MITF

Summary

MITF (melanocyte inducing transcription factor, HGNC:7105) is a protein-coding gene on chromosome 3p13, encoding Microphthalmia-associated transcription factor (O75030). Transcription factor that acts as a master regulator of melanocyte survival and differentiation as well as melanosome biogenesis. It is haploinsufficient (ClinGen: sufficient evidence).

The protein encoded by this gene is a transcription factor that contains both basic helix-loop-helix and leucine zipper structural features. The encoded protein regulates melanocyte development and is responsible for pigment cell-specific transcription of the melanogenesis enzyme genes. Heterozygous mutations in the this gene cause auditory-pigmentary syndromes, such as Waardenburg syndrome type 2 and Tietz syndrome.

Source: NCBI Gene 4286 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Waardenburg syndrome type 2 (Definitive, ClinGen) — +7 more curated relationships
• GWAS associations: 36 (top 3% of genes corpus-wide)
• Clinical variants (ClinVar): 1,386 total — 94 pathogenic, 51 likely-pathogenic (top 2% of genes corpus-wide)
• Regional missense constraint (gnomAD): 1 of 5 regions constrained (≈2% of expected missense variation)
• GTEx eGene: eQTL in 11 tissues, sQTL in 2 (q < 0.05)
• Phenotypes (HPO): 74
• ChEMBL bioactivity: 3 clinical-phase molecules tested; no curated mechanism-of-action drug
• Dosage sensitivity (ClinGen): haploinsufficiency sufficient evidence, triplosensitivity no evidence
• Constraint (gnomAD): pLI 0.99 (loss-of-function intolerant), LOEUF 0.48 (moderately constrained)
• Transcription factor: yes — 120 downstream targets (CollecTRI)
• MANE Select transcript: NM_001354604
• Interaction hub: 2,548 STRING partners (top 4% of genes corpus-wide)

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:7105
Approved symbol	MITF
Name	melanocyte inducing transcription factor
Location	3p13
Locus type	gene with protein product
Status	Approved
Aliases	MI, bHLHe32
Ensembl gene	ENSG00000187098
Ensembl biotype	protein_coding
OMIM	156845
Entrez	4286

Gene structure

Transcript identifiers

Ensembl transcripts: 46 — 33 protein_coding, 9 nonsense_mediated_decay, 4 protein_coding_CDS_not_defined

MANE Select: ENST00000352241 · MANE Plus Clinical: ENST00000394351

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 5, TSL 2: 2, TSL 3: 1, TSL 4: 2, TSL 5: 5

ENST00000352241, ENST00000394351, ENST00000314557, ENST00000314589, ENST00000394348, ENST00000429090, ENST00000433517, ENST00000448226, ENST00000451708, ENST00000461014, ENST00000461511, ENST00000472437, ENST00000478490, ENST00000495741, ENST00000531774, ENST00000642352, ENST00000687384, ENST00000689390, ENST00000693031, ENST00000693549, ENST00000894496, ENST00000894497, ENST00000894498, ENST00000894499, ENST00000956040, ENST00000956041, ENST00000956042, ENST00000956043, ENST00000956044, ENST00000956045, ENST00000956046, ENST00000956047, ENST00000990680, ENST00000990681, ENST00000990682, ENST00001016851, ENST00001016852, ENST00001016853, ENST00001016855, ENST00001016856, ENST00001016857, ENST00001016858, ENST00001016859, ENST00001016860, ENST00001143494, ENST00001143495

RefSeq mRNA: 13 — MANE Select: NM_001354604 NM_000248, NM_001184967, NM_001184968, NM_001354604, NM_001354605, NM_001354606, NM_001354607, NM_001354608, NM_006722, NM_198158, NM_198159, NM_198177, NM_198178

CCDS: CCDS2913, CCDS43106, CCDS43107, CCDS46865, CCDS46866, CCDS54607, CCDS74962, CCDS87108, CCDS93308

Canonical transcript exons

ENST00000352241 — 10 exons

Exon	Start	End
ENSE00001514168	69964847	69968332
ENSE00001940141	69739464	69739701
ENSE00003489451	69949051	69949168
ENSE00003494149	69956455	69956530
ENSE00003520446	69939098	69939181
ENSE00003546862	69959273	69959420
ENSE00003569466	69941236	69941331
ENSE00003582013	69937822	69938049
ENSE00003615407	69951812	69951886
ENSE00003788342	69879134	69879383

Expression profiles

Bgee: expression breadth ubiquitous, 293 present calls, max score 99.16.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 18.3536 / max 1473.8337, expressed in 1496 samples.

Highest expression (Bgee): pigmented layer of retina, retina, skeletal muscle tissue of biceps brachii, heart right ventricle, biceps brachii.

Genetic regulation across tissues (GTEx eQTL / sQTL)

MITF is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 11 tissues and its splicing (sQTL) in 2 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

13 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Spleen	eqtl	2.3e-16	+0.50	3:69788960:C:T
Thyroid	eqtl	5.4e-15	+0.52	3:69867486:T:G
Artery Aorta	eqtl	8.5e-10	+0.23	3:70069205:C:T
Esophagus Mucosa	eqtl	7.2e-04	+0.16	3:69746032:G:A
Adipose Subcutaneous	sqtl	1.1e-03	+0.32	3:69794386:G:A
Heart Atrial Appendage	eqtl	5.2e-03	-0.11	3:69279929:T:C
Whole Blood	eqtl	8.2e-03	+0.16	3:69742587:G:A
Nerve Tibial	eqtl	2.5e-02	-0.12	3:69967753:C:T
Brain Cerebellum	eqtl	2.8e-02	+0.22	3:69945378:G:A
Liver	eqtl	2.8e-02	-0.40	3:69552736:G:GT
Brain Cortex	eqtl	4.3e-02	-0.24	3:69857116:T:C
Pancreas	sqtl	4.5e-02	+0.44	3:69736886:T:A
Cells Cultured fibroblasts	eqtl	4.9e-02	+0.06	3:69671517:T:C

FANTOM5 promoters

showing 10 of 22 alternative TSS:

Promoter ID	TPM avg	Samples expressed
37231	12.1677	1420
37262	3.0292	59
37254	0.7030	260
37251	0.4761	37
37237	0.3851	169
37253	0.3812	156
37238	0.2833	131
37263	0.2801	44
37252	0.1075	5
37245	0.0714	21

Top tissues by expression

showing 100 of 299 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
pigmented layer of retina	UBERON:0001782	99.16	gold quality
retina	UBERON:0000966	99.13	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	97.32	gold quality
heart right ventricle	UBERON:0002080	97.29	gold quality
biceps brachii	UBERON:0001507	97.22	gold quality
gluteal muscle	UBERON:0002000	96.79	gold quality
myocardium	UBERON:0002349	96.71	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	96.65	gold quality
vastus lateralis	UBERON:0001379	96.59	gold quality
quadriceps femoris	UBERON:0001377	96.56	gold quality
left ventricle myocardium	UBERON:0006566	96.55	gold quality
deltoid	UBERON:0001476	96.31	gold quality
urethra	UBERON:0000057	96.23	gold quality
renal medulla	UBERON:0000362	96.16	gold quality
cardiac muscle of right atrium	UBERON:0003379	95.86	gold quality
skeletal muscle tissue	UBERON:0001134	95.79	gold quality
visceral pleura	UBERON:0002401	95.78	gold quality
muscle tissue	UBERON:0002385	95.37	gold quality
saphenous vein	UBERON:0007318	95.35	gold quality
secondary oocyte	CL:0000655	95.17	gold quality
body of tongue	UBERON:0011876	95.16	gold quality
diaphragm	UBERON:0001103	95.11	gold quality
upper leg skin	UBERON:0004262	95.05	gold quality
cauda epididymis	UBERON:0004360	94.99	gold quality
tibialis anterior	UBERON:0001385	94.92	gold quality
triceps brachii	UBERON:0001509	94.85	gold quality
buccal mucosa cell	CL:0002336	94.55	gold quality
seminal vesicle	UBERON:0000998	94.24	gold quality
vena cava	UBERON:0004087	94.10	gold quality
muscle organ	UBERON:0001630	94.00	gold quality
skeletal muscle organ	UBERON:0014892	94.00	gold quality
parietal pleura	UBERON:0002400	93.97	gold quality
endometrium	UBERON:0001295	93.94	gold quality
myometrium	UBERON:0001296	93.75	gold quality
mammalian vulva	UBERON:0000997	93.66	gold quality
calcaneal tendon	UBERON:0003701	93.64	gold quality
oocyte	CL:0000023	93.61	gold quality
pleura	UBERON:0000977	93.29	gold quality
gastrocnemius	UBERON:0001388	93.13	gold quality
muscle of leg	UBERON:0001383	92.97	gold quality
synovial joint	UBERON:0002217	92.97	gold quality
uterus	UBERON:0000995	92.93	gold quality
cardia of stomach	UBERON:0001162	92.75	gold quality
endothelial cell	CL:0000115	92.50	gold quality
skin of hip	UBERON:0001554	92.46	gold quality
nipple	UBERON:0002030	92.44	gold quality
penis	UBERON:0000989	92.30	gold quality
decidua	UBERON:0002450	92.08	gold quality
body of uterus	UBERON:0009853	91.92	gold quality
endocervix	UBERON:0000458	91.89	gold quality
pancreatic ductal cell	CL:0002079	91.44	gold quality
tongue	UBERON:0001723	90.95	gold quality
hindlimb stylopod muscle	UBERON:0004252	90.84	gold quality
tendon	UBERON:0000043	90.77	gold quality
hair follicle	UBERON:0002073	90.13	gold quality
upper arm skin	UBERON:0004263	89.98	gold quality
pericardium	UBERON:0002407	89.44	gold quality
layer of synovial tissue	UBERON:0007616	89.40	gold quality
smooth muscle tissue	UBERON:0001135	89.29	gold quality
mammary duct	UBERON:0001765	89.15	gold quality
corpus callosum	UBERON:0002336	89.08	gold quality
lower lobe of lung	UBERON:0008949	89.03	gold quality
superficial temporal artery	UBERON:0001614	88.99	gold quality
cardiac ventricle	UBERON:0002082	88.75	gold quality
inferior vagus X ganglion	UBERON:0005363	88.59	gold quality
uterine cervix	UBERON:0000002	88.58	gold quality
heart left ventricle	UBERON:0002084	88.46	gold quality
lower esophagus muscularis layer	UBERON:0035833	88.25	gold quality
thoracic mammary gland	UBERON:0005200	88.18	gold quality
lower esophagus	UBERON:0013473	88.17	gold quality
adult organism	UBERON:0007023	88.02	gold quality
mammary gland	UBERON:0001911	87.98	gold quality
caput epididymis	UBERON:0004358	87.86	gold quality
pylorus	UBERON:0001166	87.85	gold quality
gall bladder	UBERON:0002110	87.85	gold quality
germinal epithelium of ovary	UBERON:0001304	87.83	gold quality
bronchial epithelial cell	CL:0002328	87.81	gold quality
choroid plexus epithelium	UBERON:0003911	87.67	gold quality
subthalamic nucleus	UBERON:0001906	87.63	gold quality
ectocervix	UBERON:0012249	87.53	gold quality
epithelium of mammary gland	UBERON:0003244	87.45	gold quality
female reproductive system	UBERON:0000474	87.44	gold quality
lateral globus pallidus	UBERON:0002476	87.40	gold quality
heart	UBERON:0000948	87.39	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	86.85	gold quality
superior surface of tongue	UBERON:0007371	86.63	gold quality
cardiac atrium	UBERON:0002081	86.60	gold quality
substantia nigra pars reticulata	UBERON:0001966	86.49	gold quality
kidney	UBERON:0002113	86.22	gold quality
cranial nerve II	UBERON:0000941	86.21	gold quality
muscle layer of sigmoid colon	UBERON:0035805	86.20	gold quality
globus pallidus	UBERON:0001875	86.16	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	86.04	gold quality
mucosa of stomach	UBERON:0001199	85.88	gold quality
medial globus pallidus	UBERON:0002477	85.75	gold quality
adult mammalian kidney	UBERON:0000082	85.73	gold quality
corpus epididymis	UBERON:0004359	85.72	gold quality
cervix squamous epithelium	UBERON:0006922	85.62	silver quality
subcutaneous adipose tissue	UBERON:0002190	85.40	gold quality
oviduct epithelium	UBERON:0004804	85.31	gold quality

