MAFB

Summary

MAFB (MAF bZIP transcription factor B, HGNC:6408) is a protein-coding gene on chromosome 20q12, encoding Transcription factor MafB (Q9Y5Q3). Acts as a transcriptional activator or repressor.

The protein encoded by this gene is a basic leucine zipper (bZIP) transcription factor that plays an important role in the regulation of lineage-specific hematopoiesis. The encoded nuclear protein represses ETS1-mediated transcription of erythroid-specific genes in myeloid cells. This gene contains no introns.

Source: NCBI Gene 9935 — RefSeq curated summary.

At a glance

• Gene–disease (curated): multicentric carpo-tarsal osteolysis with or without nephropathy (Definitive, GenCC) — +2 more curated relationships
• GWAS associations: 46
• Clinical variants (ClinVar): 230 total — 16 pathogenic, 8 likely-pathogenic
• Phenotypes (HPO): 106
• Dosage sensitivity (ClinGen): haploinsufficiency no evidence, triplosensitivity no evidence
• Transcription factor: yes — 51 downstream targets (CollecTRI)
• MANE Select transcript: NM_005461

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6408
Approved symbol	MAFB
Name	MAF bZIP transcription factor B
Location	20q12
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000204103
Ensembl biotype	protein_coding
OMIM	608968
Entrez	9935

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000373313

RefSeq mRNA: 1 — MANE Select: NM_005461 NM_005461

CCDS: CCDS13311

Canonical transcript exons

ENST00000373313 — 1 exons

Exon	Start	End
ENSE00001460189	40685848	40689236

Expression profiles

Bgee: expression breadth ubiquitous, 277 present calls, max score 98.90.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 81.9256 / max 6212.6621, expressed in 1472 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
187266	81.5257	1472
187265	0.2496	107
187267	0.1504	78

Top tissues by expression

285 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
renal glomerulus	UBERON:0000074	98.90	gold quality
skin of hip	UBERON:0001554	98.82	gold quality
gingiva	UBERON:0001828	98.80	gold quality
metanephric glomerulus	UBERON:0004736	98.76	gold quality
gingival epithelium	UBERON:0001949	98.74	gold quality
layer of synovial tissue	UBERON:0007616	98.52	gold quality
penis	UBERON:0000989	98.51	gold quality
synovial joint	UBERON:0002217	98.38	gold quality
nipple	UBERON:0002030	98.07	gold quality
upper arm skin	UBERON:0004263	98.04	gold quality
tibia	UBERON:0000979	98.03	gold quality
cervix squamous epithelium	UBERON:0006922	97.99	gold quality
squamous epithelium	UBERON:0006914	97.98	gold quality
palpebral conjunctiva	UBERON:0001812	97.96	gold quality
tendon of biceps brachii	UBERON:0008188	97.85	gold quality
amniotic fluid	UBERON:0000173	97.81	gold quality
upper leg skin	UBERON:0004262	97.78	gold quality
esophagus squamous epithelium	UBERON:0006920	97.74	gold quality
mammalian vulva	UBERON:0000997	97.60	gold quality
epithelium of esophagus	UBERON:0001976	97.46	gold quality
periodontal ligament	UBERON:0008266	97.30	gold quality
parietal pleura	UBERON:0002400	97.19	gold quality
cervix epithelium	UBERON:0004801	97.00	gold quality
pleura	UBERON:0000977	96.76	gold quality
monocyte	CL:0000576	96.67	gold quality
hair follicle	UBERON:0002073	96.65	gold quality
mononuclear cell	CL:0000842	96.62	gold quality
mammary duct	UBERON:0001765	96.53	gold quality
visceral pleura	UBERON:0002401	96.50	gold quality
spleen	UBERON:0002106	96.45	gold quality

Single-cell (SCXA)

Detected in 27 experiment(s), a significant marker in 26.

Experiment	Marker?	Max mean expression
E-GEOD-114530	yes	6395.06
E-GEOD-124472	yes	2152.82
E-MTAB-9221	yes	1219.46
E-HCAD-10	yes	1185.82
E-GEOD-149689	yes	1061.57
E-MTAB-6653	yes	997.50
E-MTAB-7381	yes	626.70
E-MTAB-6701	yes	70.00
E-CURD-122	yes	67.38
E-HCAD-4	yes	58.40
E-MTAB-8410	yes	52.55
E-MTAB-6678	yes	42.46
E-MTAB-9467	yes	40.38
E-GEOD-135922	yes	39.39
E-GEOD-84465	yes	36.71

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

51 targets.

Target	Regulation
ACAN
BRF1
C1QA	Activation
CCL2
CCND2	Unknown
CD5L	Activation
CDKN2A
CDX1
CEL
CRYAA
CRYAB	Activation
CRYGD
CSNK2A2
ERVW-4
FBP1
GCG	Activation
HJV
HOXA3	Unknown
HOXB1	Unknown
HOXB3	Unknown
IFNA1	Activation
IFNB1	Activation
IL7R
INS	Activation
MAF
MAFA	Unknown
MAFB
MAPK1
MMP12	Activation
MMP13

Upstream regulators (CollecTRI, top): CDX1, CEBPB, MAFB, MYB, MYOD1, RARA, STAT3, TFE3

miRNA regulators (miRDB)

161 targeting MAFB, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-3667-3P	99.99	67.17	1636
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-485-3P	99.98	70.68	1585
HSA-MIR-539-3P	99.98	70.74	1616
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-1229-3P	99.97	66.49	906
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-1468-3P	99.96	72.74	3797

