TESMIN

Summary

TESMIN (testis expressed metallothionein like protein, HGNC:7446) is a protein-coding gene on chromosome 11q13.3, encoding Tesmin (Q9Y4I5). Essential for normal spermatogenesis and male fertility.

Metallothionein proteins are highly conserved low-molecular-weight cysteine-rich proteins that are induced by and bind to heavy metal ions and have no enzymatic activity. They may play a central role in the regulation of cell growth and differentiation and are involved in spermatogenesis. This gene encodes a metallothionein-like protein which has been shown to be expressed differentially in mouse testis and ovary. Two transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 9633 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 28 total
• MANE Select transcript: NM_004923

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:7446
Approved symbol	TESMIN
Name	testis expressed metallothionein like protein
Location	11q13.3
Locus type	gene with protein product
Status	Approved
Aliases	CXCDC2
Ensembl gene	ENSG00000132749
Ensembl biotype	protein_coding
OMIM	604374
Entrez	9633

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 7 protein_coding, 3 protein_coding_CDS_not_defined, 2 retained_intron

ENST00000255087, ENST00000432435, ENST00000438124, ENST00000443940, ENST00000538944, ENST00000540869, ENST00000543240, ENST00000544398, ENST00000544963, ENST00000865611, ENST00000936459, ENST00000936460

RefSeq mRNA: 2 — MANE Select: NM_004923 NM_001039656, NM_004923

CCDS: CCDS44661, CCDS8184

Canonical transcript exons

ENST00000255087 — 10 exons

Exon	Start	End
ENSE00000904486	68715837	68715939
ENSE00001166019	68742318	68742394
ENSE00001166037	68744991	68745111
ENSE00001291406	68750190	68750699
ENSE00001316982	68751420	68751520
ENSE00001368720	68707440	68708500
ENSE00002437930	68713270	68713407
ENSE00002493293	68710874	68711049
ENSE00003646519	68738700	68738788
ENSE00003658990	68747208	68747366

Expression profiles

Bgee: expression breadth ubiquitous, 172 present calls, max score 94.22.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 7.5307 / max 299.5204, expressed in 1159 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
121006	7.1117	1154
121005	0.3668	168
121007	0.0522	16

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right testis	UBERON:0004534	94.22	gold quality
left testis	UBERON:0004533	94.18	gold quality
testis	UBERON:0000473	91.69	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	83.96	gold quality
sperm	CL:0000019	83.64	gold quality
male germ cell	CL:0000015	82.14	gold quality
rectum	UBERON:0001052	81.07	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	79.25	gold quality
oocyte	CL:0000023	78.25	gold quality
adult organism	UBERON:0007023	77.85	gold quality
mucosa of transverse colon	UBERON:0004991	77.78	gold quality
metanephros cortex	UBERON:0010533	77.73	gold quality
right uterine tube	UBERON:0001302	76.88	gold quality
secondary oocyte	CL:0000655	74.37	gold quality
adenohypophysis	UBERON:0002196	74.33	gold quality
monocyte	CL:0000576	74.29	gold quality
leukocyte	CL:0000738	74.28	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	74.12	gold quality
mononuclear cell	CL:0000842	74.07	gold quality
transverse colon	UBERON:0001157	72.38	gold quality
pituitary gland	UBERON:0000007	71.67	gold quality
blood	UBERON:0000178	71.47	gold quality
granulocyte	CL:0000094	71.45	gold quality
minor salivary gland	UBERON:0001830	71.33	gold quality
esophagus mucosa	UBERON:0002469	71.33	gold quality
lower esophagus mucosa	UBERON:0035834	69.98	gold quality
right lobe of thyroid gland	UBERON:0001119	69.87	gold quality
bone marrow	UBERON:0002371	69.71	gold quality
bone marrow cell	CL:0002092	69.14	gold quality
saliva-secreting gland	UBERON:0001044	69.12	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.24
E-MTAB-9801	yes	3.23

