IZUMO2

Summary

IZUMO2 (IZUMO family member 2, HGNC:28518) is a protein-coding gene on chromosome 19q13.33, encoding Izumo sperm-egg fusion protein 2 (Q6UXV1).

Predicted to be located in membrane.

Source: NCBI Gene 126123 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 41 total
• MANE Select transcript: NM_152358

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28518
Approved symbol	IZUMO2
Name	IZUMO family member 2
Location	19q13.33
Locus type	gene with protein product
Status	Approved
Aliases	MGC33947, SCRL
Ensembl gene	ENSG00000161652
Ensembl biotype	protein_coding
OMIM	618895
Entrez	126123

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 3 protein_coding, 2 nonsense_mediated_decay

ENST00000293405, ENST00000486050, ENST00000594854, ENST00000600293, ENST00000916628

RefSeq mRNA: 2 — MANE Select: NM_152358 NM_001321449, NM_152358

CCDS: CCDS12792

Canonical transcript exons

ENST00000293405 — 7 exons

Exon	Start	End
ENSE00001059493	50162739	50162813
ENSE00001751544	50152548	50152651
ENSE00001918580	50162963	50163281
ENSE00003559386	50158268	50158348
ENSE00003578361	50154600	50154726
ENSE00003672786	50159230	50159250
ENSE00003676949	50159494	50159580

Expression profiles

Bgee: expression breadth broad, 82 present calls, max score 93.99.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0909 / max 38.7933, expressed in 38 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
182142	0.0629	33
182141	0.0280	5

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
left testis	UBERON:0004533	93.99	gold quality
right testis	UBERON:0004534	93.89	gold quality
sperm	CL:0000019	93.14	gold quality
testis	UBERON:0000473	90.51	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	83.37	gold quality
adult organism	UBERON:0007023	71.85	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	71.25	gold quality
upper arm skin	UBERON:0004263	64.25	gold quality
buccal mucosa cell	CL:0002336	63.83	gold quality
secondary oocyte	CL:0000655	59.46	gold quality
tibialis anterior	UBERON:0001385	58.96	silver quality
nasal cavity epithelium	UBERON:0005384	57.45	gold quality
mucosa of paranasal sinus	UBERON:0005030	57.34	gold quality
parotid gland	UBERON:0001831	56.48	gold quality
vena cava	UBERON:0004087	55.42	gold quality
cardiac muscle of right atrium	UBERON:0003379	54.84	gold quality
superficial temporal artery	UBERON:0001614	54.80	gold quality
cortical plate	UBERON:0005343	54.75	gold quality
left ventricle myocardium	UBERON:0006566	54.23	gold quality
kidney epithelium	UBERON:0004819	53.93	gold quality
pericardium	UBERON:0002407	53.72	gold quality
epithelial cell of pancreas	CL:0000083	53.62	gold quality
deltoid	UBERON:0001476	52.42	gold quality
pancreatic ductal cell	CL:0002079	51.51	silver quality
tendon of biceps brachii	UBERON:0008188	51.08	gold quality
lower lobe of lung	UBERON:0008949	50.52	silver quality
myocardium	UBERON:0002349	50.46	gold quality
oocyte	CL:0000023	47.84	gold quality
quadriceps femoris	UBERON:0001377	47.81	gold quality
trachea	UBERON:0003126	47.41	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.39
E-MTAB-7303	no	7.25

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 1)

• Expression of IZUMO2 in colorectal cancer in association with clinicopathological features. (PMID:38484656)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Izumo2	ENSMUSG00000066500
rattus_norvegicus	Izumo2	ENSRNOG00000065701

Protein

Protein identifiers

Izumo sperm-egg fusion protein 2 — Q6UXV1 (reviewed: Q6UXV1)

All UniProt accessions (4): Q6UXV1, M0QXA9, M0QZG1, M0R2L8

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Membrane.

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

Similarity. Belongs to the Izumo family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q6UXV1-1	1	yes
Q6UXV1-2	2

RefSeq proteins (2): NP_001308378, NP_689571* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR029389	IZUMO	Family
IPR042920	IZUMO2	Family

Pfam: PF15005

UniProt features (8 total): topological domain 2, signal peptide 1, chain 1, transmembrane region 1, glycosylation site 1, splice variant 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6UXV1-F1	86.82	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.

Glycosylation sites (1): 91

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: 11 (showing top): REACTOME_FERTILIZATION, REACTOME_ACROSOME_REACTION_AND_SPERM_OOCYTE_MEMBRANE_BINDING, REACTOME_REPRODUCTION, ZIM3_TARGET_GENES, ZNF596_TARGET_GENES, GSE14769_UNSTIM_VS_240MIN_LPS_BMDM_DN, GSE2706_LPS_VS_R848_AND_LPS_2H_STIM_DC_DN, chr19q13, GSE2585_CTEC_VS_THYMIC_DC_UP, GSE5589_WT_VS_IL10_KO_LPS_AND_IL6_STIM_MACROPHAGE_45MIN_UP, GSE41176_UNSTIM_VS_ANTI_IGM_STIM_TAK1_KO_BCELL_1H_DN

GO Biological Process (0):

GO Molecular Function (0):

GO Cellular Component (1): membrane (GO:0016020)

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

Protein interactions and networks

STRING

248 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
IZUMO2	IZUMO3	Q5VZ72	843
IZUMO2	IZUMO4	Q1ZYL8	825
IZUMO2	IZUMO1	Q8IYV9	726
IZUMO2	ISOC2	Q96AB3	574
IZUMO2	ADAM32	Q8TC27	560
IZUMO2	ADAM2	P78326	528
IZUMO2	OR4N5	Q8IXE1	525
IZUMO2	SPACA4	Q8TDM5	519
IZUMO2	OR4K14	Q8NGD5	507
IZUMO2	RASIP1	Q5U651	471
IZUMO2	GLIPR1L1	Q6UWM5	460
IZUMO2	UNC50	Q53HI1	447
IZUMO2	ZNF556	Q9HAH1	446
IZUMO2	SPACA1	Q9HBV2	392
IZUMO2	TEKT5	Q96M29	372

