RSBN1

Summary

RSBN1 (round spermatid basic protein 1, HGNC:25642) is a protein-coding gene on chromosome 1p13.2, encoding Lysine-specific demethylase 9 (Q5VWQ0). Histone demethylase that specifically demethylates dimethylated ‘Lys-20’ of histone H4 (H4K20me2) and trimethylated ‘Lys-20’ of histone H4 (H4K20me3) into monomethyl H4K20 (H4K20me1) thereby modulating chromosome architecture.

Predicted to enable histone H4K20 demethylase activity and metal ion binding activity. Predicted to be involved in chromatin remodeling. Predicted to be located in endoplasmic reticulum. Predicted to be active in nucleus.

Source: NCBI Gene 54665 — RefSeq curated summary.

At a glance

• GWAS associations: 10
• Clinical variants (ClinVar): 106 total
• MANE Select transcript: NM_018364

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25642
Approved symbol	RSBN1
Name	round spermatid basic protein 1
Location	1p13.2
Locus type	gene with protein product
Status	Approved
Aliases	FLJ11220, ROSBIN, KDM9
Ensembl gene	ENSG00000081019
Ensembl biotype	protein_coding
OMIM	615858
Entrez	54665

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 4 protein_coding, 1 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000261441, ENST00000369581, ENST00000476412, ENST00000612242, ENST00000615321, ENST00000934566

RefSeq mRNA: 1 — MANE Select: NM_018364 NM_018364

CCDS: CCDS862

Canonical transcript exons

ENST00000261441 — 7 exons

Exon	Start	End
ENSE00001020752	113797363	113798036
ENSE00001142071	113811710	113812476
ENSE00001450384	113761832	113766453
ENSE00003524195	113767099	113767207
ENSE00003589616	113768222	113768389
ENSE00003652248	113777671	113777808
ENSE00003670533	113777210	113777352

Expression profiles

Bgee: expression breadth ubiquitous, 292 present calls, max score 95.00.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 10.9492 / max 136.3958, expressed in 1719 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
13908	10.1234	1704
13907	0.4511	226
13910	0.3302	136
13909	0.0394	18
13911	0.0052	2

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
caput epididymis	UBERON:0004358	95.00	gold quality
cauda epididymis	UBERON:0004360	94.77	gold quality
parotid gland	UBERON:0001831	94.52	gold quality
corpus epididymis	UBERON:0004359	94.42	gold quality
cerebellar vermis	UBERON:0004720	93.99	gold quality
superficial temporal artery	UBERON:0001614	93.95	gold quality
nipple	UBERON:0002030	93.24	gold quality
vena cava	UBERON:0004087	92.94	silver quality
sperm	CL:0000019	92.42	gold quality
trabecular bone tissue	UBERON:0002483	92.05	gold quality
cardia of stomach	UBERON:0001162	91.68	gold quality
pylorus	UBERON:0001166	91.54	gold quality
pigmented layer of retina	UBERON:0001782	91.47	gold quality
retina	UBERON:0000966	91.44	gold quality
saphenous vein	UBERON:0007318	91.28	gold quality
pericardium	UBERON:0002407	91.18	gold quality
lower lobe of lung	UBERON:0008949	90.84	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	90.81	gold quality
calcaneal tendon	UBERON:0003701	90.48	gold quality
mammary duct	UBERON:0001765	90.33	gold quality
superior surface of tongue	UBERON:0007371	90.28	gold quality
bone marrow	UBERON:0002371	90.03	gold quality
jejunal mucosa	UBERON:0000399	89.98	gold quality
penis	UBERON:0000989	89.64	gold quality
urethra	UBERON:0000057	89.50	gold quality
biceps brachii	UBERON:0001507	89.50	gold quality
cartilage tissue	UBERON:0002418	89.49	gold quality
middle temporal gyrus	UBERON:0002771	89.46	gold quality
skin of hip	UBERON:0001554	89.37	gold quality
Brodmann (1909) area 23	UBERON:0013554	89.32	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	7.89