Single-cell (SCXA)

Detected in 7 experiment(s), a significant marker in 7.

Experiment	Marker?	Max mean expression
E-CURD-119	yes	53.21
E-GEOD-135922	yes	31.89
E-HCAD-10	yes	18.24
E-MTAB-8142	yes	17.59
E-CURD-112	yes	15.31
E-MTAB-9801	yes	6.31
E-ANND-3	no	0.00

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 76 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Cervix	tissue	47.8	not detected
Choroid plexus	tissue	46.9
Endometrium 1	tissue	43.6	medium
Smooth muscle	tissue	43.0	low
Tongue	tissue	40.2
Skeletal muscle	tissue	37.4	not detected
Corpus callosum	tissue	31.9
Heart muscle	tissue	29.2	medium
Spinal cord	tissue	18.9
Kidney	tissue	18.7	medium
Medulla oblongata	tissue	17.1
Vagina	tissue	15.9	not detected
Parathyroid gland	tissue	15.9	not detected
Substantia nigra	tissue	15.9
Gallbladder	tissue	15.8	not detected
Midbrain	tissue	15.2
Superior colliculi	tissue	14.7
Ventral forebrain	tissue	14.6
Putamen	tissue	14.5
Ovary	tissue	13.9	not detected
Thalamus	tissue	13.7
Seminal vesicle	tissue	13.4	not detected
Nucleus accumbens	tissue	13.3
Olfactory bulb	tissue	13.2
Periaqueductal gray	tissue	12.1
Pons	tissue	11.0
Basal ganglia	tissue	10.7	not detected
Skin 1	tissue	10.4	high
Hippocampus	tissue	10.4	not detected
Locus coeruleus	tissue	10.0
Septum	tissue	10.0
Adipose tissue	tissue	9.8	not detected
Hypothalamus	tissue	9.7
Postcentral gyrus	tissue	9.3
Breast	tissue	9.1	not detected
Lung	tissue	9.1	medium
Hippocampal formation	tissue	9.1
Cerebral cortex	tissue	8.5	not detected
Somatosensory cortex	tissue	8.5
Esophagus	tissue	8.4	not detected
Prostate	tissue	7.9	not detected
Stomach 1	tissue	7.8	low
Amygdala	tissue	7.8
Retrosplenial cortex	tissue	7.7
Occipital cortex	tissue	7.6
Motor cortex	tissue	7.4
Fallopian tube	tissue	7.4	not detected
Thyroid gland	tissue	7.2	not detected
Urinary bladder	tissue	7.1	not detected
Temporal cortex	tissue	7.1
Insular cortex	tissue	6.9
Retrosplenial and cingulate cortex	tissue	6.8
Prefrontal cortex	tissue	6.7
Entorhinal cortex	tissue	6.5
Caudate putamen	tissue	5.8
Cerebellum	tissue	4.5	not detected
Salivary gland	tissue	4.3	not detected
Colon	tissue	4.3	low
Rectum	tissue	4.2	low
Epididymis	tissue	4.2	low

Brain sub-regions (HPA Brain Atlas): detected in 190; highest nTPM — White matter (31.9), Corpus callosum, splenium (white matter) (29.4), Nucleus gracilis (28.4), Temporal white matter (27.2), Parieto-temporal junction (white matter) (26.8).

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

showing 30 of 120 targets:

Target	Regulation
ACP5	Activation
AKT1
APEX1	Activation
ATP6V0D2
ATP6V1B2
BAD	Unknown
BCL2	Activation
BCL2A1	Repression
BEST1	Activation
BIRC7	Unknown
BRAF
CADM1	Unknown
CD40
CD40LG	Activation
CDH1	Activation
CDK2	Unknown
CDK6
CDKN1A	Repression
CDKN1B	Repression
CDKN2A	Repression
CLCN7	Activation
CMA1	Unknown
CSF1
CTSK	Activation
CXCL8	Activation
DCSTAMP	Activation
DCT	Activation
DIAPH1	Activation
DICER1
DIO2

JASPAR motifs

Motif	Name	Family
MA0620.2	MITF	bHLH-ZIP
MA0620.3	MITF	bHLH-ZIP
MA0620.4	MITF	bHLH-ZIP

JASPAR matrix evidence (PMIDs): PMID:12086670

Upstream regulators (CollecTRI, top): ATF1, CDH3, CREB1, DIDO1, EWSR1, FOXD3, GLI2, HOXA1, IRF6, JUN, LEF1, MITF, ONECUT1, ONECUT2, OTX2, PAX2, PAX3, PAX6, POU3F2, SOX10, SOX9, SSRP1, TBX2, TCF4, TRRAP, ZEB2, ZNF382

miRNA regulators (miRDB)

Targeting MITF by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 155 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-3162-3P	100.00	65.37	363
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-9-3P	99.96	70.88	2068
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163
HSA-MIR-23C	99.95	73.92	3192
HSA-MIR-96-5P	99.95	72.80	2140
HSA-MIR-3910	99.95	71.13	2227

Functional genomics

gnomAD constraint: pLI 0.992, LOEUF 0.482, missense Z 1.04 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD)

ENST00000352241 splits into 5 regions with different missense tolerance; 1 is missense-constrained (≈2% of the expected missense variation). Missense variants in a constrained region (low observed/expected) are more likely to be pathogenic. gnomAD

Region (GRCh38)	Missense obs / exp	o/e	Constrained
3:69,739,598–69,879,378	149 / 157.8	0.94	no
3:69,879,379–69,937,857	3 / 16.6	0.18	yes (p 8.6e-04)
3:69,937,858–69,951,846	215 / 224.8	0.96	no
3:69,951,847–69,959,337	31 / 74.8	0.41	no
3:69,959,338–69,965,245	224 / 209.5	1.07	no
ClinGen dosage: haploinsufficiency 3 (sufficient evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 40)

