MAFA (MAF bZIP transcription factor A)

Gene

• Entrez ID: 389692
• Gene name: MAF bZIP transcription factor A
• Gene symbol: MAFA
• Synonyms (NCBI Gene): INSDM, RIPE3b1, hMafA
• Chromosome: 8
• Chromosome location: 8q24.3
• Summary: MAFA is a transcription factor that binds RIPE3b, a conserved enhancer element that regulates pancreatic beta cell-specific expression of the insulin gene (INS; MIM 176730) (Olbrot et al., 2002 [PubMed 12011435]).[supplied by OMIM, Mar 2008]

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs1554635488	G>A	Likely-pathogenic	Coding sequence variant, missense variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT1125272	hsa-miR-1197	CLIP-seq
MIRT1125273	hsa-miR-214	CLIP-seq
MIRT1125274	hsa-miR-3144-5p	CLIP-seq
MIRT1125275	hsa-miR-3179	CLIP-seq
MIRT1125276	hsa-miR-34b	CLIP-seq
MIRT1125277	hsa-miR-3619-5p	CLIP-seq
MIRT1125278	hsa-miR-4263	CLIP-seq
MIRT1125279	hsa-miR-4650-5p	CLIP-seq
MIRT1125280	hsa-miR-4690-5p	CLIP-seq
MIRT1125281	hsa-miR-576-5p	CLIP-seq
MIRT1125282	hsa-miR-761	CLIP-seq
MIRT1125283	hsa-miR-766	CLIP-seq

Transcription factors

Transcription factor	Regulation	Reference
ATF6	Repression	18450959

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000785	Component	Chromatin	ISA
GO:0000978	Function	RNA polymerase II cis-regulatory region sequence-specific DNA binding	IBA
GO:0000978	Function	RNA polymerase II cis-regulatory region sequence-specific DNA binding	IEA
GO:0000981	Function	DNA-binding transcription factor activity, RNA polymerase II-specific	IBA
GO:0000981	Function	DNA-binding transcription factor activity, RNA polymerase II-specific	ISA
GO:0001228	Function	DNA-binding transcription activator activity, RNA polymerase II-specific	IEA
GO:0003677	Function	DNA binding	IDA	12368292
GO:0003677	Function	DNA binding	IEA
GO:0003700	Function	DNA-binding transcription factor activity	IDA	17941991
GO:0003700	Function	DNA-binding transcription factor activity	IEA
GO:0003700	Function	DNA-binding transcription factor activity	TAS	12368292
GO:0005634	Component	Nucleus	IBA
GO:0005634	Component	Nucleus	IDA	12368292
GO:0005634	Component	Nucleus	IEA
GO:0006355	Process	Regulation of DNA-templated transcription	IEA
GO:0006355	Process	Regulation of DNA-templated transcription	TAS	12368292
GO:0006357	Process	Regulation of transcription by RNA polymerase II	IBA
GO:0009749	Process	Response to glucose	IBA
GO:0009749	Process	Response to glucose	IDA	12368292
GO:0030073	Process	Insulin secretion	IBA
GO:0030073	Process	Insulin secretion	IDA	17941991
GO:0045893	Process	Positive regulation of DNA-templated transcription	IEA
GO:0045944	Process	Positive regulation of transcription by RNA polymerase II	IDA	17941991
GO:0045944	Process	Positive regulation of transcription by RNA polymerase II	IEA
GO:1990837	Function	Sequence-specific double-stranded DNA binding	IDA	28473536

Other IDs

• MIM: 610303
• HGNC: 23145
• e!Ensembl: ENSG00000182759

Protein

• UniProt ID: Q8NHW3
• Protein name: Transcription factor MafA (Pancreatic beta-cell-specific transcriptional activator) (RIPE3b1 factor) (V-maf musculoaponeurotic fibrosarcoma oncogene homolog A)
• Protein function: Transcription factor that activates insulin gene expression (PubMed:12011435, PubMed:15993959). Acts synergistically with NEUROD1/BETA2 and PDX1 (PubMed:15993959). Binds the insulin enhancer C1/RIPE3b element (PubMed:12011435). Binds to consensu
• PDB: 4EOT
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF08383	Maf_N	111 → 144	Maf N-terminal region	Family
  PF03131	bZIP_Maf	227 → 318	bZIP Maf transcription factor	Coiled-coil

