SPACA9

Summary

SPACA9 (sperm acrosome associated 9, HGNC:1367) is a protein-coding gene on chromosome 9q34.13, encoding Sperm acrosome-associated protein 9 (Q96E40). Microtubule inner protein (MIP) part of the dynein-decorated doublet microtubules (DMTs) of multiciliated respiratory cells and the distal singlet microtubules of monoflagellated spermatozoa.

Enables microtubule binding activity. Involved in axoneme assembly. Located in axonemal microtubule.

Source: NCBI Gene 11092 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 5 total
• MANE Select transcript: NM_001316897

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1367
Approved symbol	SPACA9
Name	sperm acrosome associated 9
Location	9q34.13
Locus type	gene with protein product
Status	Approved
Aliases	Mast
Ensembl gene	ENSG00000165698
Ensembl biotype	protein_coding
OMIM	618552
Entrez	11092

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 6 protein_coding

ENST00000350499, ENST00000356311, ENST00000372136, ENST00000855798, ENST00000944246, ENST00000944247

RefSeq mRNA: 4 — MANE Select: NM_001316897 NM_001316897, NM_001316898, NM_001316900, NM_018956

CCDS: CCDS6955, CCDS83434

Canonical transcript exons

ENST00000356311 — 4 exons

Exon	Start	End
ENSE00001095608	132887369	132887571
ENSE00001095610	132883911	132884091
ENSE00001412168	132878898	132879014
ENSE00003848759	132888290	132890030

Expression profiles

Bgee: expression breadth ubiquitous, 239 present calls, max score 97.69.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 9.1289 / max 284.6346, expressed in 1729 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
99171	4.9386	1656
99172	2.6477	1411
99173	1.4769	637
99174	0.0657	23

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
left testis	UBERON:0004533	97.69	gold quality
right testis	UBERON:0004534	97.55	gold quality
right uterine tube	UBERON:0001302	95.65	gold quality
testis	UBERON:0000473	94.55	gold quality
sperm	CL:0000019	92.91	gold quality
male germ cell	CL:0000015	91.26	gold quality
adult organism	UBERON:0007023	90.84	gold quality
bronchial epithelial cell	CL:0002328	90.64	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	90.56	gold quality
corpus epididymis	UBERON:0004359	90.50	gold quality
epithelium of bronchus	UBERON:0002031	89.36	gold quality
bronchus	UBERON:0002185	88.29	gold quality
parotid gland	UBERON:0001831	87.24	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	84.80	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	84.16	gold quality
anterior cingulate cortex	UBERON:0009835	83.40	gold quality
cingulate cortex	UBERON:0003027	83.35	gold quality
left lobe of thyroid gland	UBERON:0001120	83.27	gold quality
nucleus accumbens	UBERON:0001882	83.17	gold quality
right lobe of thyroid gland	UBERON:0001119	83.11	gold quality
prefrontal cortex	UBERON:0000451	83.03	gold quality
caudate nucleus	UBERON:0001873	82.77	gold quality
right frontal lobe	UBERON:0002810	82.56	gold quality
hypothalamus	UBERON:0001898	82.27	gold quality
spinal cord	UBERON:0002240	82.24	gold quality
thyroid gland	UBERON:0002046	82.20	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	81.82	gold quality
amygdala	UBERON:0001876	81.59	gold quality
cranial nerve II	UBERON:0000941	81.28	gold quality
adenohypophysis	UBERON:0002196	80.96	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	9.34
E-MTAB-4850	no	39.05

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 2)

• SPACA9 is a lumenal protein of human ciliary singlet and doublet microtubules. (PMID:36191189)
• Loss of Tumor Suppressor C9orf9 Promotes Metastasis in Colorectal Cancer. (PMID:36830681)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	spaca9	ENSDARG00000068130
mus_musculus	Spaca9	ENSMUSG00000026809
rattus_norvegicus	Spaca9	ENSRNOG00000012697

Protein

Protein identifiers

Sperm acrosome-associated protein 9 — Q96E40 (reviewed: Q96E40)

All UniProt accessions (1): Q96E40

UniProt curated annotations — full annotation on UniProt →

Function. Microtubule inner protein (MIP) part of the dynein-decorated doublet microtubules (DMTs) of multiciliated respiratory cells and the distal singlet microtubules of monoflagellated spermatozoa. Forms an extensive interaction network cross-linking the lumen of axonemal doublet microtubules.

