MANF (mesencephalic astrocyte derived neurotrophic factor)

Gene

• Entrez ID: 7873
• Gene name: Mesencephalic astrocyte derived neurotrophic factor
• Gene symbol: MANF
• Synonyms (NCBI Gene): ARMET, ARP, DDDS
• Chromosome: 3
• Chromosome location: 3p21.2
• Summary: The protein encoded by this gene is localized in the endoplasmic reticulum (ER) and golgi, and is also secreted. Reducing expression of this gene increases susceptibility to ER stress-induced death and results in cell proliferation. Activity of this prote

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT024847	hsa-miR-215-5p	Microarray	19074876
MIRT026482	hsa-miR-192-5p	Microarray	19074876
MIRT050039	hsa-miR-26b-5p	CLASH	23622248
MIRT1127540	hsa-miR-1226	CLIP-seq
MIRT1127541	hsa-miR-1252	CLIP-seq
MIRT1127542	hsa-miR-3202	CLIP-seq
MIRT1127543	hsa-miR-338-3p	CLIP-seq
MIRT1127544	hsa-miR-3616-5p	CLIP-seq
MIRT1127545	hsa-miR-3647-5p	CLIP-seq
MIRT1127546	hsa-miR-4476	CLIP-seq
MIRT1127547	hsa-miR-4640-5p	CLIP-seq
MIRT1127548	hsa-miR-4726-5p	CLIP-seq
MIRT1127549	hsa-miR-573	CLIP-seq
MIRT1127550	hsa-miR-603	CLIP-seq
MIRT1127551	hsa-miR-634	CLIP-seq
MIRT1127552	hsa-miR-873	CLIP-seq
MIRT1127540	hsa-miR-1226	CLIP-seq
MIRT1127544	hsa-miR-3616-5p	CLIP-seq
MIRT1127545	hsa-miR-3647-5p	CLIP-seq
MIRT1127549	hsa-miR-573	CLIP-seq
MIRT1127551	hsa-miR-634	CLIP-seq
MIRT2565854	hsa-miR-101	CLIP-seq
MIRT2565855	hsa-miR-144	CLIP-seq
MIRT2565856	hsa-miR-2052	CLIP-seq
MIRT2565857	hsa-miR-3122	CLIP-seq
MIRT2565858	hsa-miR-3689a-3p	CLIP-seq
MIRT2565859	hsa-miR-3689c	CLIP-seq
MIRT2565860	hsa-miR-3913-5p	CLIP-seq
MIRT2565861	hsa-miR-4433	CLIP-seq
MIRT2565862	hsa-miR-4459	CLIP-seq
MIRT2565863	hsa-miR-4687-3p	CLIP-seq
MIRT2565864	hsa-miR-4768-3p	CLIP-seq
MIRT2565865	hsa-miR-520d-5p	CLIP-seq
MIRT2565866	hsa-miR-524-5p	CLIP-seq
MIRT2565854	hsa-miR-101	CLIP-seq
MIRT2684435	hsa-miR-125a-3p	CLIP-seq
MIRT2565855	hsa-miR-144	CLIP-seq
MIRT2565856	hsa-miR-2052	CLIP-seq
MIRT2565857	hsa-miR-3122	CLIP-seq
MIRT2684436	hsa-miR-3545-3p	CLIP-seq
MIRT2684437	hsa-miR-3679-3p	CLIP-seq
MIRT2565858	hsa-miR-3689a-3p	CLIP-seq
MIRT2565859	hsa-miR-3689c	CLIP-seq
MIRT2565860	hsa-miR-3913-5p	CLIP-seq
MIRT2684438	hsa-miR-3934	CLIP-seq
MIRT2565861	hsa-miR-4433	CLIP-seq
MIRT2684439	hsa-miR-4446-5p	CLIP-seq
MIRT2565862	hsa-miR-4459	CLIP-seq
MIRT2684440	hsa-miR-452	CLIP-seq
MIRT2684441	hsa-miR-4676-3p	CLIP-seq
MIRT2565863	hsa-miR-4687-3p	CLIP-seq
MIRT2565864	hsa-miR-4768-3p	CLIP-seq
MIRT2565865	hsa-miR-520d-5p	CLIP-seq
MIRT2565866	hsa-miR-524-5p	CLIP-seq
MIRT2684442	hsa-miR-764	CLIP-seq

