MAFA

Summary

MAFA (MAF bZIP transcription factor A, HGNC:23145) is a protein-coding gene on chromosome 8q24.3, encoding Transcription factor MafA (Q8NHW3). Transcription factor that activates insulin gene expression.

MAFA is a transcription factor that binds RIPE3b, a conserved enhancer element that regulates pancreatic beta cell-specific expression of the insulin gene (INS; MIM 176730) (Olbrot et al., 2002 [PubMed 12011435]).

Source: NCBI Gene 389692 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 87 total — 1 pathogenic, 1 likely-pathogenic
• MANE Select transcript: NM_201589

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:23145
Approved symbol	MAFA
Name	MAF bZIP transcription factor A
Location	8q24.3
Locus type	gene with protein product
Status	Approved
Aliases	RIPE3b1, hMafA
Ensembl gene	ENSG00000182759
Ensembl biotype	protein_coding
OMIM	610303
Entrez	389692

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 1 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000333480, ENST00000528185

RefSeq mRNA: 1 — MANE Select: NM_201589 NM_201589

CCDS: CCDS34955

Canonical transcript exons

ENST00000333480 — 1 exons

Exon	Start	End
ENSE00001295451	143428064	143430732

Expression profiles

Bgee: expression breadth broad, 89 present calls, max score 89.68.

FANTOM5 (CAGE): breadth broad, TPM avg 0.5688 / max 114.2033, expressed in 225 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
95469	0.5688	225

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
quadriceps femoris	UBERON:0001377	89.68	gold quality
hindlimb stylopod muscle	UBERON:0004252	86.81	gold quality
gastrocnemius	UBERON:0001388	86.67	gold quality
skeletal muscle tissue	UBERON:0001134	85.25	gold quality
thymus	UBERON:0002370	84.89	silver quality
muscle of leg	UBERON:0001383	84.79	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	81.18	gold quality
islet of Langerhans	UBERON:0000006	80.83	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	77.05	silver quality
muscle tissue	UBERON:0002385	73.45	gold quality
cerebellar vermis	UBERON:0004720	67.75	gold quality
pancreas	UBERON:0001264	66.28	gold quality
right testis	UBERON:0004534	61.68	gold quality
testis	UBERON:0000473	61.14	gold quality
left testis	UBERON:0004533	60.85	gold quality
body of pancreas	UBERON:0001150	58.37	gold quality
placenta	UBERON:0001987	58.26	gold quality
mucosa of stomach	UBERON:0001199	58.00	gold quality
ganglionic eminence	UBERON:0004023	54.03	gold quality
apex of heart	UBERON:0002098	53.00	gold quality
popliteal artery	UBERON:0002250	51.73	gold quality
tibial artery	UBERON:0007610	51.71	gold quality
heart left ventricle	UBERON:0002084	50.95	gold quality
stromal cell of endometrium	CL:0002255	50.75	silver quality
ascending aorta	UBERON:0001496	50.38	gold quality
thoracic aorta	UBERON:0001515	50.38	gold quality
temporal lobe	UBERON:0001871	48.73	gold quality
amygdala	UBERON:0001876	48.59	gold quality
bone marrow cell	CL:0002092	48.45	gold quality
heart	UBERON:0000948	47.41	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-MTAB-5061	yes	151.16
E-GEOD-83139	yes	61.12
E-GEOD-81608	yes	26.18
E-ENAD-27	yes	18.53
E-ANND-3	no	1.08

Regulation

Is transcription factor: yes

JASPAR motifs

Motif	Name	Family
MA1521.1	MAFA	Maf-related
MA1521.2	MAFA	Maf-related

JASPAR matrix evidence (PMIDs): PMID:9571165

miRNA regulators (miRDB)

