MT1HL1

Summary

MT1HL1 (metallothionein 1H like 1, HGNC:31864) is a protein-coding gene on chromosome 1q43, encoding Metallothionein 1H-like protein 1 (P0DM35). Metallothioneins have a high content of cysteine residues that bind various heavy metals; these proteins are transcriptionally regulated by both heavy metals and glucocorticoids.

This gene is a retrotransposed gene, compared to MT1H (GeneID:4496). This retrogene is transcribed. It retains a full-length CDS, and is assumed to be translated. Compared to the MT1H product, this protein product differs at three internal amino acids, two of which are at metal-binding sites.

Source: NCBI Gene 645745 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 3 total
• MANE Select transcript: NM_001276687

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:31864
Approved symbol	MT1HL1
Name	metallothionein 1H like 1
Location	1q43
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000244020
Ensembl biotype	protein_coding
Entrez	645745

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000464121

RefSeq mRNA: 1 — MANE Select: NM_001276687 NM_001276687

CCDS: CCDS31068

Canonical transcript exons

ENST00000464121 — 1 exons

Exon	Start	End
ENSE00001908246	237004103	237004441

Expression profiles

Bgee: expression breadth broad, 84 present calls, max score 96.10.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0187 / max 11.2886, expressed in 7 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
18234	0.0187	7

Top tissues by expression

110 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	96.10	gold quality
heart left ventricle	UBERON:0002084	68.26	gold quality
apex of heart	UBERON:0002098	67.84	gold quality
heart	UBERON:0000948	60.11	gold quality
right atrium auricular region	UBERON:0006631	60.03	gold quality
mucosa of stomach	UBERON:0001199	49.34	gold quality
gastrocnemius	UBERON:0001388	44.80	gold quality
muscle of leg	UBERON:0001383	43.36	gold quality
right lobe of liver	UBERON:0001114	39.18	gold quality
colonic epithelium	UBERON:0000397	37.20	gold quality
thoracic aorta	UBERON:0001515	36.86	gold quality
ascending aorta	UBERON:0001496	36.62	gold quality
ventricular zone	UBERON:0003053	36.48	gold quality
cortical plate	UBERON:0005343	36.47	gold quality
bone marrow cell	CL:0002092	36.16	gold quality
skeletal muscle tissue	UBERON:0001134	36.04	gold quality
liver	UBERON:0002107	35.91	gold quality
ganglionic eminence	UBERON:0004023	35.49	gold quality
right lobe of thyroid gland	UBERON:0001119	34.22	silver quality
prefrontal cortex	UBERON:0000451	33.62	gold quality
descending thoracic aorta	UBERON:0002345	33.61	gold quality
muscle tissue	UBERON:0002385	33.01	gold quality
adult mammalian kidney	UBERON:0000082	32.36	gold quality
putamen	UBERON:0001874	32.31	gold quality
hindlimb stylopod muscle	UBERON:0004252	32.15	gold quality
bone marrow	UBERON:0002371	31.74	gold quality
frontal cortex	UBERON:0001870	31.71	gold quality
lymph node	UBERON:0000029	31.31	gold quality
caudate nucleus	UBERON:0001873	31.16	gold quality
popliteal artery	UBERON:0002250	31.12	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.23

Regulation

Is transcription factor: no

Cross-species orthologs

1 orthologs

Organism	Symbol	Gene ID
danio_rerio	mt2	ENSDARG00000041623

Paralogs (11): MT3 (ENSG00000087250), MT4 (ENSG00000102891), MT1G (ENSG00000125144), MT2A (ENSG00000125148), MT1B (ENSG00000169688), MT1E (ENSG00000169715), MT1X (ENSG00000187193), MT1F (ENSG00000198417), MT1H (ENSG00000205358), MT1A (ENSG00000205362), MT1M (ENSG00000205364)

Protein

Protein identifiers

Metallothionein 1H-like protein 1 — P0DM35 (reviewed: P0DM35)

All UniProt accessions (1): P0DM35

UniProt curated annotations — full annotation on UniProt →

Function. Metallothioneins have a high content of cysteine residues that bind various heavy metals; these proteins are transcriptionally regulated by both heavy metals and glucocorticoids.

Domain organisation. Class I metallothioneins contain 2 metal-binding domains: four divalent ions are chelated within cluster A of the alpha domain and are coordinated via cysteinyl thiolate bridges to 11 cysteine ligands. Cluster B, the corresponding region within the beta domain, can ligate three divalent ions to 9 cysteines.

Similarity. Belongs to the metallothionein superfamily. Type 1 family.