Functional genomics

ClinGen dosage: haploinsufficiency 0 (no evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 40)

• strong proliferative signals mediated by T-cell activation and interleukins (IL-4 and IL-12) downregulate the mafB messenger RNA transcript level when resting naive CD4+ T-helper cells enter the differentiation pathway in vitro. (PMID:12542795)
• Our data show that human monocytes, but not neutrophils, macrophages, dendritic or natural killer cells, downregulate the expression of Mac-1 after overnight exposure to surface-bound IgG. (PMID:12542796)
• novel role for MafB as a regulator of ERK-induced gene expression (PMID:15121870)
• Low-density lipoprotein receptor-related protein intracellular domain co-localizes with MafB to the nucleus and negatively regulates its transcriptional activity (PMID:15135046)
• high PU.1 activity favors dendritic cells at the expense of macrophage fate by inhibiting expression and activity of the macrophage factor MafB. (PMID:15598817)
• MafB is a key regulator of monocytopoiesis (PMID:16456583)
• Microarray analysis of Dupuytren’s disease tissue has identified significant upregulated gene expression of MafB (PMID:16473681)
• MafB may be a prognostic marker in the risk stratification of MM patients. (PMID:18830254)
• the vitamin D(3)/Hox-A10 pathway supports MafB function during the induction of monocyte differentiation. (PMID:18832725)
• Identification of primary MAFB target genes in multiple myeloma (PMID:19013005)
• identified a Tfe3-binding site (EBox) in the MAFB promoter region (PMID:19332055)
• Both OH-2 and primary cells have a complex secondary translocation in which the IGK 3’ enhancer is inserted between MYC and MAFB, resulting in dysregulation of both oncogenes (PMID:19395026)
• Expression studies support a role for MAFB in palatal development. (PMID:20436469)
• These results suggest a suppressive effect of HBZ on Maf function, which may have a significant role in HTLV-1 related pathogenesis. (PMID:20506502)
• MafB acts as a metastable switch to control expression of IFN-beta. (PMID:20581830)
• MafB expression was higher in smokers with airflow limitation than in smokers without airflow limitation. (PMID:20969674)
• Abnormal expression of maf-b correlates with abnormal proliferation of acute myeloid leukemia cells. (PMID:21129249)
• An association of ABCA4 and MAFB with non-syndromic cleft lip with or without cleft palate. (PMID:21567910)
• findings confirmed the contribution of MAFB in the etiology of nonsyndromic orofacial clefts (PMID:21834038)
• The homozygous kreisler mutation eliminates most of rhombomere 5 and mis-specifies rhombomere 6, abolishes an early decrease in respiratory frequency within 10 min of hypoxia and an intrinsic hypoxic activation. (PMID:21839147)
• Identified previously unreported missense mutations clustering within a 51 base pair region of the single exon of MAFB, validated by Sanger sequencing. (PMID:22387013)
• MAFB gene suggest a role for the development of orofacial clefting in hispanic population. (PMID:22753311)
• the haematopoietic progenitor population can be the target for transformation in MafB-associated plasma cell neoplasias (PMID:22903061)
• miR-148a directly targeted MAFB mRNA by binding to the 3’ untranslated region (3’UTR) and repressed MAFB protein expression (PMID:23225151)
• MAFA, MAFB, NKX6.1, and PDX1 activity provides a gauge of islet beta cell function, with loss of MAFA (and/or MAFB) representing an early indicator of beta cell inactivity (PMID:23863625)
• We identified MAFB mutations in all, including three novel missense mutations clustering within the hot spot mutation region (PMID:23956186)
• Mafb is responsible for executing one branch of the SGN differentiation program orchestrated by the Gata3 transcriptional network (PMID:24327562)
• data support the existence of a signaling cascade by which stimulation of macrophages with the IL-10 cytokine determines a sequential activation of STAT3 and MafB transcription factors (PMID:24472656)
• rs6065259 was the most important single nucleotide polymorphism in MAFB (OR6065259-AA=0.45; 95% CI: 0.28 to 0.71; p=0.0027), followed by rs13041247; no association was found between rs11696257 and NSCLP. (PMID:24972815)
• These findings indicate that only a few transactivation domain-specific mutations within MAFB cause multicentric carpotarsal osteolysis. (PMID:24989131)
• DNMT3A R882 mutation is associated with elevated expression of MAFB and M4/M5 immunophenotype of acute myeloid leukemia blasts. (PMID:25721756)
• Gata3 interacted with Gcm2 and MafB, two known transcriptional regulators of parathyroid development, and synergistically stimulated the PTH promoter. (PMID:25917456)
• MiR-223 negatively regulates the growth and migration of NPC cells via reducing MAFB expression, and this finding provides a novel insight into understanding miR-223 regulation mechanism in nasopharyngeal carcinoma tumorigenesis. (PMID:26055874)
• MAFB is a regulator and a marker of adipose tissue inflammation, a process that subsequently causes insulin resistance (PMID:26115698)
• The rs2902940A allele carriers in the MAFB conferred a decreased serum ApoAI level in controls and an increased risk of coronary artery disease and ischemic stroke. (PMID:26204962)
• MAFB represents a unique signature and likely important regulator of the primate islet beta-cell. (PMID:26554594)
• Epidermal differentiation gene regulatory networks are controlled by MAF and MAFB. (PMID:27097296)
• Loss of MAFB Function Causes Duane Syndrome, Aberrant Extraocular Muscle Innervation, and Inner-Ear Defects. (PMID:27181683)
• Results indicate a hepatocellular carcinoma (HCC) regulatory pathway involving MafB transcription factor and cyclin D1, the dysfunction of which drives proliferative character in HCC. (PMID:27448450)
• Data suggest that SUMOylated MAFB promotes colorectal cancer tumorigenesis through cell cycle regulation. (PMID:27829226)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	mafba	ENSDARG00000017121
mus_musculus	Mafb	ENSMUSG00000074622
rattus_norvegicus	Mafb	ENSRNOG00000016037
drosophila_melanogaster	tj	FBGN0000964
drosophila_melanogaster	maf-S	FBGN0034534
caenorhabditis_elegans	maf-1	WBGENE00077521