23 targeting MAFA, 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-3646	100.00	73.56	5283
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-6508-5P	99.92	70.67	2465
HSA-MIR-627-3P	99.90	71.42	3316
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-4271	99.88	68.32	2244
HSA-MIR-7978	99.86	66.90	856
HSA-MIR-8067	99.86	69.59	2260
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-5010-3P	99.83	70.60	2357
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-6883-5P	99.69	68.05	3785
HSA-MIR-1207-5P	99.49	69.11	2983
HSA-MIR-223-5P	99.24	68.82	1206
HSA-MIR-3978	99.24	68.39	2201
HSA-MIR-6809-5P	99.13	68.45	1223
HSA-MIR-4763-3P	99.10	67.83	2649
HSA-MIR-548Q	98.71	65.35	563
HSA-MIR-4299	98.28	66.96	850
HSA-MIR-4456	97.50	64.88	1678
HSA-MIR-548AO-3P	92.80	65.04	148
HSA-MIR-4707-5P	90.95	65.69	110

Literature-anchored findings (GeneRIF, showing 40)

• MafA selectively induces endogenous insulin transcription in non-beta cells (PMID:14973194)
• mafA has a role in regulating insulin gene expression in the liver (PMID:15664997)
• MafA plays a key role in coordinating and controlling the level of insulin gene expression in islet beta cells. (PMID:15665000)
• Co-expression and functional synergism of these beta-cell enriched transactivators, MafA, Pdx1, and Beta2, are critical for establishing the beta-cell-specific and efficient expression of the insulin gene. (PMID:15993959)
• Data show that FoxA2, Nkx2.2, and PDX-1 regulate islet beta-cell-specific mafA expression through conserved sequences located between base pairs -8118 and -7750 upstream from the transcription start site. (PMID:16847327)
• MafA has a critical role in islet beta-cell function (PMID:17636040)
• Transcriptional and transforming activities of MafA are positively regulated by GSK-3-mediated phosphorylation. (PMID:18042454)
• Under diabetic conditions, expression and/or activities of PDX-1 and MafA in beta-cells are reduced [REVIEW]. (PMID:18508668)
• Significance of large Maf proteins to Pdx1 expression in beta cells, and in particular MafB during pancreatic development. (PMID:18522939)
• Data suggest that a group of transcription factors, including MafA and Foxa2, regulate expression of two major autoantigens in type 1 diabetes, including islet-specific glucose-6-phosphatase catalytic subunit-related protein. (PMID:18753309)
• MafA levels are tightly controlled by the coordinated action of multiple kinase pathways (PMID:18948074)
• MafA plays a crucial role in pancreatic beta-cells and could be a novel therapeutic target for diabetes (PMID:19393272)
• p38 MAPK is a major regulator of MafA protein stability under oxidative stress (PMID:19407223)
• gene is unlikely to have a significant role in monogenic diabetes in humans (PMID:19573128)
• Data suggest that MafA plays a novel role in the reprogramming of stem cells into pancreatic beta-progenitors, promotes the islet-like characteristics of PDMSCs, as well as functionally regulation of blood glucose levels in transplanted grafts. (PMID:20158571)
• a novel relationship between the phosphoamino acid-rich transactivation and b-Zip domains in controlling MafA DNA-binding activity. (PMID:20208071)
• In addition to its expression in pancreatic beta cells, MafA also identifies the early ret-expressing sensory neurons in the dorsal root ganglia. (PMID:20213756)
• ATF2 interacts with beta-cell-enriched transcription factors, MafA, Pdx1, and beta2, and activates insulin gene transcription. (PMID:21278380)
• MafA transcription is upregulated in beta-cells acutely cultured in high glucose similar to what may occur in vivo under normoglycemic conditions. (PMID:21278484)
