IZUMO3

Summary

IZUMO3 (IZUMO family member 3, HGNC:31421) is a protein-coding gene on chromosome 9p21.3, encoding Izumo sperm-egg fusion protein 3 (Q5VZ72). Plays an important role in the biogenesis of the acrosome during sperm development.

Predicted to enable protein homodimerization activity. Predicted to be involved in acrosome assembly. Predicted to be located in inner acrosomal membrane.

Source: NCBI Gene 100129669 — RefSeq curated summary.

At a glance

• GWAS associations: 7
• Clinical variants (ClinVar): 5 total
• MANE Select transcript: NM_001365008

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:31421
Approved symbol	IZUMO3
Name	IZUMO family member 3
Location	9p21.3
Locus type	gene with protein product
Status	Approved
Aliases	bA20A20.1
Ensembl gene	ENSG00000205442
Ensembl biotype	protein_coding
OMIM	618896
Entrez	100129669

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 3 protein_coding

ENST00000418122, ENST00000543880, ENST00000604921

RefSeq mRNA: 2 — MANE Select: NM_001365008 NM_001271706, NM_001365008

CCDS: CCDS65020, CCDS94393

Canonical transcript exons

ENST00000543880 — 7 exons

Exon	Start	End
ENSE00001483721	24543664	24543754
ENSE00001483723	24544201	24544281
ENSE00001483726	24544972	24545061
ENSE00001595754	24544743	24544760
ENSE00001681117	24542952	24543367
ENSE00001794258	24545212	24545286
ENSE00002220238	24545424	24545897

Expression profiles

Bgee: expression breadth tissue_specific, 10 present calls, max score 87.67.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0113 / max 10.3750, expressed in 3 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
100302	0.0113	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	87.67	gold quality
left testis	UBERON:0004533	78.72	gold quality
testis	UBERON:0000473	78.43	gold quality
right testis	UBERON:0004534	77.93	gold quality
granulocyte	CL:0000094	44.65	silver quality
bone marrow cell	CL:0002092	38.73	gold quality
sural nerve	UBERON:0015488	38.28	gold quality
colonic epithelium	UBERON:0000397	37.20	gold quality
ventricular zone	UBERON:0003053	36.48	gold quality
cortical plate	UBERON:0005343	36.47	gold quality
ganglionic eminence	UBERON:0004023	35.49	gold quality
skeletal muscle tissue	UBERON:0001134	33.38	gold quality
bone marrow	UBERON:0002371	33.06	gold quality
hindlimb stylopod muscle	UBERON:0004252	32.15	gold quality
muscle tissue	UBERON:0002385	31.06	gold quality
stromal cell of endometrium	CL:0002255	29.87	gold quality
monocyte	CL:0000576	29.25	silver quality
prefrontal cortex	UBERON:0000451	29.04	gold quality
duodenum	UBERON:0002114	28.14	gold quality
liver	UBERON:0002107	28.04	gold quality
lymph node	UBERON:0000029	27.57	gold quality
tonsil	UBERON:0002372	27.05	gold quality
islet of Langerhans	UBERON:0000006	26.55	gold quality
vermiform appendix	UBERON:0001154	26.42	gold quality
gall bladder	UBERON:0002110	25.98	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	25.89	gold quality
placenta	UBERON:0001987	25.81	gold quality
calcaneal tendon	UBERON:0003701	25.81	gold quality
urinary bladder	UBERON:0001255	25.72	gold quality
muscle of leg	UBERON:0001383	25.68	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.28

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 1)

• two sex-specific loci(SPTB in females and IZUMO3 in males), yielding associations that were particularly strong at a specific skeletal site, were identified. (PMID:28181694)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Izumo3	ENSMUSG00000028533
rattus_norvegicus	Izumo3	ENSRNOG00000022488

Protein

Protein identifiers

Izumo sperm-egg fusion protein 3 — Q5VZ72 (reviewed: Q5VZ72)

All UniProt accessions (3): Q5VZ72, H7BZS5, S4R3E6

UniProt curated annotations — full annotation on UniProt →

Function. Plays an important role in the biogenesis of the acrosome during sperm development.

Subunit / interactions. Monomer and homodimer.

Subcellular location. Cell membrane. Cytoplasmic vesicle. Secretory vesicle. Acrosome inner membrane.

Miscellaneous. Izumo is the name of a Japanese shrine to marriage.

Similarity. Belongs to the Izumo family.

