ROPN1

Summary

ROPN1 (rhophilin associated tail protein 1, HGNC:17692) is a protein-coding gene on chromosome 3q21.1, encoding Ropporin-1A (Q9HAT0). Important for male fertility.

The protein encoded by this gene is found in the fibrous sheath of spermatazoa, where it interacts with rhophilin, a Rho GTPase binding protein. The encoded protein also can bind an A-kinase anchoring protein (AKAP110) and a calcium-binding tyrosine phosphorylation-regulated protein (CABYR). This protein may be involved in sperm motility and has been shown to be a cancer-testis antigen in hematologic malignancies. Several transcript variants, some protein-coding and some non-protein coding, have been found for this gene.

Source: NCBI Gene 54763 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 43 total
• MANE Select transcript: NM_001317774

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17692
Approved symbol	ROPN1
Name	rhophilin associated tail protein 1
Location	3q21.1
Locus type	gene with protein product
Status	Approved
Aliases	ODF6, ropporin, ROPN1A, CT91
Ensembl gene	ENSG00000065371
Ensembl biotype	protein_coding
OMIM	611757
Entrez	54763

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 10 protein_coding, 1 retained_intron

ENST00000184183, ENST00000405845, ENST00000459660, ENST00000460743, ENST00000467907, ENST00000479867, ENST00000484329, ENST00000487124, ENST00000495093, ENST00000496145, ENST00000620893

RefSeq mRNA: 6 — MANE Select: NM_001317774 NM_001317774, NM_001317775, NM_001394217, NM_001394218, NM_001394219, NM_017578

CCDS: CCDS3026

Canonical transcript exons

ENST00000405845 — 6 exons

Exon	Start	End
ENSE00001789371	123991922	123992124
ENSE00002419548	123975379	123975540
ENSE00003229843	123969015	123969221
ENSE00003287342	123970042	123970217
ENSE00003554449	123976864	123976981
ENSE00003598725	123980366	123980493

Expression profiles

Bgee: expression breadth ubiquitous, 120 present calls, max score 98.75.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sperm	CL:0000019	98.75	gold quality
left testis	UBERON:0004533	97.70	gold quality
right testis	UBERON:0004534	97.38	gold quality
adult organism	UBERON:0007023	97.09	gold quality
testis	UBERON:0000473	95.41	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	88.67	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	76.83	silver quality
epithelium of mammary gland	UBERON:0003244	73.60	gold quality
mammary duct	UBERON:0001765	73.44	gold quality
ileal mucosa	UBERON:0000331	71.50	silver quality
upper leg skin	UBERON:0004262	69.47	gold quality
mammary gland	UBERON:0001911	69.31	gold quality
thoracic mammary gland	UBERON:0005200	69.15	gold quality
corpus epididymis	UBERON:0004359	68.79	gold quality
upper arm skin	UBERON:0004263	66.69	gold quality
buccal mucosa cell	CL:0002336	63.97	gold quality
skin of hip	UBERON:0001554	63.78	gold quality
parotid gland	UBERON:0001831	63.63	gold quality
tibialis anterior	UBERON:0001385	62.98	silver quality
olfactory segment of nasal mucosa	UBERON:0005386	62.70	gold quality
saliva-secreting gland	UBERON:0001044	61.59	gold quality
pancreatic ductal cell	CL:0002079	61.10	silver quality
minor salivary gland	UBERON:0001830	59.69	gold quality
myocardium	UBERON:0002349	59.15	gold quality
cauda epididymis	UBERON:0004360	59.01	gold quality
mucosa of transverse colon	UBERON:0004991	58.86	gold quality
caput epididymis	UBERON:0004358	58.58	gold quality
nasal cavity mucosa	UBERON:0001826	58.54	gold quality
zone of skin	UBERON:0000014	58.13	gold quality
skin of abdomen	UBERON:0001416	57.74	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.13

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

10 targeting ROPN1, 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-LET-7C-3P	99.95	73.42	2862
HSA-MIR-4307	99.82	70.45	3374
HSA-MIR-141-5P	99.57	67.86	897
HSA-MIR-3192-3P	98.62	65.80	970
HSA-MIR-3613-5P	98.40	68.91	604
HSA-MIR-4483	98.09	64.12	1642
HSA-MIR-5585-5P	97.95	68.80	1024
HSA-MIR-4695-3P	96.71	67.21	836
HSA-MIR-3115	96.45	67.49	470
HSA-MIR-1293	96.16	64.69	916

Literature-anchored findings (GeneRIF, showing 9)