Paralogs (6): NRL (ENSG00000129535), MAF (ENSG00000178573), MAFA (ENSG00000182759), MAFF (ENSG00000185022), MAFG (ENSG00000197063), MAFK (ENSG00000198517)

Protein

Protein identifiers

Transcription factor MafB — Q9Y5Q3 (reviewed: Q9Y5Q3)

Alternative names: V-maf musculoaponeurotic fibrosarcoma oncogene homolog B

All UniProt accessions (1): Q9Y5Q3

UniProt curated annotations — full annotation on UniProt →

Function. Acts as a transcriptional activator or repressor. 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. Involved either as an oncogene or as a tumor suppressor, depending on the cell context. Required for the transcriptional activation of HOXB3 in the rhombomere r5 in the hindbrain.

Subunit / interactions. Homodimer or heterodimer with other bHLH-Zip transcription factors. Binds DNA as a homodimer or a heterodimer. Forms homodimers and heterodimers with FOS, FOSB and FOSL2, but not with JUN proteins (JUN, JUNB and JUND). Interacts with PAX6; the interaction is direct. Interacts with ETS1 and LRP1. Interacts with the intracellular cytoplasmic domain of LRP1 (LRPICD); the interaction results in a moderate reduction of MAFB transcriptional potential.

Subcellular location. Nucleus.

Tissue specificity. Ubiquitous.

Post-translational modifications. Phosphorylated by GSK3 and MAPK13 on serine and threonine residues. Sumoylated. Sumoylation on Lys-32 and Lys-297 stimulates its transcriptional repression activity and promotes macrophage differentiation from myeloid progenitors.

Disease relevance. 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. Intellectual disability and minor facial anomalies have been noted in some patients. The disease is caused by variants affecting the gene represented in this entry. 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. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. The leucine-zipper domain is involved in the interaction with LRPICD.

Similarity. Belongs to the bZIP family. Maf subfamily.

RefSeq proteins (1): NP_005452* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004826	bZIP_Maf	Domain
IPR004827	bZIP	Domain
IPR008917	TF_DNA-bd_sf	Homologous_superfamily
IPR013592	Maf_TF_N	Domain
IPR024874	Transcription_factor_Maf_fam	Family
IPR046347	bZIP_sf	Homologous_superfamily

Pfam: PF03131, PF08383

UniProt features (25 total): sequence variant 10, compositionally biased region 5, region of interest 4, cross-link 2, sequence conflict 2, chain 1, domain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9Y5Q3-F1	63.87	0.31

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (2): 32, 297

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-5617472	Activation of anterior HOX genes in hindbrain development during early embryogenesis
R-HSA-1266738	Developmental Biology
R-HSA-5619507	Activation of HOX genes during differentiation

MSigDB gene sets: 683 (showing top): GOBP_MYELOID_CELL_DIFFERENTIATION, GSE45365_NK_CELL_VS_CD11B_DC_DN, GSE45365_NK_CELL_VS_CD8A_DC_UP, TGGTGCT_MIR29A_MIR29B_MIR29C, GOBP_HINDBRAIN_DEVELOPMENT, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_NEGATIVE_REGULATION_OF_CELL_DEVELOPMENT, TAATAAT_MIR126, GOBP_RESPIRATORY_GASEOUS_EXCHANGE_BY_RESPIRATORY_SYSTEM, GOBP_REGULATION_OF_OSTEOCLAST_DIFFERENTIATION, BENPORATH_ES_WITH_H3K27ME3, GOBP_MYELOID_CELL_HOMEOSTASIS, GOBP_MEMBRANE_BIOGENESIS, PEREZ_TP63_TARGETS

GO Biological Process (26): negative regulation of transcription by RNA polymerase II (GO:0000122), in utero embryonic development (GO:0001701), regulation of DNA-templated transcription (GO:0006355), regulation of transcription by RNA polymerase II (GO:0006357), segment specification (GO:0007379), sensory organ development (GO:0007423), response to nutrient (GO:0007584), respiratory gaseous exchange by respiratory system (GO:0007585), protein processing (GO:0016485), rhombomere 5 development (GO:0021571), rhombomere 6 development (GO:0021572), abducens nerve formation (GO:0021599), keratinocyte differentiation (GO:0030216), T cell differentiation in thymus (GO:0033077), brain segmentation (GO:0035284), inner ear morphogenesis (GO:0042472), fat cell differentiation (GO:0045444), regulation of myeloid cell differentiation (GO:0045637), negative regulation of erythrocyte differentiation (GO:0045647), negative regulation of osteoclast differentiation (GO:0045671), positive regulation of DNA-templated transcription (GO:0045893), thymus development (GO:0048538), integrated stress response signaling (GO:0140467), cornified envelope assembly (GO:1903575), gene expression (GO:0010467), positive regulation of transcription by RNA polymerase II (GO:0045944)