• Combined transfection of the three transcriptional factors, PDX-1, NeuroD1, and MafA, causes differentiation of bone marrow mesenchymal stem cells into insulin-producing cells (PMID:22761608)
• Beta cell nuclear MafA is markedly decreased in humans with type 2 diabetes, which may contribute to impaired beta cell dysfunction. (PMID:22847061)
• under oxidative and nonoxidative conditions p38 MAPK directly binds to MafA and triggers MafA degradation via ubiquitin proteasomal pathway. (PMID:23660596)
• 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)
• MAFA nuclear expression in pancreatic alpha and beta cells, and the percentage of alpha cells expressing PAX4 are altered in patients with type 2 diabetes. (PMID:24013263)
• Loss of MAFA expression is associated with insulinoma. (PMID:24157940)
• These findings demonstrate that regulation of monoamine levels by Mao activity in beta cells is pivotal for physiological insulin secretion and that loss of MaoB expression may contribute to the beta cell dysfunction in type 2 diabetes. (PMID:26546820)
• Pdx1 and MafA play crucial roles in the pancreas and maintain mature beta-cell function. Our results showed that the expression of Pdx1 and MafA were significantly upregulated after a sleeve gastrectomy for morbid obesity. (PMID:26781599)
• MAFA controls autonomic nervous system-mediated insulin secretion by activating the transcription of nicotinic (ChrnB2 and ChrnB4) receptor genes, which is impaired in patients with type 2 diabetes. (PMID:26904947)
• USP5 regulates c-Maf stability and multiple myeloma cell survival. (PMID:28933784)
• confirm the association of miR-204 with a beta cell endocrine phenotype in human pancreatic islets, but do not support its direct role in regulating the levels of insulin mRNA through MAFA (PMID:29070792)
• PDX1, Neurogenin-3, and MAFA are critical transcription regulators for beta cell development and regeneration. (Review) (PMID:29096722)
• We investigated a large pedigree with autosomal dominant inheritance of diabetes mellitus or insulinomatosis, an adult-onset condition of recurrent hyperinsulinemic hypoglycemia caused by multiple insulin-secreting neuroendocrine tumors of the pancreas. Using exome sequencing, we identified a missense MAFA mutation (p.Ser64Phe, c.191C>T) segregating with both phenotypes of insulinomatosis and diabetes. (PMID:29339498)
• These findings suggest that PIASy binds to MafA through the SAP domain and negatively regulates the insulin gene promoter through a novel SIM1-dependent mechanism. (PMID:31614335)
• The deubiquitinase USP7 stabilizes Maf proteins to promote myeloma cell survival. (PMID:31822558)
• The MafA-target gene PPP1R1A regulates GLP1R-mediated amplification of glucose-stimulated insulin secretion in beta-cells. (PMID:33631146)
• Sex-biased islet beta cell dysfunction is caused by the MODY MAFA S64F variant by inducing premature aging and senescence in males. (PMID:34644565)
• Oxidative Stress Leads to beta-Cell Dysfunction Through Loss of beta-Cell Identity. (PMID:34804002)
• Adult Proinsulinomatosis Associated With a MAFA Germline Mutation as a Rare Cause of Recurrent Hypoglycemia. (PMID:35041347)
• The ubiquitin ligase HERC4 suppresses MafA transcriptional activity triggered by GSK3beta in myeloma by atypical K63-linked polyubiquitination. (PMID:37028761)
• CREB activates the MafA promoter through proximal E-boxes and a CCAAT motif in pancreatic beta-cells. (PMID:39189982)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	mafaa	ENSDARG00000044155
mus_musculus	Mafa	ENSMUSG00000047591
rattus_norvegicus	Mafa	ENSRNOG00000007668
drosophila_melanogaster	tj	FBGN0000964
drosophila_melanogaster	maf-S	FBGN0034534
caenorhabditis_elegans	maf-1	WBGENE00077521

