MAF

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

Basic information

Region (hg38): 16:79585842-79600737

Links

ENSG00000178573 ∙ NCBI:4094 ∙ OMIM:177075 ∙ HGNC:6776 ∙ Uniprot:O75444 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• cataract 21 multiple types (Definitive), mode of inheritance: AD
• cataract - microcornea syndrome (Supportive), mode of inheritance: AD
• Fine-Lubinsky syndrome (Supportive), mode of inheritance: AR
• pulverulent cataract (Supportive), mode of inheritance: AD
• cerulean cataract (Supportive), mode of inheritance: AD
• Ayme-Gripp syndrome (Definitive), mode of inheritance: AD
• Ayme-Gripp syndrome (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Ayme-Gripp syndrome	AD	Audiologic/Otolaryngologic	In Ayme-Gripp syndrome, early recognition and treatment of hearing impairment may improve outcomes, including speech and language development	Audiologic/Otolaryngologic; Craniofacial; Neurologic; Ophthalmologic	8834052; 8867660; 11772997; 16470690; 17935251; 24664492; 25865493

ClinVar

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

• not provided (66 variants)
• Cataract 21 multiple types;Ayme-Gripp syndrome (53 variants)
• Inborn genetic diseases (17 variants)
• Ayme-Gripp syndrome (11 variants)
• not specified (9 variants)
• Cataract 21 multiple types (8 variants)
• MAF-related condition (3 variants)
• Developmental cataract (1 variants)
• Seizure;Intellectual disability (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the MAF 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			1	18	1	20
missense	5	9	48	5	3	70
nonsense						0
start loss						0
frameshift	2	1				3
inframe indel		1	1	6	1	9
splice donor/acceptor (+/-2bp)			1			1
splice region						0
non coding				13	15	28
Total	7	11	51	42	20

Variants in MAF

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

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

Position	Type	Phenotype	Significance	ClinVar
16-79594241-C-G			Likely benign (Nov 20, 2018)
16-79594275-C-G			Benign (Jun 26, 2018)
16-79594284-T-C			Benign (Jun 26, 2018)
16-79594427-GA-G			Benign (Aug 07, 2018)
16-79594493-C-T		Cataract 21 multiple types;Ayme-Gripp syndrome • MAF-related disorder	Benign/Likely benign (Oct 11, 2023)
16-79594534-A-T		Inborn genetic diseases	Uncertain significance (Apr 05, 2023)
16-79594535-C-T			Uncertain significance (Mar 01, 2024)
16-79594540-G-T			Uncertain significance (Dec 12, 2019)
16-79594555-T-C		MAF-related disorder	Uncertain significance (Oct 09, 2022)
16-79594565-A-G		Cataract 21 multiple types;Ayme-Gripp syndrome	Likely benign (Nov 27, 2023)
16-79594639-AT-A			Benign (Aug 15, 2019)
16-79594639-ATT-A			Benign (Aug 16, 2019)
16-79594712-G-GA			Benign (Aug 15, 2019)
16-79594732-G-A			Likely benign (Jul 31, 2018)
16-79598568-G-A			Benign (Jun 26, 2018)
16-79598581-GGT-G			Benign (Aug 18, 2019)
16-79598581-GGTGT-G			Likely benign (Aug 31, 2019)
16-79598581-G-GGT			Benign (Aug 15, 2019)
16-79598581-G-GGTGT			Benign (Aug 15, 2019)
16-79598581-G-GGTGTGT			Likely benign (Feb 06, 2020)
16-79598581-G-GGTGTGTGT			Likely benign (Aug 14, 2020)
16-79598601-T-TGTGC			Likely benign (Oct 02, 2019)
16-79598718-A-G			Likely benign (Mar 21, 2019)
16-79598749-T-A			Likely benign (Sep 18, 2018)
16-79598793-C-G		Cataract 21 multiple types;Ayme-Gripp syndrome	Uncertain significance (Sep 13, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
MAF	protein_coding	protein_coding	ENST00000326043	2	14872

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.744	0.254	125465	0	1	125466	0.00000399

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.18	131	175	0.749	0.00000838	2581
Missense in Polyphen		34	46.865	0.72549		562
Synonymous	-2.55	108	79.2	1.36	0.00000393	850
Loss of Function	2.44	1	8.83	0.113	3.88e-7	105