• Tissue specificity: TISSUE SPECIFICITY: Expressed in the islets of Langerhans (at protein level). {ECO:0000269|PubMed:12917329}.
• Sequence:

  MAAELAMGAELPSSPLAIEYVNDFDLMKFEVKKEPPEAERFCHRLPPGSLSSTPLSTPCS
  SVPSSPSFCAPSPGTGGGGGAGGGGGSSQAGGAPGPPSGGPGAVGGTSGKPALEDLYWMS
  GYQHHLNPEALNLTPEDAVEALIGSGHHGAHHGAHHPAAAAAYEAFRGPGFAGGGGADDM
  GAGHHHGAHHAAHHHHAAHHHHHHHHHHGGAGHGGGAGHHVRLEERFSDDQLVSMSVREL
  NRQLRGFSKEEVIRLKQKRRTLKNRGYAQSCRFKRVQQRHILESEKCQLQSQVEQLKLEV
  GRLAKERDLYKEKYEKLAGRGGPGSAGGAGFPREPSPPQAGPGGAKGTADFFL

• Sequence length: 353

Pathways

KEGG:

Type II diabetes mellitus
Maturity onset diabetes of the young

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
Islet cell adenomatosis	Pathogenic; Likely pathogenic	rs1819520149, rs1554635488	RCV003325633 RCV000590882	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
INSULINOMATOSIS AND DIABETES MELLITUS	—	HPO	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
JUVENILE-ONSET DIABETES MELLITUS, CENTRAL AND PERIPHERAL NEURODEGENERATION SYNDROME	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Juvenile-onset diabetes mellitus-central and peripheral neurodegeneration syndrome	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MAFA-related disorder	Uncertain significance; Benign; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Osteopetrosis, autosomal dominant 3	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
TYPE 2 DIABETES MELLITUS	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Anaplasia	Anaplasia	BEFREE	30372580		★☆☆☆☆ Found in Text Mining only
Carcinoma Mucoepidermoid	Mucoepidermoid carcinoma	Pubtator	23018873	Associate	★☆☆☆☆ Found in Text Mining only
Cataract	Cataract	Pubtator	29339498	Associate	★☆☆☆☆ Found in Text Mining only
Colorectal Neoplasms	Colorectal neoplasm	Pubtator	32869528	Inhibit	★☆☆☆☆ Found in Text Mining only
Congenital Hyperinsulinism	Hyperinsulinemic hypoglycemia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Diabetes	Diabetes	BEFREE	23975026		★☆☆☆☆ Found in Text Mining only
Diabetes Mellitus	Diabetes Mellitus	BEFREE	22293672, 23975026		★☆☆☆☆ Found in Text Mining only
Diabetes Mellitus	Diabetes mellitus	Pubtator	29339498	Associate	★☆☆☆☆ Found in Text Mining only
Diabetes Mellitus	Diabetes Mellitus	HPO_DG			★☆☆☆☆ Found in Text Mining only
Diabetes Mellitus Type 2	Diabetes mellitus, type 2	Pubtator	30372580	Associate	★☆☆☆☆ Found in Text Mining only
Diabetes Mellitus, Insulin-Dependent	Diabetes Mellitus	BEFREE	20682694		★☆☆☆☆ Found in Text Mining only
Diabetes Mellitus, Non-Insulin-Dependent	Diabetes Mellitus	BEFREE	23863625, 24013263, 26904947, 28424732, 30372580		★☆☆☆☆ Found in Text Mining only
Glaucoma	Glaucoma	Pubtator	29339498	Associate	★☆☆☆☆ Found in Text Mining only
Hyperglycemia	Hyperglycemia	BEFREE	23863625		★☆☆☆☆ Found in Text Mining only
Hyperinsulinemic hypoglycemia	Hyperinsulinemic hypoglycemia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Insulin Resistance	Diabetes mellitus, type 2	Pubtator	35872977	Associate	★☆☆☆☆ Found in Text Mining only
Islet cell adenomatosis	Islet Cell Adenomatosis	UNIPROT_DG	29339498		★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Islet cell adenomatosis	Islet Cell Adenomatosis	CLINVAR_DG	29339498		★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Multiple pancreatic beta-cell adenomas	Multiple pancreatic beta-cell adenomas	HPO_DG			★☆☆☆☆ Found in Text Mining only
Periodontitis	Periodontitis	Pubtator	27531006	Associate	★☆☆☆☆ Found in Text Mining only