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

47 targeting TESMIN, 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-5193	100.00	67.26	1744
HSA-MIR-518D-5P	100.00	67.51	979
HSA-MIR-518E-5P	100.00	67.66	954
HSA-MIR-518F-5P	100.00	67.51	979
HSA-MIR-519A-5P	100.00	67.66	954
HSA-MIR-519B-5P	100.00	67.66	954
HSA-MIR-519C-5P	100.00	67.66	954
HSA-MIR-520C-5P	100.00	67.51	979
HSA-MIR-522-5P	100.00	67.66	954
HSA-MIR-523-5P	100.00	67.66	954
HSA-MIR-526A-5P	100.00	67.51	979
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-1297	99.91	73.41	3162
HSA-MIR-3529-3P	99.90	73.55	3045
HSA-MIR-4799-5P	99.82	70.60	2663
HSA-MIR-26A-5P	99.78	73.52	2303
HSA-MIR-26B-5P	99.78	73.51	2305
HSA-MIR-3934-3P	99.76	65.51	1351
HSA-MIR-3617-5P	99.75	69.41	1968
HSA-MIR-641	99.75	69.35	1975
HSA-MIR-4516	99.61	67.78	3390
HSA-MIR-5003-5P	99.61	69.13	1624
HSA-MIR-7844-5P	99.55	68.56	1428
HSA-MIR-12123	99.52	71.79	2990
HSA-MIR-5697	99.39	67.74	1249
HSA-MIR-4434	99.10	67.01	1984
HSA-MIR-5703	99.10	67.09	2053
HSA-MIR-4716-5P	98.82	68.57	1168

Literature-anchored findings (GeneRIF, showing 2)

• Metallothionein-like 5 expression is correlated with poor prognosis and promotes proliferation of cervical squamous cell carcinoma. (PMID:35249447)
• Clinical Significance and Functional Insights of Tesmin in Hepatocellular Carcinoma. (PMID:38283987)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	tesmin	ENSDARG00000097662
mus_musculus	Tesmin	ENSMUSG00000024905
rattus_norvegicus	Tesmin	ENSRNOG00000014671
drosophila_melanogaster	mip120	FBGN0033846
caenorhabditis_elegans		WBGENE00003037

Paralogs (1): LIN54 (ENSG00000189308)

Protein

Protein identifiers

Tesmin — Q9Y4I5 (reviewed: Q9Y4I5)

Alternative names: Metallothionein-like 5, testis-specific, Testis-specific metallothionein-like protein

All UniProt accessions (2): Q9Y4I5, H3BMB2

UniProt curated annotations — full annotation on UniProt →

Function. Essential for normal spermatogenesis and male fertility. Required for the completion of meiosis in male germ cells.

Subcellular location. Cytoplasm. Nucleus.

Tissue specificity. Expressed specifically in testis.

Similarity. Belongs to the lin-54 family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q9Y4I5-1	1	yes
Q9Y4I5-2	2
Q9Y4I5-3	3

RefSeq proteins (2): NP_001034745, NP_004914* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR005172	CRC	Domain
IPR028307	Lin-54_fam	Family
IPR033467	Tesmin/TSO1-like_CXC	Domain

Pfam: PF03638

UniProt features (9 total): splice variant 3, sequence variant 2, chain 1, domain 1, modified residue 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9Y4I5-F1	54.24	0.26

Functional residue map

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

Post-translational modifications (1): 40

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 116 (showing top): GOBP_MALE_GAMETE_GENERATION, chr11q13, GOBP_RESPONSE_TO_METAL_ION, GOBP_ORGANELLE_FISSION, SMID_BREAST_CANCER_LUMINAL_B_UP, GOBP_MONOATOMIC_ION_HOMEOSTASIS, GOBP_DEVELOPMENTAL_PROCESS_INVOLVED_IN_REPRODUCTION, NIKOLSKY_BREAST_CANCER_11Q12_Q14_AMPLICON, GOBP_MEIOTIC_CELL_CYCLE_PROCESS, RIGGINS_TAMOXIFEN_RESISTANCE_DN, GOBP_MEIOTIC_CELL_CYCLE, NUYTTEN_EZH2_TARGETS_DN, GOBP_HOMEOSTATIC_PROCESS, GOBP_CHEMICAL_HOMEOSTASIS, GOBP_CELL_CYCLE_PROCESS

GO Biological Process (7): regulation of DNA-templated transcription (GO:0006355), male meiotic nuclear division (GO:0007140), spermatogenesis (GO:0007283), response to metal ion (GO:0010038), intracellular monoatomic cation homeostasis (GO:0030003), cell differentiation (GO:0030154), meiotic cell cycle (GO:0051321)

GO Molecular Function (2): metal ion binding (GO:0046872), protein binding (GO:0005515)