IntAct

0 interactions, top by confidence:

BioGRID (1): IZUMO2 (Two-hybrid)

ESM2 similar proteins: A0A1B0GUA7, A0A3Q1LRJ2, A2T6Z6, E9Q8Q8, O46673, O77049, O88823, P01588, P07865, P22301, P29676, P43480, P46651, P48411, P51496, P51497, P51746, P55029, P79338, Q0Z972, Q25BC1, Q28374, Q28C41, Q2PE73, Q3KNT9, Q4VK74, Q5Q0V6, Q5ZJY9, Q6A2H4, Q6AY06, Q6H8S9, Q6H8T0, Q6H8T1, Q6H8T2, Q6UXV1, Q865X4, Q8BGT0, Q8CGK6, Q8CJ70, Q8IU54

Diamond homologs: A6PWV3, A6QL94, Q5VZ72, Q6UXV1, Q9DA16

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

41 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	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

917 predictions. Top by Δscore:

Variant	Effect	Δscore
19:50158262:GCTTA:G	donor_loss	1.0000
19:50158263:CTTAC:C	donor_loss	1.0000
19:50158265:TA:T	donor_loss	1.0000
19:50158266:ACC:A	donor_loss	1.0000
19:50158267:C:CG	donor_loss	1.0000
19:50158346:AGCC:A	acceptor_loss	1.0000
19:50158347:GCCT:G	acceptor_loss	1.0000
19:50158348:CCTA:C	acceptor_loss	1.0000
19:50158349:CT:C	acceptor_loss	1.0000
19:50158350:T:A	acceptor_loss	1.0000
19:50159521:T:A	donor_gain	1.0000
19:50159529:T:TA	donor_gain	1.0000
19:50162812:CT:C	acceptor_gain	1.0000
19:50162814:C:CC	acceptor_gain	1.0000
19:50162959:GCAC:G	donor_loss	1.0000
19:50162962:C:CA	donor_loss	1.0000
19:50162962:CCCA:C	donor_gain	1.0000
19:50162965:A:AC	donor_gain	1.0000
19:50162966:C:CC	donor_gain	1.0000
19:50162969:T:A	donor_gain	1.0000
19:50162984:T:A	donor_gain	1.0000
19:50162993:AGT:A	donor_gain	1.0000
19:50162993:AGTC:A	donor_gain	1.0000
19:50158266:A:AC	donor_gain	0.9900
19:50158267:C:CC	donor_gain	0.9900
19:50158344:CAAGC:C	acceptor_gain	0.9900
19:50158347:GC:G	acceptor_gain	0.9900
19:50158348:CC:C	acceptor_gain	0.9900
19:50158349:C:CC	acceptor_gain	0.9900
19:50162809:TGTCT:T	acceptor_gain	0.9900

AlphaMissense

1418 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:50162976:A:C	F73L	0.979
19:50162976:A:T	F73L	0.979
19:50162978:A:G	F73L	0.979
19:50158273:C:G	C164S	0.967
19:50158274:A:T	C164S	0.967
19:50158322:A:G	C148R	0.966
19:50163001:A:C	F65C	0.966
19:50159247:C:T	C133Y	0.964
19:50158272:G:C	C164W	0.963
19:50159247:C:G	C133S	0.961
19:50159248:A:T	C133S	0.961
19:50159546:C:A	R114S	0.960
19:50159546:C:G	R114S	0.960
19:50159522:C:A	K122N	0.959
19:50159522:C:G	K122N	0.959
19:50159559:A:G	L110P	0.959
19:50163003:G:C	F64L	0.958
19:50163003:G:T	F64L	0.958
19:50163005:A:G	F64L	0.958
19:50158273:C:T	C164Y	0.956
19:50158321:C:G	C148S	0.956
19:50158322:A:T	C148S	0.956
19:50163063:G:C	F44L	0.956
19:50163063:G:T	F44L	0.956
19:50163065:A:G	F44L	0.956
19:50163064:A:C	F44C	0.955
19:50158274:A:G	C164R	0.953
19:50159232:C:G	C138S	0.953
19:50159233:A:T	C138S	0.953
19:50163134:A:G	C21R	0.952

dbSNP variants (sampled 300 via entrez): RS1000234823 (19:50163190 G>A), RS1000291839 (19:50156871 C>T), RS1000349301 (19:50160544 G>A), RS1000524192 (19:50154421 G>A), RS1000992310 (19:50160784 C>A,T), RS1001434997 (19:50155689 T>G), RS1002082787 (19:50153775 A>C,T), RS1002502064 (19:50160448 T>C), RS1002723444 (19:50164789 T>G), RS1002994364 (19:50152489 G>A), RS1003101295 (19:50159010 T>C), RS1003487882 (19:50165116 A>G), RS1004217555 (19:50157909 A>AT), RS1004375298 (19:50154794 A>C,G), RS1004689549 (19:50163738 G>A,C,T)

Disease associations

OMIM: gene MIM:618895 | 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

8 total (human), top 8 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases methylation	1
sodium arsenite	increases expression	1
perfluorooctanoic acid	increases expression	1
aflatoxin B2	increases methylation	1
perfluorooctane sulfonic acid	increases expression	1
Acetaminophen	increases expression	1
Benzo(a)pyrene	affects methylation, decreases methylation, increases methylation	1
Aflatoxin B1	decreases methylation	1

Clinical trials (associated diseases)

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