• MAZR and MITF synergistically transactivated the mMCP-6 gene. MAZR appeared to play important roles in the normal phenotypic expression of mast cells in association with MITF (PMID:11751862)
• Microphthalmia-associated transcription factor (MITF) regulates the differentiation and development of melanocytes and retinal pigment epithelium and is also responsible for pigment cell-specific transcription of the melanogenesis enzyme genes. Review. (PMID:11764295)
• Microphthalmia-associated transcription factor interacts with LEF-1, a mediator of Wnt signaling (PMID:12032083)
• MITF-M transactivates its own promoter (M promoter) by interacting with LEF-1 (PMID:12048204)
• Bcl2 regulation by the melanocyte master regulator Mitf modulates lineage survival and melanoma cell viability (PMID:12086670)
• MITF regulates not only the expression of enzymes involved in melanin synthesis, but also the expression of a receptor which plays an essential role in melanocyte functions (PMID:12204775)
• Beta catenin induced human melanoma growth requires the downstream target MITF (PMID:12235125)
• MITF gene may be implicated in Waardenburg syndrome. (PMID:12666593)
• MITF-M plays dual roles in the Wnt signaling pathway; MITF-M represents a downstream target and a nuclear mediator of Wnt signals in melanocytes (PMID:12753399)
• Data show that MITF appears to regulate the expression of the SILV and MLANA genes. (PMID:12819038)
• MITF expression in melanocytes is regulated by alpha-melanocyte-stimulating hormone modulated by SOX10 (PMID:12944398)
• MITF and STAT3 cooperatively induce c-fos, resulting in cellular transformation (PMID:14737107)
• MITF as a major transcriptional regulator of studies identify MITF as a major transcriptional regulator of TRPM1 and suggest that its prognostic value may be linked to MITF-mediated regulation of cellular differentiation (PMID:14744763)
• Mitf might play a role in the multinucleation process of giant cells and giant cell lesions. (PMID:15205688)
• the functional consequences of MITF sumoylation depend on promoter context. Sumoylation provides a possible mechanism for altering the effects of MITF by affecting the target genes that it activates (PMID:15507434)
• MITF regulates p16INK4A expression in melanocytes. (PMID:15623583)
• The majority of isoforms were found to be broadly expressed, with the M- and Mc-isoforms being tissue-restricted to melanocytes and mast cells, respectively. (PMID:15715979)
• Simultaneous expression of the EWSR1-ATF1 and MITF-M transcripts in clear cell carcinoma has led to the proposal that the MITF-M promoter is transactivated by EWSR1-ATF1. (PMID:15884099)
• We therefore conclude that the alpha-MSH/cAMP pathway, using MITF as a signal transducer and HIF1alpha as a target, might contribute to melanoma progression. (PMID:15983061)
• MITF represents a distinct class of ’lineage survival’ or ’lineage addiction’ oncogenes required for both tissue-specific cancer development and tumour progression (PMID:16001072)
• These data suggest that MITF is an anti-proliferation factor that is down-regulated by B-RAF signaling and that this is a crucial event for the progression of melanomas that harbor oncogenic B-RAF. (PMID:16129781)
• identified MITF as a new substrate of caspases and we characterized the cleavage site after Asp 345 in the C-terminal domain (PMID:16140982)
• MITF, specifically MITF-M, is a key transcription factor for protein kinase C-beta (PKC-beta), linking the PKC- and cAMP-dependent pathways in regulation of melanogenesis (PMID:16411896)
• The results of this study demonstrate a role for glutamate in MiTF regulation that may have implications in melanocyte associated disorders. (PMID:16420247)
• c-Met expression is regulated by Mitf in the melanocyte lineage (PMID:16455654)
• Mitf detection in blood can indicate subclinical metastatic disease and predict treatment outcome in melanoma patients. (PMID:16489066)
• The transcription factor MITF is an amplified oncogene in melanoma that is critical for anchoring lineage dependence and malignant character. (PMID:16510564)
• Sphingosylphosphorylcholine reduces melanin synthesis via MITF downregulation. (PMID:16524430)
• Tacrolimus or cyclosporine A act on human osteoclast precursors in rheumatoid arthritis patients by targeting the calcineurin-dependent NFAT pathway and activation pathway for c-Jun or MITF. (PMID:16586042)
• MITF and TFE3 reciprocally rescue one another in lines derived from CCS or pediatric renal carcinoma. (PMID:16766266)
• Of special interest was the rapid decrease in expression of MITF in melanocytes treated with DKK1, which is concurrent with the decreased activities of beta-catenin and of glucose-synthase kinase 3beta. (PMID:17159916)
• findings show that in melanomas invasiveness can be regulated epigenetically by Mitf, via regulation of the DIAPH1 gene; Mitf, via regulation of Dia1, can both inhibit invasiveness & promote proliferation (PMID:17182868)
• MITF evokes transcription of a paradigmatic MITF target tyrosinase and show that the adenoviral E1A protein represses the MITF-driven transcription in these cells. (PMID:17250547)
• analysis of the Mitf gene reveals novel conserved domains in human, mouse and Drosophila (PMID:17516926)
• Detection of both partial and whole gene deletions of MITF increase mutation detection in Waardenburg syndrome. (PMID:17627390)
• Microphthalmia-associated transcription factor gene amplification in metastatic melanoma may have a role in patient survival (PMID:17975146)
• link between microphthalmia-associated transcription factor haploinsufficiency and endothelin signaling (PMID:18039926)
• These results show that RAB27A is a new direct transcriptional target of MITF and link MITF to melanosome transport, another key parameter of melanocyte differentiation and skin pigmentation. (PMID:18281284)
• a novel MITF isoform, MITF-CM, which possesses a unique amino terminus was identified. (PMID:18284417)
• expression of mature miR-137 in melanoma cell lines down-regulates MITF expression (PMID:18316599)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	mitfa	ENSDARG00000003732
danio_rerio	mitfb	ENSDARG00000037833
mus_musculus	Mitf	ENSMUSG00000035158
rattus_norvegicus	Mitf	ENSRNOG00000008658
drosophila_melanogaster	Mitf	FBGN0263112
caenorhabditis_elegans		WBGENE00020930

Paralogs (3): TFE3 (ENSG00000068323), TFEC (ENSG00000105967), TFEB (ENSG00000112561)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:104554) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 125 distinct phenotype terms.

Mouse phenotype (MP)	Records
absent coat pigmentation	25
microphthalmia	17
decreased eye pigmentation	17
diluted coat color	11
belly spot	9
abnormal coat/hair pigmentation	9
white spotting	9
abnormal iris pigmentation	6
decreased tail pigmentation	6
osteopetrosis	5
irregular coat pigmentation	5
abnormal eye pigmentation	5
failure of tooth eruption	4
head spot	4
abnormal retina pigmentation	4
abnormal retina pigment epithelium morphology	4
abnormal foot pigmentation	4
decreased ear pigmentation	4
abnormal eye development	3
abnormal retina morphology	3
female infertility	3
abnormal osteoclast morphology	3
eyelids fail to open	3
abnormal stria vascularis morphology	2
decreased body size	2

+100 more (showing top 25).

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Pongo pygmaeus	A2T7L8	100.0%	Diamond
Pan troglodytes	A2T713	99.4%	Diamond
Oryctolagus cuniculus	O02818	99.4%	Diamond
Bos taurus	Q6XBT4	99.4%	Diamond
Psilocybe cyanescens	A0A286LEZ9	81.4%	Diamond
Psilocybe cubensis	P0DPB0	81.4%	Diamond
Gallus gallus	Q5XFQ6	70.3%	Diamond
Xenopus laevis	Q6GQ26	66.0%	Diamond
Schizosaccharomyces pombe 972h-	Q9UUD1	57.4%	Diamond
Saccharomyces cerevisiae S288C	P38165	46.0%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
SAMMSON	ncRNA	101927152
MDFIC2	protein-coding	107986096
ARL6IP5	protein-coding	10550
FRMD4B	protein-coding	23150
LMOD3	protein-coding	56203
UBA3	protein-coding	9039

Protein

Protein identifiers

Microphthalmia-associated transcription factor — O75030 (reviewed: O75030)

Alternative names: Class E basic helix-loop-helix protein 32

All UniProt accessions (9): A0A087WXU1, A0A8I5KRZ6, A0A8I5KSZ4, A0A8I5KTU3, C9J845, C9JBI8, C9K0S7, E9PKJ8, O75030

UniProt curated annotations — full annotation on UniProt →

Function. Transcription factor that acts as a master regulator of melanocyte survival and differentiation as well as melanosome biogenesis. Binds to M-boxes (5’-TCATGTG-3’) and symmetrical DNA sequences (E-boxes) (5’-CACGTG-3’) found in the promoter of pigmentation genes, such as tyrosinase (TYR). Involved in the cellular response to amino acid availability by acting downstream of MTOR: in the presence of nutrients, MITF phosphorylation by MTOR promotes its inactivation. Upon starvation or lysosomal stress, inhibition of MTOR induces MITF dephosphorylation, resulting in transcription factor activity. Plays an important role in melanocyte development by regulating the expression of tyrosinase (TYR) and tyrosinase-related protein 1 (TYRP1). Plays a critical role in the differentiation of various cell types, such as neural crest-derived melanocytes, mast cells, osteoclasts and optic cup-derived retinal pigment epithelium.

Subunit / interactions. Homodimer or heterodimer; dimerization is mediated via the coiled coil region. Efficient DNA binding requires dimerization with another bHLH protein. Binds DNA in the form of homodimer or heterodimer with either TFE3, TFEB or TFEC. Interacts with small GTPases Rag (RagA/RRAGA, RagB/RRAGB, RagC/RRAGC and/or RagD/RRAGD); promoting its recruitment to lysosomal membrane in the presence of nutrients. Interacts with KARS1. Identified in a complex with HINT1 and CTNNB1. Interacts with VSX2.

Subcellular location. Nucleus. Cytoplasm. Lysosome membrane.

Tissue specificity. Expressed in melanocytes (at protein level). Expressed in the retinal pigment epithelium, brain, and placenta. Expressed in the kidney. Expressed in the kidney and retinal pigment epithelium. Expressed in the kidney. Expressed in the kidney. Expressed in melanocytes. Expressed in melanocytes.