Paralogs (6): NRL (ENSG00000129535), MAF (ENSG00000178573), MAFF (ENSG00000185022), MAFG (ENSG00000197063), MAFK (ENSG00000198517), MAFB (ENSG00000204103)

Protein

Protein identifiers

Transcription factor MafA — Q8NHW3 (reviewed: Q8NHW3)

Alternative names: Pancreatic beta-cell-specific transcriptional activator, RIPE3b1 factor, V-maf musculoaponeurotic fibrosarcoma oncogene homolog A

All UniProt accessions (1): Q8NHW3

UniProt curated annotations — full annotation on UniProt →

Function. Transcription factor that activates insulin gene expression. Acts synergistically with NEUROD1/BETA2 and PDX1. Binds the insulin enhancer C1/RIPE3b element. Binds to consensus TRE-type MARE 5’-TGCTGACTCAGCA-3’ DNA sequence.

Subunit / interactions. Forms homodimers or heterodimers. Monomers and dimers are able to bind DNA, but the off-rate is faster for monomers. Interacts with NEUROD1 and PDX1. May interact with MAFB, FOS, JUN and PCAF.

Subcellular location. Nucleus.

Tissue specificity. Expressed in the islets of Langerhans (at protein level).

Post-translational modifications. Ubiquitinated, leading to its degradation by the proteasome. Phosphorylated at tyrosines.

Disease relevance. 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. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the bZIP family. Maf subfamily.

RefSeq proteins (1): NP_963883* (*=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 (24 total): modified residue 6, region of interest 5, compositionally biased region 4, helix 3, chain 1, domain 1, cross-link 1, sequence variant 1, sequence conflict 1, turn 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
4EOT	X-RAY DIFFRACTION	2.85

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8NHW3-F1	64.06	0.30

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 (7): 14, 49, 53, 57, 61, 65, 32

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-210745	Regulation of gene expression in beta cells
R-HSA-1266738	Developmental Biology
R-HSA-186712	Regulation of beta-cell development

MSigDB gene sets: 114 (showing top): GOBP_INSULIN_SECRETION, GOBP_REGULATION_OF_HORMONE_LEVELS, GOBP_HORMONE_TRANSPORT, MEF2_02, GOBP_CELL_CELL_SIGNALING, NKX62_Q2, GOBP_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, GOBP_SECRETION, GOBP_SIGNAL_RELEASE, AACTTT_UNKNOWN, REACTOME_REGULATION_OF_GENE_EXPRESSION_IN_BETA_CELLS, TURJANSKI_MAPK1_AND_MAPK2_TARGETS, MEF2_Q6_01, REACTOME_REGULATION_OF_BETA_CELL_DEVELOPMENT, NIKOLSKY_BREAST_CANCER_8Q23_Q24_AMPLICON

GO Biological Process (6): regulation of DNA-templated transcription (GO:0006355), regulation of transcription by RNA polymerase II (GO:0006357), response to glucose (GO:0009749), insulin secretion (GO:0030073), positive regulation of transcription by RNA polymerase II (GO:0045944), positive regulation of DNA-templated transcription (GO:0045893)

GO Molecular Function (6): 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), DNA binding (GO:0003677), DNA-binding transcription factor activity (GO:0003700), sequence-specific double-stranded DNA binding (GO:1990837)

GO Cellular Component (2): chromatin (GO:0000785), nucleus (GO:0005634)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Regulation of beta-cell development	1
Developmental Biology	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
regulation of DNA-templated transcription	3
RNA polymerase II transcription regulatory region sequence-specific DNA binding	3
DNA-templated transcription	2
transcription by RNA polymerase II	2
regulation of transcription by RNA polymerase II	2
regulation of gene expression	1
regulation of RNA biosynthetic process	1
response to hexose	1
protein secretion	1
peptide hormone secretion	1
positive regulation of DNA-templated transcription	1
positive regulation of RNA biosynthetic process	1
cis-regulatory region sequence-specific DNA binding	1
chromatin	1
DNA-binding transcription factor activity	1
DNA-binding transcription factor activity, RNA polymerase II-specific	1
DNA-binding transcription activator activity	1
positive regulation of transcription by RNA polymerase II	1
nucleic acid binding	1
transcription cis-regulatory region binding	1
transcription regulator activity	1
double-stranded DNA binding	1
sequence-specific DNA binding	1
chromosome	1
cellular anatomical structure	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

456 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MAFA	NEUROG3	Q9Y4Z2	785
MAFA	NEUROD1	Q13562	782
MAFA	SLC2A2	P11168	779
MAFA	INS	P01308	740
MAFA	PDX1	P52945	725
MAFA	NKX6-1	P78426	662
MAFA	GCK	P35557	647
MAFA	INSR	P06213	586
MAFA	NKX6-2	Q9C056	575
MAFA	FOXM1	Q08050	572
MAFA	PAX4	O43316	556
MAFA	SOX9	P48436	555
MAFA	GCG	P01275	538
MAFA	IGF1R	P08069	515
MAFA	NKX2-2	O95096	483

IntAct

3 interactions, top by confidence:

A	B	Type	Score
MAFA	DBN1	psi-mi:“MI:0915”(physical association)	0.400
MAFA	H2BC9	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (19): NCOA6 (Affinity Capture-Western), KDM6A (Affinity Capture-Western), RBBP5 (Affinity Capture-Western), KAT2B (Affinity Capture-Western), PAX6 (Affinity Capture-Western), ISL1 (Affinity Capture-Western), NEUROD1 (Affinity Capture-Western), PDX1 (Affinity Capture-Western), PDX1 (Reconstituted Complex), NEUROD1 (Reconstituted Complex), MAFA (Affinity Capture-MS), MAFA (Proximity Label-MS), HIST1H2BH (Proximity Label-MS), MAFA (Affinity Capture-Western), MAFA (Affinity Capture-Western)

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

26 interactions.