GO Molecular Function (10): RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), DNA-binding transcription activator activity, RNA polymerase II-specific (GO:0001228), identical protein binding (GO:0042802), sequence-specific DNA binding (GO:0043565), protein-containing complex binding (GO:0044877), DNA binding (GO:0003677), DNA-binding transcription factor activity (GO:0003700), protein binding (GO:0005515), sequence-specific double-stranded DNA binding (GO:1990837)

GO Cellular Component (4): chromatin (GO:0000785), nucleus (GO:0005634), RNA polymerase II transcription regulator complex (GO:0090575), transcription regulator complex (GO:0005667)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Activation of HOX genes during differentiation	1
Developmental Biology	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
RNA polymerase II transcription regulatory region sequence-specific DNA binding	3
regulation of transcription by RNA polymerase II	2
transcription by RNA polymerase II	2
regulation of DNA-templated transcription	2
segmentation	2
rhombomere development	2
binding	2
negative regulation of DNA-templated transcription	1
chordate embryonic development	1
DNA-templated transcription	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
pattern specification process	1
animal organ development	1
response to nutrient levels	1
response to chemical	1
multicellular organismal process	1
proteolysis	1
protein maturation	1
abducens nerve morphogenesis	1
cranial nerve formation	1
epidermal cell differentiation	1
skin development	1
T cell differentiation	1
brain development	1
central nervous system segmentation	1
ear morphogenesis	1
embryonic morphogenesis	1
inner ear development	1
cell differentiation	1
myeloid cell differentiation	1
regulation of hemopoiesis	1
erythrocyte differentiation	1
negative regulation of myeloid cell differentiation	1
regulation of erythrocyte differentiation	1
negative regulation of myeloid leukocyte differentiation	1
osteoclast differentiation	1
regulation of osteoclast differentiation	1
cis-regulatory region sequence-specific DNA binding	1
chromatin	1

Protein interactions and networks

STRING

2370 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MAFB	FOS	P01100	955
MAFB	JUN	P05412	905
MAFB	ETS1	P14921	870
MAFB	NKX6-1	P78426	814
MAFB	IRF6	O14896	805
MAFB	CCND3	P30281	747
MAFB	IRF8	Q02556	746
MAFB	SPI1	P17947	717
MAFB	DEPTOR	Q8TB45	708
MAFB	WNT5B	Q9H1J7	707
MAFB	IGHV4-38-2	P0DP08	694
MAFB	NKX6-2	Q9C056	676
MAFB	TESC	Q96BS2	665
MAFB	NSD2	O96028	665
MAFB	CCND2	P30279	657

IntAct

46 interactions, top by confidence:

A	B	Type	Score
CREBBP	IRF3	psi-mi:“MI:0914”(association)	0.930
BACH1	MAFG	psi-mi:“MI:0914”(association)	0.870
MAFB	BACH1	psi-mi:“MI:0407”(direct interaction)	0.750
BACH1	MAFB	psi-mi:“MI:0407”(direct interaction)	0.750
MAFB	BACH1	psi-mi:“MI:0915”(physical association)	0.750
MAFB	MAFB	psi-mi:“MI:0407”(direct interaction)	0.710
MAFB	MAFB	psi-mi:“MI:0915”(physical association)	0.710
FOS	MAFB	psi-mi:“MI:0407”(direct interaction)	0.620
MAF	MAFB	psi-mi:“MI:0407”(direct interaction)	0.620
MAFB	MAF	psi-mi:“MI:0407”(direct interaction)	0.620
MAFB	HBZ	psi-mi:“MI:0407”(direct interaction)	0.560
HBZ	MAFB	psi-mi:“MI:0407”(direct interaction)	0.560
KRTAP4-2	MAFB	psi-mi:“MI:0915”(physical association)	0.560
MAFB	IRF3	psi-mi:“MI:0915”(physical association)	0.560
IRF3	MAFB	psi-mi:“MI:0915”(physical association)	0.560
IRF3	MAFB	psi-mi:“MI:0403”(colocalization)	0.560
ATF3	MAFB	psi-mi:“MI:0407”(direct interaction)	0.440
FOSL2	MAFB	psi-mi:“MI:0407”(direct interaction)	0.440
NFE2L1	MAFB	psi-mi:“MI:0407”(direct interaction)	0.440
MAFB	ATF4	psi-mi:“MI:0407”(direct interaction)	0.440
MAFB		psi-mi:“MI:0915”(physical association)	0.400
IRF7	MAFB	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (255): NCOA6 (Affinity Capture-Western), KDM6A (Affinity Capture-Western), RBBP5 (Affinity Capture-Western), KAT2B (Affinity Capture-Western), PAX6 (Affinity Capture-Western), ISL1 (Affinity Capture-Western), MAFB (Two-hybrid), USP5 (Affinity Capture-Western), MAFB (Two-hybrid), MAFB (Affinity Capture-MS), KRTAP4-2 (Two-hybrid), LRPPRC (Affinity Capture-MS), DHX30 (Affinity Capture-MS), MYBBP1A (Affinity Capture-MS), YTHDC2 (Affinity Capture-MS)