GO Cellular Component (3): male germ cell nucleus (GO:0001673), nucleus (GO:0005634), cytoplasm (GO:0005737)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
male gamete generation	2
meiotic nuclear division	2
DNA-templated transcription	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
meiotic cell cycle	1
developmental process involved in reproduction	1
response to chemical	1
intracellular monoatomic ion homeostasis	1
monoatomic cation homeostasis	1
cellular developmental process	1
cell cycle	1
sexual reproduction	1
reproductive process	1
cation binding	1
binding	1
germ cell nucleus	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
cellular anatomical structure	1

Protein interactions and networks

STRING

628 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TESMIN	H3BSS0	H3BSS0	870
TESMIN	LIN52	Q52LA3	625
TESMIN	LIN9	Q5TKA1	605
TESMIN	NAF1	Q96HR8	563
TESMIN	LIN37	Q96GY3	541
TESMIN	ACR	P10323	451
TESMIN	IQCH	Q86VS3	447
TESMIN	PRM2	P04554	428
TESMIN	TNP1	P09430	412
TESMIN	PIWIL2	Q8TC59	407
TESMIN	RBBP4	P31149	388
TESMIN	KCTD19	Q17RG1	386
TESMIN	SYCP1	Q15431	382
TESMIN	EMCN	Q9ULC0	382
TESMIN	ZNF318	Q5VUA4	371

IntAct

10 interactions, top by confidence:

A	B	Type	Score
LIN37	MYBL1	psi-mi:“MI:0914”(association)	0.640
TESMIN	NR3C2	psi-mi:“MI:0915”(physical association)	0.580
LIN9	MYBL1	psi-mi:“MI:0914”(association)	0.530
TESMIN	MYDGF	psi-mi:“MI:0915”(physical association)	0.400
TESMIN	TRAPPC3	psi-mi:“MI:0914”(association)	0.350
OR4X2	PCBP3	psi-mi:“MI:0914”(association)	0.350
TESMIN	HSPA9	psi-mi:“MI:0914”(association)	0.350

BioGRID (25): MTL5 (Affinity Capture-RNA), MTL5 (Two-hybrid), MTL5 (Two-hybrid), MTL5 (Proximity Label-MS), TRAPPC10 (Affinity Capture-MS), HSPA9 (Affinity Capture-MS), TRAPPC9 (Affinity Capture-MS), TRAPPC6B (Affinity Capture-MS), TRAPPC3 (Affinity Capture-MS), TRAPPC5 (Affinity Capture-MS), MTL5 (Affinity Capture-MS), MTHFD2L (Affinity Capture-MS), GRPEL1 (Affinity Capture-MS), TRAPPC4 (Affinity Capture-MS), TRAPPC2L (Affinity Capture-MS)

ESM2 similar proteins: A0A1D5RMD1, A0A1W2PPK0, A0A1W2PPM1, B2RQL2, B2RRE4, D2HQI1, D3YU32, G3X9U1, O15016, O75362, Q3U1U7, Q3URK3, Q3URS2, Q3UT54, Q3V089, Q3V0A6, Q3V3Q4, Q4JK59, Q5DTZ0, Q5ND04, Q5W1J6, Q66HG9, Q68A65, Q6P1W5, Q6ZRS4, Q6ZSB9, Q75NT5, Q7Z4V0, Q80UF7, Q8BII1, Q8BXX2, Q8C4A5, Q8CEE6, Q8IV76, Q8K1S5, Q8N5Q1, Q8NDZ0, Q8NFU7, Q8VCF0, Q921B4

Diamond homologs: A1Z9E2, F4JIF5, F4JY84, Q08CM4, Q0IHV2, Q571G4, Q5RBN8, Q5XHX9, Q641Z1, Q6MZP7, Q700D0, Q84JZ8, Q8L548, Q95QD7, Q9LUI3, Q9SL70, Q9SZD1, Q9WTJ6, Q9Y4I5

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	6
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2108 predictions. Top by Δscore:

Variant	Effect	Δscore
11:68711013:CAA:C	acceptor_gain	1.0000
11:68711018:CATT:C	acceptor_gain	1.0000
11:68711021:T:C	acceptor_gain	1.0000
11:68711021:T:TC	acceptor_gain	1.0000
11:68715832:ATTAC:A	donor_loss	1.0000
11:68715833:TTAC:T	donor_loss	1.0000
11:68715834:TACCT:T	donor_loss	1.0000
11:68715835:A:C	donor_loss	1.0000
11:68715939:CCTG:C	acceptor_loss	1.0000
11:68715940:C:CA	acceptor_loss	1.0000
11:68715941:T:C	acceptor_loss	1.0000
11:68744982:A:C	donor_gain	1.0000
11:68747248:T:TA	donor_gain	1.0000
11:68747257:T:TA	donor_gain	1.0000
11:68747363:CAAC:C	acceptor_gain	1.0000
11:68747366:CCTA:C	acceptor_loss	1.0000
11:68747367:C:CC	acceptor_gain	1.0000
11:68747367:CTAG:C	acceptor_loss	1.0000
11:68747368:T:G	acceptor_loss	1.0000
11:68750188:A:AC	donor_gain	1.0000
11:68750189:C:CC	donor_gain	1.0000
11:68711014:A:T	acceptor_gain	0.9900
11:68715847:TTAA:T	donor_gain	0.9900
11:68715940:C:CC	acceptor_gain	0.9900
11:68723390:A:AC	donor_gain	0.9900
11:68723391:C:CC	donor_gain	0.9900
11:68742316:A:AC	donor_gain	0.9900
11:68742317:C:CC	donor_gain	0.9900
11:68744990:CCTGA:C	donor_gain	0.9900
11:68747203:ATT:A	donor_loss	0.9900

AlphaMissense

3331 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:68708447:A:G	L463P	0.981
11:68711018:C:G	C397S	0.980
11:68711019:A:T	C397S	0.980
11:68708371:A:C	F488L	0.978
11:68708371:A:T	F488L	0.978
11:68708373:A:G	F488L	0.978
11:68711009:C:G	C400S	0.973
11:68711010:A:T	C400S	0.973
11:68711019:A:G	C397R	0.973
11:68711036:C:G	C391S	0.969
11:68711037:A:T	C391S	0.969
11:68713378:G:C	F350L	0.967
11:68713378:G:T	F350L	0.967
11:68713380:A:G	F350L	0.967
11:68711024:C:G	C395S	0.965
11:68711025:A:T	C395S	0.965
11:68708427:C:G	A470P	0.964
11:68715924:A:C	F311L	0.963
11:68715924:A:T	F311L	0.963
11:68715926:A:G	F311L	0.963
11:68711017:G:C	C397W	0.961
11:68711037:A:G	C391R	0.959
11:68713277:C:G	C384S	0.959
11:68713278:A:T	C384S	0.959
11:68708463:C:G	A458P	0.958
11:68713283:C:T	C382Y	0.958
11:68711024:C:T	C395Y	0.957
11:68711010:A:G	C400R	0.956
11:68711023:G:C	C395W	0.955
11:68711025:A:G	C395R	0.955

dbSNP variants (sampled 300 via entrez): RS1000026241 (11:68708204 C>A,G), RS1000035724 (11:68745480 G>A), RS1000040954 (11:68712052 G>C), RS1000043185 (11:68705400 TGGTGAGA>T), RS1000100605 (11:68737150 C>T), RS1000160741 (11:68742889 T>C), RS1000196040 (11:68708113 A>C,G,T), RS1000270457 (11:68733180 AG>A), RS1000280383 (11:68705158 C>G,T), RS1000296351 (11:68742764 C>T), RS1000354491 (11:68749415 C>A), RS1000433307 (11:68711796 T>C), RS1000530293 (11:68711907 A>C), RS1000639576 (11:68736935 A>T), RS1000765375 (11:68724485 T>A,G)

Disease associations

OMIM: gene MIM:604374 | 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

24 total (human), top 24 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression, affects expression, increases methylation	5
Silicon Dioxide	decreases expression, increases expression	3
Vorinostat	affects cotreatment, decreases expression	2
Phenylmercuric Acetate	decreases expression, affects cotreatment	2
triphenyl phosphate	affects expression	1
beta-lapachone	decreases expression	1
sodium arsenite	decreases expression	1
butyraldehyde	decreases expression	1
zinc chromate	decreases expression, increases abundance	1
versicolorin A	increases expression	1
chromium hexavalent ion	decreases expression, increases abundance	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	decreases expression, affects cotreatment	1
dorsomorphin	affects cotreatment, decreases expression	1
(+)-JQ1 compound	decreases expression	1
Atrazine	increases expression	1
Benzo(a)pyrene	decreases expression	1
Carbamazepine	affects expression	1
Diethylhexyl Phthalate	decreases expression	1
Hydrogen Peroxide	affects expression	1
Niclosamide	increases expression	1
Ozone	increases expression	1
Tobacco Smoke Pollution	decreases expression	1
Cadmium Chloride	decreases expression	1

Clinical trials (associated diseases)

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