Subunit / interactions. Microtubule inner protein component of sperm flagellar doublet microtubules. Interacts with CABP1 and CALR. Interacts with INCA1. Interacts with microtubules.

Subcellular location. Cytoplasm. Cytoplasmic vesicle. Secretory vesicle. Acrosome. Cytoskeleton. Cilium basal body. Flagellum axoneme. Cilium axoneme. Nucleus.

Isoforms (2)

UniProt ID	Names	Canonical?
Q96E40-1	1	yes
Q96E40-2	2

RefSeq proteins (4): NP_001303826, NP_001303827, NP_001303829, NP_061829 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR027818	SPACA9	Family

Pfam: PF15120

UniProt features (7 total): site 2, splice variant 2, chain 1, region of interest 1, sequence variant 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
7UNG	ELECTRON MICROSCOPY	3.6
8J07	ELECTRON MICROSCOPY	4.1
7UN1	ELECTRON MICROSCOPY	6

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96E40-F1	80.92	0.68

Functional residue map

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

Catalytic / active sites (2): 117 (essential for interaction with inca1); 119 (essential for interaction with inca1)

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 139 (showing top): GOCC_SECRETORY_GRANULE, MEF2_02, GOCC_MICROTUBULE_ORGANIZING_CENTER, NKX61_01, GOBP_CILIUM_ORGANIZATION, GOBP_CILIUM_MOVEMENT, GOBP_CILIUM_OR_FLAGELLUM_DEPENDENT_CELL_MOTILITY, GOBP_ORGANELLE_ASSEMBLY, GNF2_CCNA1, GOBP_MICROTUBULE_BUNDLE_FORMATION, RYTTCCTG_ETS2_B, CDPCR3HD_01, GOBP_CELL_PROJECTION_ORGANIZATION, MODULE_48, GOBP_AXONEME_ASSEMBLY

GO Biological Process (2): flagellated sperm motility (GO:0030317), axoneme assembly (GO:0035082)

GO Molecular Function (3): microtubule binding (GO:0008017), calcium-dependent protein binding (GO:0048306), protein binding (GO:0005515)

GO Cellular Component (15): acrosomal vesicle (GO:0001669), nucleus (GO:0005634), axonemal microtubule (GO:0005879), cytoplasmic microtubule (GO:0005881), axoneme (GO:0005930), ciliary basal body (GO:0036064), sperm flagellum (GO:0036126), ciliary base (GO:0097546), axonemal microtubule doublet inner sheath (GO:0160110), cytoplasm (GO:0005737), cytoskeleton (GO:0005856), cilium (GO:0005929), cytoplasmic vesicle (GO:0031410), motile cilium (GO:0031514), cell projection (GO:0042995)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
cilium	3
cytoplasm	2
microtubule	2
cilium-dependent cell motility	1
cilium movement involved in cell motility	1
sperm motility	1
microtubule bundle formation	1
cellular component assembly	1
cilium assembly	1
tubulin binding	1
calcium ion binding	1
protein binding	1
binding	1
secretory granule	1
intracellular membrane-bounded organelle	1
cytoplasmic microtubule	1
axoneme	1
cytoskeleton	1
ciliary plasm	1
microtubule organizing center	1
9+2 motile cilium	1
ciliary transition zone	1
ciliary transition fiber	1
axonemal doublet microtubule	1
intracellular anatomical structure	1
intracellular membraneless organelle	1
intraciliary transport particle	1
membrane-bounded organelle	1
plasma membrane bounded cell projection	1
intracellular vesicle	1

Protein interactions and networks

STRING

408 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SPACA9	SPACA7	Q96KW9	604
SPACA9	FAM209A	Q5JX71	562
SPACA9	SERPINE3	A8MV23	558
SPACA9	ANKRD29	Q8N6D5	541
SPACA9	FAM124A	Q86V42	482
SPACA9	CFAP210	Q0VFZ6	479
SPACA9	CFAP77	Q6ZQR2	474
SPACA9	AK8	Q96MA6	450
SPACA9	CCDC17	Q96LX7	447
SPACA9	TMEM31	Q5JXX7	445
SPACA9	IZUMO4	Q1ZYL8	434
SPACA9	GLIPR1L1	Q6UWM5	424
SPACA9	OLA1	Q9NTK5	408
SPACA9	SPACA4	Q8TDM5	402
SPACA9	GTF3C5	Q9Y5Q8	401