A	Effect	B	Mechanism
MAPK1	“up-regulates activity”	MAFA	phosphorylation
GSK3A	“up-regulates activity”	MAFA	phosphorylation
GSK3A	“down-regulates quantity by destabilization”	MAFA	phosphorylation
GSK3B	“up-regulates activity”	MAFA	phosphorylation
GSK3B	“down-regulates quantity by destabilization”	MAFA	phosphorylation
MAFA	“up-regulates quantity by expression”	PC	“transcriptional regulation”
MAFA	“up-regulates quantity by expression”	PDX1	“transcriptional regulation”
MAFA	“up-regulates quantity by expression”	GLP1R	“transcriptional regulation”
MAFA	“up-regulates quantity by expression”	NKX6-1	“transcriptional regulation”
MAFA	“up-regulates quantity by expression”	SLC2A2	“transcriptional regulation”
MAFA	“up-regulates quantity by expression”	PCSK1	“transcriptional regulation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	1
Uncertain significance	68
Likely benign	9
Benign	8

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
2578034	NM_201589.4(MAFA):c.170C>G (p.Thr57Arg)	Pathogenic
496645	NM_201589.4(MAFA):c.191C>T (p.Ser64Phe)	Likely pathogenic

SpliceAI

61 predictions. Top by Δscore:

Variant	Effect	Δscore
8:143429461:T:TA	donor_gain	0.6600
8:143430310:TCTTC:T	donor_gain	0.5900
8:143429511:T:TA	donor_gain	0.5500
8:143430313:TC:T	donor_gain	0.5300
8:143429523:TGCTC:T	donor_gain	0.4900
8:143428366:C:CT	acceptor_gain	0.4200
8:143429472:T:TA	donor_gain	0.4100
8:143429527:C:CT	donor_gain	0.4000
8:143429526:TC:T	donor_gain	0.3800
8:143429528:C:CT	donor_gain	0.3700
8:143430308:CTTCT:C	donor_gain	0.3400
8:143430309:TTCTT:T	donor_gain	0.3400
8:143429507:C:CT	donor_gain	0.3200
8:143429435:C:CA	donor_gain	0.3100
8:143429504:C:CA	donor_gain	0.3100
8:143430311:CT:C	donor_gain	0.3100
8:143430312:TT:T	donor_gain	0.3100
8:143429214:TGGC:T	donor_gain	0.3000
8:143429506:C:CT	donor_gain	0.3000
8:143429522:CTGCT:C	donor_gain	0.2700
8:143429655:T:TA	donor_gain	0.2600
8:143429694:C:CT	acceptor_gain	0.2600
8:143429700:G:T	acceptor_gain	0.2600
8:143428366:C:T	acceptor_gain	0.2500
8:143429257:T:TA	donor_gain	0.2500
8:143429574:TGCTG:T	donor_gain	0.2500
8:143429699:C:CT	acceptor_gain	0.2500
8:143429504:CCCCA:C	donor_loss	0.2400
8:143429505:CCCA:C	donor_loss	0.2400
8:143429506:CCACC:C	donor_loss	0.2400