RefSeq proteins (2): NP_001258635, NP_001351937* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR029389	IZUMO	Family

Pfam: PF15005

UniProt features (7 total): topological domain 2, glycosylation site 2, signal peptide 1, chain 1, transmembrane region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q5VZ72-F1	86.94	0.66

Functional residue map

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

Glycosylation sites (2): 96, 126

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-1300645	Acrosome Reaction and Sperm:Oocyte Membrane Binding
R-HSA-1187000	Fertilization
R-HSA-1474165	Reproduction

MSigDB gene sets: 28 (showing top): GOCC_SECRETORY_GRANULE, GOBP_VESICLE_ORGANIZATION, GOBP_MALE_GAMETE_GENERATION, GOBP_SECRETORY_GRANULE_ORGANIZATION, GOBP_CELLULAR_COMPONENT_ASSEMBLY_INVOLVED_IN_MORPHOGENESIS, GOBP_ACROSOME_ASSEMBLY, GOBP_ORGANELLE_ASSEMBLY, GOBP_CELLULAR_PROCESS_INVOLVED_IN_REPRODUCTION_IN_MULTICELLULAR_ORGANISM, GOBP_ENDOMEMBRANE_SYSTEM_ORGANIZATION, GOBP_DEVELOPMENTAL_PROCESS_INVOLVED_IN_REPRODUCTION, GOCC_ACROSOMAL_MEMBRANE, GOCC_SECRETORY_VESICLE, GOCC_SECRETORY_GRANULE_MEMBRANE, GOCC_ACROSOMAL_VESICLE, GOMF_PROTEIN_DIMERIZATION_ACTIVITY

GO Biological Process (3): acrosome assembly (GO:0001675), spermatogenesis (GO:0007283), cell differentiation (GO:0030154)

GO Molecular Function (1): protein homodimerization activity (GO:0042803)

GO Cellular Component (4): inner acrosomal membrane (GO:0002079), plasma membrane (GO:0005886), membrane (GO:0016020), cytoplasmic vesicle (GO:0031410)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Fertilization	1
Reproduction	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
developmental process involved in reproduction	2
spermatid development	1
cellular component assembly involved in morphogenesis	1
cellular process involved in reproduction in multicellular organism	1
secretory granule organization	1
organelle assembly	1
male gamete generation	1
cellular developmental process	1
identical protein binding	1
protein dimerization activity	1
acrosomal membrane	1
cytoplasmic vesicle membrane	1
membrane	1
cell periphery	1
cellular anatomical structure	1
cytoplasm	1
intracellular vesicle	1

Protein interactions and networks

STRING

258 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
IZUMO3	IZUMO2	Q6UXV1	843
IZUMO3	IZUMO4	Q1ZYL8	828
IZUMO3	IZUMO1	Q8IYV9	746
IZUMO3	ADAM2	P78326	534
IZUMO3	TBPL2	Q6SJ96	518
IZUMO3	CRISP2	P16562	493
IZUMO3	PKDREJ	Q9NTG1	491
IZUMO3	CPED1	A4D0V7	480
IZUMO3	ACRV1	P26436	480
IZUMO3	CRISP1	P54107	469
IZUMO3	CD9	P21926	452
IZUMO3	TSSK6	Q9BXA6	439
IZUMO3	TUSC1	Q2TAM9	435
IZUMO3	ZP1	P60852	431
IZUMO3	ZP3	P21754	428

IntAct

0 interactions, top by confidence:

BioGRID (1): IZUMO3 (Affinity Capture-MS)

ESM2 similar proteins: A0A2R8QHQ6, A0A8M9PDM1, A6PWV3, A6QL94, D3Z690, F5HC71, O02699, O12980, O77515, P04401, P05402, P0DJF3, P0DP43, P12401, P17150, P18917, P19159, P20826, P21583, P21702, P33579, P33580, P46685, P52173, P79169, Q08125, Q14512, Q28586, Q29030, Q4R6V5, Q5VZ72, Q60440, Q62575, Q6AY06, Q6P7N7, Q920I0, Q95J76, Q95MD2, Q95N18, Q9CQ58

Diamond homologs: A6PWV3, A6QL94, Q5VZ72, Q6UXV1

SIGNOR signaling

0 interactions.