ESM2 similar proteins: A3KMR8, A7Z017, B3DM47, B4R090, D3ZNT6, O35317, O35984, O42290, O57342, O75030, O75444, P10083, P23091, P25932, P40424, P40425, P40426, P41778, P54841, P54842, P54843, P54844, P56224, P57102, P61295, P61296, P79745, P79746, Q05192, Q0V9K1, Q27350, Q2PFS4, Q32NP8, Q4U1U2, Q504L8, Q61039, Q6DE84, Q6PFG8, Q789F3, Q7RTU3

Diamond homologs: A3KMR8, A5PJV0, A7YY73, A7Z017, D3ZNT6, O15525, O42290, O54790, O54791, O57342, O60675, O75444, P23091, P54841, P54842, P54843, P54844, P54845, P54846, Q0V9K1, Q2PFS4, Q4U1U2, Q504L8, Q61827, Q6DE84, Q76MX4, Q789F3, Q8CF90, Q8NHW3, Q90370, Q90595, Q90596, Q90888, Q90889, Q98UK4, Q98UK5, Q9ULX9, Q9Y5Q3

SIGNOR signaling

6 interactions.

A	Effect	B	Mechanism
GSK3A	up-regulates	MAFB	phosphorylation
GSK3A	down-regulates	MAFB	phosphorylation
GSK3B	up-regulates	MAFB	phosphorylation
GSK3B	down-regulates	MAFB	phosphorylation
HOXD12	“down-regulates activity”	MAFB	binding
PRRX1	“down-regulates activity”	MAFB	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 23 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Nuclear events mediated by NFE2L2	5	93.3×	3e-07
Cellular response to chemical stress	5	39.6×	7e-06
KEAP1-NFE2L2 pathway	5	33.4×	1e-05
Cellular responses to stress	6	12.3×	1e-04
Cellular responses to stimuli	6	10.5×	3e-04

GO biological processes:

GO term	Partners	Fold	FDR
positive regulation of gene expression	6	10.6×	6e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

230 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	16
Likely pathogenic	8
Uncertain significance	146
Likely benign	23
Benign	20

Top pathogenic / likely-pathogenic (24)

Variant ID	HGVS	Classification
1386827	NC_000020.10:g.(?39316519)(39317490_?)del	Pathogenic
2031466	NM_005461.5(MAFB):c.187C>T (p.Pro63Ser)	Pathogenic
224626	NM_005461.5(MAFB):c.440del (p.Gly147fs)	Pathogenic
224627	NM_005461.5(MAFB):c.644del (p.Gln215fs)	Pathogenic
224628	NM_005461.5(MAFB):c.803del (p.Asn268fs)	Pathogenic
224629	NC_000020.11:g.(?40687489)(40688460_?)del	Pathogenic
2634426	NM_005461.5(MAFB):c.188C>T (p.Pro63Leu)	Pathogenic
30768	NM_005461.5(MAFB):c.184A>C (p.Thr62Pro)	Pathogenic
30769	NM_005461.5(MAFB):c.208T>G (p.Ser70Ala)	Pathogenic
30771	NM_005461.5(MAFB):c.211C>T (p.Pro71Ser)	Pathogenic
30772	NM_005461.5(MAFB):c.212C>T (p.Pro71Leu)	Pathogenic
30773	NM_005461.5(MAFB):c.161C>T (p.Ser54Leu)	Pathogenic
4624155	NM_005461.5(MAFB):c.509C>A (p.Ser170Ter)	Pathogenic
504138	NM_005461.5(MAFB):c.135del (p.Cys46fs)	Pathogenic
803608	NM_005461.5(MAFB):c.185C>T (p.Thr62Ile)	Pathogenic
807627	NM_005461.5(MAFB):c.184A>G (p.Thr62Ala)	Pathogenic
2501713	NM_005461.5(MAFB):c.203C>T (p.Pro68Leu)	Likely pathogenic
2575898	NM_005461.5(MAFB):c.11A>G (p.Glu4Gly)	Likely pathogenic
2630087	NM_005461.5(MAFB):c.745C>G (p.Arg249Gly)	Likely pathogenic
2685646	GRCh37/hg19 20q12(chr20:39294079-39611802)x1	Likely pathogenic
3234800	NM_005461.5(MAFB):c.781C>T (p.Gln261Ter)	Likely pathogenic
3235198	NM_005461.5(MAFB):c.176C>G (p.Pro59Arg)	Likely pathogenic
684763	NM_005461.5(MAFB):c.173C>G (p.Thr58Arg)	Likely pathogenic
813951	NM_005461.5(MAFB):c.197C>T (p.Ser66Phe)	Likely pathogenic

SpliceAI

15 predictions. Top by Δscore:

Variant	Effect	Δscore
20:40687962:TG:T	donor_gain	0.7800
20:40687929:C:CA	donor_gain	0.3500
20:40687881:A:AC	donor_gain	0.3400
20:40687882:C:CC	donor_gain	0.3400
20:40686830:C:CC	acceptor_gain	0.3200
20:40687608:G:GT	acceptor_gain	0.3100
20:40687514:C:CT	acceptor_gain	0.2800
20:40686829:A:AC	acceptor_gain	0.2700
20:40687883:A:C	donor_gain	0.2700
20:40689193:CG:C	donor_gain	0.2700
20:40687592:G:GA	acceptor_gain	0.2600
20:40687593:A:AA	acceptor_gain	0.2600
20:40689193:CGCT:C	donor_gain	0.2300
20:40688003:T:TA	donor_gain	0.2100
20:40687591:G:GC	acceptor_gain	0.2000