RefSeq proteins (1): NP_001263616* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000006	Metalthion_vert	Family
IPR001368	TNFR/NGFR_Cys_rich_reg	Domain
IPR017854	Metalthion_dom_sf	Homologous_superfamily
IPR023587	Metalthion_dom_sf_vert	Homologous_superfamily

Pfam: PF00131

UniProt features (29 total): binding site 25, region of interest 2, chain 1, modified residue 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P0DM35-F1	74.02	0.00

Functional residue map

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

Ligand- & substrate-binding residues (25): 24; 24; 26; 29; 33; 34; 34; 36; 37; 37; 41; 44 …

Post-translational modifications (1): 1

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 56 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_BRAIN_TUMORAL_MACROPHAGE_UP, GSE18804_SPLEEN_MACROPHAGE_VS_TUMORAL_MACROPHAGE_UP, GOBP_RESPONSE_TO_ZINC_ION, GOBP_CELLULAR_RESPONSE_TO_CADMIUM_ION, GOBP_RESPONSE_TO_COPPER_ION, GOBP_RESPONSE_TO_METAL_ION, GOBP_DETOXIFICATION, GOBP_CELLULAR_RESPONSE_TO_ZINC_ION, GOBP_MONOATOMIC_ION_HOMEOSTASIS, GOBP_RESPONSE_TO_TOXIC_SUBSTANCE, GOBP_RESPONSE_TO_CADMIUM_ION, chr1q43, GOBP_HOMEOSTATIC_PROCESS, GOBP_CHEMICAL_HOMEOSTASIS, GOBP_CELLULAR_RESPONSE_TO_COPPER_ION

GO Biological Process (5): intracellular zinc ion homeostasis (GO:0006882), detoxification of copper ion (GO:0010273), cellular response to cadmium ion (GO:0071276), cellular response to copper ion (GO:0071280), cellular response to zinc ion (GO:0071294)

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

GO Cellular Component (2): nucleus (GO:0005634), cytoplasm (GO:0005737)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular response to metal ion	3
intracellular monoatomic cation homeostasis	1
inorganic ion homeostasis	1
detoxification of inorganic compound	1
stress response to copper ion	1
response to cadmium ion	1
response to copper ion	1
response to zinc ion	1
cation binding	1
binding	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
cellular anatomical structure	1

Protein interactions and networks

STRING

206 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MT1HL1	AAMDC	Q9H7C9	376
MT1HL1	MTF1	Q14872	374
MT1HL1	C11orf52	Q96A22	370
MT1HL1	MAP1S	Q66K74	350
MT1HL1	GPX4	P36969	341
MT1HL1	CEP55	Q53EZ4	333
MT1HL1	TOMM20L	Q6UXN7	317
MT1HL1	MT3	P25713	312
MT1HL1	MAP1A	P78559	308
MT1HL1	GSTP1	P09211	306
MT1HL1	SLC30A1	Q9Y6M5	294
MT1HL1	MTARC2	Q969Z3	293
MT1HL1	ZSWIM5	Q9P217	290
MT1HL1	MFAP3	P55082	269
MT1HL1	GPX7	Q96SL4	256

IntAct

2 interactions, top by confidence:

A	B	Type	Score
MT1HL1	SMIM11	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (1): SMIM11 (Proximity Label-MS)

ESM2 similar proteins: A1L3X4, O18842, O42152, P02797, P02798, P02800, P02801, P02802, P02803, P02804, P04355, P04731, P04733, P07438, P09577, P09578, P0DM35, P11957, P13640, P14425, P15786, P17808, P18055, P25713, P27087, P37360, P55942, P55943, P55944, P58280, P67981, P67982, P67983, P68041, P68301, P68302, P68303, P68304, P79376, P79377

Diamond homologs: O18842, O19000, P02795, P02797, P02798, P02800, P02801, P02802, P02803, P02804, P04355, P04731, P04732, P04733, P07438, P09577, P09578, P0DM35, P11957, P13640, P14425, P17808, P18055, P47944, P47945, P49068, P55942, P55943, P58280, P67981, P67982, P67983, P68041, P68301, P68302, P68303, P68304, P79376, P79377, P79378

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	3
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

51 predictions. Top by Δscore:

Variant	Effect	Δscore
1:237004282:T:TA	donor_gain	0.7100
1:237004316:G:A	donor_gain	0.6800
1:237004336:AGGAG:A	donor_gain	0.6700
1:237004246:TGGC:T	donor_gain	0.6600
1:237004145:CGTGT:C	donor_gain	0.6200
1:237004144:A:AC	donor_gain	0.5600
1:237004145:C:CC	donor_gain	0.5600
1:237004343:T:TA	donor_gain	0.5600
1:237004303:A:AC	donor_gain	0.5000
1:237004304:C:CC	donor_gain	0.5000
1:237004300:TGC:T	donor_gain	0.4800
1:237004305:T:C	donor_gain	0.4600
1:237004145:CGTG:C	donor_gain	0.4400
1:237004139:ACTTT:A	donor_loss	0.4200
1:237004140:CTTT:C	donor_loss	0.4200
1:237004141:TTTA:T	donor_loss	0.4200
1:237004142:TTACG:T	donor_loss	0.4200
1:237004143:T:TG	donor_loss	0.4200
1:237004245:TTGG:T	donor_gain	0.4200
1:237004163:T:TA	donor_gain	0.4100
1:237004118:T:TC	acceptor_gain	0.4000
1:237004298:TTTGC:T	donor_gain	0.4000
1:237004307:TTTGC:T	donor_gain	0.3900
1:237004314:T:C	donor_gain	0.3900
1:237004139:A:AC	donor_gain	0.3600
1:237004140:C:CC	donor_gain	0.3600
1:237004118:T:C	acceptor_gain	0.3400
1:237004146:G:GA	donor_loss	0.3400
1:237004299:TTGC:T	donor_gain	0.3400
1:237004312:A:AC	donor_gain	0.3400

AlphaMissense

395 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000016336 (1:237005561 A>G), RS1000471326 (1:237005911 G>T), RS1001540425 (1:237005325 G>T), RS1001933349 (1:237003696 G>C), RS1002083272 (1:237004193 A>G), RS1002281260 (1:237004002 G>A), RS1004927448 (1:237004617 C>T), RS1005932481 (1:237006276 G>A,T), RS1006533571 (1:237005058 C>T), RS1008261301 (1:237004140 C>T), RS1009022510 (1:237004337 G>A), RS1009727058 (1:237004025 A>G), RS1009883756 (1:237005876 T>C), RS1010191822 (1:237003760 C>G,T), RS1011144380 (1:237005392 T>A)

Disease associations

OMIM: gene `` | disease phenotypes: MIM:600996, MIM:604772

GenCC curated gene-disease

Mondo (2): primary ovarian failure (MONDO:0005387), catecholaminergic polymorphic ventricular tachycardia 1 (MONDO:0011484)

Orphanet (2): Catecholaminergic polymorphic ventricular tachycardia (Orphanet:3286), NON RARE IN EUROPE: Primary ovarian failure (Orphanet:619)

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST009391_721	Metabolite levels	7.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0010532	salicylurate measurement

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D016649	Primary Ovarian Insufficiency	C12.050.351.500.056.630.750; C12.100.250.056.630.750; C19.391.630.750
C563409	Arrhythmogenic Right Ventricular Dysplasia, Familial, 2 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