• Ropporin gene expression in tumor cells is associated with the presence of high titer IgG antibodies against Ropporin, suggesting the in vivo translation of the mRNA into protein and the immunogenicity of the protein to the autologous hosts. (PMID:17551920)
• One SNP (rs4499545) in the ROPN1-KALRN intergenic region showed significant allelic and genotypic association with ischemic stroke risk. (PMID:20107840)
• ropporin was predominantly expressed in round spermatids in human testis, and located in the principal piece and end piece of spermatozoa flagella. Expression level of ropporin was significantly lower in asthenozoospermic men than in normozoospermic men. (PMID:20705794)
• CABYR variants form a complex not only with the scaffolding protein AKAP3 but also with another RII-like domain-containing protein in the sperm fibrous sheath. (PMID:21240291)
• We suggest that ropporin is a promising target for MM immunotherapy, as we were able to generate human leukocyte antigen class I-restricted cytotoxic lymphocytes able to kill autologous MM cells. (PMID:21654522)
• Lack of ROPN1 had no effect on ciliary motility. (PMID:22021175)
• Ropporin gene expression is related to the sperm motility. Its abnormal expression in the sperm of asthenozoospermic men with varicocele is associated with impaired sperm motility that is improved after varicocelectomy. (PMID:25704993)
• There is downregulation of both ROPN1 and CABYR in asthenozoospermic samples and importantly, a positive correlation between the expression of the two genes, suggesting that ROPN1 and CABYR co-expression is a prerequisite for normal flagellar function and sperm motility. (PMID:29247344)
• Rhophilin-associated tail protein 1 promotes migration and metastasis in triple negative breast cancer via activation of RhoA. (PMID:32427399)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Ropn1	ENSMUSG00000022832
rattus_norvegicus	Ropn1	ENSRNOG00000002187

Paralogs (2): ROPN1B (ENSG00000114547), ROPN1L (ENSG00000145491)

Protein

Protein identifiers

Ropporin-1A — Q9HAT0 (reviewed: Q9HAT0)

Alternative names: Cancer/testis antigen 91, Rhophilin-associated protein 1A

All UniProt accessions (5): Q9HAT0, A0A140VKB2, C9J012, C9J6H4, C9JP07

UniProt curated annotations — full annotation on UniProt →

Function. Important for male fertility. With ROPN1L, involved in fibrous sheath integrity and sperm motility, plays a role in PKA-dependent signaling processes required for spermatozoa capacitation.

Subunit / interactions. Homodimer. Interacts with AKAP3 and RHPN1. May interact with SPA17. Interacts with FSCB; the interaction increases upon spermatozoa capacitation conditions. Interacts with CFAP61.

Subcellular location. Cell projection. Cilium. Flagellum.

Tissue specificity. Testis specific in adult. Overexpressed in hematologic tumor cells.

Post-translational modifications. Sumoylated, sumoylation decreases upon spermatozoa capacitation conditions.

Domain organisation. The RIIa domain mediates interaction with AKAP3.

Miscellaneous. ‘Ropporin’ comes from the Japanese word ‘oppo’ which means ’tail’.

Similarity. Belongs to the ropporin family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9HAT0-1	1	yes
Q9HAT0-2	2

RefSeq proteins (6): NP_001304703, NP_001304704, NP_001381146, NP_001381147, NP_001381148, NP_060048 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR047844	ROP_DD	Domain

UniProt features (6 total): splice variant 2, chain 1, domain 1, region of interest 1, modified residue 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9HAT0-F1	85.54	0.55

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): 56

Function

Pathways and Gene Ontology

Reactome pathways

5 pathways

ID	Pathway
R-HSA-5666185	RHO GTPases Activate Rhotekin and Rhophilins
R-HSA-162582	Signal Transduction
R-HSA-194315	Signaling by Rho GTPases
R-HSA-195258	RHO GTPase Effectors
R-HSA-9716542	Signaling by Rho GTPases, Miro GTPases and RHOBTB3

MSigDB gene sets: 73 (showing top): GOBP_PROTEIN_LOCALIZATION_TO_CILIUM, GOBP_MALE_GAMETE_GENERATION, GOBP_SPERM_CAPACITATION, GOBP_ANATOMICAL_STRUCTURE_MATURATION, MODULE_195, GOBP_CELL_MATURATION, GOBP_CILIUM_ORGANIZATION, GOBP_CILIUM_MOVEMENT, GOBP_CILIUM_OR_FLAGELLUM_DEPENDENT_CELL_MOTILITY, GOBP_CELLULAR_PROCESS_INVOLVED_IN_REPRODUCTION_IN_MULTICELLULAR_ORGANISM, GNF2_CCNA1, MODULE_147, GOBP_PROTEIN_LOCALIZATION_TO_ORGANELLE, GOBP_DEVELOPMENTAL_PROCESS_INVOLVED_IN_REPRODUCTION, chr3q21