AlphaMissense

2133 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
20:40687966:C:A	K295N	1.000
20:40687966:C:G	K295N	1.000
20:40687971:A:C	Y294D	1.000
20:40687978:T:A	R291S	1.000
20:40687978:T:G	R291S	1.000
20:40687991:A:G	L287P	1.000
20:40688012:A:G	L280P	1.000
20:40688024:T:G	Q276P	1.000
20:40688033:A:G	L273P	1.000
20:40688054:A:G	L266P	1.000
20:40688062:C:A	K263N	1.000
20:40688062:C:G	K263N	1.000
20:40688066:T:G	Q262P	1.000
20:40688072:A:T	V260D	1.000
20:40688075:C:G	R259P	1.000
20:40688076:G:A	R259C	1.000
20:40688076:G:T	R259S	1.000
20:40688077:T:A	K258N	1.000
20:40688077:T:G	K258N	1.000
20:40688078:T:A	K258I	1.000
20:40688079:T:C	K258E	1.000
20:40688083:C:A	R256S	1.000
20:40688083:C:G	R256S	1.000
20:40688084:C:A	R256M	1.000
20:40688084:C:G	R256T	1.000
20:40688084:C:T	R256K	1.000
20:40688085:T:A	R256W	1.000
20:40688085:T:C	R256G	1.000
20:40688086:G:C	C255W	1.000
20:40688087:C:A	C255F	1.000

dbSNP variants (sampled 300 via entrez): RS1000122958 (20:40686137 A>T), RS1000373269 (20:40690784 G>A), RS1000640684 (20:40689442 C>A,T), RS1001260996 (20:40690347 G>T), RS1002016916 (20:40685690 A>G), RS1002446542 (20:40686029 C>A,T), RS1002460743 (20:40690146 C>A), RS1002937853 (20:40689406 C>T), RS1003467280 (20:40689156 A>C), RS1003582284 (20:40689340 G>C), RS1003682274 (20:40688276 G>C,T), RS1003843739 (20:40685747 C>T), RS1003982118 (20:40689703 T>G), RS1004162622 (20:40686036 T>G), RS1004444703 (20:40685452 G>A)

Disease associations

OMIM: gene MIM:608968 | disease phenotypes: MIM:166300, MIM:617041, MIM:604356, MIM:126800, MIM:119530, MIM:616407, MIM:250620

GenCC curated gene-disease

Disease	Classification	Inheritance
multicentric carpo-tarsal osteolysis with or without nephropathy	Definitive	Autosomal dominant
Duane retraction syndrome 3 with or without deafness	Strong	Autosomal dominant
Duane retraction syndrome	Supportive	Autosomal dominant

Mondo (9): multicentric carpo-tarsal osteolysis with or without nephropathy (MONDO:0008152), Duane retraction syndrome 3 with or without deafness (MONDO:0014880), Duane retraction syndrome 2 (MONDO:0011444), Duane syndrome type 1 (MONDO:0024265), orofacial cleft 1 (MONDO:0007335), Brown syndrome (MONDO:0014624), intellectual disability (MONDO:0001071), 3-hydroxyisobutyryl-CoA hydrolase deficiency (MONDO:0009603), Duane retraction syndrome (MONDO:0007473)

Orphanet (4): Duane retraction syndrome (Orphanet:233), Multicentric carpo-tarsal osteolysis with or without nephropathy (Orphanet:2774), Neurodegeneration due to 3-hydroxyisobutyryl-CoA hydrolase deficiency (Orphanet:88639), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

106 total (30 of 106 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000083	Renal insufficiency
HP:0000086	Ectopic kidney
HP:0000093	Proteinuria
HP:0000112	Nephropathy
HP:0000175	Cleft palate
HP:0000232	Everted lower lip vermilion
HP:0000252	Microcephaly
HP:0000324	Facial asymmetry
HP:0000325	Triangular face
HP:0000327	Hypoplasia of the maxilla
HP:0000347	Micrognathia
HP:0000365	Hearing impairment
HP:0000377	Abnormal pinna morphology
HP:0000384	Preauricular skin tag
HP:0000402	Stenosis of the external auditory canal
HP:0000407	Sensorineural hearing impairment
HP:0000431	Wide nasal bridge
HP:0000463	Anteverted nares
HP:0000465	Webbed neck
HP:0000470	Short neck
HP:0000482	Microcornea
HP:0000486	Strabismus
HP:0000490	Deeply set eye
HP:0000496	Abnormality of eye movement
HP:0000506	Telecanthus
HP:0000508	Ptosis
HP:0000520	Proptosis
HP:0000526	Aniridia
HP:0000542	Impaired ocular adduction

GWAS associations

46 associations (top):

