MAFA

MAF bZIP transcription factor A, the group of Basic leucine zipper proteins

Basic information

Region (hg38): 8:143419182-143430732

Links

ENSG00000182759 ∙ NCBI:389692 ∙ OMIM:610303 ∙ HGNC:23145 ∙ Uniprot:Q8NHW3 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Insulinomatosis and diabetes mellitus syndrome	AD	Endocrine; Oncologic; Ophthalmologic	The condition can include hypoglycemia due to insulomas, and management (with diazoxide and diet, though surgery has also been described) has been described as beneficial; Individuals have been described with glaucoma, and awareness may allow early diagnosis and management	Endocrine; Oncologic; Ophthalmologic	19011561; 29339498

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the MAFA gene.

• not_specified (61 variants)
• Islet_cell_adenomatosis (7 variants)
• MAFA-related_disorder (5 variants)
• Osteopetrosis,_autosomal_dominant_3 (1 variants)
• Juvenile-onset_diabetes_mellitus-central_and_peripheral_neurodegeneration_syndrome (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the MAFA gene is commonly pathogenic or not. These statistics are base on transcript: NM_000201589.4. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				1	3	4
missense	1	1	57	4	2	65
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	1	1	57	5	5

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
MAFA	protein_coding	protein_coding	ENST00000333480	1	11225

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00337	0.629	0	0	0	0	0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.610	109	128	0.849	0.00000604	2225
Missense in Polyphen		34	38.899	0.87406		530
Synonymous	1.39	45	58.5	0.770	0.00000295	733
Loss of Function	0.490	4	5.21	0.768	2.23e-7	77

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.00	0.00
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Transcription factor that activates insulin gene expression (PubMed:15993959, PubMed:12011435). Acts synergistically with NEUROD1/BETA2 and PDX1 (PubMed:15993959). Binds the insulin enhancer C1/RIPE3b element (PubMed:12011435). Binds to consensus TRE-type MARE 5'-TGCTGACTCAGCA-3' DNA sequence (PubMed:23148532, PubMed:29339498). {ECO:0000269|PubMed:12011435, ECO:0000269|PubMed:15993959, ECO:0000269|PubMed:23148532, ECO:0000269|PubMed:29339498}.
• Disease: DISEASE: Insulinomatosis and diabetes mellitus (INSDM) [MIM:147630]: An autosomal dominant disorder characterized by the occurrence of multicentric insulinomas, hyperinsulinemic hypoglycemia, non insulin-dependent diabetes mellitus, and impaired glucose tolerance. Some patients also exhibit congenital cataract and/or congenital glaucoma. {ECO:0000269|PubMed:29339498}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Type II diabetes mellitus - Homo sapiens (human);Maturity onset diabetes of the young - Homo sapiens (human);Anti-diabetic Drug Potassium Channel Inhibitors Pathway, Pharmacodynamics;Tacrolimus/Cyclosporine Pathway, Pharmacodynamics;Type II diabetes mellitus (Consensus)

Haploinsufficiency Scores

• pHI: 0.318
• ghis: 0.500

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.834

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Mafa
• Phenotype: renal/urinary system phenotype; normal phenotype; homeostasis/metabolism phenotype; endocrine/exocrine gland phenotype; growth/size/body region phenotype

Gene ontology

• Biological process: regulation of transcription, DNA-templated;nitric oxide mediated signal transduction;response to glucose;insulin secretion;positive regulation of transcription by RNA polymerase II
• Cellular component: nucleus
• Molecular function: RNA polymerase II proximal promoter sequence-specific DNA binding;DNA-binding transcription factor activity, RNA polymerase II-specific;DNA binding;DNA-binding transcription factor activity;protein homodimerization activity;sequence-specific DNA binding;protein heterodimerization activity