss	1.0000
17:4959759:CCA:C	donor_gain	1.0000
17:4959776:A:AC	donor_gain	1.0000
17:4959776:ATTGG:A	donor_gain	1.0000
17:4959813:C:CA	donor_gain	1.0000
17:4959912:AGCTC:A	acceptor_gain	1.0000
17:4959914:CTC:C	acceptor_gain	1.0000
17:4959915:TC:T	acceptor_gain	1.0000
17:4959916:CC:C	acceptor_gain	1.0000
17:4959917:C:CC	acceptor_gain	1.0000
17:4959923:G:C	acceptor_gain	1.0000
17:4959923:G:GC	acceptor_gain	1.0000
17:4960015:AGCT:A	donor_gain	1.0000
17:4960018:TCAC:T	donor_loss	1.0000
17:4960019:CA:C	donor_loss	1.0000
17:4960020:A:AC	donor_gain	1.0000
17:4960020:AC:A	donor_gain	1.0000
17:4960020:ACCTT:A	donor_gain	1.0000
17:4960021:C:CC	donor_gain	1.0000
17:4960021:C:G	donor_loss	1.0000
17:4960021:CC:C	donor_gain	1.0000
17:4960021:CCT:C	donor_gain	1.0000
17:4960021:CCTT:C	donor_gain	1.0000
17:4960021:CCTTC:C	donor_gain	1.0000
17:4960107:AACTC:A	acceptor_gain	1.0000

AlphaMissense

1510 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:4959602:C:G	A206P	1.000
17:4959610:A:T	I203N	1.000
17:4959627:C:A	K197N	1.000
17:4959627:C:G	K197N	1.000
17:4959589:A:G	I210T	0.999
17:4959606:T:A	E204D	0.999
17:4959606:T:G	E204D	0.999
17:4959610:A:C	I203S	0.999
17:4959613:G:A	S202F	0.999
17:4959617:G:T	R201S	0.999
17:4959621:G:C	D199E	0.999
17:4959621:G:T	D199E	0.999
17:4959622:T:A	D199V	0.999
17:4959622:T:G	D199A	0.999
17:4959623:C:G	D199H	0.999
17:4959629:T:C	K197E	0.999
17:4959765:C:T	G190D	0.999
17:4959825:A:G	L170P	0.999
17:4959835:A:G	Y167H	0.999
17:4960237:T:A	K108N	0.999
17:4960237:T:G	K108N	0.999
17:4960292:A:G	L90P	0.999
17:4960298:G:T	A88D	0.999
17:4960317:G:C	H82D	0.999
17:4960462:A:T	I80K	0.999
17:4960467:C:A	R78S	0.999
17:4960467:C:G	R78S	0.999
17:4960468:C:A	R78M	0.999
17:4960468:C:G	R78T	0.999
17:4967782:A:G	I8T	0.999

dbSNP variants (sampled 300 via entrez): RS1000105806 (17:4967406 G>A,C), RS1000414575 (17:4964668 T>C), RS1000456742 (17:4967579 G>A,C), RS1000749234 (17:4966304 C>T), RS1000999789 (17:4963119 G>A), RS1001058184 (17:4968892 A>G,T), RS1001161052 (17:4968314 C>G), RS1001201473 (17:4968774 C>G,T), RS1001273520 (17:4969089 G>A), RS1001506477 (17:4958774 C>A), RS1001602539 (17:4964607 C>A,T), RS1001864761 (17:4958813 A>G), RS1002003345 (17:4964328 T>C), RS1002660958 (17:4965476 A>T), RS1002784460 (17:4960199 G>A,C,T)

Disease associations

OMIM: gene MIM:610056 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
PFAPA syndrome	Limited	Autosomal dominant

Mondo (1): PFAPA syndrome (MONDO:0018540)

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST004599_114	Mean platelet volume	4.000000e-09
GCST012020_148	Serum metabolite levels	3.000000e-11
GCST90013442_27	Keratoconus	2.000000e-14

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

28 total (human), top 28 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression	3
bisphenol A	decreases expression, increases expression	2
FR900359	decreases phosphorylation	1
beta-lapachone	increases expression	1
manganese chloride	decreases expression, increases abundance	1
CGP 52608	affects binding, increases reaction	1
K 7174	increases expression	1
abrine	increases expression	1
jinfukang	increases expression	1
Caffeine	decreases phosphorylation	1
Cannabidiol	affects cotreatment, decreases expression	1
Cuprizone	affects cotreatment, decreases expression	1
Dexamethasone	decreases expression	1
Diazinon	increases methylation	1
Dimethyl Sulfoxide	increases expression	1
Doxorubicin	increases expression	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Ivermectin	increases expression	1
Lead	decreases expression	1
Manganese	decreases expression, increases abundance	1
Paraquat	increases expression	1
Rotenone	increases expression	1
Smoke	decreases expression	1
Urethane	decreases expression	1
Vitamin E	increases expression	1
Palmitic Acid	increases phosphorylation	1
Copper Sulfate	decreases expression	1
Lactic Acid	decreases expression	1

Cellosaurus cell lines

1 cell lines: 1 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B3HZ	Abcam HEK293T SPAG7 KO	Transformed cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT02811705	Not specified	COMPLETED	Life Quality Study for PFAPA Patient
NCT03331497	Not specified	COMPLETED	Tonsillotomy or Follow-up in PFAPA Syndrome
NCT05200715	Not specified	RECRUITING	AutoInflammatory Disease Alliance Registry (AIDA)