Study	Trait	p-value
GCST000211_8	Response to TNF antagonist treatment	2.000000e-07
GCST000287_6	LDL cholesterol	4.000000e-09
GCST000759_32	LDL cholesterol	1.000000e-08
GCST000760_44	Cholesterol, total	6.000000e-11
GCST000942_2	Drug-induced Stevens-Johnson syndrome or toxic epidermal necrolysis (SJS/TEN)	1.000000e-06
GCST001144_11	Dupuytren’s disease	8.000000e-10
GCST001762_147	Obesity-related traits	6.000000e-06
GCST002221_66	Cholesterol, total	9.000000e-10
GCST002222_37	LDL cholesterol	2.000000e-11
GCST002647_171	Height	2.000000e-08
GCST002811_5	Nonsyndromic cleft lip with or without cleft palate	2.000000e-11
GCST002896_20	Cholesterol, total	2.000000e-15
GCST002898_17	LDL cholesterol	4.000000e-16
GCST003075_65	Cognitive decline rate in late mild cognitive impairment	5.000000e-07
GCST003075_78	Cognitive decline rate in late mild cognitive impairment	1.000000e-06
GCST004166_54	Nonsyndromic cleft lip with cleft palate	9.000000e-12
GCST004233_37	LDL cholesterol levels	2.000000e-34
GCST004233_64	LDL cholesterol levels	3.000000e-06
GCST004251_2	Paneth cell defects in Crohn’s disease	5.000000e-07
GCST004642_6	QT interval (ambient particulate matter interaction)	5.000000e-06
GCST004858_27	Dupuytren’s disease	2.000000e-18
GCST005146_21	Birth weight	4.000000e-10
GCST005348_43	Total body bone mineral density	4.000000e-08
GCST005989_33	Serum total protein levels	3.000000e-13
GCST006431_15	Plasma parathyroid hormone levels	2.000000e-06
GCST006444_16	Bone mineral density (hip)	6.000000e-06
GCST008362_41	Birth weight	1.000000e-19
GCST009357_3	Nonsyndromic cleft lip	2.000000e-17
GCST010243_172	Apolipoprotein B levels	3.000000e-54
GCST010243_52	Apolipoprotein B levels	2.000000e-08

EFO canonical traits (19, from GWAS)

EFO ID	Trait name
EFO:0004653	response to TNF antagonist
EFO:0004611	low density lipoprotein cholesterol measurement
EFO:0004574	total cholesterol measurement
EFO:0004229	Dupuytren Contracture
EFO:0004908	testosterone measurement
EFO:0003959	cleft lip
EFO:0007710	cognitive decline measurement
EFO:0007963	abnormal paneth cell measurement
EFO:0004682	QT interval
EFO:0008255	particulate matter air pollution measurement
EFO:0004344	birth weight
EFO:0007702	hip bone mineral density
EFO:0004615	apolipoprotein B measurement
EFO:0004530	triglyceride measurement
EFO:0004459	ferritin measurement
EFO:0004305	erythrocyte count
EFO:0004736	aspartate aminotransferase measurement
EFO:0004533	alkaline phosphatase measurement
EFO:0007788	BMI-adjusted waist-hip ratio

MeSH disease descriptors (5)

Descriptor	Name	Tree numbers
D004370	Duane Retraction Syndrome	C10.292.562.700.375.500; C11.270.235; C11.590.436.400.500; C16.320.290.235
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
C562803	Beta-Hydroxyisobutyryl CoA Deacylase Deficiency (supp.)
C566121	Orofacial Cleft 1 (supp.)
C567171	Osteolysis, Hereditary, Of Carpal Bones With Or Without Nephropathy (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

PharmGKB clinical annotations

2 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs6028945	Efficacy	3	Tumor necrosis factor alpha (TNF-alpha) inhibitors	Rheumatoid arthritis
rs6071980	Efficacy	3	Tumor necrosis factor alpha (TNF-alpha) inhibitors	Rheumatoid arthritis

PharmGKB variants

2 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs6028945	MAFB	3	2.75	1	Tumor necrosis factor alpha (TNF-alpha) inhibitors
rs6071980	MAFB	3	2.25	1	Tumor necrosis factor alpha (TNF-alpha) inhibitors

CTD chemical–gene interactions

92 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression, decreases methylation, increases expression	5
trichostatin A	decreases reaction, affects cotreatment, increases expression, affects expression	4
Tretinoin	decreases expression, increases expression	4
Acetaminophen	affects expression, decreases expression, increases expression	3
Tetrachlorodibenzodioxin	affects expression, decreases expression	3
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression, increases expression	3
Aflatoxin B1	increases expression, decreases expression	3
methylmercuric chloride	decreases expression, increases expression	2
sodium arsenite	increases expression	2
dinophysistoxin 1	increases expression	2
bisphenol S	decreases expression, increases expression	2
Benzo(a)pyrene	affects methylation, increases expression, increases methylation	2
Calcitriol	decreases expression, increases expression	2
Cisplatin	affects reaction, increases expression, affects cotreatment	2
Copper	affects binding, increases expression, decreases expression	2
Formaldehyde	increases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Genistein	increases expression	2
aristolochic acid I	increases expression	1
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
Esketamine	increases expression	1
urushiol	decreases expression	1
triphenyl phosphate	affects expression	1
propionaldehyde	increases expression	1
pirinixic acid	increases activity, affects binding, decreases expression	1
bisphenol A	increases expression	1
lead acetate	decreases expression	1
sodium arsenate	decreases expression, increases abundance	1
2-methyl-4-isothiazolin-3-one	increases expression	1
hydroxyhydroquinone	increases expression	1

Cellosaurus cell lines

1 cell lines: 1 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_A5MF	GM28026	Transformed cell line	Female

Clinical trials (associated diseases)