GO Biological Process (4): flagellated sperm motility (GO:0030317), cilium organization (GO:0044782), sperm capacitation (GO:0048240), protein localization to cilium (GO:0061512)

GO Molecular Function (2): identical protein binding (GO:0042802), protein binding (GO:0005515)

GO Cellular Component (5): nucleus (GO:0005634), cytoplasm (GO:0005737), motile cilium (GO:0031514), cilium (GO:0005929), cell projection (GO:0042995)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
RHO GTPase Effectors	1
Signaling by Rho GTPases, Miro GTPases and RHOBTB3	1
Signaling by Rho GTPases	1
Signal Transduction	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
cilium-dependent cell motility	1
cilium movement involved in cell motility	1
sperm motility	1
organelle organization	1
plasma membrane bounded cell projection organization	1
developmental process involved in reproduction	1
spermatid development	1
cellular process involved in reproduction in multicellular organism	1
cell maturation	1
protein localization to organelle	1
protein binding	1
binding	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
cilium	1
intraciliary transport particle	1
membrane-bounded organelle	1
plasma membrane bounded cell projection	1

Protein interactions and networks

STRING

826 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ROPN1	AKAP3	O75969	985
ROPN1	RHPN1	Q8TCX5	974
ROPN1	CABYR	O75952	953
ROPN1	SPA17	Q15506	927
ROPN1	AKAP1	Q92667	635
ROPN1	AKAP4	Q5JQC9	633
ROPN1	TSSK4	Q6SA08	608
ROPN1	TEKT4	Q8WW24	604
ROPN1	FSCB	Q5H9T9	578
ROPN1	ODF1	Q14990	576
ROPN1	SPATA6	Q9NWH7	552
ROPN1	ZPBP	Q9BS86	550
ROPN1	ODF2	Q5BJF6	531
ROPN1	CATIP	Q7Z7H3	503
ROPN1	DNAH1	Q9P2D7	501

IntAct

206 interactions, top by confidence:

A	B	Type	Score
ROPN1	SPA17	psi-mi:“MI:0915”(physical association)	0.810
SPA17	ROPN1	psi-mi:“MI:0915”(physical association)	0.810
ROPN1	LENG1	psi-mi:“MI:0915”(physical association)	0.780
GNL3L	ROPN1	psi-mi:“MI:0915”(physical association)	0.780
LENG1	ROPN1	psi-mi:“MI:0915”(physical association)	0.780
ROPN1	GNL3L	psi-mi:“MI:0915”(physical association)	0.780
ROPN1	ROPN1	psi-mi:“MI:0915”(physical association)	0.760
LNX1	ROPN1	psi-mi:“MI:0915”(physical association)	0.740
CNST	ROPN1	psi-mi:“MI:0915”(physical association)	0.740
ROPN1	LNX1	psi-mi:“MI:0915”(physical association)	0.740
ROPN1	CNST	psi-mi:“MI:0915”(physical association)	0.740

BioGRID (76): ROPN1 (Two-hybrid), ROPN1 (Two-hybrid), ROPN1 (Two-hybrid), ROPN1 (Two-hybrid), ROPN1 (Two-hybrid), ROPN1 (Two-hybrid), ROPN1 (Two-hybrid), ROPN1 (Two-hybrid), ROPN1 (Two-hybrid), ROPN1 (Two-hybrid), ROPN1 (Two-hybrid), ROPN1 (Two-hybrid), ROPN1 (Two-hybrid), UBE2W (Two-hybrid), KIF9 (Two-hybrid)

ESM2 similar proteins: A6NFE3, B3LF48, C7A639, F1SSF9, I2DDG2, O13728, P02635, P02636, P05946, P08733, P14202, P32070, P45961, P81128, P83509, P97393, Q01449, Q02045, Q13017, Q3SZE5, Q3T064, Q4KLL5, Q4R6C5, Q4V7T8, Q52K82, Q54MF3, Q5E9G1, Q5R629, Q66IC9, Q6AXZ3, Q6DCF6, Q6DJ05, Q6NU25, Q803V3, Q91YM2, Q94CF0, Q969Q6, Q96C74, Q9BZX4, Q9D581

Diamond homologs: P86196, Q3T064, Q4KLL5, Q4R6C5, Q9BZX4, Q9ESG2, Q9HAT0, Q3T024, Q4R760, Q4V7T8, Q66IC9, Q96C74, Q9EQ00, P13861