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000289	0.0000289
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: Acts as a transcriptional activator or repressor. Involved in embryonic lens fiber cell development. Recruits the transcriptional coactivators CREBBP and/or EP300 to crystallin promoters leading to up-regulation of crystallin gene during lens fiber cell differentiation. Activates the expression of IL4 in T helper 2 (Th2) cells. Increases T-cell susceptibility to apoptosis by interacting with MYB and decreasing BCL2 expression. Together with PAX6, transactivates strongly the glucagon gene promoter through the G1 element. Activates transcription of the CD13 proximal promoter in endothelial cells. Represses transcription of the CD13 promoter in early stages of myelopoiesis by affecting the ETS1 and MYB cooperative interaction. Involved in the initial chondrocyte terminal differentiation and the disappearance of hypertrophic chondrocytes during endochondral bone development. Binds to the sequence 5'-[GT]G[GC]N[GT]NCTCAGNN-3' in the L7 promoter. Binds to the T-MARE (Maf response element) sites of lens-specific alpha- and beta-crystallin gene promoters. Binds element G1 on the glucagon promoter. Binds an AT-rich region adjacent to the TGC motif (atypical Maf response element) in the CD13 proximal promoter in endothelial cells (By similarity). When overexpressed, represses anti-oxidant response element (ARE)- mediated transcription. Involved either as an oncogene or as a tumor suppressor, depending on the cell context. Binds to the ARE sites of detoxifying enzyme gene promoters. {ECO:0000250, ECO:0000269|PubMed:12149651, ECO:0000269|PubMed:14998494, ECO:0000269|PubMed:15007382, ECO:0000269|PubMed:16247450, ECO:0000269|PubMed:19143053}.
• Disease: DISEASE: Note=A chromosomal aberration involving MAF is found in some forms of multiple myeloma (MM). Translocation t(14;16)(q32.3;q23) with an IgH locus.; DISEASE: Cataract 21, multiple types (CTRCT21) [MIM:610202]: An opacification of the crystalline lens of the eye that frequently results in visual impairment or blindness. Opacities vary in morphology, are often confined to a portion of the lens, and may be static or progressive. In general, the more posteriorly located and dense an opacity, the greater the impact on visual function. CTRCT21 includes cerulean and pulverulent cataracts. Cerulean cataracts are characterized by peripheral bluish and white opacifications organized in concentric layers with occasional central lesions arranged radially. The opacities are observed in the superficial layers of the fetal nucleus as well as the adult nucleus of the lens. Involvement is usually bilateral. Visual acuity is only mildly reduced in childhood. In adulthood, the opacifications may progress, making lens extraction necessary. Histologically the lesions are described as fusiform cavities between lens fibers which contain a deeply staining granular material. Although the lesions may take on various colors, a dull blue is the most common appearance and is responsible for the designation cerulean cataract. Pulverulent cataracts are characterized by a dust-like, 'pulverised' appearance of the opacities which can be found in any part of the lens. In some cases cataract is associated with microcornea without any other systemic anomaly or dysmorphism. Microcornea is defined by a corneal diameter inferior to 10 mm in both meridians in an otherwise normal eye. {ECO:0000269|PubMed:11772997, ECO:0000269|PubMed:16470690, ECO:0000269|PubMed:24664492}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Ayme-Gripp syndrome (AYGRP) [MIM:601088]: A multisystem disorder characterized by congenital cataracts, sensorineural deafness, intellectual disability, seizures, brachycephaly, distinctive flat facial appearance, skeletal anomalies, mammary gland hypoplasia, and reduced growth. {ECO:0000269|PubMed:25865493}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Inflammatory bowel disease (IBD) - Homo sapiens (human);Th1 and Th2 cell differentiation - Homo sapiens (human);Transcriptional misregulation in cancer - Homo sapiens (human);Tacrolimus/Cyclosporine Pathway, Pharmacodynamics;Transcriptional activation by NRF2;TYROBP Causal Network;RUNX2 regulates osteoblast differentiation;RUNX2 regulates bone development;Transcriptional regulation by RUNX2;Gene expression (Transcription);gata3 participate in activating the th2 cytokine genes expression;Generic Transcription Pathway;RNA Polymerase II Transcription;C-MYB transcription factor network;Calcineurin-regulated NFAT-dependent transcription in lymphocytes;AP-1 transcription factor network (Consensus)

Haploinsufficiency Scores

• pHI: 0.260
• hipred: Y
• hipred_score: 0.751
• ghis: 0.592

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.801

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Maf
• Phenotype: renal/urinary system phenotype; immune system phenotype; vision/eye phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); homeostasis/metabolism phenotype; craniofacial phenotype; growth/size/body region phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan)

Gene ontology

• Biological process: negative regulation of transcription by RNA polymerase II;cytokine production;transcription by RNA polymerase II;regulation of chondrocyte differentiation;positive regulation of transcription by RNA polymerase II;cell development;inner ear development;lens fiber cell differentiation
• Cellular component: chromatin;nucleus;cytoplasm
• Molecular function: RNA polymerase II proximal promoter sequence-specific DNA binding;DNA-binding transcription factor activity, RNA polymerase II-specific;DNA-binding transcription factor activity;protein binding;sequence-specific DNA binding