198 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT05657860	PHASE4	COMPLETED	Guanfacine Extended Release for the Reduction of Aggression and Self-injurious Behavior Associated With Prader-Willi Syndrome
NCT05744479	PHASE4	RECRUITING	Metformin for Antipsychotic-induced Weight Gain in Adults With Intellectual Disability
NCT06107829	PHASE4	WITHDRAWN	Valbenazine Treatment of Tardive Dyskinesia in Adults With Intellectual/Developmental Disabilities
NCT06997198	PHASE4	NOT_YET_RECRUITING	Deutetrabenazine Treatment for Tardive Dyskinesia in Intellectual/Developmental Disabilities
NCT02270736	PHASE3	COMPLETED	Clinical Study to Investigate the Efficacy and Safety of NT 201 Compared to Placebo in the Treatment of Chronic Troublesome Drooling Associated With Neurological Disorders and/or Intellectual Disability
NCT02304302	PHASE2	COMPLETED	Down Syndrome Memantine Follow-up Study
NCT03862950	PHASE2	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome (Met)
NCT04529226	PHASE2	UNKNOWN	Study to Compare Clozapine vs Treatment as Usual in People With Intellectual Disability & Treatment-resistant Psychosis
NCT04821856	PHASE2	COMPLETED	Evaluation of the Effectiveness of Cannabidiol in Treating Severe Behavioural Problems in Children and Adolescents With Intellectual Disability
NCT05273320	PHASE1	COMPLETED	Clinical Trial of Nabilone for Aggression in Adults With Intellectual and Developmental Disabilities
NCT05301361	PHASE1	ENROLLING_BY_INVITATION	Sensitivity of the NIH Toolbox to Stimulant Treatment in Intellectual Disabilities
NCT06016764	PHASE1	COMPLETED	Use of MRI and cTBS for Catatonia in Autism
NCT06586827	PHASE1	COMPLETED	Impact of Competency-Based Training and Technical Assistance Employment Outcomes of Individuals With ID/DD
NCT07531940	PHASE1	NOT_YET_RECRUITING	Escalating Doses of Memantine in Down Syndrome (MEDS-123)
NCT03059420	Not specified	RECRUITING	Genetic Studies of Strabismus, Congenital Cranial Dysinnervation Disorders (CCDDs), and Their Associated Anomalies
NCT03479476	PHASE2/PHASE3	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome
NCT02616796	PHASE1/PHASE2	COMPLETED	Effects of Social Gaze Training on Brain and Behavior in Fragile X Syndrome
NCT06860672	EARLY_PHASE1	RECRUITING	Clinical Trial of the Dual Vector Base Editor for the Treatment of the CHD3-R1025W Mutation
NCT00597948	Not specified	COMPLETED	Healthy Lifestyles for People With Intellectual Disabilities
NCT01087320	Not specified	RECRUITING	Genome Medical Sequencing for Gene Discovery
NCT01652963	Not specified	UNKNOWN	Picture-based Computerised Assessment and Training of Cognitive Behaviour Therapy Skills
NCT01695395	Not specified	COMPLETED	Mental Health Care Provision for Adults With Intellectual Disability and a Mental Disorder
NCT01867554	Not specified	COMPLETED	Research and Characterization of New Genes Involved in Intellectual Disability
NCT01915381	Not specified	COMPLETED	Improving Adherence Healthy Lifestyle With a Smartphone Application Based on Adults With Intellectual Disabilities
NCT01988623	Not specified	COMPLETED	Pivotal Response Treatment for Individuals With Intellectual Disabilities
NCT02099773	Not specified	COMPLETED	Support Staff-client Interactions With Augmentative and Alternative Communication
NCT02136849	Not specified	COMPLETED	Inter-regional Project of the Great Western Exploration Approach for Exome Molecular Causes Severe Intellectual Disability Isolated or Syndromic
NCT02225041	Not specified	COMPLETED	Sedation Strategy and Cognitive Outcome After Critical Illness in Early Childhood
NCT02414438	Not specified	COMPLETED	Establishing the Clinical Utility of First StepDx PLUS and NextStepDx PLUS Study
NCT02451761	Not specified	COMPLETED	Apparently Balanced Chromosomal Translocation/ Next-generation Sequencing/ Intellectual Disability
NCT02461420	Not specified	ACTIVE_NOT_RECRUITING	Mapping the Genotype, Phenotype, and Natural History of Phelan-McDermid Syndrome
NCT02461459	Not specified	ACTIVE_NOT_RECRUITING	Autism Spectrum Disorder (ASD) and Intellectual Disability (ID) Determinants in Tuberous Sclerosis Complex (TSC)
NCT02486081	Not specified	COMPLETED	Development and Application-Smart Football for Movement Evaluation and Training in the Special Education Population
NCT02504502	Not specified	COMPLETED	Enhancing Genomic Laboratory Reports to Enhance Communication and Empower Patients
NCT02513277	Not specified	COMPLETED	Diabetes Screening & Prevention for People With Learning (Intellectual) Disabilities:STOP Diabetes Study
NCT02561754	Not specified	COMPLETED	Weight Management for Adolescents With IDD
NCT02591446	Not specified	COMPLETED	Transcranial Magnetic Stimulation Studies in Autism Spectrum Disorders
NCT02714868	Not specified	COMPLETED	Evaluation of Project TEAM (Teens Making Environmental and Activity Modifications)
NCT02721394	Not specified	UNKNOWN	FCT With Young Children With ID in the UK: A Feasibility Project V.1
NCT02746614	Not specified	COMPLETED	Psychomotor Therapy Effects in Adaptive Behavior and Motor Proficiency in Intellectual Disability