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	36
Likely benign	4
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

708 predictions. Top by Δscore:

Variant	Effect	Δscore
3:123975371:TAAC:T	donor_loss	1.0000
3:123975372:AACT:A	donor_loss	1.0000
3:123975373:ACTT:A	donor_loss	1.0000
3:123975374:CTT:C	donor_loss	1.0000
3:123975375:TTACA:T	donor_loss	1.0000
3:123975376:TA:T	donor_loss	1.0000
3:123975377:A:AC	donor_gain	1.0000
3:123975377:A:T	donor_loss	1.0000
3:123975378:C:CC	donor_gain	1.0000
3:123975378:CA:C	donor_gain	1.0000
3:123975378:CAA:C	donor_gain	1.0000
3:123975378:CAACT:C	donor_gain	1.0000
3:123975383:C:CA	donor_gain	1.0000
3:123975414:T:TA	donor_gain	1.0000
3:123976982:C:CC	acceptor_gain	1.0000
3:123980273:T:TA	donor_gain	1.0000
3:123980364:A:AC	donor_gain	1.0000
3:123980365:C:CC	donor_gain	1.0000
3:123980365:CTCGG:C	donor_gain	1.0000
3:123975373:A:AC	donor_gain	0.9900
3:123975374:C:CC	donor_gain	0.9900
3:123975376:TACA:T	donor_gain	0.9900
3:123975377:ACAA:A	donor_gain	0.9900
3:123975378:CAAC:C	donor_gain	0.9900
3:123975537:CAAC:C	acceptor_gain	0.9900
3:123975541:CTG:C	acceptor_loss	0.9900
3:123975542:T:A	acceptor_loss	0.9900
3:123975550:A:T	acceptor_gain	0.9900
3:123976858:CCTTA:C	donor_loss	0.9900
3:123976859:CTTAC:C	donor_loss	0.9900

AlphaMissense

1381 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:123975420:A:G	W119R	0.979
3:123975420:A:T	W119R	0.979
3:123975495:A:G	W94R	0.962
3:123975495:A:T	W94R	0.962
3:123975409:A:C	F122L	0.954
3:123975409:A:T	F122L	0.954
3:123975411:A:G	F122L	0.954
3:123969185:A:C	F203L	0.945
3:123969185:A:T	F203L	0.945
3:123969187:A:G	F203L	0.945
3:123980419:A:C	F21L	0.945
3:123980419:A:T	F21L	0.945
3:123980421:A:G	F21L	0.945
3:123970131:G:C	F161L	0.935
3:123970131:G:T	F161L	0.935
3:123970133:A:G	F161L	0.935
3:123970125:A:C	F163L	0.932
3:123970125:A:T	F163L	0.932
3:123970127:A:G	F163L	0.932
3:123975418:C:A	W119C	0.931
3:123975418:C:G	W119C	0.931
3:123969186:A:G	F203S	0.930
3:123975410:A:G	F122S	0.921
3:123976883:A:G	L72S	0.920
3:123970140:G:C	F158L	0.911
3:123970140:G:T	F158L	0.911
3:123970142:A:G	F158L	0.911
3:123970121:A:C	Y165D	0.909
3:123975396:A:G	C127R	0.897
3:123970132:A:G	F161S	0.894

dbSNP variants (sampled 300 via entrez): RS1000096992 (3:123972805 T>C), RS1000147937 (3:123973067 C>T), RS1000732115 (3:123985356 C>T), RS1000791034 (3:123990417 G>A), RS1001103238 (3:123986206 G>A), RS1001123041 (3:123988881 C>G), RS1001142259 (3:123984006 C>T), RS1001150464 (3:123991818 C>T), RS1001555400 (3:123972223 C>T), RS1001941813 (3:123973869 G>C), RS1002004830 (3:123972501 C>T), RS1002216137 (3:123978625 T>C), RS1002268505 (3:123978300 G>T), RS1002290875 (3:123973490 C>A,G), RS1002435973 (3:123992700 A>G)

Disease associations

OMIM: gene MIM:611757 | 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
GCST009523_21	Household income	1.000000e-10
GCST009524_64	Household income (MTAG)	1.000000e-10
GCST010566_2	Benign childhood epilepsy with centro-temporal spikes	2.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0009695	household income

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

3 total (human), top 3 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Nickel	decreases expression	2
Benzo(a)pyrene	affects methylation	1
Etoposide	affects response to substance	1

Clinical trials (associated diseases)

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