IZUMO4

Summary

IZUMO4 (IZUMO family member 4, HGNC:26950) is a protein-coding gene on chromosome 19p13.3, encoding Izumo sperm-egg fusion protein 4 (Q1ZYL8).

Located in nucleus.

Source: NCBI Gene 113177 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 54 total
• MANE Select transcript: NM_001039846

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:26950
Approved symbol	IZUMO4
Name	IZUMO family member 4
Location	19p13.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000099840
Ensembl biotype	protein_coding
OMIM	618897
Entrez	113177

Gene structure

Transcript identifiers

Ensembl transcripts: 13 — 6 protein_coding, 6 retained_intron, 1 nonsense_mediated_decay

ENST00000395296, ENST00000395301, ENST00000395307, ENST00000478879, ENST00000481489, ENST00000497445, ENST00000498554, ENST00000588003, ENST00000590985, ENST00000591894, ENST00000593185, ENST00000610800, ENST00000620263

RefSeq mRNA: 3 — MANE Select: NM_001039846 NM_001031735, NM_001039846, NM_001363588

CCDS: CCDS35499, CCDS42458, CCDS86690

Canonical transcript exons

ENST00000395301 — 10 exons

Exon	Start	End
ENSE00000892350	2096915	2097162
ENSE00001521272	2098976	2099029
ENSE00003469484	2098287	2098334
ENSE00003500215	2097424	2097495
ENSE00003515160	2097252	2097332
ENSE00003517574	2098436	2098450
ENSE00003673814	2098787	2098804
ENSE00003685274	2097929	2097955
ENSE00003686957	2098052	2098127
ENSE00003743971	2099255	2099590

Expression profiles

Bgee: expression breadth ubiquitous, 191 present calls, max score 99.48.

FANTOM5 (CAGE): breadth broad, TPM avg 3.7926 / max 760.9804, expressed in 798 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
173032	1.7914	565
173030	1.1200	218
173033	0.6078	295
173031	0.2735	131

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
left testis	UBERON:0004533	99.48	gold quality
right testis	UBERON:0004534	99.34	gold quality
adult organism	UBERON:0007023	98.42	gold quality
testis	UBERON:0000473	97.38	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	96.86	gold quality
tibial nerve	UBERON:0001323	91.22	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	91.17	gold quality
adenohypophysis	UBERON:0002196	89.93	gold quality
left ovary	UBERON:0002119	89.26	gold quality
right frontal lobe	UBERON:0002810	87.62	gold quality
right ovary	UBERON:0002118	87.33	gold quality
spinal cord	UBERON:0002240	87.30	gold quality
pituitary gland	UBERON:0000007	87.06	gold quality
amygdala	UBERON:0001876	86.88	gold quality
cingulate cortex	UBERON:0003027	86.50	gold quality
anterior cingulate cortex	UBERON:0009835	86.45	gold quality
right hemisphere of cerebellum	UBERON:0014890	86.13	gold quality
sural nerve	UBERON:0015488	85.98	gold quality
body of pancreas	UBERON:0001150	85.88	gold quality
caudate nucleus	UBERON:0001873	85.35	gold quality
cerebellar hemisphere	UBERON:0002245	84.81	gold quality
Brodmann (1909) area 9	UBERON:0013540	84.68	gold quality
putamen	UBERON:0001874	84.65	gold quality
lower esophagus mucosa	UBERON:0035834	84.63	gold quality
nucleus accumbens	UBERON:0001882	84.48	gold quality
cerebellar cortex	UBERON:0002129	84.47	gold quality
left uterine tube	UBERON:0001303	83.83	gold quality
cerebellum	UBERON:0002037	82.03	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	81.95	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	81.71	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-GEOD-134144	yes	30.82
E-ANND-3	no	1.41

Regulation

Is transcription factor: no

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Izumo4	ENSMUSG00000055862
rattus_norvegicus	Izumo4	ENSRNOG00000031950

Protein

Protein identifiers

Izumo sperm-egg fusion protein 4 — Q1ZYL8 (reviewed: Q1ZYL8)

Alternative names: Sperm 22 kDa protein c113

All UniProt accessions (6): Q1ZYL8, A0A087WXR1, A0A087X160, A0A087X1M1, A0A087X221, A0A0A0MS61

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Secreted.

Tissue specificity. Detected in sperm.

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

Similarity. Belongs to the Izumo family.