Post-translational modifications. When nutrients are present, phosphorylation by MTOR at Ser-5 via non-canonical mTORC1 pathway promotes ubiquitination by the SCF(BTRC) complex, followed by degradation. Phosphorylation at Ser-405 significantly enhances the ability to bind the tyrosinase promoter. Phosphorylation by MARK3/cTAK1 at Ser-280 promotes association with 14-3-3/YWHA adapters and retention in the cytosol. Phosphorylated at Ser-180 and Ser-516 following KIT signaling, triggering a short live activation: Phosphorylation at Ser-180 and Ser-516 by MAPK and RPS6KA1, respectively, activate the transcription factor activity but also promote ubiquitination and subsequent degradation by the proteasome. Phosphorylated in response to blue light (415nm). Ubiquitinated by the SCF(BTRC) and SCF(FBXW11) complexes following phosphorylation ar Ser-5 by MTOR, leading to its degradation by the proteasome. Ubiquitinated following phosphorylation at Ser-180, leading to subsequent degradation by the proteasome. Deubiquitinated by USP13, preventing its degradation.

Disease relevance. Waardenburg syndrome 2A (WS2A) [MIM:193510] WS2 is a genetically heterogeneous, autosomal dominant disorder characterized by sensorineural deafness, pigmentary disturbances, and absence of dystopia canthorum. The frequency of deafness is higher in WS2 than in WS1. The disease is caused by variants affecting the gene represented in this entry. Tietz albinism-deafness syndrome (TADS) [MIM:103500] An autosomal dominant disorder characterized by generalized hypopigmentation and congenital, bilateral, profound sensorineural deafness. The disease is caused by variants affecting the gene represented in this entry. Melanoma, cutaneous malignant 8 (CMM8) [MIM:614456] A malignant neoplasm of melanocytes, arising de novo or from a pre-existing benign nevus, which occurs most often in the skin but may also involve other sites. Disease susceptibility is associated with variants affecting the gene represented in this entry. Coloboma, osteopetrosis, microphthalmia, macrocephaly, albinism, and deafness (COMMAD) [MIM:617306] An autosomal recessive syndrome characterized by severe microphthalmia, profound congenital sensorineural hearing loss, lack of pigment in the hair, skin, and eyes, macrocephaly, facial dysmorphism, and osteopetrosis. The disease is caused by variants affecting the gene represented in this entry. An allelic combination involving at least one dominant-negative mutation, inherited in a recessive manner, represents the underlying molecular mechanism leading to COMMAD syndrome. Variations affecting this gene are associated with susceptibility to pheochromocytomas and paragangliomas, rare neural crest-derived tumors with an approximate incidence of 1:300,000/year.

Domain organisation. The leucine zipper region is part of a larger coiled coil.

Similarity. Belongs to the MiT/TFE family.

Isoforms (12)

UniProt ID	Names	Canonical?
O75030-1	A1	yes
O75030-2	A2
O75030-3	B1
O75030-4	B2
O75030-5	C1
O75030-6	C2
O75030-7	H1
O75030-8	H2
O75030-9	M1
O75030-10	M2
O75030-11	Mdel
O75030-12	12

RefSeq proteins (13): NP_000239, NP_001171896, NP_001171897, NP_001341533, NP_001341534, NP_001341535, NP_001341536, NP_001341537, NP_006713, NP_937801, NP_937802, NP_937820, NP_937821 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR011598	bHLH_dom	Domain
IPR021802	MiT/TFE_C	Domain
IPR031867	MiT/TFE_N	Domain
IPR036638	HLH_DNA-bd_sf	Homologous_superfamily

Pfam: PF00010, PF11851, PF15951

UniProt features (52 total): sequence variant 10, splice variant 8, modified residue 7, mutagenesis site 7, helix 6, region of interest 5, compositionally biased region 3, cross-link 2, chain 1, domain 1, sequence conflict 1, coiled-coil region 1

Structure

Experimental structures (PDB)

12 structures by resolution:

PDB	Title	Method	Resolution (Å)
9H7Q	MITF in complex with 5-chloro-3-phenyl-1H-indole-2-carboxylic acid	X-RAY DIFFRACTION	1.72
9H5H	MITF in complex with 1-(phenylethynyl)cyclohexan-1-ol	X-RAY DIFFRACTION	1.74
9H7T	MITF in complex with …	X-RAY DIFFRACTION	1.85
7EOD	MITF HLHLZ Delta AKE	X-RAY DIFFRACTION	1.9
9H7S	MITF in complex with …	X-RAY DIFFRACTION	1.99
4C7N	Crystal Structure of the synthetic peptide iM10 in complex with the coiled-coil region of …	X-RAY DIFFRACTION	2.1
7D8S	MITF bHLHLZ apo structure	X-RAY DIFFRACTION	2.28
9H5F	MITF(217-296)	X-RAY DIFFRACTION	2.3
9H7R	MITF in complex with 6-((1-hydroxycyclohexyl)ethynyl)-1-phenyl-1H-indole-2-carboxylic acid	X-RAY DIFFRACTION	2.52
7D8R	MITF HLHLZ structure	X-RAY DIFFRACTION	3
7D8T	MITF bHLHLZ complex with M-box DNA	X-RAY DIFFRACTION	3.2
8E1D	NMR-derived ensemble of the TAZ2 domain of p300 bound to the microphthalmia-associated …	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O75030-F1	62.25	0.21

Human Protein Atlas

Protein class: Predicted intracellular proteins, Transcription factors, Basic domains, Cancer-related genes, Disease related genes, Human disease related genes, Congenital disorders of metabolism, Congenital disorders of amino acid metabolism, Other congenital disorders of metabolism

Protein evidence: Evidence at protein level

Antibody reliability (HPA): IH enhanced

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 (9)

Type	Positions
Phosphoserine	5, 180, 280, 405, 414, 491, 516
Glycyl lysine isopeptide (lys-gly) (interchain with g-cter in sumo)	289, 423

Mutagenesis-validated functional residues (7)

Position	Phenotype
5	impaired phosphorylation by mtor, leading to abolished ubiquitination and degradation by the scf(btrc) complex.
180	abolishes both transcription factor activity and ubiquitination, leading to an inert and stable protein; when associated with a-516.
280	accumulates in the nucleus due to impaired phosphorylation.
289	loss of sumoylation; when associated with r-423.
405	loss of phosphorylation and function.
423	loss of sumoylation; when associated with r-289.
516	abolishes both transcription factor activity and ubiquitination, leading to an inert and stable protein; when associated with a-180.

Function

Pathways and Gene Ontology

Reactome pathways

8 curated (TAS) of 16; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

16 pathways:

ID	Pathway	Evidence
R-HSA-9854909	Regulation of MITF-M dependent genes involved in invasion	curated
R-HSA-9854907	Regulation of MITF-M dependent genes involved in metabolism	curated
R-HSA-9825895	Regulation of MITF-M-dependent genes involved in DNA replication, damage repair and senescence	curated
R-HSA-9824594	Regulation of MITF-M-dependent genes involved in apoptosis	curated
R-HSA-9825892	Regulation of MITF-M-dependent genes involved in cell cycle and proliferation	curated
R-HSA-9926550	Regulation of MITF-M-dependent genes involved in extracellular matrix, focal adhesion and epithelial-to-mesenchymal transition	curated
R-HSA-9857377	Regulation of MITF-M-dependent genes involved in lysosome biogenesis and autophagy	curated
R-HSA-3232118	SUMOylation of transcription factors	curated
R-HSA-1266738	Developmental Biology	—
R-HSA-9730414	MITF-M-regulated melanocyte development	—
R-HSA-392499	Metabolism of proteins	—
R-HSA-597592	Post-translational protein modification	—
R-HSA-9824585	Regulation of MITF-M-dependent genes involved in pigmentation	electronic
R-HSA-3108232	SUMO E3 ligases SUMOylate target proteins	—
R-HSA-2990846	SUMOylation	—
R-HSA-9856649	Transcriptional and post-translational regulation of MITF-M expression and activity	electronic

MSigDB gene sets: 0 (showing top):

GO Biological Process (13): negative regulation of transcription by RNA polymerase II (GO:0000122), DNA-templated transcription (GO:0006351), regulation of DNA-templated transcription (GO:0006355), regulation of transcription by RNA polymerase II (GO:0006357), positive regulation of gene expression (GO:0010628), melanocyte differentiation (GO:0030318), negative regulation of cell migration (GO:0030336), positive regulation of DNA-templated transcription (GO:0045893), positive regulation of transcription by RNA polymerase II (GO:0045944), protein-containing complex assembly (GO:0065003), positive regulation of DNA-templated transcription initiation (GO:2000144), regulation of RNA biosynthetic process (GO:2001141), developmental pigmentation (GO:0048066)

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 repressor activity, RNA polymerase II-specific (GO:0001227), DNA-binding transcription activator activity, RNA polymerase II-specific (GO:0001228), chromatin binding (GO:0003682), protein dimerization activity (GO:0046983), E-box binding (GO:0070888), DNA binding (GO:0003677), DNA-binding transcription factor activity (GO:0003700), protein binding (GO:0005515)

GO Cellular Component (7): chromatin (GO:0000785), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), lysosomal membrane (GO:0005765), cytosol (GO:0005829), protein-containing complex (GO:0032991)

Reactome top-level categories

7 top-level categories:

Category	Pathways
MITF-M-dependent gene expression	8
SUMO E3 ligases SUMOylate target proteins	1
MITF-M-regulated melanocyte development	1
Post-translational protein modification	1
SUMOylation	1
Metabolism of proteins	1
Developmental Biology	1

GO top-level categories

47 GO namespaces:

Category	Terms
RNA polymerase II transcription regulatory region sequence-specific DNA binding	4
cellular anatomical structure	4
regulation of transcription by RNA polymerase II	3
transcription by RNA polymerase II	3
regulation of DNA-templated transcription	3
gene expression	2
RNA biosynthetic process	2
DNA-templated transcription	2
regulation of gene expression	2
positive regulation of DNA-templated transcription	2
DNA-binding transcription factor activity, RNA polymerase II-specific	2
binding	2
negative regulation of DNA-templated transcription	1
regulation of RNA biosynthetic process	1
positive regulation of macromolecule biosynthetic process	1
pigment cell differentiation	1
cell migration	1
regulation of cell migration	1
negative regulation of cell motility	1
positive regulation of RNA biosynthetic process	1
cellular component assembly	1
protein-containing complex organization	1
DNA-templated transcription initiation	1
regulation of DNA-templated transcription initiation	1
regulation of macromolecule biosynthetic process	1
regulation of RNA metabolic process	1
pigmentation	1
cis-regulatory region sequence-specific DNA binding	1
chromatin	1
DNA-binding transcription factor activity	1
negative regulation of transcription by RNA polymerase II	1
DNA-binding transcription repressor activity	1
DNA-binding transcription activator activity	1
positive regulation of transcription by RNA polymerase II	1
protein binding	1
RNA polymerase II cis-regulatory region sequence-specific DNA binding	1
nucleic acid binding	1
transcription cis-regulatory region binding	1
transcription regulator activity	1
chromosome	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
intracellular anatomical structure	1
lysosome	1
lytic vacuole membrane	1
cytoplasm	1
cellular_component	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 16 of 30 annotations. The rest are phylogenetic / computational / electronic (IEA).

16 experimentally-supported GO terms:

GO term	NS	Evidence
negative regulation of cell migration	BP	mutant phenotype
negative regulation of transcription by RNA polymerase II	BP	mutant phenotype
positive regulation of DNA-templated transcription	BP	direct assay
positive regulation of DNA-templated transcription initiation	BP	direct assay
positive regulation of gene expression	BP	direct assay
positive regulation of transcription by RNA polymerase II	BP	direct assay
protein-containing complex assembly	BP	direct assay
regulation of DNA-templated transcription	BP	mutant phenotype
regulation of RNA biosynthetic process	BP	direct assay
cytoplasm	CC	direct assay
lysosomal membrane	CC	direct assay
nucleus	CC	direct assay
protein-containing complex	CC	direct assay
DNA-binding transcription activator activity, RNA polymerase II-specific	MF	direct assay
E-box binding	MF	direct assay
RNA polymerase II cis-regulatory region sequence-specific DNA binding	MF	direct assay

Protein interactions and networks

STRING

showing 15 of 2,548 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MITF	TYR	P14679	952
MITF	TYRP1	P17643	927
MITF	DCT	P40126	908
MITF	SOX10	P56693	895
MITF	PAX3	P23760	866
MITF	MC1R	Q01726	840
MITF	POMC	P01189	781
MITF	KIT	P10721	756
MITF	PMEL	P40967	756
MITF	SNAI2	O43623	725
MITF	BRAF	P15056	716
MITF	CTSK	P43235	709
MITF	CTNNB1	P35222	704
MITF	MLANA	Q16655	703
MITF	GPR143	P51810	694

IntAct

Human interaction partners of MITF in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

19 partners by confidence:

Partner	Interaction type	MIscore	Records
TFEB	physical association	0.560	3
TFE3	physical association	0.560	1
CLTC	direct interaction	0.440	1
SUMO1	physical association	0.400	2
RBPJ	physical association	0.400	1
ADRB2	physical association	0.370	1
EBP	physical association	0.370	1
HK3	physical association	0.370	1
STUB1	physical association	0.370	1
XCL1	physical association	0.370	1
YWHAZ	association	0.350	1
FBXW7	proximity	0.270	4
SMARCA4	proximity	0.270	4
SMAD4	proximity	0.270	3
SPOP	proximity	0.270	3
EGFR	proximity	0.270	1
PTEN	proximity	0.270	1
PTPN11	proximity	0.270	1
TP53	proximity	0.270	1

BioGRID (86 interactions; top human partners by supporting records): CLK4 (Affinity Capture-Western; 5 records), PIAS3 (Reconstituted Complex; 5 records), LEF1 (Affinity Capture-Western; 4 records), TFE3 (Affinity Capture-MS; 4 records), TFEB (Affinity Capture-MS; 4 records), BTRC (Affinity Capture-Western; 3 records), FBXW11 (Affinity Capture-Western; 3 records), PATZ1 (Affinity Capture-Western; 3 records), UBE2I (Reconstituted Complex; 3 records), ATG16L1 (Proximity Label-MS; 2 records), EPAS1 (Affinity Capture-MS; 2 records), HINT1 (Two-hybrid; 2 records), PIAS2 (Reconstituted Complex; 2 records), PSMD14 (Two-hybrid; 2 records), RBM6 (Affinity Capture-MS; 2 records)

SIGNOR signaling

showing 29 of 35 signaling interactions:

A	Effect	B	Mechanism
RPS6KA1	down-regulates	MITF	phosphorylation
ERK1/2	down-regulates	MITF	phosphorylation
MITF	“up-regulates quantity by expression”	TPSAB1	“transcriptional regulation”
RPS6K	down-regulates	MITF	phosphorylation
MITF	“up-regulates quantity by expression”	OCA2	“transcriptional regulation”
MITF	“up-regulates quantity by expression”	BEST1	“transcriptional regulation”
MITF	“up-regulates quantity by expression”	SERPINF1	“transcriptional regulation”
MITF	“up-regulates quantity by expression”	PMEL	“transcriptional regulation”
MITF	“up-regulates quantity by expression”	MLANA	“transcriptional regulation”
MITF	“up-regulates quantity by expression”	TYRP1	“transcriptional regulation”
MITF	“up-regulates quantity by expression”	DCT	“transcriptional regulation”
MITF	“up-regulates quantity by expression”	TYR	“transcriptional regulation”
CLK4	“down-regulates quantity by destabilization”	MITF	phosphorylation
GSK3B	“up-regulates activity”	MITF	phosphorylation
GSK3B	“up-regulates quantity by stabilization”	MITF	phosphorylation
AKT1	“down-regulates quantity by destabilization”	MITF	phosphorylation
PRKDC	“up-regulates activity”	MITF	phosphorylation
GSK3B	“down-regulates quantity by destabilization”	MITF	phosphorylation
GSK3A	up-regulates	MITF	phosphorylation
MAPK1	down-regulates	MITF	phosphorylation
UBE2I	down-regulates	MITF	ubiquitination
MITF	“up-regulates quantity by expression”	ACP5	“transcriptional regulation”
MITF	“up-regulates quantity by expression”	TRPM1	“transcriptional regulation”
SOX9	“up-regulates activity”	MITF	binding
POU3F2	“up-regulates quantity by expression”	MITF	“transcriptional regulation”
MITF	“up-regulates quantity by expression”	BCL2	“transcriptional regulation”
CREB1	“up-regulates quantity by expression”	MITF	“transcriptional regulation”
MAPK3	“down-regulates quantity by destabilization”	MITF	phosphorylation
Gbeta	“down-regulates quantity by destabilization”	MITF	phosphorylation

Protein complexes (CORUM) (3)

Experimentally-characterized complexes this protein is a subunit of (★ = the complex contains a known drug target).

3 complexes by size:

Complex	Subunits	Members
ARAF-MITF complex	2	ARAF, MITF
★ BRAF-MITF complex	2	BRAF, MITF
★ MITF -RAF1 complex	2	MITF, RAF1

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 19 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
MITF-M-regulated melanocyte development	5	30.1×	2e-04

GO biological processes:

GO term	Partners	Fold	FDR
protein stabilization	5	17.6×	8e-04

Disease & clinical

Genetic variants

Variant evidence for MITF: 1,386 ClinVar records (145 pathogenic / likely pathogenic); 36 GWAS associations. Per-variant detail is on Sugi Variant.