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0002014	Process	Vasoconstriction of artery involved in ischemic response to lowering of systemic arterial blood pressure	IEA
GO:0003723	Function	RNA binding	HDA	22658674
GO:0005515	Function	Protein binding	IPI	25543119, 28514442, 33961781
GO:0005576	Component	Extracellular region	IEA
GO:0005576	Component	Extracellular region	TAS
GO:0005615	Component	Extracellular space	IBA
GO:0005634	Component	Nucleus	HDA	21630459
GO:0005783	Component	Endoplasmic reticulum	IBA
GO:0005783	Component	Endoplasmic reticulum	IEA
GO:0005788	Component	Endoplasmic reticulum lumen	IDA	29497057
GO:0005788	Component	Endoplasmic reticulum lumen	IEA
GO:0005829	Component	Cytosol	TAS
GO:0006986	Process	Response to unfolded protein	IEA
GO:0008083	Function	Growth factor activity	IEA
GO:0008289	Function	Lipid binding	IEA
GO:0016529	Component	Sarcoplasmic reticulum	IEA
GO:0031175	Process	Neuron projection development	IBA
GO:0033018	Component	Sarcoplasmic reticulum lumen	IEA
GO:0036500	Process	ATF6-mediated unfolded protein response	IMP	27984733
GO:0071542	Process	Dopaminergic neuron differentiation	IBA
GO:0120146	Function	Sulfatide binding	IDA	29497057
GO:0120146	Function	Sulfatide binding	IPI	29497057
GO:1905897	Process	Regulation of response to endoplasmic reticulum stress	IMP	29497057

Other IDs

• MIM: 601916
• HGNC: 15461
• e!Ensembl: ENSG00000145050

Protein

• UniProt ID: P55145
• Protein name: Mesencephalic astrocyte-derived neurotrophic factor (Arginine-rich protein) (Protein ARMET)
• Protein function: Selectively promotes the survival of dopaminergic neurons of the ventral mid-brain (PubMed:12794311). Modulates GABAergic transmission to the dopaminergic neurons of the substantia nigra (By similarity). Enhances spontaneous, as well as evoked,
• PDB: 2KVD, 2KVE, 2W51
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF10208	Armet	29 → 174	Degradation arginine-rich protein for mis-folding	Family

• Sequence:

  MRRMWATQGLAVALALSVLPGSRALRPGDCEVCISYLGRFYQDLKDRDVTFSPATIENEL
  IKFCREARGKENRLCYYIGATDDAATKIINEVSKPLAHHIPVEKICEKLKKKDSQICELK
  YDKQIDLSTVDLKKLRVKELKKILDDWGETCKGCAEKSDYIRKINELMPKYAPKAASART
  DL

• Sequence length: 182

Pathways

Reactome:

Platelet degranulation

Associated diseases

Evidence Score:

• ★☆☆☆☆  Gene-disease association found in Text Mining only
• ★★☆☆☆  Found in Text Mining and Unknown/Other Associations
• ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources
• ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants)
• ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Causal
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession	Evidence Score
Cerebro-costo-mandibular syndrome	Likely pathogenic	rs1005998005	RCV005860376	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Diabetes, deafness, developmental delay, and short stature syndrome	Likely pathogenic; Pathogenic	rs1005998005, rs1559452572	RCV003447448 RCV003447449	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
MANF-related disorder	Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
PARKINSONIAN DISORDERS	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Acute pancreatitis	Pancreatitis	BEFREE	28440306		★☆☆☆☆ Found in Text Mining only
Arthritis Rheumatoid	Rheumatoid arthritis	Pubtator	35008858	Stimulate	★☆☆☆☆ Found in Text Mining only
Atrial Fibrillation	Atrial Fibrillation	BEFREE	31789884		★☆☆☆☆ Found in Text Mining only
Autoimmune Diseases	Autoimmune Diseases	BEFREE	25640174, 28740209		★☆☆☆☆ Found in Text Mining only
Azoospermia	Azoospermia	Pubtator	39237030	Associate	★☆☆☆☆ Found in Text Mining only
B-Cell Lymphomas	B-Cell Lymphoma	BEFREE	30211660		★☆☆☆☆ Found in Text Mining only
Carcinogenesis	Carcinogenesis	Pubtator	32382531	Associate	★☆☆☆☆ Found in Text Mining only
Carcinoma Hepatocellular	Hepatocellular carcinoma	Pubtator	31469428	Inhibit	★☆☆☆☆ Found in Text Mining only
Carcinoma Hepatocellular	Hepatocellular carcinoma	Pubtator	32382531	Stimulate	★☆☆☆☆ Found in Text Mining only
Carcinoma Hepatocellular	Hepatocellular carcinoma	Pubtator	33891607	Associate	★☆☆☆☆ Found in Text Mining only
Cerebral Infarction	Cerebral Infarction	BEFREE	25001514, 30760285, 31785307		★☆☆☆☆ Found in Text Mining only
Cerebrovascular accident	Stroke	BEFREE	20685313, 29050872, 29806020, 31785307		★☆☆☆☆ Found in Text Mining only
Chondrocalcinosis 2	Chondrocalcinosis	Pubtator	35008858	Associate	★☆☆☆☆ Found in Text Mining only
Colonic Neoplasms	Colonic neoplasm	Pubtator	33891607	Associate	★☆☆☆☆ Found in Text Mining only
Congestive heart failure	Congestive Heart Failure	BEFREE	20970425		★☆☆☆☆ Found in Text Mining only
Depressive disorder	Mental Depression	BEFREE	31555085		★☆☆☆☆ Found in Text Mining only
Developmental Disabilities	Developmental disability	Pubtator	33500254	Associate	★☆☆☆☆ Found in Text Mining only
Diabetes	Diabetes	BEFREE	27425895, 28719799, 30386256		★☆☆☆☆ Found in Text Mining only
Diabetes Mellitus	Diabetes mellitus	Pubtator	27356471, 30032427, 32965004, 33500254	Associate	★☆☆☆☆ Found in Text Mining only
Diabetes Mellitus	Diabetes Mellitus	BEFREE	27425895, 28719799, 30386256		★☆☆☆☆ Found in Text Mining only
Diabetes Mellitus Type 1	Diabetes mellitus, type 1	Pubtator	27356471	Associate	★☆☆☆☆ Found in Text Mining only
Diabetes Mellitus, Non-Insulin-Dependent	Diabetes Mellitus	BEFREE	28216543		★☆☆☆☆ Found in Text Mining only
Esophageal carcinoma	Esophageal Carcinoma	BEFREE	10767373		★☆☆☆☆ Found in Text Mining only
Esophageal Neoplasms	Esophagus Neoplasm	BEFREE	10767373		★☆☆☆☆ Found in Text Mining only
Focal glomerulosclerosis	Glomerulosclerosis	BEFREE	31235574		★☆☆☆☆ Found in Text Mining only
Heart failure	Heart Failure	BEFREE	20970425		★☆☆☆☆ Found in Text Mining only