Isoforms (4)

UniProt ID	Names	Canonical?
Q1ZYL8-1	1	yes
Q1ZYL8-2	2
Q1ZYL8-3	3
Q1ZYL8-4	4

RefSeq proteins (3): NP_001026905, NP_001034935, NP_001350517 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR029389	IZUMO	Family
IPR052868	Izumo_fusion	Family

Pfam: PF15005

UniProt features (11 total): splice variant 4, sequence variant 3, glycosylation site 2, signal peptide 1, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q1ZYL8-F1	81.83	0.50

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): 24, 219

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: 77 (showing top): GSE45365_NK_CELL_VS_CD11B_DC_UP, CAGCTG_AP4_Q5, KIM_RESPONSE_TO_TSA_AND_DECITABINE_UP, KESHELAVA_MULTIPLE_DRUG_RESISTANCE, HELLER_HDAC_TARGETS_SILENCED_BY_METHYLATION_UP, BOGNI_TREATMENT_RELATED_MYELOID_LEUKEMIA_UP, ZHAN_MULTIPLE_MYELOMA_LB_UP, MARSON_BOUND_BY_FOXP3_UNSTIMULATED, chr19p13, MARTENS_BOUND_BY_PML_RARA_FUSION, REACTOME_FERTILIZATION, REACTOME_ACROSOME_REACTION_AND_SPERM_OOCYTE_MEMBRANE_BINDING, REACTOME_REPRODUCTION, PTEN_DN.V2_DN, GSE13547_2H_VS_12_H_ANTI_IGM_STIM_ZFX_KO_BCELL_UP

GO Biological Process (0):

GO Molecular Function (0):

GO Cellular Component (2): extracellular region (GO:0005576), nucleus (GO:0005634)

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
cellular anatomical structure	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

1021 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
IZUMO4	IZUMO3	Q5VZ72	828
IZUMO4	IZUMO2	Q6UXV1	825
IZUMO4	IZUMO1	Q8IYV9	819
IZUMO4	ADAM2	P78326	543
IZUMO4	ADAM32	Q8TC27	535
IZUMO4	ODF2	Q5BJF6	525
IZUMO4	CAPZB	P47756	498
IZUMO4	ITPRID2	P28290	497
IZUMO4	SPESP1	Q6UW49	495
IZUMO4	ACRBP	Q8NEB7	489
IZUMO4	SPACA1	Q9HBV2	464
IZUMO4	TEX2	Q8IWB9	464
IZUMO4	SPACA9	Q96E40	434
IZUMO4	SPACA3	Q8IXA5	433
IZUMO4	CCNI2	Q6ZMN8	422

IntAct

3 interactions, top by confidence:

A	B	Type	Score
TEX101	GGT3P	psi-mi:“MI:0914”(association)	0.350
M		psi-mi:“MI:0914”(association)	0.350

BioGRID (2): IZUMO4 (Affinity Capture-MS), IZUMO4 (Affinity Capture-RNA)

ESM2 similar proteins: A6PWV3, A6QL94, C8AW45, D3Z690, O02699, O62757, O77515, P04141, P04401, P05112, P05113, P06740, P08700, P11052, P15248, P20096, P28773, P46652, P46685, P47966, P48093, P48749, P51492, P51748, P52173, P60568, P60569, P79339, Q08125, Q1ZYL8, Q28586, Q28809, Q29118, Q3ZRW9, Q4R6V5, Q5VZ72, Q60440, Q60481, Q62575, Q6EBC2

Diamond homologs: D3Z690, Q1ZYL8, Q4R6V5

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	45
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1323 predictions. Top by Δscore:

Variant	Effect	Δscore
19:2097158:GATCA:G	donor_gain	1.0000
19:2097159:A:G	donor_gain	1.0000
19:2097163:G:GG	donor_gain	1.0000
19:2097496:G:GG	donor_gain	1.0000
19:2098128:G:GG	donor_gain	1.0000
19:2097316:G:GT	donor_gain	0.9900
19:2097316:G:T	donor_gain	0.9900
19:2097416:C:CA	acceptor_gain	0.9900
19:2097492:GAAA:G	donor_gain	0.9900
19:2097522:G:T	donor_gain	0.9900
19:2097674:G:A	acceptor_gain	0.9900
19:2097923:CCACA:C	acceptor_loss	0.9900
19:2097924:CACAG:C	acceptor_loss	0.9900
19:2097926:CA:C	acceptor_loss	0.9900
19:2097927:A:AC	acceptor_loss	0.9900
19:2097927:A:AG	acceptor_gain	0.9900
19:2097928:G:A	acceptor_loss	0.9900
19:2097928:G:GG	acceptor_gain	0.9900
19:2098124:GCGA:G	donor_gain	0.9900
19:2098126:GA:G	donor_gain	0.9900
19:2098161:GGCCC:G	donor_gain	0.9900
19:2098335:G:GG	donor_gain	0.9900
19:2099253:AGCCT:A	acceptor_gain	0.9900
19:2099254:GCCTG:G	acceptor_gain	0.9900
19:2097250:A:AG	acceptor_gain	0.9800
19:2097251:G:GG	acceptor_gain	0.9800
19:2097493:A:T	donor_gain	0.9800
19:2097504:A:AG	donor_gain	0.9800
19:2097673:C:CA	acceptor_gain	0.9800
19:2098140:C:T	donor_gain	0.9800

AlphaMissense

1534 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:2097113:G:C	W56C	0.980
19:2097113:G:T	W56C	0.980
19:2098302:G:C	W163C	0.979
19:2098302:G:T	W163C	0.979
19:2097030:T:C	F29L	0.977
19:2097032:C:A	F29L	0.977
19:2097032:C:G	F29L	0.977
19:2097018:T:C	F25L	0.972
19:2097020:C:A	F25L	0.972
19:2097020:C:G	F25L	0.972
19:2097111:T:A	W56R	0.968
19:2097111:T:C	W56R	0.968
19:2098111:T:C	F153L	0.964
19:2098113:T:A	F153L	0.964
19:2098113:T:G	F153L	0.964
19:2097031:T:G	F29C	0.957
19:2097430:T:G	F102C	0.952
19:2097453:T:C	F110L	0.952
19:2097455:C:A	F110L	0.952
19:2097455:C:G	F110L	0.952
19:2097483:G:C	A120P	0.949
19:2098300:T:A	W163R	0.947
19:2098300:T:C	W163R	0.947
19:2097429:T:C	F102L	0.939
19:2097431:C:A	F102L	0.939
19:2097431:C:G	F102L	0.939
19:2097442:T:C	L106P	0.939
19:2097019:T:G	F25C	0.934
19:2097472:T:C	L116P	0.934
19:2098123:T:A	C157S	0.932

dbSNP variants (sampled 300 via entrez): RS1000975361 (19:2097184 A>C), RS1001980324 (19:2096280 G>T), RS1002488507 (19:2095234 A>C), RS1002752915 (19:2098903 G>A,C,T), RS1002980328 (19:2095299 A>T), RS1003389583 (19:2098662 C>A,T), RS1005193723 (19:2099748 T>C), RS1005354378 (19:2096763 C>T), RS1005407987 (19:2096937 G>A,C), RS1006359946 (19:2095568 G>A,C), RS1006412862 (19:2095859 C>T), RS1006962140 (19:2099115 C>A,T), RS1007419280 (19:2099478 G>A,C), RS1007487050 (19:2095797 T>A,G), RS1007627594 (19:2096410 G>A)

Disease associations

OMIM: gene MIM:618897 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST009391_189	Metabolite levels	3.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0010482	gamma-aminoisobutyric acid measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

21 total (human), top 21 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
triphenyl phosphate	affects expression	1
sodium arsenate	increases expression, increases abundance	1
sodium arsenite	decreases expression	1
jinfukang	affects cotreatment, increases expression	1
(+)-JQ1 compound	increases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Sunitinib	decreases expression	1
Zoledronic Acid	increases expression	1
Arsenic	increases abundance, increases expression	1
Vehicle Emissions	increases abundance, increases expression	1
Cisplatin	affects cotreatment, increases expression	1
Diethylhexyl Phthalate	decreases expression	1
Estradiol	affects cotreatment, decreases expression	1
Methyl Methanesulfonate	decreases expression	1
Plant Extracts	decreases expression, affects cotreatment	1
Smoke	increases expression	1
Tobacco Smoke Pollution	decreases expression	1
Valproic Acid	increases methylation	1
Okadaic Acid	increases expression	1
Acrylamide	decreases expression	1
Particulate Matter	increases abundance, increases expression	1

Clinical trials (associated diseases)

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