33 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression	5
mercuric bromide	increases expression, affects cotreatment	2
motexafin gadolinium	increases expression, increases reaction	2
Arsenic Trioxide	increases expression	2
Cadmium	increases abundance, increases expression	2
Nickel	increases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Cadmium Chloride	increases abundance, increases expression	2
p-Chloromercuribenzoic Acid	affects cotreatment, increases expression	2
GSK-J4	increases expression	1
methylmercuric chloride	increases expression	1
lead acetate	increases expression	1
zinc chloride	increases expression	1
avobenzone	increases expression	1
entinostat	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
2,2’,4,4’,5-brominated diphenyl ether	increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
NSC 689534	affects binding, increases expression	1
PCI 5002	increases expression	1
Air Pollutants	decreases expression, increases abundance	1
Copper	affects binding, increases expression	1
Demecolcine	increases expression	1
Diethylhexyl Phthalate	increases expression	1
Estradiol	affects cotreatment, decreases expression, increases expression	1
Tetrachlorodibenzodioxin	affects cotreatment, decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Vincristine	increases expression	1
Zinc	increases expression	1
Aflatoxin B1	increases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00417066	PHASE4	COMPLETED	Flexible GnRH Antagonist vs Flare up GnRH Agonist Protocol in Poor Responders
NCT00732693	PHASE4	COMPLETED	Evaluation of Physiologic and Standard Sex Steroid Replacement Regimens in Women With Premature Ovarian Failure
NCT00837616	PHASE4	COMPLETED	Estrogen Dosing in Turner Syndrome: Pharmacology and Metabolism
NCT01853501	PHASE4	UNKNOWN	Effects of ADSC Therapy in Women With POF
NCT02783937	PHASE4	COMPLETED	Filgrastim for Premature Ovarian Insufficiency
NCT03535480	PHASE4	UNKNOWN	Autologous Bone Marrow Stem Cell Ovarian Transplantation to Restore Ovarian Function in Premature Ovarian Failure
NCT00140998	PHASE3	COMPLETED	Estrogen Treatment (Oral vs. Patches) in Turner Syndrome
NCT00001951	PHASE2	COMPLETED	Hormone Replacement in Young Women With Premature Ovarian Failure
NCT00370019	PHASE2	WITHDRAWN	Effects of an Estrogen Replacement Therapy Skin Patch on Ovulation in Women With Premature Ovarian Failure
NCT00429494	PHASE2	COMPLETED	GnRH Analogue for Ovarian Function Preservation in Hematopoietic Stem Cell Transplantation Patients
NCT03816852	PHASE2	SUSPENDED	The Safety and Efficiency Study of Mesenchymal Stem Cell (19#iSCLife®-POI) in Premature Ovarian Insufficiency
NCT04536467	PHASE2	UNKNOWN	Prevention of Chemotherapy-Induced Ovarian Failure With Goserelin in Premenopausal Lymphoma Patients
NCT06117982	PHASE2	COMPLETED	The Impact of Granulocyte Colony Stimulating Factor on Premature Ovarian Insufficiency
NCT05122975	PHASE2	TERMINATED	Treatment of an Inherited Ventricular Arrhythmia
NCT06005428	PHASE2	TERMINATED	Effectiveness of CRD-4730 in Participants With Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT)
NCT02912104	PHASE1	COMPLETED	A Therapeutic Trial of Human Amniotic Epithelial Cells Transplantation for Primary Ovarian Failure
NCT03178695	PHASE1	COMPLETED	Inovium Ovarian Rejuvenation Trials
NCT04815213	PHASE1	ACTIVE_NOT_RECRUITING	The Use of Expandeded Mesenchymal Stromal Cells (MSC) in Premature Ovarian Failure (POF) in Adult Humans
NCT05138367	PHASE1	COMPLETED	Effects of UCA-PSCs in Women With POF
NCT06132542	PHASE1	UNKNOWN	Autologous ADMSC Transplantation in Patients With POI
NCT00948857	PHASE2/PHASE3	TERMINATED	Dehydroepiandrosterone (DHEA) Treatment and Premature Ovarian Failure (POF)
NCT04031456	PHASE2/PHASE3	RECRUITING	Autologous PRP Infusion May Restore Ovarian Function and May Promote Folliculogenesis in POI Patients
NCT02043743	PHASE1/PHASE2	UNKNOWN	Autologous Stem Cells Transplantation in Patients With Idiopathic and Drug Induced Premature Ovarian Failure
NCT02062931	PHASE1/PHASE2	UNKNOWN	Autologous Mesenchymal Stem Cells Transplantation In Women With Premature Ovarian Failure
NCT02151890	PHASE1/PHASE2	COMPLETED	Pregnancy After Stem Cell Transplantation in Premature Ovarian Failure
NCT02372474	PHASE1/PHASE2	COMPLETED	It is a Real The First Baby Of Autologous Stem Cell Therapy in Premature Ovarian Failure
NCT02603744	PHASE1/PHASE2	UNKNOWN	Autologous Adipose Derived Mesenchymal Stromal Cells Transplantation in Women With Premature Ovarian Failure (POF)
NCT02644447	PHASE1/PHASE2	COMPLETED	Transplantation of HUC-MSCs With Injectable Collagen Scaffold for POF
NCT03069209	PHASE1/PHASE2	UNKNOWN	Autologous Bone Marrow-Derived Stem Cell Transplantation in Patients With Premature Ovarian Failure (POF)
NCT03985462	PHASE1/PHASE2	WITHDRAWN	Very Small Embryonic-like Stem Cells for Ovary
NCT04009473	PHASE1/PHASE2	UNKNOWN	Stem Cell Therapy and Growth Factor Ovarian in Vitro Activation
NCT04071574	PHASE1/PHASE2	COMPLETED	Comparative Study on the Efficacy of Ovarian Stimulation Protocols on the Success Rate of ICSI in Female Infertility
NCT04922398	PHASE1/PHASE2	UNKNOWN	Ovarian Injection of PRP (Platelet -Rich Plasma) Vs Normal Saline in Premature Ovarian Insufficiency
NCT05462379	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Autologous Heterotopic Fresh Ovarian Graft in Woman With LACC Eligible for Pelvic Radiotherapy Treatment.
NCT06202547	PHASE1/PHASE2	UNKNOWN	Intra-ovarian Injection of MSC-EVs in Idiopathic Premature Ovarian Failure
NCT01129947	EARLY_PHASE1	WITHDRAWN	The Use of DHEA in Women With Premature Ovarian Failure
NCT05522634	EARLY_PHASE1	UNKNOWN	A Clinical Study of Chinese Herbal Compound TJAOA101 in the Treatment of Premature Ovarian Insufficiency
NCT07308327	EARLY_PHASE1	ACTIVE_NOT_RECRUITING	The Influence of Gut Microbiota on Ovarian Function: A Single-center, Randomized,Double Blind, Parallel-controlled, Exploratory Clinical Trial
NCT00001275	Not specified	COMPLETED	Ovarian Follicle Function in Patients With Primary Ovarian Failure
NCT00001306	Not specified	COMPLETED	Steroid Therapy in Autoimmune Premature Ovarian Failure