MAFB

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

Basic information

Region (hg38): 20:40685847-40689236

Previous symbols: [ "KRML" ]

Links

ENSG00000204103 ∙ NCBI:9935 ∙ OMIM:608968 ∙ HGNC:6408 ∙ Uniprot:Q9Y5Q3 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• multicentric carpo-tarsal osteolysis with or without nephropathy (Definitive), mode of inheritance: AD
• multicentric carpo-tarsal osteolysis with or without nephropathy (Moderate), mode of inheritance: AD
• Duane retraction syndrome (Supportive), mode of inheritance: AD
• multicentric carpo-tarsal osteolysis with or without nephropathy (Supportive), mode of inheritance: AD
• Duane retraction syndrome 3 with or without deafness (Strong), mode of inheritance: AD
• multicentric carpo-tarsal osteolysis with or without nephropathy (Strong), mode of inheritance: AD
• Duane retraction syndrome 3 with or without deafness (Moderate), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Duane retraction syndrome-3 (DURS3) with or without deafness	AD	Audiologic/Otolaryngologic	Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development	Audiologic/Otolaryngologic; Craniofacial; Musculoskeletal; Neurologic; Renal	22387013; 27181683
Individuals with Multicentric carpotarsal osteolysis frequently have progressive renal disease

ClinVar

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

• Multicentric carpo-tarsal osteolysis with or without nephropathy (4 variants)
• not provided (4 variants)
• Duane retraction syndrome 3 with or without deafness (3 variants)
• Duane retraction syndrome 2;Duane syndrome type 1 (2 variants)
• MAFB-related disorder (1 variants)
• Duane syndrome type 1;Duane retraction syndrome 2 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the MAFB 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			6	19	1	26
missense	6	8	46	3	3	66
nonsense		1				1
start loss						0
frameshift	4					4
inframe indel			1			1
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding			44	6	14	64
Total	10	9	97	28	18

Variants in MAFB

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

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

Position	Type	Phenotype	Significance	ClinVar
20-40685871-A-T		Multicentric carpo-tarsal osteolysis with or without nephropathy	Benign (Jun 14, 2016)
20-40686030-G-A		Multicentric carpo-tarsal osteolysis with or without nephropathy	Benign (Jun 14, 2016)
20-40686076-G-A		Multicentric carpo-tarsal osteolysis with or without nephropathy	Uncertain significance (Jan 13, 2018)
20-40686092-A-G		Multicentric carpo-tarsal osteolysis with or without nephropathy	Uncertain significance (Jan 13, 2018)
20-40686128-G-A		Multicentric carpo-tarsal osteolysis with or without nephropathy	Uncertain significance (Jan 13, 2018)
20-40686142-T-C		Multicentric carpo-tarsal osteolysis with or without nephropathy	Benign (Jan 13, 2018)
20-40686189-C-T		Multicentric carpo-tarsal osteolysis with or without nephropathy	Benign (Jan 13, 2018)
20-40686200-G-A		Multicentric carpo-tarsal osteolysis with or without nephropathy	Uncertain significance (Jan 13, 2018)
20-40686286-GA-G		Multicentric carpo-tarsal osteolysis with or without nephropathy	Benign (Jun 14, 2016)
20-40686286-G-GA		Multicentric carpo-tarsal osteolysis with or without nephropathy	Uncertain significance (Jun 14, 2016)
20-40686288-A-G		Multicentric carpo-tarsal osteolysis with or without nephropathy	Uncertain significance (Jan 13, 2018)
20-40686328-C-T		Multicentric carpo-tarsal osteolysis with or without nephropathy	Uncertain significance (Jan 12, 2018)
20-40686359-G-C		Multicentric carpo-tarsal osteolysis with or without nephropathy	Likely benign (Jun 14, 2016)
20-40686360-G-C		Multicentric carpo-tarsal osteolysis with or without nephropathy	Uncertain significance (Jan 12, 2018)
20-40686360-G-T		Multicentric carpo-tarsal osteolysis with or without nephropathy	Uncertain significance (Apr 27, 2017)
20-40686446-T-C		Multicentric carpo-tarsal osteolysis with or without nephropathy	Uncertain significance (Jan 13, 2018)
20-40686565-T-C		Multicentric carpo-tarsal osteolysis with or without nephropathy	Benign (Jan 13, 2018)
20-40686624-G-A		Multicentric carpo-tarsal osteolysis with or without nephropathy	Uncertain significance (Jan 13, 2018)
20-40686653-G-A		Multicentric carpo-tarsal osteolysis with or without nephropathy	Uncertain significance (Jan 13, 2018)
20-40686666-T-TTCCTC		Multicentric carpo-tarsal osteolysis with or without nephropathy	Uncertain significance (Jun 14, 2016)
20-40686669-C-T		Multicentric carpo-tarsal osteolysis with or without nephropathy	Uncertain significance (Jan 13, 2018)
20-40686708-T-G		Multicentric carpo-tarsal osteolysis with or without nephropathy	Uncertain significance (Jan 13, 2018)
20-40686860-T-C		Multicentric carpo-tarsal osteolysis with or without nephropathy	Benign (Jan 12, 2018)
20-40686860-T-G		Multicentric carpo-tarsal osteolysis with or without nephropathy	Uncertain significance (Jan 13, 2018)
20-40686903-C-T		Multicentric carpo-tarsal osteolysis with or without nephropathy	Uncertain significance (Jan 12, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
MAFB	protein_coding	protein_coding	ENST00000373313	1	3393