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

307 targeting RSBN1, 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-4673	100.00	66.64	1490
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-3689D	100.00	66.14	1181
HSA-MIR-6851-5P	100.00	65.63	1294
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-32-5P	99.98	75.21	1964
HSA-MIR-92A-3P	99.98	75.21	1960
HSA-MIR-92B-3P	99.98	75.25	1955
HSA-MIR-499A-5P	99.98	70.79	1323
HSA-MIR-25-3P	99.98	74.60	1817
HSA-MIR-363-3P	99.98	74.72	1821
HSA-MIR-367-3P	99.98	74.83	1819
HSA-MIR-4645-5P	99.98	65.81	1284
HSA-MIR-433-3P	99.98	69.37	1203
HSA-MIR-103A-3P	99.98	69.14	1595
HSA-MIR-107	99.98	69.14	1595

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	RSBN1	ENSDARG00000098968
mus_musculus	Rsbn1	ENSMUSG00000044098
rattus_norvegicus	Rsbn1	ENSRNOG00000019671
drosophila_melanogaster	CG10600	FBGN0032717
caenorhabditis_elegans		WBGENE00001080

Paralogs (1): RSBN1L (ENSG00000187257)

Protein

Protein identifiers

Lysine-specific demethylase 9 — Q5VWQ0 (reviewed: Q5VWQ0)

Alternative names: Round spermatid basic protein 1

All UniProt accessions (3): Q5VWQ0, A0A087WWP8, A0A0C4DH79

UniProt curated annotations — full annotation on UniProt →

Function. Histone demethylase that specifically demethylates dimethylated ‘Lys-20’ of histone H4 (H4K20me2) and trimethylated ‘Lys-20’ of histone H4 (H4K20me3) into monomethyl H4K20 (H4K20me1) thereby modulating chromosome architecture. May play a critical role in regulating H4K20 methylation during spermatogenesis.

Subcellular location. Nucleus. Cytoplasm. Perinuclear region.

Post-translational modifications. Phosphorylated by PKA.

Cofactor. Binds 1 Fe(2+) ion per subunit.

Similarity. Belongs to the round spermatid basic protein 1 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q5VWQ0-1	1	yes
Q5VWQ0-4	4

RefSeq proteins (1): NP_060834* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR026306	RSBN1/Dpy-2/CEP530	Family

Catalyzed reactions (Rhea), 2 shown:

• N(6),N(6)-dimethyl-L-lysyl(20)-[histone H4] + 2-oxoglutarate + O2 = N(6)-methyl-L-lysyl(20)-[histone H4] + formaldehyde + succinate + CO2 (RHEA:85907)
• N(6),N(6),N(6)-trimethyl-L-lysyl(20)-[histone H4] + 2-oxoglutarate + O2 = N(6),N(6)-dimethyl-L-lysyl(20)-[histone H4] + formaldehyde + succinate + CO2 (RHEA:85911)

UniProt features (22 total): binding site 5, compositionally biased region 5, cross-link 4, sequence conflict 3, chain 1, region of interest 1, modified residue 1, splice variant 1, short sequence motif 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q5VWQ0-F1	62.96	0.34

Functional residue map

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

Ligand- & substrate-binding residues (5): 584; 676; 684; 579; 582

Post-translational modifications (5): 81, 290, 313, 740, 781

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 312 (showing top): AAGCAAT_MIR137, ZHAN_MULTIPLE_MYELOMA_PR_DN, GOMF_OXIDOREDUCTASE_ACTIVITY_ACTING_ON_PAIRED_DONORS_WITH_INCORPORATION_OR_REDUCTION_OF_MOLECULAR_OXYGEN, TGCTGCT_MIR15A_MIR16_MIR15B_MIR195_MIR424_MIR497, GCANCTGNY_MYOD_Q6, CMYB_01, TTTGTAG_MIR520D, TACAATC_MIR508, GOBP_MALE_GAMETE_GENERATION, CCATCCA_MIR432, MODULE_66, MODULE_331, AGTCTTA_MIR499, FISCHER_G2_M_CELL_CYCLE, TGTGTGA_MIR377

GO Biological Process (3): spermatogenesis (GO:0007283), chromatin organization (GO:0006325), chromatin remodeling (GO:0006338)