IntAct

34 interactions, top by confidence:

A	B	Type	Score
	SPACA9	psi-mi:“MI:0915”(physical association)	0.560
SPACA9	KRTAP10-5	psi-mi:“MI:0915”(physical association)	0.560
KRTAP10-7	SPACA9	psi-mi:“MI:0915”(physical association)	0.560
SPACA9	KRTAP10-8	psi-mi:“MI:0915”(physical association)	0.560
KRTAP10-9	SPACA9	psi-mi:“MI:0915”(physical association)	0.560
EXOC5	SPACA9	psi-mi:“MI:0915”(physical association)	0.560
KRTAP10-8	SPACA9	psi-mi:“MI:0915”(physical association)	0.560
SPACA9	KRTAP10-7	psi-mi:“MI:0915”(physical association)	0.560
SPACA9	EXOC5	psi-mi:“MI:0915”(physical association)	0.560
KRTAP1-1	SPACA9	psi-mi:“MI:0915”(physical association)	0.560
EFEMP2	SPACA9	psi-mi:“MI:0915”(physical association)	0.560
SPACA9	H3-4	psi-mi:“MI:0915”(physical association)	0.400
TSC22D1	SPACA9	psi-mi:“MI:0915”(physical association)	0.370
SPACA9	RIOX2	psi-mi:“MI:0914”(association)	0.350
TEX101	GGT3P	psi-mi:“MI:0914”(association)	0.350
SPACA9	ODR4	psi-mi:“MI:0914”(association)	0.350
	EBAG9	psi-mi:“MI:0914”(association)	0.350
SPACA9	KRTAP1-1	psi-mi:“MI:0915”(physical association)	0.000
SPACA9	EFEMP2	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (25): C9orf9 (Two-hybrid), KRTAP10-7 (Two-hybrid), KRTAP10-9 (Two-hybrid), KRTAP10-5 (Two-hybrid), KRTAP10-8 (Two-hybrid), KRTAP10-3 (Two-hybrid), MUCL1 (Affinity Capture-MS), NXN (Affinity Capture-MS), MINA (Affinity Capture-MS), MINA (Affinity Capture-MS), MUCL1 (Affinity Capture-MS), C9orf9 (Affinity Capture-MS), C9orf9 (Two-hybrid), EFEMP2 (Two-hybrid), KRTAP1-1 (Two-hybrid)

ESM2 similar proteins: A0A1B0GVH6, A0A1L8FZ84, A0A2K1J5A5, A0A2K1JJ00, A4IGV6, B3DHS1, O94243, O95561, P03209, P04605, P05909, P17759, P18098, P22051, P24109, P24433, P32845, Q00039, Q03233, Q03937, Q06616, Q09824, Q0VCV7, Q12418, Q13352, Q19541, Q1T763, Q3KPS4, Q5R5R7, Q5RD08, Q5XHY8, Q5XIU7, Q6AXY9, Q6DFB0, Q703I1, Q759B7, Q8N9R6, Q8TAL5, Q8WWF3, Q95JJ2

Diamond homologs: Q4V8P4, Q7TPM5, Q96E40

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 16 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
Keratinization	5	23.2×	3e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

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

Top pathogenic / likely-pathogenic (0)

SpliceAI

1100 predictions. Top by Δscore:

Variant	Effect	Δscore
9:132879013:GG:G	donor_gain	1.0000
9:132879014:GG:G	donor_gain	1.0000
9:132879023:GGA:G	donor_gain	1.0000
9:132883906:CATA:C	acceptor_loss	1.0000
9:132883908:T:G	acceptor_gain	1.0000
9:132883908:TA:T	acceptor_loss	1.0000
9:132883909:A:AG	acceptor_gain	1.0000
9:132883909:A:G	acceptor_loss	1.0000
9:132883910:G:GC	acceptor_gain	1.0000
9:132883910:GA:G	acceptor_gain	1.0000
9:132883910:GAT:G	acceptor_gain	1.0000
9:132883910:GATT:G	acceptor_gain	1.0000
9:132883910:GATTC:G	acceptor_gain	1.0000
9:132884088:ACAGG:A	donor_loss	1.0000
9:132884089:CAGGT:C	donor_loss	1.0000
9:132884090:AGGT:A	donor_loss	1.0000
9:132884091:GGT:G	donor_loss	1.0000
9:132884092:GTGGG:G	donor_loss	1.0000
9:132884093:T:G	donor_loss	1.0000
9:132887567:GCAAA:G	donor_gain	1.0000
9:132887568:CAAAG:C	donor_loss	1.0000
9:132887570:AA:A	donor_gain	1.0000
9:132887570:AAGTA:A	donor_loss	1.0000
9:132887571:AG:A	donor_loss	1.0000
9:132887572:G:GG	donor_gain	1.0000
9:132887572:G:T	donor_loss	1.0000
9:132887573:TAAGT:T	donor_loss	1.0000
9:132888434:GCAC:G	donor_gain	1.0000
9:132888438:G:GG	donor_gain	1.0000
9:132888442:G:GG	donor_gain	1.0000

AlphaMissense

1475 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:132888357:A:C	S139R	0.998
9:132888359:C:A	S139R	0.998
9:132888359:C:G	S139R	0.998
9:132884020:T:C	F25L	0.995
9:132884021:T:C	F25S	0.995
9:132884022:C:A	F25L	0.995
9:132884022:C:G	F25L	0.995
9:132887429:T:C	F69L	0.995
9:132887431:C:A	F69L	0.995
9:132887431:C:G	F69L	0.995
9:132887430:T:C	F69S	0.994
9:132888393:T:A	W151R	0.994
9:132888393:T:C	W151R	0.994
9:132884046:G:C	R33S	0.992
9:132884046:G:T	R33S	0.992
9:132884000:T:C	F18S	0.991
9:132887522:T:C	C100R	0.990
9:132888355:T:A	V138D	0.989
9:132888346:G:A	G135D	0.988
9:132884030:C:A	A28D	0.987
9:132884045:G:T	R33M	0.987
9:132884045:G:C	R33T	0.986
9:132888330:G:C	A130P	0.986
9:132884033:T:C	L29P	0.985
9:132887451:T:C	L76P	0.985
9:132887430:T:G	F69C	0.984
9:132888291:T:G	Y117D	0.984
9:132888291:T:C	Y117H	0.983
9:132888294:C:T	P118S	0.983
9:132888316:T:C	L125P	0.983

dbSNP variants (sampled 300 via entrez): RS1000177188 (9:132884932 G>A), RS1000229577 (9:132884718 G>GT), RS1000304673 (9:132878335 G>A,C), RS1000440912 (9:132889576 A>G,T), RS1000601599 (9:132884534 G>A,C), RS1000748398 (9:132889868 C>T), RS1000811466 (9:132890231 C>G), RS1001591535 (9:132878963 C>T), RS1001818163 (9:132881669 T>G), RS1001994189 (9:132890473 G>A), RS1002094927 (9:132885176 T>C), RS1002145719 (9:132885424 A>G), RS1002343322 (9:132890308 C>T), RS1002421194 (9:132880487 C>G,T), RS1002565286 (9:132888076 C>T)

Disease associations

OMIM: gene MIM:618552 | 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

25 total (human), top 25 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Smoke	decreases expression, increases abundance, increases expression	2
Tunicamycin	increases expression	2
Valproic Acid	affects expression, increases methylation	2
afuresertib	increases expression	1
methylmercuric chloride	decreases expression	1
bisphenol A	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
4-aminophenylarsenoxide	affects binding, decreases reaction	1
di-n-butylphosphoric acid	affects expression	1
MRK 003	decreases expression	1
jinfukang	increases expression	1
Arsenic Trioxide	affects binding, decreases reaction	1
Air Pollutants	increases abundance, increases expression	1
Benzo(a)pyrene	decreases methylation	1
Doxorubicin	decreases expression	1
Ethyl Methanesulfonate	increases expression	1
Formaldehyde	increases expression	1
Methyl Methanesulfonate	increases expression	1
Rotenone	increases expression	1
Silicon Dioxide	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Tretinoin	decreases expression	1
Thapsigargin	increases expression	1
Okadaic Acid	decreases expression	1
Acrylamide	decreases expression	1

Clinical trials (associated diseases)

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