MN1

Summary

MN1 (MN1 proto-oncogene, transcriptional regulator, HGNC:7180) is a protein-coding gene on chromosome 22q12.1, encoding Transcriptional activator MN1 (Q10571). Transcriptional activator which specifically regulates expression of TBX22 in the posterior region of the developing palate.

Meningioma 1 (MN1) contains two sets of CAG repeats. It is disrupted by a balanced translocation (4;22) in a meningioma, and its inactivation may contribute to meningioma 32 pathogenesis.

Source: NCBI Gene 4330 — RefSeq curated summary.

At a glance

• Gene–disease (curated): CEBALID syndrome (Definitive, ClinGen) — +1 more curated relationship
• GWAS associations: 31
• Clinical variants (ClinVar): 489 total — 13 pathogenic, 15 likely-pathogenic
• Phenotypes (HPO): 40
• MANE Select transcript: NM_002430

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:7180
Approved symbol	MN1
Name	MN1 proto-oncogene, transcriptional regulator
Location	22q12.1
Locus type	gene with protein product
Status	Approved
Aliases	MGCR1-PEN, MGCR1
Ensembl gene	ENSG00000169184
Ensembl biotype	protein_coding
OMIM	156100
Entrez	4330

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 2 protein_coding_CDS_not_defined, 1 protein_coding, 1 nonsense_mediated_decay

ENST00000302326, ENST00000424656, ENST00000497225, ENST00000703102

RefSeq mRNA: 1 — MANE Select: NM_002430 NM_002430

CCDS: CCDS42998

Canonical transcript exons

ENST00000302326 — 2 exons

Exon	Start	End
ENSE00001150378	27748277	27751096
ENSE00001150385	27796763	27801756

Expression profiles

Bgee: expression breadth ubiquitous, 252 present calls, max score 97.52.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 13.5050 / max 344.9965, expressed in 1274 samples.

FANTOM5 promoters (12 alternative TSS)

Promoter ID	TPM avg	Samples expressed
193471	10.6153	1219
193469	0.8016	393
193461	0.5664	291
193470	0.3041	103
193468	0.2850	152
193467	0.2277	107
193466	0.2179	91
193472	0.2156	99
193474	0.1005	38
193465	0.0699	24

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ganglionic eminence	UBERON:0004023	97.52	gold quality
vastus lateralis	UBERON:0001379	96.17	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	95.98	gold quality
cortical plate	UBERON:0005343	95.95	gold quality
quadriceps femoris	UBERON:0001377	95.84	gold quality
biceps brachii	UBERON:0001507	95.32	gold quality
triceps brachii	UBERON:0001509	95.10	gold quality
skeletal muscle tissue	UBERON:0001134	94.56	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	94.03	gold quality
hindlimb stylopod muscle	UBERON:0004252	93.83	gold quality
muscle organ	UBERON:0001630	92.62	gold quality
ventricular zone	UBERON:0003053	91.93	gold quality
deltoid	UBERON:0001476	91.85	gold quality
body of tongue	UBERON:0011876	91.75	gold quality
muscle of leg	UBERON:0001383	91.56	gold quality
gastrocnemius	UBERON:0001388	91.56	gold quality
embryo	UBERON:0000922	91.48	gold quality
muscle tissue	UBERON:0002385	90.86	gold quality
gluteal muscle	UBERON:0002000	90.69	gold quality
saphenous vein	UBERON:0007318	90.40	gold quality
diaphragm	UBERON:0001103	89.58	gold quality
blood vessel layer	UBERON:0004797	89.30	gold quality
lateral globus pallidus	UBERON:0002476	89.07	gold quality
tibialis anterior	UBERON:0001385	88.77	gold quality
popliteal artery	UBERON:0002250	87.79	gold quality
tibial artery	UBERON:0007610	87.77	gold quality
urethra	UBERON:0000057	87.35	gold quality
artery	UBERON:0001637	87.07	gold quality
pericardium	UBERON:0002407	86.22	gold quality
aorta	UBERON:0000947	86.04	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	10.62

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

3 targets.

Target	Regulation
IGFBP5
TBX22
TNFSF11

miRNA regulators (miRDB)

169 targeting MN1, 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-190A-3P	100.00	80.35	5520
HSA-MIR-6798-5P	100.00	65.77	699
HSA-MIR-4455	100.00	65.48	1587
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-518D-5P	100.00	67.51	979
HSA-MIR-518E-5P	100.00	67.66	954
HSA-MIR-518F-5P	100.00	67.51	979
HSA-MIR-519A-5P	100.00	67.66	954
HSA-MIR-519B-5P	100.00	67.66	954
HSA-MIR-519C-5P	100.00	67.66	954
HSA-MIR-520C-5P	100.00	67.51	979
HSA-MIR-522-5P	100.00	67.66	954
HSA-MIR-523-5P	100.00	67.66	954
HSA-MIR-526A-5P	100.00	67.51	979
HSA-MIR-520G-5P	99.99	66.76	658
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-9-3P	99.96	70.88	2068
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-141-3P	99.94	72.79	2421

Literature-anchored findings (GeneRIF, showing 40)