GO Molecular Function (4): histone H4K20 demethylase activity (GO:0035575), metal ion binding (GO:0046872), oxidoreductase activity (GO:0016491), dioxygenase activity (GO:0051213)

GO Cellular Component (3): nucleus (GO:0005634), perinuclear region of cytoplasm (GO:0048471), endoplasmic reticulum (GO:0005783)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
intracellular membrane-bounded organelle	2
cytoplasm	2
developmental process involved in reproduction	1
male gamete generation	1
cellular component organization	1
chromatin organization	1
2-oxoglutarate-dependent dioxygenase activity	1
histone H4 demethylase activity	1
cation binding	1
catalytic activity	1
oxidoreductase activity	1
cellular anatomical structure	1
endomembrane system	1

Protein interactions and networks

STRING

890 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RSBN1	PHTF1	Q9UMS5	698
RSBN1	BCL2L15	Q5TBC7	548
RSBN1	AP4B1	Q9Y6B7	523
RSBN1	PTPN22	Q9Y2R2	501
RSBN1	QARS1	P47897	482
RSBN1	DNAJB12	Q9NXW2	445
RSBN1	SPAG4	Q9NPE6	438
RSBN1	OLFML3	Q9NRN5	438
RSBN1	BCAS2	O75934	423
RSBN1	TGM4	P49221	418
RSBN1	DCLRE1B	Q9H816	407
RSBN1	CPEB2	Q7Z5Q1	404
RSBN1	KMT5B	Q4FZB7	403
RSBN1	MTMR10	Q9NXD2	402
RSBN1	RAD23A	P54725	396

IntAct

245 interactions, top by confidence:

A	B	Type	Score
EAF1	ELL2	psi-mi:“MI:0914”(association)	0.840
DYNLL1	BLTP3B	psi-mi:“MI:0914”(association)	0.730
DYNLL2	BLTP3B	psi-mi:“MI:0914”(association)	0.640
LIN28A	IGF2BP3	psi-mi:“MI:0914”(association)	0.640
ZRANB2	PIP4K2A	psi-mi:“MI:0914”(association)	0.610
H1-6	ZNF724	psi-mi:“MI:0914”(association)	0.530
RSBN1	SETD1A	psi-mi:“MI:0914”(association)	0.530
MACROH2A2	PPM1G	psi-mi:“MI:0914”(association)	0.530
RPL18A	RRP8	psi-mi:“MI:0914”(association)	0.530
N	RBM47	psi-mi:“MI:0914”(association)	0.530
RPS3	ZNF316	psi-mi:“MI:0914”(association)	0.530
MAGEB2	POLRMT	psi-mi:“MI:0914”(association)	0.530
RSBN1	MAGEB2	psi-mi:“MI:0914”(association)	0.530
ABT1	ZNF316	psi-mi:“MI:0914”(association)	0.530
MAGEB2	GTPBP10	psi-mi:“MI:0914”(association)	0.530
RPL13	RRP8	psi-mi:“MI:0914”(association)	0.530
RSBN1	MAST2	psi-mi:“MI:0407”(direct interaction)	0.440
SNX27	RSBN1	psi-mi:“MI:0407”(direct interaction)	0.440
RSBN1	MAST1	psi-mi:“MI:0407”(direct interaction)	0.440
RSBN1	PDZD2	psi-mi:“MI:0407”(direct interaction)	0.440

BioGRID (206): RSBN1 (Affinity Capture-MS), RSBN1 (Affinity Capture-MS), RSBN1 (Affinity Capture-MS), RSBN1 (Affinity Capture-MS), RSBN1 (Affinity Capture-MS), RSBN1 (Synthetic Lethality), RSBN1 (Proximity Label-MS), RSBN1 (Affinity Capture-MS), SPTBN4 (Affinity Capture-MS), RSBN1 (Affinity Capture-MS), ZNF317 (Affinity Capture-MS), SETD2 (Affinity Capture-MS), CDK11B (Affinity Capture-MS), CDC16 (Affinity Capture-MS), RSBN1 (Affinity Capture-MS)