AlphaMissense

2297 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:143429474:C:A	K311N	1.000
8:143429474:C:G	K311N	1.000
8:143429479:A:C	Y310D	1.000
8:143429487:C:G	R307P	1.000
8:143429499:A:G	L303P	1.000
8:143429520:A:G	L296P	1.000
8:143429541:A:G	L289P	1.000
8:143429562:A:G	L282P	1.000
8:143429562:A:T	L282Q	1.000
8:143429571:C:G	R279P	1.000
8:143429574:T:G	Q278P	1.000
8:143429577:T:G	Q277P	1.000
8:143429583:C:G	R275P	1.000
8:143429584:G:A	R275W	1.000
8:143429585:C:A	K274N	1.000
8:143429585:C:G	K274N	1.000
8:143429586:T:A	K274M	1.000
8:143429587:T:C	K274E	1.000
8:143429592:C:G	R272P	1.000
8:143429593:G:A	R272C	1.000
8:143429593:G:C	R272G	1.000
8:143429593:G:T	R272S	1.000
8:143429594:G:C	C271W	1.000
8:143429595:C:A	C271F	1.000
8:143429595:C:G	C271S	1.000
8:143429595:C:T	C271Y	1.000
8:143429596:A:C	C271G	1.000
8:143429596:A:G	C271R	1.000
8:143429596:A:T	C271S	1.000
8:143429598:G:A	S270F	1.000

dbSNP variants (sampled 300 via entrez): RS1000236441 (8:143430275 G>A,C), RS1000880922 (8:143431486 G>A), RS1000936167 (8:143431289 A>T), RS1000975846 (8:143428747 G>A,T), RS1001598046 (8:143429203 G>A), RS1001705947 (8:143427605 C>T), RS1001766450 (8:143427968 G>A), RS1001886251 (8:143432517 C>G,T), RS1001937115 (8:143432359 C>T), RS1001979333 (8:143428320 C>T), RS1002698594 (8:143428481 T>C), RS1002720726 (8:143431632 T>C), RS1002812192 (8:143428809 G>A), RS1003486931 (8:143431940 T>C), RS1005037065 (8:143428854 T>C)

Disease associations

OMIM: gene MIM:610303 | disease phenotypes: MIM:147630, MIM:616192, MIM:618107

GenCC curated gene-disease

Mondo (3): islet cell adenomatosis (MONDO:0007834), juvenile-onset diabetes mellitus-central and peripheral neurodegeneration syndrome (MONDO:0014523), osteopetrosis, autosomal dominant 3 (MONDO:0020848)

Orphanet (1): Juvenile-onset diabetes mellitus-central and peripheral neurodegeneration syndrome (Orphanet:445062)

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST009356_4	Nonsyndromic cleft palate	1.000000e-06
GCST010241_370	Apolipoprotein A1 levels	3.000000e-10
GCST010242_361	HDL cholesterol levels	1.000000e-10

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004614	apolipoprotein A 1 measurement
EFO:0004612	high density lipoprotein cholesterol measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C563258	Islet Cell Adenomatosis (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
(+)-JQ1 compound	increases expression	2
OTX015	increases expression	1
mivebresib	increases expression	1
bisphenol A	increases methylation	1
2-methyl-4-isothiazolin-3-one	increases expression	1
tributyltin	decreases expression	1
dimethylselenide	increases expression, increases oxidation	1
arsenite	increases methylation	1
mono-(2-ethylhexyl)phthalate	affects expression	1
sodium arsenite	increases expression	1
3-aminobenzamide	affects binding, decreases reaction	1
tri-o-cresyl phosphate	decreases expression	1
monobutyl phthalate	increases expression	1
S-(1,2-dichlorovinyl)cysteine	affects cotreatment, increases expression	1
3,4-dihydro-5-methyl-1(2H)-isoquinolinone	affects binding, decreases reaction	1
nutlin 3	affects cotreatment, increases expression	1
abrine	increases expression	1
Scutellaria barbata extract	decreases expression	1
licochalcone B	increases expression	1
bisphenol S	decreases expression	1
jinfukang	affects cotreatment, increases expression	1
imeglimin	increases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Benzo(a)pyrene	increases methylation, affects methylation	1
Cadmium	increases expression	1
Camptothecin	increases expression	1
Cisplatin	affects cotreatment, increases expression	1
Dactinomycin	affects cotreatment, increases expression	1
Glucose	affects binding, decreases reaction	1
Harmine	increases expression	1

Cellosaurus cell lines

3 cell lines: 3 embryonic stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_A3Z8	SEES3-1V human MAFA, clone1	Embryonic stem cell	Male
CVCL_A3Z9	SEES3-1V human MAFA, clone2	Embryonic stem cell	Male
CVCL_A4A0	SEES3-1V human MAFA, clone3	Embryonic stem cell	Male

Clinical trials (associated diseases)

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