TEX46

Summary

TEX46 (testis expressed 46, HGNC:44651) is a protein-coding gene on chromosome 1p36.12, encoding Testis-expressed protein 46 (H3BTG2). Essential for male fertility, sperm head formation and sperm penetration through the egg zona pellucida.

Predicted to be involved in single fertilization. Predicted to be located in membrane.

Source: NCBI Gene 729059 — RefSeq curated summary.

At a glance

• GWAS associations: 8
• Clinical variants (ClinVar): 2 total
• MANE Select transcript: NM_001242521

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:44651
Approved symbol	TEX46
Name	testis expressed 46
Location	1p36.12
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000227868
Ensembl biotype	protein_coding
Entrez	729059

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 3 protein_coding

ENST00000440767, ENST00000566855, ENST00000622840

RefSeq mRNA: 1 — MANE Select: NM_001242521 NM_001242521

CCDS: CCDS57978

Canonical transcript exons

ENST00000566855 — 3 exons

Exon	Start	End
ENSE00001787129	23013883	23014045
ENSE00002615611	23010834	23011101
ENSE00002623552	23015772	23015852

Expression profiles

Bgee: expression breadth ubiquitous, 144 present calls, max score 95.65.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0703 / max 60.4454, expressed in 5 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
10931	0.0262	4
10932	0.0259	3
10933	0.0100	3
10934	0.0049	3
10935	0.0034	4

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
left testis	UBERON:0004533	95.65	gold quality
right testis	UBERON:0004534	95.58	gold quality
sperm	CL:0000019	93.89	gold quality
testis	UBERON:0000473	92.58	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	92.30	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	92.22	gold quality
adult organism	UBERON:0007023	80.34	gold quality
kidney epithelium	UBERON:0004819	55.31	gold quality
cardiac muscle of right atrium	UBERON:0003379	54.34	gold quality
left ventricle myocardium	UBERON:0006566	54.23	gold quality
right uterine tube	UBERON:0001302	53.97	gold quality
epithelial cell of pancreas	CL:0000083	53.53	gold quality
upper arm skin	UBERON:0004263	53.52	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	52.77	gold quality
cerebellar vermis	UBERON:0004720	52.72	gold quality
spinal cord	UBERON:0002240	51.71	gold quality
pancreatic ductal cell	CL:0002079	50.73	silver quality
olfactory segment of nasal mucosa	UBERON:0005386	50.33	gold quality
myocardium	UBERON:0002349	50.25	gold quality
nucleus accumbens	UBERON:0001882	49.54	gold quality
caudate nucleus	UBERON:0001873	48.82	gold quality
deltoid	UBERON:0001476	48.73	gold quality
substantia nigra	UBERON:0002038	48.11	gold quality
right coronary artery	UBERON:0001625	48.01	gold quality
putamen	UBERON:0001874	47.95	gold quality
tibialis anterior	UBERON:0001385	47.25	silver quality
midbrain	UBERON:0001891	47.13	gold quality
nasal cavity epithelium	UBERON:0005384	47.03	gold quality
quadriceps femoris	UBERON:0001377	46.92	gold quality
amygdala	UBERON:0001876	46.57	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.45

Regulation

Is transcription factor: no

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Tex46	ENSMUSG00000036921
rattus_norvegicus	Tex46	ENSRNOG00000022257

Protein

Protein identifiers

Testis-expressed protein 46 — H3BTG2 (reviewed: H3BTG2)

All UniProt accessions (3): H3BTG2, A0A0D9SG37, A0A0D9SG83

UniProt curated annotations — full annotation on UniProt →

Function. Essential for male fertility, sperm head formation and sperm penetration through the egg zona pellucida.

Subcellular location. Membrane.

Tissue specificity. Testis-specific.

Isoforms (2)

UniProt ID	Names	Canonical?
H3BTG2-1	1	yes
H3BTG2-2	2

RefSeq proteins (1): NP_001229450* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR038788	TEX46-like	Family

Pfam: PF17671

UniProt features (5 total): splice variant 2, signal peptide 1, chain 1, transmembrane region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-H3BTG2-F1	68.24	0.07

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 15 (showing top): GSE37336_LY6C_POS_VS_NEG_NAIVE_CD4_TCELL_DN, GOBP_SINGLE_FERTILIZATION, GOBP_FERTILIZATION, chr1p36, ZFHX3_TARGET_GENES, GSE11864_CSF1_IFNG_VS_CSF1_PAM3CYS_IN_MAC_DN, GOBP_SEXUAL_REPRODUCTION, ZNF320_TARGET_GENES, GOBP_REPRODUCTIVE_PROCESS, GSE29614_CTRL_VS_DAY3_TIV_FLU_VACCINE_PBMC_UP, GSE25088_CTRL_VS_ROSIGLITAZONE_STIM_MACROPHAGE_DN, GSE16385_IFNG_TNF_VS_UNSTIM_MACROPHAGE_ROSIGLITAZONE_TREATED_UP, GSE46242_TH1_VS_ANERGIC_TH1_CD4_TCELL_DN, GSE43863_NAIVE_VS_TFH_CD4_EFF_TCELL_D6_LCMV_DN, GSE46606_UNSTIM_VS_CD40L_IL2_IL5_3DAY_STIMULATED_IRF4_KO_BCELL_UP

GO Biological Process (1): single fertilization (GO:0007338)

GO Molecular Function (0):

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

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
fertilization	1
cellular anatomical structure	1

Protein interactions and networks

STRING

0 interactions, top by confidence (×1000):

IntAct

0 interactions, top by confidence:

ESM2 similar proteins: A0A140LFM6, A2APA5, A6H754, A6NKT7, A8MZ97, C5DZR8, E9Q555, H3BTG2, O14715, O39519, O43310, O88677, P0CAX8, P25049, P33802, P50615, Q14201, Q14CH0, Q2KIK3, Q3SZY8, Q4R309, Q4V9P3, Q5CCK0, Q5JX69, Q5JX71, Q5R7R7, Q5RA87, Q5RBQ2, Q5RF07, Q5XIC3, Q60664, Q7L3B6, Q7Z3J3, Q8BLN6, Q8K190, Q8N0W7, Q8N2C7, Q90YM4, Q91VT8, Q95JR4

Diamond homologs: H3BTG2, Q9CPU3

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

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

Top pathogenic / likely-pathogenic (0)

SpliceAI

471 predictions. Top by Δscore:

Variant	Effect	Δscore
1:23011214:C:CT	acceptor_gain	0.9900
1:23011215:A:T	acceptor_gain	0.9900
1:23011220:C:CT	acceptor_gain	0.9900
1:23011220:C:T	acceptor_gain	0.9900
1:23011221:A:T	acceptor_gain	0.9900
1:23015770:A:AC	donor_gain	0.9900
1:23015771:C:CC	donor_gain	0.9900
1:23011214:C:T	acceptor_gain	0.9800
1:23011217:C:CT	acceptor_gain	0.9800
1:23014043:CTC:C	acceptor_gain	0.9400
1:23015771:CAT:C	donor_gain	0.9400
1:23011204:T:C	acceptor_gain	0.9300
1:23015764:CCACT:C	donor_loss	0.9300
1:23015767:CT:C	donor_loss	0.9300
1:23015768:TTA:T	donor_loss	0.9300
1:23015770:A:G	donor_loss	0.9300
1:23015771:C:A	donor_loss	0.9300
1:23015771:CATGA:C	donor_gain	0.9300
1:23015771:CATG:C	donor_gain	0.8900
1:23015771:CA:C	donor_gain	0.8800
1:23011204:T:TC	acceptor_gain	0.8500
1:23011200:CCTTT:C	acceptor_gain	0.8300
1:23012204:AGC:A	donor_gain	0.8300
1:23013921:TG:T	donor_gain	0.8300
1:23012255:A:AC	donor_gain	0.8200
1:23013877:GCTCA:G	donor_loss	0.8200
1:23013878:CT:C	donor_loss	0.8200
1:23013879:TCACC:T	donor_loss	0.8200
1:23013880:C:CC	donor_loss	0.8200
1:23013881:A:T	donor_loss	0.8200

AlphaMissense

810 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:23013934:G:C	S38R	0.980
1:23013934:G:T	S38R	0.980
1:23013936:T:G	S38R	0.980
1:23013962:C:T	G29E	0.974
1:23013976:C:A	K24N	0.969
1:23013976:C:G	K24N	0.969
1:23013963:C:G	G29R	0.965
1:23013963:C:T	G29R	0.965
1:23011049:T:A	E73V	0.964
1:23011063:C:A	K68N	0.949
1:23011063:C:G	K68N	0.949
1:23013935:C:A	S38I	0.944
1:23013944:A:G	L35P	0.932
1:23011064:T:A	K68M	0.923
1:23013944:A:T	L35Q	0.922
1:23011048:T:A	E73D	0.917
1:23011048:T:G	E73D	0.917
1:23011070:T:A	E66V	0.917
1:23013944:A:C	L35R	0.916
1:23013956:A:C	L31R	0.914
1:23011043:T:G	Q75P	0.909
1:23013950:A:C	L33R	0.908
1:23013956:A:T	L31Q	0.908
1:23013964:A:C	F28L	0.908
1:23013964:A:T	F28L	0.908
1:23013966:A:G	F28L	0.908
1:23011027:C:A	W80C	0.901
1:23011027:C:G	W80C	0.901
1:23013956:A:G	L31P	0.895
1:23011029:A:G	W80R	0.894

dbSNP variants (sampled 300 via entrez): RS1000442140 (1:23012220 G>A), RS1000786323 (1:23017353 C>G,T), RS1001405265 (1:23014832 T>C), RS1001454249 (1:23011220 C>G), RS1002314490 (1:23017713 C>T), RS1002852286 (1:23014828 ATTATT>A,ATTATTTTATT), RS1002925860 (1:23014380 A>T), RS1003069404 (1:23013213 C>G), RS1003121509 (1:23012782 G>A), RS1003231910 (1:23016278 A>G), RS1003861797 (1:23013268 G>A), RS1003935392 (1:23013011 C>T), RS1004002176 (1:23016265 C>T), RS1004747877 (1:23011560 C>T), RS1005413612 (1:23017629 A>G)

Disease associations

OMIM: gene `` | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

8 associations (top):

Study	Trait	p-value
GCST010696_9	Cortical thickness (min-P)	3.000000e-08
GCST010697_34	Cortical surface area (min-P)	5.000000e-08
GCST010698_71	Subcortical volume (min-P)	4.000000e-14
GCST010699_32	Brain morphology (min-P)	6.000000e-09
GCST010700_65	Cortical thickness (MOSTest)	3.000000e-09
GCST010701_93	Cortical surface area (MOSTest)	2.000000e-13
GCST010702_34	Subcortical volume (MOSTest)	1.000000e-10
GCST010703_189	Brain morphology (MOSTest)	7.000000e-11

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004346	neuroimaging measurement
EFO:0004840	cortical thickness

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

1 total (human), top 1 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression	1

Clinical trials (associated diseases)

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