ESM2 similar proteins: A0A1L8HBI7, A0A1L8HJK9, A0A1L8HTT5, A4QP16, A6NP61, B2RVL6, C0SPG1, C3VD30, K7SGN7, O54880, P56163, Q1XFL1, Q29RJ0, Q2KI52, Q32L09, Q3V0J4, Q4R2Y2, Q4R739, Q58D79, Q5RAK6, Q5TKR9, Q5VWQ0, Q6PDK8, Q768S4, Q7T3T8, Q7T3T9, Q80T69, Q86US8, Q86Y01, Q8AW93, Q8BMD7, Q8BRB7, Q8BZ21, Q8CAK3, Q8CDN1, Q8HXK7, Q8K3Y6, Q8N2G6, Q8N9V6, Q8TE76

Diamond homologs: Q28DE6, Q5VWQ0, Q6PCB5, Q80T69, Q9GRZ3

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 180 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
Peptide chain elongation	23	23.4×	8e-24
Viral mRNA Translation	23	23.4×	8e-24
PELO:HBS1L and ABCE1 dissociate a ribosome on a non-stop mRNA	23	23.1×	9e-24
Selenocysteine synthesis	23	22.1×	2e-23
Eukaryotic Translation Termination	23	22.1×	2e-23
Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC)	23	21.7×	3e-23
ZNF598 and the Ribosome-associated Quality Trigger (RQT) complex dissociate a ribosome stalled on a no-go mRNA	23	21.7×	3e-23
SRP-dependent cotranslational protein targeting to membrane	26	20.8×	5e-25

GO biological processes:

GO term	Partners	Fold	FDR
cytoplasmic translation	26	28.3×	4e-28
maturation of SSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA)	5	19.8×	6e-04
receptor clustering	5	18.4×	8e-04
ribosomal large subunit biogenesis	7	18.3×	2e-05
establishment or maintenance of epithelial cell apical/basal polarity	5	17.1×	1e-03
ribosomal small subunit biogenesis	10	13.4×	1e-06
translation	22	13.3×	5e-16
negative regulation of translation	8	9.2×	4e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	99
Likely benign	0
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

1339 predictions. Top by Δscore:

Variant	Effect	Δscore
1:113765976:CATA:C	donor_gain	1.0000
1:113765980:T:C	donor_gain	1.0000
1:113766450:CGCA:C	acceptor_gain	1.0000
1:113766452:CA:C	acceptor_gain	1.0000
1:113766454:C:CC	acceptor_gain	1.0000
1:113767095:TTAC:T	donor_loss	1.0000
1:113767096:TACC:T	donor_loss	1.0000
1:113767097:A:AC	donor_gain	1.0000
1:113767097:A:C	donor_loss	1.0000
1:113767098:C:CC	donor_gain	1.0000
1:113767098:C:CG	donor_loss	1.0000
1:113767203:CACTC:C	acceptor_gain	1.0000
1:113767205:CTC:C	acceptor_gain	1.0000
1:113767206:TC:T	acceptor_gain	1.0000
1:113767207:CC:C	acceptor_gain	1.0000
1:113767207:CCTA:C	acceptor_loss	1.0000
1:113767208:C:CC	acceptor_gain	1.0000
1:113767208:CTA:C	acceptor_loss	1.0000
1:113767209:T:C	acceptor_loss	1.0000
1:113767214:T:C	acceptor_gain	1.0000
1:113767214:T:TC	acceptor_gain	1.0000
1:113768217:C:G	donor_loss	1.0000
1:113768218:T:TA	donor_loss	1.0000
1:113768219:C:CG	donor_loss	1.0000
1:113768220:A:C	donor_loss	1.0000
1:113768396:T:C	acceptor_gain	1.0000
1:113768396:T:TC	acceptor_gain	1.0000
1:113768405:T:C	acceptor_gain	1.0000
1:113768405:T:TC	acceptor_gain	1.0000
1:113768408:T:C	acceptor_gain	1.0000