ClinVar

1,386 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	94
Likely pathogenic	51
Uncertain significance	732
Likely benign	372
Benign	42

Top pathogenic / likely-pathogenic (15)

Showing the 15 best-reviewed of 145 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
14272	NM_001354604.2(MITF):c.964AGA[2] (p.Arg324del)	Pathogenic	criteria provided, multiple submitters, no conflicts	11
14276	NM_001354604.2(MITF):c.961C>T (p.Arg321Ter)	Pathogenic	criteria provided, multiple submitters, no conflicts	10
995923	NM_001354604.2(MITF):c.1198C>T (p.Arg400Ter)	Pathogenic	criteria provided, multiple submitters, no conflicts	8
545015	NM_001354604.2(MITF):c.1031+1G>A	Pathogenic	criteria provided, multiple submitters, no conflicts	6
995922	NM_001354604.2(MITF):c.1096C>T (p.Arg366Ter)	Pathogenic	criteria provided, multiple submitters, no conflicts	5
375217	NM_001354604.2(MITF):c.956-1G>A	Pathogenic	criteria provided, multiple submitters, no conflicts	4
228364	NM_001354604.2(MITF):c.704C>G (p.Ser235Ter)	Pathogenic	criteria provided, multiple submitters, no conflicts	2
2203401	NM_001354604.2(MITF):c.815del (p.Pro272fs)	Pathogenic	criteria provided, multiple submitters, no conflicts	2
3601242	NM_001354604.2(MITF):c.673del (p.Asp225fs)	Pathogenic	criteria provided, multiple submitters, no conflicts	2
3601257	NM_001354604.2(MITF):c.896_897del (p.Thr299fs)	Pathogenic	criteria provided, multiple submitters, no conflicts	2
3601267	NM_001354604.2(MITF):c.970A>T (p.Arg324Ter)	Pathogenic	criteria provided, multiple submitters, no conflicts	2
3601275	NM_001354604.2(MITF):c.1179+1G>A	Pathogenic	criteria provided, multiple submitters, no conflicts	2
425300	NM_001354604.2(MITF):c.1180-2A>G	Likely pathogenic	criteria provided, multiple submitters, no conflicts	3
995918	NM_001354604.2(MITF):c.928A>G (p.Arg310Gly)	Likely pathogenic	criteria provided, multiple submitters, no conflicts	3
1048556	NM_001354604.2(MITF):c.1052G>A (p.Gly351Glu)	Likely pathogenic	criteria provided, multiple submitters, no conflicts	3

Per-variant reference — Sugi Variant

Explore MITF’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 27 predictions of 1,710):

Position(s)	Effect	Δscore	Sites
3:69739702	donor_loss	1.0000
3:69879131	acceptor_gain	1.0000
3:69879384–69879385	donor_loss	1.0000	5
3:69937809–69937810	acceptor_gain	1.0000	3
3:69941324	donor_gain	1.0000
3:69949049–69949050	acceptor_loss	1.0000	6
3:69956450	acceptor_gain	1.0000
3:69959261	acceptor_gain	1.0000
3:69959267–69959268	acceptor_gain	1.0000	2
3:69959271–69959272	acceptor_loss	1.0000	6

HPA cancer prognostics

RNA cancer specificity: Cancer enhanced (Skin Cutaneous Melanoma)

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

1 prognostic cancer types:

Cancer	Prognostic	p-value
Kidney Renal Clear Cell Carcinoma (TCGA)	favorable	3.17e-06

Disease associations

OMIM: gene MIM:156845 | disease phenotypes: MIM:193510, MIM:103500, MIM:614456, MIM:617306, MIM:193500, MIM:128600, MIM:142500, MIM:124900

GenCC curated gene-disease

8 curated gene-disease records:

Disease	Classification	Inheritance	Records
Waardenburg syndrome type 2A	Definitive	Autosomal dominant	3
Tietz syndrome	Definitive	Autosomal dominant	3
Waardenburg syndrome type 2	Definitive	Autosomal dominant	3
melanoma, cutaneous malignant, susceptibility to, 8	Strong	Autosomal dominant	4
coloboma, osteopetrosis, microphthalmia, macrocephaly, albinism, and deafness	Strong	Autosomal recessive	3
Waardenburg syndrome	Moderate	Autosomal recessive
renal cell carcinoma	Moderate	Autosomal dominant
Waardenburg-Shah syndrome	Supportive	Autosomal dominant

ClinGen Gene-Disease Validity

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

1 validity classifications:

Disease	Classification	Inheritance
Waardenburg syndrome type 2	Definitive	AD

Genomics England panels (PanelApp)

Clinical diagnostic gene panels including this gene (8 panels, 5 green/diagnostic-grade). Confidence: green = diagnostic, amber = moderate.

8 panels:

Panel	Rating
DDG2P	green
Monogenic hearing loss	green
Paediatric disorders	green
Pigmentary skin disorders	green
Structural eye disease	green
Familial melanoma	amber
Fetal anomalies	amber
Inherited renal cancer	amber

Mondo (17): Waardenburg syndrome type 2A (MONDO:0008671), Tietz syndrome (MONDO:0007077), melanoma, cutaneous malignant, susceptibility to, 8 (MONDO:0013759), coloboma, osteopetrosis, microphthalmia, macrocephaly, albinism, and deafness (MONDO:0015014), Waardenburg syndrome (MONDO:0018094), hearing loss disorder (MONDO:0005365), ear malformation (MONDO:0007500), heterochromia iridis (MONDO:0007722), Waardenburg syndrome type 2 (MONDO:0019517), melanoma (MONDO:0005105), hereditary neoplastic syndrome (MONDO:0015356), familial melanoma (MONDO:0018961), autosomal dominant nonsyndromic hearing loss (MONDO:0019587), Waardenburg syndrome type 1 (MONDO:0008670), nonsyndromic genetic hearing loss (MONDO:0019497), renal cell carcinoma (MONDO:0005086), Waardenburg-Shah syndrome (MONDO:0019518)

Orphanet (12): Waardenburg syndrome (Orphanet:3440), MITF-related melanoma and renal cell carcinoma predisposition syndrome (Orphanet:293822), Tietz syndrome (Orphanet:42665), Coloboma-osteopetrosis-microphthalmia-macrocephaly-albinism-deafness syndrome (Orphanet:603494), Rare genetic deafness (Orphanet:96210), Waardenburg syndrome type 2 (Orphanet:895), Inherited cancer-predisposing syndrome (Orphanet:140162), Familial melanoma (Orphanet:618), Rare autosomal dominant non-syndromic sensorineural deafness type DFNA (Orphanet:90635), Waardenburg syndrome type 1 (Orphanet:894), Rare non-syndromic genetic deafness (Orphanet:87884), NON RARE IN EUROPE: Melanoma (Orphanet:411533)

HPO phenotypes

showing 60 of 74 phenotypes (HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000077	Abnormality of the kidney
HP:0000256	Macrocephaly
HP:0000347	Micrognathia
HP:0000358	Posteriorly rotated ears
HP:0000365	Hearing impairment
HP:0000366	Abnormality of the nose
HP:0000407	Sensorineural hearing impairment
HP:0000426	Prominent nasal bridge
HP:0000430	Underdeveloped nasal alae
HP:0000431	Wide nasal bridge
HP:0000478	Abnormality of the eye
HP:0000482	Microcornea
HP:0000488	Retinopathy
HP:0000504	Abnormality of vision
HP:0000506	Telecanthus
HP:0000508	Ptosis
HP:0000518	Cataract
HP:0000534	Abnormal eyebrow morphology
HP:0000568	Microphthalmia
HP:0000586	Shallow orbits
HP:0000589	Coloboma
HP:0000593	Abnormal anterior chamber morphology
HP:0000635	Blue irides
HP:0000664	Synophrys
HP:0000958	Dry skin
HP:0001000	Abnormal skin pigmentation
HP:0001010	Hypopigmentation of the skin
HP:0001022	Albinism
HP:0001053	Hypopigmented skin patches
HP:0001100	Heterochromia iridis
HP:0001103	Abnormal macular morphology
HP:0001252	Hypotonia
HP:0001341	Olfactory lobe agenesis
HP:0001480	Freckling
HP:0001595	Abnormal hair morphology
HP:0002007	Frontal bossing
HP:0002019	Constipation
HP:0002027	Abdominal pain
HP:0002071	Abnormality of extrapyramidal motor function
HP:0002211	White forelock
HP:0002216	Premature graying of hair
HP:0002226	White eyebrow
HP:0002227	White eyelashes
HP:0002242	Abnormal intestine morphology
HP:0002251	Aganglionic megacolon
HP:0002389	Cavum septum pellucidum
HP:0002861	Melanoma
HP:0002894	Neoplasm of the pancreas
HP:0003577	Congenital onset
HP:0003764	Nevus
HP:0004209	Clinodactyly of the 5th finger
HP:0004322	Short stature
HP:0004325	Decreased body weight
HP:0004414	Abnormality of the pulmonary artery
HP:0004467	Preauricular pit
HP:0004482	Relative macrocephaly
HP:0005214	Intestinal obstruction
HP:0005599	Hypopigmentation of hair

GWAS associations

showing 30 of 36 associations:

Study	Trait	p-value
GCST90002403_194	Red blood cell count	5e-33
GCST90002383_318	Hematocrit	3e-26
GCST90002384_451	Hemoglobin	3e-25
GCST010304_5	Cutaneous malignant melanoma	5e-25
GCST010083_13	Hemoglobin levels	2e-19
GCST90002402_583	Platelet count	2e-17
GCST006988_42	Blond vs. brown/black hair color	1e-13
GCST90002400_46	Plateletcrit	4e-13
GCST004601_138	Red blood cell count	1e-12
GCST010204_129	Low density lipoprotein cholesterol levels	3e-12
GCST010701_56	Cortical surface area (MOSTest)	9e-12
GCST003123_10	Severe influenza A (H1N1) infection	2e-11
GCST004604_79	Hematocrit	2e-11
GCST010866_104	Coronary artery disease	1e-10
GCST010243_40	Apolipoprotein B levels	2e-10
GCST004615_64	Hemoglobin concentration	4e-10
GCST010245_210	LDL cholesterol levels	5e-10
GCST010303_59	Nevus count or cutaneous melanoma	1e-9
GCST90002398_469	Neutrophil count	2e-9
GCST010083_7	Hemoglobin levels	3e-9
GCST007099_100	Systolic blood pressure	5e-9
GCST003872_6	QRS complex (12-leadsum)	9e-9
GCST010703_337	Brain morphology (MOSTest)	9e-9
GCST010699_22	Brain morphology (min-P)	2e-8
GCST90020027_950	Waist-hip index	2e-8
GCST010698_63	Subcortical volume (min-P)	3e-8
GCST90020027_949	Waist-hip index	4e-8
GCST007576_99	Chronotype	5e-8
GCST010244_412	Triglyceride levels	5e-8
GCST010702_51	Subcortical volume (MOSTest)	5e-8

