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.

• Islet cell adenomatosis (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.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous					3	3
missense	1	1	25	4	3	34
nonsense						0
start loss						0
frameshift						0
inframe indel				2	1	3
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding				1		1
Total	1	1	25	7	7

Variants in MAFA

This is a list of pathogenic ClinVar variants found in the MAFA region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
8-143429343-G-A		MAFA-related disorder	Likely benign (Aug 18, 2022)
8-143429354-G-T		not specified	Uncertain significance (Aug 09, 2021)
8-143429368-C-A		MAFA-related disorder	Benign (Dec 09, 2019)
8-143429410-G-A		not specified	Uncertain significance (Dec 27, 2023)
8-143429436-C-A		not specified	Uncertain significance (Sep 21, 2023)
8-143429540-G-C		MAFA-related disorder	Likely benign (May 14, 2024)
8-143429566-T-C		not specified	Uncertain significance (Oct 06, 2021)
8-143429583-C-T		not specified	Uncertain significance (May 11, 2022)
8-143429585-C-T		MAFA-related disorder	Benign (Apr 11, 2019)
8-143429611-C-A		Islet cell adenomatosis	Benign (-)
8-143429631-C-G		not specified	Uncertain significance (Oct 06, 2023)
8-143429640-T-G		Juvenile-onset diabetes mellitus-central and peripheral neurodegeneration syndrome	Uncertain significance (Jun 02, 2022)
8-143429660-C-G		not specified	Uncertain significance (Sep 27, 2022)
8-143429699-C-T		not specified	Benign (May 02, 2022)
8-143429710-C-A		not specified	Uncertain significance (Apr 11, 2023)
8-143429754-C-T		not specified	Uncertain significance (Oct 16, 2023)
8-143429776-C-T		Islet cell adenomatosis	Uncertain significance (-)
8-143429783-ATGGTGG-A		MAFA-related disorder	Benign (Mar 01, 2019)
8-143429783-ATGGTGGTGG-A		not specified • MAFA-related disorder	Likely benign (Jun 09, 2022)
8-143429786-G-C		not specified	Uncertain significance (Mar 16, 2024)
8-143429804-GTGGTGGTGGGCGGCGTGGTGA-G		MAFA-related disorder	Uncertain significance (May 16, 2024)
8-143429825-A-G		MAFA-related disorder	Benign (Oct 21, 2019)
8-143429886-C-T		not specified	Uncertain significance (Dec 27, 2023)
8-143429901-G-T		not specified	Likely benign (Apr 07, 2023)
8-143429934-G-T		not specified	Uncertain significance (Mar 06, 2023)

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