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	3
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

776 predictions. Top by Δscore:

Variant	Effect	Δscore
9:24543662:A:AC	donor_gain	1.0000
9:24543663:C:CC	donor_gain	1.0000
9:24543678:T:TA	donor_gain	1.0000
9:24543679:C:A	donor_gain	1.0000
9:24543750:CTCGT:C	acceptor_gain	1.0000
9:24543752:CGT:C	acceptor_gain	1.0000
9:24543753:GTC:G	acceptor_loss	1.0000
9:24543754:TC:T	acceptor_loss	1.0000
9:24543755:C:CC	acceptor_gain	1.0000
9:24543755:CTG:C	acceptor_loss	1.0000
9:24543756:T:A	acceptor_loss	1.0000
9:24544282:C:CC	acceptor_gain	1.0000
9:24544968:TTACC:T	donor_loss	1.0000
9:24544970:A:AC	donor_gain	1.0000
9:24544970:AC:A	donor_gain	1.0000
9:24544971:C:CA	donor_gain	1.0000
9:24544971:CC:C	donor_gain	1.0000
9:24544971:CCA:C	donor_gain	1.0000
9:24544971:CCAA:C	donor_gain	1.0000
9:24544971:CCAAT:C	donor_gain	1.0000
9:24545417:C:A	donor_gain	1.0000
9:24543365:AATCT:A	acceptor_loss	0.9900
9:24543367:TCTAG:T	acceptor_loss	0.9900
9:24543368:C:CC	acceptor_gain	0.9900
9:24543369:T:G	acceptor_loss	0.9900
9:24543685:A:AC	donor_gain	0.9900
9:24543751:TCGT:T	acceptor_gain	0.9900
9:24543752:CGTC:C	acceptor_gain	0.9900
9:24543753:GT:G	acceptor_gain	0.9900
9:24544202:T:TA	donor_gain	0.9900

AlphaMissense

1563 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:24543675:A:C	S190R	0.977
9:24543675:A:T	S190R	0.977
9:24543677:T:G	S190R	0.977
9:24544250:C:A	W147C	0.963
9:24544250:C:G	W147C	0.963
9:24544982:G:C	F127L	0.963
9:24544982:G:T	F127L	0.963
9:24544984:A:G	F127L	0.963
9:24545216:C:A	W99C	0.956
9:24545216:C:G	W99C	0.956
9:24545218:A:G	W99R	0.949
9:24545218:A:T	W99R	0.949
9:24545566:A:C	F28L	0.940
9:24545566:A:T	F28L	0.940
9:24545568:A:G	F28L	0.940
9:24544255:A:G	C146R	0.935
9:24544253:A:C	C146W	0.933
9:24544252:A:G	W147R	0.924
9:24544252:A:T	W147R	0.924
9:24544246:A:G	C149R	0.922
9:24545016:A:G	L116P	0.922
9:24544254:C:T	C146Y	0.920
9:24545212:C:G	G101R	0.919
9:24544256:A:C	D145E	0.918
9:24544256:A:T	D145E	0.918
9:24545580:A:G	C24R	0.916
9:24545004:A:G	L120P	0.915
9:24544206:C:G	C162S	0.911
9:24544207:A:T	C162S	0.911
9:24544244:A:C	C149W	0.907

dbSNP variants (sampled 300 via entrez): RS1000108008 (9:24544476 G>A), RS1000509659 (9:24547732 G>A), RS1000563755 (9:24543797 A>C,G), RS1000614351 (9:24544022 G>T), RS1001524427 (9:24546523 T>A,C,G), RS1002020073 (9:24547444 A>C), RS1002060080 (9:24546295 T>C), RS1002116505 (9:24543613 T>C), RS1002297574 (9:24547514 G>A), RS1002454557 (9:24547275 A>G), RS1002932652 (9:24545652 C>G,T), RS1002971352 (9:24546552 T>C), RS1003002590 (9:24546456 T>C), RS1003319929 (9:24542643 C>A), RS1003533359 (9:24542698 C>T)

Disease associations

OMIM: gene MIM:618896 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

7 associations (top):

Study	Trait	p-value
GCST004181_3	Pediatric bone mineral density (spine)	1.000000e-08
GCST004182_1	Pediatric bone mineral content (spine)	1.000000e-07
GCST007576_282	Chronotype	2.000000e-09
GCST008597_2	Fish intake frequency	9.000000e-06
GCST010059_3	Physiological traits	6.000000e-06
GCST010059_8	Physiological traits	6.000000e-06
GCST012307_13	Bipolar disorder x sex interaction	2.000000e-07

EFO canonical traits (7, from GWAS)

EFO ID	Trait name
EFO:0007701	spine bone mineral density
EFO:0007621	bone mineral content measurement
EFO:0008328	chronotype measurement
EFO:0010139	fish consumption measurement
EFO:0004338	body weight
EFO:0005937	longitudinal BMI measurement
EFO:0008343	sex interaction measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

Clinical trials (associated diseases)

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