EFO canonical traits (from GWAS)

20 canonical traits:

EFO ID	Trait name
EFO:1001488	influenza A (H1N1)
EFO:0005054	QRS complex
EFO:0007742	QRS amplitude
EFO:0004305	erythrocyte count
EFO:0004348	hematocrit
EFO:0004509	hemoglobin measurement
EFO:0003924	hair color
EFO:0005763	pulse pressure measurement
EFO:0006335	systolic blood pressure
EFO:0008328	chronotype measurement
EFO:0006527	smoking status measurement
EFO:0004611	low density lipoprotein cholesterol measurement
EFO:0004615	apolipoprotein B measurement
EFO:0004530	triglyceride measurement
EFO:0004632	nevus count
EFO:0004346	neuroimaging measurement
EFO:0004833	neutrophil count
EFO:0007985	platelet crit
EFO:0004309	platelet count
EFO:0007788	BMI-adjusted waist-hip ratio

MeSH disease descriptors

10 disease descriptors:

Descriptor	Name	Tree numbers
D002292	Carcinoma, Renal Cell	C04.557.470.200.025.390; C04.588.945.947.535.160; C12.050.351.937.820.535.160; C12.050.351.968.419.473.160; C12.200.758.820.750.160; C12.200.777.419.473.160; C12.900.820.535.160; C12.950.419.473.160; C12.950.983.535.160
D034381	Hearing Loss	C09.218.458.341; C10.597.751.418.341; C23.888.592.763.393.341
D008545	Melanoma	C04.557.465.625.650.510; C04.557.580.625.650.510; C04.557.665.510; C04.588.805.377; C17.800.882.445
D009386	Neoplastic Syndromes, Hereditary	C04.700; C16.320.700
D014849	Waardenburg Syndrome	C16.131.077.938
C538115	Heterochromia iridis *(supp.)*
C580334	Nonsyndromic Deafness *(supp.)*
C536919	Tietz syndrome *(supp.)*
C536463	Waardenburg syndrome type 2 *(supp.)*
C536464	Waardenburg syndrome type 2A *(supp.)*

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL1741165 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

Phase ≥1, by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 151,095 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

3 molecules by phase:

Molecule	Name	Phase	Patents
CHEMBL1334033	PERHEXILINE MALEATE	4	1,063
CHEMBL244888	NIFUROXAZIDE	3	1,475
CHEMBL284328	HOMIDIUM BROMIDE	2	148,557

PharmGKB: 1 entry (CPIC guideline: no)

ChEMBL bioactivities

1851 potent at pChembl≥5 of 3024 total, top 34 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.72	AC50	19	nM	CHEMBL1971760
7.64	AC50	23	nM	CHEMBL1521172
7.62	AC50	24	nM	CHEMBL1470676
7.52	AC50	30	nM	CHEMBL1507250
7.41	AC50	39	nM	CHEMBL1342896
7.25	AC50	56	nM	CHEMBL1573994
7.25	AC50	56	nM	CHEMBL87
6.91	AC50	122	nM	CHEMBL1299637
6.77	AC50	171	nM	CHEMBL1307091
6.76	AC50	175	nM	CHEMBL1701797
6.56	AC50	275	nM	CHEMBL1559811
6.53	AC50	293	nM	CHEMBL1718830
6.48	AC50	333	nM	CHEMBL3199673
6.48	AC50	329	nM	CHEMBL1537098
6.47	AC50	337	nM	CHEMBL1534546
6.44	AC50	365	nM	CHEMBL1312935
6.43	AC50	371	nM	CHEMBL1370991
6.31	AC50	487	nM	CHEMBL1394409
6.30	AC50	495	nM	CHEMBL1352969
6.29	AC50	511	nM	CHEMBL1518647
6.28	AC50	528	nM	CHEMBL1699881
6.24	AC50	577	nM	CHEMBL1400379
6.22	AC50	601	nM	CHEMBL373137
6.22	AC50	599	nM	CHEMBL1386804
6.22	AC50	601	nM	CHEMBL1601979
6.18	AC50	666	nM	CHEMBL1513566
6.17	AC50	681	nM	CHEMBL1698608
6.16	AC50	696	nM	CHEMBL1976507
6.12	AC50	756	nM	CHEMBL1570216
6.06	AC50	875	nM	8-AZAGUANINE
6.06	AC50	866	nM	CHEMBL1468011
6.05	AC50	899	nM	CHEMBL1336277
6.05	AC50	894	nM	CHEMBL1321427
6.04	AC50	921	nM	CHEMBL1305475

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, decreases expression	7
trichostatin A	affects cotreatment, increases expression, affects expression	4
sodium arsenite	affects methylation, decreases reaction, increases expression, affects cotreatment, decreases expression (+1 more)	4
Cyclosporine	decreases expression, increases methylation	3
mercuric bromide	increases expression, affects cotreatment	2
2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one	increases degradation, decreases reaction, increases expression, affects cotreatment	2
Air Pollutants	increases expression, affects cotreatment, affects expression, increases abundance	2
Benzo(a)pyrene	decreases expression, increases methylation	2
Estradiol	affects cotreatment, increases expression, decreases expression	2
Colforsin	increases expression	2
Ozone	increases expression, affects cotreatment, affects expression, increases abundance	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Cadmium Chloride	decreases expression	2
aristolochic acid I	decreases expression	1
4-(4-cyanophenyl)-2-(2-cyclopentylidenehydrazinyl)thiazole	decreases expression	1
FR900359	affects phosphorylation	1
bisphenol F	increases expression	1
TAK-243	decreases sumoylation	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, affects expression, increases abundance	1
pirinixic acid	affects binding, decreases expression, increases activity	1
bisphenol A	affects methylation, affects cotreatment, decreases methylation	1
methylselenic acid	increases expression	1
arsenite	affects binding, decreases reaction	1
manganese chloride	decreases expression, increases abundance, affects cotreatment	1
benzo(e)pyrene	increases methylation	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
4-hydroxy-2-nonenal	decreases expression	1
nickel sulfate	increases expression	1
coumarin	affects phosphorylation	1

ChEMBL screening assays

10 unique, capped per target: 10 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1737866	Functional	PUBCHEM_BIOASSAY: MITF Measured in Cell-Based System Using Plate Reader - 2084-01_Inhibitor_DoseNoFile_CherryPick_Activity_Set2. (Class of assay: confirmatory) [Related pubchem assays (depositor defined):AID488944]	PubChem BioAssay data set

Cellosaurus cell lines

9 cell lines: 5 cancer cell line, 3 embryonic stem cell, 1 induced pluripotent stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_A1MU	CSUXHi003-A	Induced pluripotent stem cell	Male
CVCL_A4D7	SEES3-1V human MITF, clone1	Embryonic stem cell	Male
CVCL_A4D8	SEES3-1V human MITF, clone2	Embryonic stem cell	Male
CVCL_A4D9	SEES3-1V human MITF, clone3	Embryonic stem cell	Male
CVCL_B8KI	Abcam HCT 116 MITF KO	Cancer cell line	Male
CVCL_B8YV	Abcam MCF-7 MITF KO	Cancer cell line	Female
CVCL_B9MS	Abcam A-549 MITF KO	Cancer cell line	Male
CVCL_SY42	HAP1 MITF (-)	Cancer cell line	Male
CVCL_VJ84	11CM	Cancer cell line	Sex unspecified

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.

showing 60 of 599 trials:

NCT	Phase	Status	Title
NCT00414765	Phase 4	COMPLETED	Aldesleukin in Participants With Metastatic Renal Cell Carcinoma or Metastatic Melanoma
NCT00777504	Phase 4	UNKNOWN	Study to the Optimal Duration of Therapy With Oral Angiogenesis Inhibitors
NCT00930345	Phase 4	TERMINATED	Biological, Pathological and Imagery Markers in the First-line Treatment of Metastatic Clear-cell Renal Cell Carcinoma
NCT01206764	Phase 4	COMPLETED	A Trial of Everolimis in Patients With Advanced Renal Cell Carcinoma.
NCT01266837	Phase 4	COMPLETED	Open Label, Single Arm Trial to Characterize Patients With Metastatic RCC Treated With Everolimus After Failure of the First VEGF-targeted Therapy (MARC-2)
NCT02056587	Phase 4	COMPLETED	Everolimus in Patients With Metastatic Renal Cell Carcinoma Following Progression on Prior Bevacizumab Treatment
NCT02338570	Phase 4	TERMINATED	Outcome-related Factors in Patients With Metastatic Renal Cell Carcinoma Treated With Everolimus (ORCHIDEE)
NCT02596035	Phase 4	COMPLETED	An Investigational Immuno-therapy Safety Trial of Nivolumab in Patients With Advanced or Metastatic Renal Cell Carcinoma
NCT02982954	Phase 4	COMPLETED	A Study to Evaluate the Safety of Nivolumab and Ipilimumab in Subjects With Previously Untreated Advanced or Metastatic Renal Cell Cancer
NCT05949424	Phase 4	UNKNOWN	OPTI - DOSE: Optimal Dosing of Oral Anticancer Drugs in Older Adults
NCT07028125	Phase 4	RECRUITING	Digital Monitoring of Self-reported Symptoms by Patients Treated With Cabozantinib Plus Nivolumab for Advanced Clear-cell Renal Carcinoma
NCT07405086	Phase 4	RECRUITING	Morning Versus Afternoon Administration of Immunotherapy for the Treatment of Advanced or Metastatic Solid Tumors, The Knight SHIFT Study
NCT00205881	Phase 4	COMPLETED	Bilateral Benefit in Adult Users of the HiRes 90K Bionic Ear System
NCT00331539	Phase 4	UNKNOWN	Relationship Between Auto NRT and Behavioural T & C Levels With the Nucleus Freedom Cochlear Implant
NCT00424307	Phase 4	UNKNOWN	Bilateral Cochlear Implant Benefit in Young Children
NCT00765635	Phase 4	COMPLETED	Chlorobutanol, Potassium Carbonate, and Irrigation in Cerumen Removal
NCT03321006	Phase 4	COMPLETED	Treating Hearing Loss to Improve Mood and Cognition in Older Adults
NCT00033904	Phase 3	COMPLETED	Survival Study Of Oncophage® vs. Observation In Patients With Kidney Cancer
NCT00126178	Phase 3	TERMINATED	Clinical Trial Studying a Personalized Cancer Vaccine in Patients With Non-metastatic Kidney Cancer
NCT00291369	Phase 3	COMPLETED	Cytokines in Patients With Metastatic Renal Cell Carcinoma of Intermediate Prognosis
NCT00410124	Phase 3	COMPLETED	RAD001 Plus Best Supportive Care (BSC) Versus BSC Plus Placebo in Patients With Metastatic Carcinoma of the Kidney Which Has Progressed After Treatment With Sorafenib and/or Sunitinib
NCT00474786	Phase 3	COMPLETED	Temsirolimus Versus Sorafenib As Second-Line Therapy In Patients With Advanced RCC Who Have Failed First-Line Sunitinib
NCT00478114	Phase 3	COMPLETED	Efficacy and Safety of Sorafenib in Advanced Renal Cell Carcinoma (RCC)
NCT00606632	Phase 3	COMPLETED	Pre-surgical Detection of Clear Cell Renal Cell Carcinoma (ccRCC) Using Radiolabeled G250-Antibody
NCT00606866	Phase 3	COMPLETED	MRI Study of BAY 43-9006 in Metastatic Renal Cell Carcinoma
NCT00631371	Phase 3	COMPLETED	Study Comparing Bevacizumab + Temsirolimus vs. Bevacizumab + Interferon-Alfa In Advanced Renal Cell Carcinoma Subjects
NCT00732914	Phase 3	COMPLETED	Sequential Study to Treat Renal Cell Carcinoma
NCT00869011	Phase 3	UNKNOWN	Exercise for Patients With Renal Cell Cancer Receiving Sunitinib
NCT00930033	Phase 3	COMPLETED	Clinical Trial to Assess the Importance of Nephrectomy
NCT01030783	Phase 3	COMPLETED	A Study to Compare Tivozanib (AV-951) to Sorafenib in Subjects With Advanced Renal Cell Carcinoma
NCT01076010	Phase 3	COMPLETED	An Extension Treatment Protocol for Subjects Who Have Participated in a Study of Tivozanib Versus Sorafenib in Kidney Carcinoma (Protocol AV-951-09-301).
NCT01198158	Phase 3	TERMINATED	Everolimus With or Without Bevacizumab in Treating Patients With Advanced Kidney Cancer That Progressed After First-Line Therapy
NCT01223027	Phase 3	COMPLETED	Study of Dovitinib Versus Sorafenib in Patients With Metastatic Renal Cell Carcinoma
NCT01224288	Phase 3	ACTIVE_NOT_RECRUITING	Dynamic Contrast Enhancement Computed Tomography for Evaluating Tumor Perfusion in Patients With Metastatic Renal Cell Carcinoma Receiving Targeted Therapies: Renal Cell Carcinoma (RCC) Scramble
NCT01235962	Phase 3	COMPLETED	A Study to Evaluate Pazopanib as an Adjuvant Treatment for Localized Renal Cell Carcinoma (RCC)
NCT01265810	Phase 3	COMPLETED	Caphosol in Oral Mucositis Due to Targeted Therapy
NCT01265901	Phase 3	COMPLETED	IMA901 in Patients Receiving Sunitinib for Advanced/Metastatic Renal Cell Carcinoma
NCT01481870	Phase 3	UNKNOWN	Comparison of Sequential Therapies With Sunitinib and Sorafenib in Advanced Renal Cell Carcinoma
NCT01582672	Phase 3	TERMINATED	Phase 3 Trial of Autologous Dendritic Cell Immunotherapy Plus Standard Treatment of Advanced Renal Cell Carcinoma
NCT01613846	Phase 3	COMPLETED	Phase III Sequential Open-label Study to Evaluate the Efficacy and Safety of Sorafenib Followed by Pazopanib Versus Pazopanib Followed by Sorafenib in the Treatment of Advanced / Metastatic Renal Cell Carcinoma (SWITCH-II)
NCT01762592	Phase 3	WITHDRAWN	REDECT 2: REnal Masses: Pivotal Trial to DEteCT Clear Cell Renal Cell Carcinoma With PET/CT
NCT01865747	Phase 3	COMPLETED	A Study of Cabozantinib (XL184) vs Everolimus in Subjects With Metastatic Renal Cell Carcinoma
NCT02231749	Phase 3	COMPLETED	Nivolumab Combined With Ipilimumab Versus Sunitinib in Previously Untreated Advanced or Metastatic Renal Cell Carcinoma (CheckMate 214)
NCT02420821	Phase 3	COMPLETED	A Study of Atezolizumab in Combination With Bevacizumab Versus Sunitinib in Participants With Untreated Advanced Renal Cell Carcinoma (RCC)
NCT02811861	Phase 3	ACTIVE_NOT_RECRUITING	Lenvatinib/Everolimus or Lenvatinib/Pembrolizumab Versus Sunitinib Alone as Treatment of Advanced Renal Cell Carcinoma
NCT02853331	Phase 3	COMPLETED	Study to Evaluate the Efficacy and Safety of Pembrolizumab (MK-3475) in Combination With Axitinib Versus Sunitinib Monotherapy in Participants With Renal Cell Carcinoma (MK-3475-426/KEYNOTE-426)
NCT03024996	Phase 3	TERMINATED	A Study of Atezolizumab as Adjuvant Therapy in Participants With Renal Cell Carcinoma (RCC) at High Risk of Developing Metastasis Following Nephrectomy
NCT03055013	Phase 3	ACTIVE_NOT_RECRUITING	Nivolumab in Treating Patients With Localized Kidney Cancer Undergoing Nephrectomy
NCT03141177	Phase 3	COMPLETED	A Study of Nivolumab Combined With Cabozantinib Compared to Sunitinib in Previously Untreated Advanced or Metastatic Renal Cell Carcinoma
NCT03142334	Phase 3	COMPLETED	Safety and Efficacy Study of Pembrolizumab (MK-3475) as Monotherapy in the Adjuvant Treatment of Renal Cell Carcinoma Post Nephrectomy (MK-3475-564/KEYNOTE-564)
NCT03260894	Phase 3	COMPLETED	Pembrolizumab (MK-3475) Plus Epacadostat vs Standard of Care in mRCC (KEYNOTE-679/ECHO-302)
NCT03288532	Phase 3	RECRUITING	Renal Adjuvant MultiPle Arm Randomised Trial
NCT03408652	Phase 3	TERMINATED	Efficacy and Safety of Systemic Treatments of Bone Metastases From Kidney Cancer in Patients Treated With Targeted Therapies
NCT03592472	Phase 3	RECRUITING	A Study of Pazopanib With or Without Abexinostat in Patients With Locally Advanced or Metastatic Renal Cell Carcinoma (RENAVIV)
NCT03693573	Phase 3	WITHDRAWN	A Study of Atezolizumab in Combination With Bevacizumab in Untreated Locally Advanced or Metastatic Clear Cell or Non-Clear Cell Renal Cell Carcinoma
NCT03729245	Phase 3	TERMINATED	A Study of Bempegaldesleukin (NKTR-214: BEMPEG) in Combination With Nivolumab Compared With the Investigator’s Choice of a Tyrosine Kinase Inhibitor (TKI) Therapy (Either Sunitinib or Cabozantinib Monotherapy) for Advanced Metastatic Renal Cell Carcinoma (RCC)
NCT03873402	Phase 3	ACTIVE_NOT_RECRUITING	A Study of Nivolumab Combined With Ipilimumab Versus Nivolumab Alone in Participants With Advanced Kidney Cancer
NCT03937219	Phase 3	ACTIVE_NOT_RECRUITING	Study of Cabozantinib in Combination With Nivolumab and Ipilimumab in Patients With Previously Untreated Advanced or Metastatic Renal Cell Carcinoma
NCT04510597	Phase 3	RECRUITING	Comparing the Outcome of Immunotherapy-Based Drug Combination Therapy With or Without Surgery to Remove the Kidney in Metastatic Kidney Cancer, the PROBE Trial
NCT04588246	Phase 3	TERMINATED	Comparing Whole Brain Radiotherapy Using a Technique That Avoids the Hippocampus to Stereotactic Radiosurgery in Patients With Cancer That Has Spread to the Brain and Come Back in Other Areas of the Brain After Earlier Stereotactic Radiosurgery

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for MITF across ~30M SureChEMBL compounds — explore on Sugi Predict.