Hyperlipoproteinemias	Hyperlipoproteinemia	BEFREE	215348		★☆☆☆☆ Found in Text Mining only
Insulin-Like Growth Factor I Deficiency	Insulin-Like Growth Factor I Deficiency	BEFREE	30708048		★☆☆☆☆ Found in Text Mining only
Ischemic stroke	Ischemic Stroke	BEFREE	31785307		★☆☆☆☆ Found in Text Mining only
Kidney Diseases	Kidney Disease	BEFREE	28719799, 30099615		★☆☆☆☆ Found in Text Mining only
Leukemia Myeloid Acute	Myeloid leukemia	Pubtator	12384146	Associate	★☆☆☆☆ Found in Text Mining only
Liver carcinoma	Liver carcinoma	BEFREE	31469428		★☆☆☆☆ Found in Text Mining only
Liver Cirrhosis	Liver Cirrhosis	BEFREE	31469428		★☆☆☆☆ Found in Text Mining only
Liver Cirrhosis	Liver cirrhosis	Pubtator	31469428	Associate	★☆☆☆☆ Found in Text Mining only
Lupus Erythematosus, Systemic	Lupus Erythematosus	BEFREE	25226532, 25665148		★☆☆☆☆ Found in Text Mining only
Lymphatic Metastasis	Lymphatic metastasis	Pubtator	31469428	Associate	★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of esophagus	Esophagus Neoplasm	BEFREE	10767373		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of liver	Liver Cancer	BEFREE	31469428		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of pancreas	Pancreatic cancer	BEFREE	17072959, 9174057		★☆☆☆☆ Found in Text Mining only
Malignant Neoplasms	Malignant Neoplasm	BEFREE	31469428		★☆☆☆☆ Found in Text Mining only
Melanoma	Melanoma	Pubtator	33891607	Associate	★☆☆☆☆ Found in Text Mining only
Mental Depression	Mental Depression	BEFREE	31555085		★☆☆☆☆ Found in Text Mining only
Metaphyseal chondrodysplasia Schmid type	Metaphyseal chondrodysplasia	BEFREE	30543055		★☆☆☆☆ Found in Text Mining only
Multiple Epiphyseal Dysplasia	Multiple Epiphyseal Dysplasia	BEFREE	30543055		★☆☆☆☆ Found in Text Mining only
Myocardial Ischemia	Myocardial Ischemia	BEFREE	20970425		★☆☆☆☆ Found in Text Mining only
Neoplasms	Neoplasms	BEFREE	31469428, 9174057		★☆☆☆☆ Found in Text Mining only
Nephrotic Syndrome	Nephrotic Syndrome	BEFREE	31235574		★☆☆☆☆ Found in Text Mining only
nervous system disorder	Nervous System Disorder	BEFREE	28685189, 30760285		★☆☆☆☆ Found in Text Mining only
Neuroblastoma	Neuroblastoma	BEFREE	23255601		★☆☆☆☆ Found in Text Mining only
Neurodegenerative Disorders	Neurodegenerative Disorders	BEFREE	27425895, 30234112, 31781038		★☆☆☆☆ Found in Text Mining only
Osteoarthritis	Osteoarthritis	Pubtator	35008858	Associate	★☆☆☆☆ Found in Text Mining only
Pancreatic carcinoma	Pancreatic carcinoma	BEFREE	17072959, 9174057		★☆☆☆☆ Found in Text Mining only
Pancreatitis	Pancreatitis	BEFREE	28440306		★☆☆☆☆ Found in Text Mining only
Parkinson Disease	Parkinson disease	BEFREE	12794311, 19164766, 21047780, 25369767, 26616211, 27425895, 28131727, 29305570, 29349573, 29887945, 29959908, 30386256, 30760285, 31555085		★☆☆☆☆ Found in Text Mining only
Renal Cell Carcinoma	Renal Carcinoma	BEFREE	8649854, 9230196		★☆☆☆☆ Found in Text Mining only
Retinal Diseases	Retinal Diseases	BEFREE	28367115		★☆☆☆☆ Found in Text Mining only
Rheumatoid Arthritis	Rheumatoid arthritis	BEFREE	29649564		★☆☆☆☆ Found in Text Mining only
SPINOCEREBELLAR ATAXIA 17	Spinocerebellar Ataxia	BEFREE	29378605		★☆☆☆☆ Found in Text Mining only
Squamous cell carcinoma of esophagus	Esophagus Neoplasm	BEFREE	10767373		★☆☆☆☆ Found in Text Mining only
Subarachnoid Hemorrhage	Subarachnoid hemorrhage	BEFREE	30211660		★☆☆☆☆ Found in Text Mining only