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.903	0.0962	0	0	0	0	0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.17	107	191	0.559	0.00000873	2093
Missense in Polyphen		24	69.253	0.34655		737
Synonymous	-0.00929	88	87.9	1.00	0.00000418	652
Loss of Function	2.54	0	7.54	0.00	3.26e-7	81

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: Acts as a transcriptional activator or repressor (PubMed:27181683). Plays a pivotal role in regulating lineage- specific hematopoiesis by repressing ETS1-mediated transcription of erythroid-specific genes in myeloid cells. Required for monocytic, macrophage, osteoclast, podocyte and islet beta cell differentiation. Involved in renal tubule survival and F4/80 maturation. Activates the insulin and glucagon promoters. Together with PAX6, transactivates weakly the glucagon gene promoter through the G1 element. SUMO modification controls its transcriptional activity and ability to specify macrophage fate. Binds element G1 on the glucagon promoter (By similarity). Involved either as an oncogene or as a tumor suppressor, depending on the cell context. {ECO:0000250|UniProtKB:P54841, ECO:0000269|PubMed:19143053, ECO:0000269|PubMed:27181683}.
• Disease: DISEASE: Multicentric carpotarsal osteolysis syndrome (MCTO) [MIM:166300]: A rare skeletal disorder, usually presenting in early childhood with a clinical picture mimicking juvenile rheumatoid arthritis. Progressive destruction of the carpal and tarsal bone usually occurs and other bones may also be involved. Chronic renal failure is a frequent component of the syndrome. Mental retardation and minor facial anomalies have been noted in some patients. {ECO:0000269|PubMed:22387013}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Duane retraction syndrome 3 with or without deafness (DURS3) [MIM:617041]: A form of Duane retraction syndrome, a congenital eye movement disorder characterized by a failure of cranial nerve VI (the abducens nerve) to develop normally, resulting in restriction or absence of abduction, adduction or both, narrowing of the palpebral fissure, and retraction of the globe on attempted adduction. Undiagnosed in children, it can lead to amblyopia, a permanent uncorrectable loss of vision. Some DURS3 patients manifest sensorineural hearing loss. {ECO:0000269|PubMed:27181683}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Tacrolimus/Cyclosporine Pathway, Pharmacodynamics;Ectoderm Differentiation (Consensus)

Recessive Scores

• pRec: 0.260

Intolerance Scores

• rvis_EVS: -0.14
• rvis_percentile_EVS: 42.88

Haploinsufficiency Scores

• pHI: 0.675
• ghis: 0.605

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.970

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Mafb
• Phenotype: craniofacial phenotype; homeostasis/metabolism phenotype; cellular phenotype; endocrine/exocrine gland phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); normal phenotype; 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); reproductive system phenotype; hearing/vestibular/ear 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); renal/urinary system phenotype; skeleton phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); respiratory system phenotype; embryo phenotype

Zebrafish Information Network

• Gene name: mafba
• Affected structure: blood cell
• Phenotype tag: abnormal
• Phenotype quality: decreased amount

Gene ontology

• Biological process: regulation of transcription, DNA-templated;segment specification;sensory organ development;respiratory gaseous exchange;rhombomere 5 development;rhombomere 6 development;abducens nerve formation;T cell differentiation in thymus;brain segmentation;inner ear morphogenesis;negative regulation of erythrocyte differentiation;negative regulation of osteoclast differentiation;positive regulation of transcription by RNA polymerase II;thymus development
• Cellular component: nucleus;transcription factor complex
• 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;transcription factor binding;protein homodimerization activity;sequence-specific DNA binding;protein heterodimerization activity