AlphaMissense

5266 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:113766295:A:C	H698Q	1.000
1:113766295:A:T	H698Q	1.000
1:113766296:T:C	H698R	1.000
1:113766297:G:C	H698D	1.000
1:113766300:A:G	W697R	1.000
1:113766300:A:T	W697R	1.000
1:113766307:G:C	S694R	1.000
1:113766307:G:T	S694R	1.000
1:113766309:T:G	S694R	1.000
1:113766331:G:C	F686L	1.000
1:113766331:G:T	F686L	1.000
1:113766332:A:C	F686C	1.000
1:113766332:A:G	F686S	1.000
1:113766333:A:G	F686L	1.000
1:113766333:A:T	F686I	1.000
1:113766337:A:C	H684Q	1.000
1:113766337:A:T	H684Q	1.000
1:113766338:T:C	H684R	1.000
1:113766339:G:C	H684D	1.000
1:113766344:A:T	V682D	1.000
1:113766350:C:A	R680I	1.000
1:113766350:C:G	R680T	1.000
1:113766363:A:C	Y676D	1.000
1:113766380:A:G	L670P	1.000
1:113766396:A:C	Y665D	1.000
1:113766410:C:G	R660P	1.000
1:113766413:C:G	R659T	1.000
1:113766419:T:G	Q657P	1.000
1:113766421:G:C	N656K	1.000
1:113766421:G:T	N656K	1.000

dbSNP variants (sampled 300 via entrez): RS1000067145 (1:113812982 G>A), RS1000106716 (1:113765602 A>G), RS1000121326 (1:113806629 C>T), RS1000134467 (1:113771738 A>G), RS1000152370 (1:113806979 C>T), RS1000345679 (1:113812572 C>T), RS1000463809 (1:113806258 C>A), RS1000472694 (1:113769795 A>G), RS1000483255 (1:113792001 T>A,C), RS1000490716 (1:113808464 G>C), RS1000584791 (1:113810948 C>T), RS1000637024 (1:113811251 G>T), RS1000650954 (1:113762916 G>C), RS1000717919 (1:113801737 G>T), RS1000788086 (1:113804424 C>G,T)

Disease associations

OMIM: gene MIM:615858 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

10 associations (top):

Study	Trait	p-value
GCST001474_13	Hypothyroidism	3.000000e-13
GCST001762_676	Obesity-related traits	2.000000e-06
GCST004132_97	Crohn’s disease	4.000000e-06
GCST004866_5	Alopecia areata	7.000000e-07
GCST005194_197	Coronary artery disease	6.000000e-06
GCST005568_13	Rheumatoid arthritis (ACPA-positive)	8.000000e-77
GCST005569_36	Rheumatoid arthritis	9.000000e-62
GCST007933_1	Medication use (immunosuppressants)	3.000000e-19
GCST008644_21	Celiac disease and Rheumatoid arthritis	1.000000e-53
GCST90002395_318	Mean platelet volume	1.000000e-09

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0005134	amino acid measurement
EFO:0009934	Immunosuppressant use measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs6679677	PHTF1, RSBN1		0.00	0

CTD chemical–gene interactions

35 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases expression, decreases methylation, increases expression	4
Formaldehyde	decreases expression	2
Phenylmercuric Acetate	decreases expression, affects cotreatment	2
p-Chloromercuribenzoic Acid	affects cotreatment, decreases expression	2
aristolochic acid I	decreases expression	1
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
FR900359	affects phosphorylation	1
TAK-243	decreases sumoylation	1
triphenyl phosphate	affects expression	1
bisphenol A	increases expression	1
kojic acid	decreases expression	1
trichostatin A	decreases expression	1
beta-methylcholine	affects expression	1
di-n-butylphosphoric acid	affects expression	1
pentabromodiphenyl ether	increases expression	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
ICG 001	decreases expression	1
abrine	increases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
jinfukang	decreases expression	1
Sunitinib	increases expression	1
Vorinostat	decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Arbutin	decreases expression	1
Atrazine	increases expression	1
Benzo(a)pyrene	increases methylation	1
Doxorubicin	decreases expression	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Ethyl Methanesulfonate	decreases expression	1

Clinical trials (associated diseases)

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