• MN1 is a 1,25-(OH)2D3-induced vitamin D receptor coactivator that also may have critical roles in modulating osteoblast proliferation. (PMID:15890672)
• MN1-translocation-ETS-leukemia exerts its nonlineage-specific leukemogenic effects by promoting the growth of primitive progenitors and blocking their differentiation (PMID:16081688)
• leukemogenic effect of MN1-ets variant gene 6 L in our knock-in mice is pleiotropic, and the type of secondary mutation determines disease outcome (PMID:16105979)
• Up-regulates Insulin-Like Growth Factor Binding Protein 5 at a specific promoter consensus sequence. (PMID:17242174)
• MN1 is a unique oncogene in hematopoiesis that both promotes proliferation/self-renewal and blocks differentiation, and may become useful as a predictive marker in AML treatment. (PMID:17494859)
• MN1 overexpression is associated with the development of inv(16) acute myeloid leukemia (PMID:17525718)
• role of MN1 in myeloid leukemia [review] (PMID:17698380)
• MN1 and MN1-TEL interfere with the ATRA pathway and this might explain the differentiation block in leukemias in which these genes are involved. (PMID:18632758)
• Data demonstrate that MN1 overexpression correlates with progression from MDS to sAML and therefore might be involved in the pathogenesis of sAML (PMID:19391034)
• MN1 expression independently predicts outcome in cytogenetically normal acute myeloid leukemia (PMID:19451432)
• Down-regulation of CEBPA activity contributes to MN1-modulated proliferation and impaired myeloid differentiation of hematopoietic cells. (PMID:19561324)
• high MN1 levels are important for the growth of leukemic cells, and that increased MN1 expression can synergize with MLL-ENL and probably other transforming fusion genes in leukemia induction. (PMID:20072157)
• MN1-ETV6 fusion gene arising from Myelodysplastic Syndrome with 5q trisomy is associated with acute myeloid leukemia. (PMID:21600651)
• low MN1 expression confers better prognosis in older CN-AML patients and may refine the European LeukemiaNet classification. Biologic features associated with MN1 expression may help identify new treatment targets. (PMID:21828125)
• analysis of genetic variants hints at the contribution of TGFB3 and MN1 in the aetiology of submucous cleft palate (PMID:22409215)
• A high MEBE (MN1,ERG, BAALC, EVI1) expression score is an unfavorable prognostic marker in Myelodysplastic syndrome and is associated with an increased risk for progression to Acute myeloid leukemia. (PMID:22488406)
• Overexpression of MN1 confers resistance to chemotherapy, accelerates leukemia onset, and suppresses p53 and Bim induction (PMID:22905229)
• MN1 overexpression independently predicts bad clinical outcome in CN-AML patients (PMID:23394438)
• High MN1 expression confers worse prognosis in Chinese adult patients with de novo acute myeloid leukemia. (PMID:23515710)
• cotransduction of an activated HOX gene (NUP98HOXD13) with MN1 induces a serially transplantable acute myeloid leukemia (AML). (PMID:25339361)
• identified potential driver mutations in NF2 (neurofibromatosis type 2) and MN1 (meningioma 1). (PMID:25549701)
• genotype-phenotype correlation among our patients and those previously reported with overlapping 22q12 deletions, we identified a 560 kb critical region containing the MN1 gene that is implicated in human cleft palate formation (PMID:25810350)
• Chromosome 22q12.1 microdeletions involving the MN1 gene confirm it as a candidate gene for cleft palate. (PMID:25944382)
• these results suggest that deregulated MN1 expression contributes to the pathogenesis of pediatric B-ALL. (PMID:26111797)
• MN1 deletion is associated with Craniofacial Abnormalities. (PMID:26545049)
• MLL1 and DOT1L cooperate with meningioma-1 to induce acute myeloid leukemia. (PMID:26927674)
• The data obtained show that normal cells consistently express low levels of MN1 transcript. In contrast, high levels of MN1 expression are present in 47% of patients with normal karyotype and in all cases with inv(16). (PMID:27765915)
• MN1 gene expression in acute myeloid leukemia. (PMID:27983532)
• Study suggests a role for DNMT3B in leukemogenesis in inv(16) acute myeloid leukemia, through MN1 methylation regulation. (PMID:28892045)
• Patients with t(12;22)/MN1-EVT6 oncogene, are frequently associated with myeloid neoplasms, poor response to chemotherapy, and inferior outcome. (PMID:29273914)
• MN1-rearranged astroblastoma brain tumors were characterized by better overall survival compared to other genetic subtypes. (PMID:30876455)
• results indicate that (1) high levels of MN1 expression contribute to poor colorectal cancer (CRC) prognosis and (2) MN1 can serve as a novel potential biomarker in predicting the prognosis of CRC patients. (PMID:31133374)
• Meningioma 1 is indispensable for mixed lineage leukemia-rearranged acute myeloid leukemia. (PMID:31413090)
• MN1 C-terminal truncation syndrome is a novel neurodevelopmental and craniofacial disorder with partial rhombencephalosynapsis. (PMID:31834374)
• Gain-of-Function MN1 Truncation Variants Cause Craniofacial and Brain Abnormalities. (PMID:31839203)
• Spinal cord astroblastoma with an EWSR1-BEND2 fusion classified as a high-grade neuroepithelial tumour with MN1 alteration. (PMID:31863478)
• MN1 Linked to Syndrome Characterized by Craniofacial Abnormalities and Severe Developmental Delay. (PMID:32153127)
• Allogeneic stem cell transplantation mitigates the adverse prognostic impact of high diagnostic BAALC and MN1 expression in AML. (PMID:32862286)
• MN1 overexpression with varying tumor grade is a promising predictor of survival of glioma patients. (PMID:33105486)
• Frequent MN1 Gene Mutations in Malignant Peripheral Nerve Sheath Tumor. (PMID:33109559)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	mn1a	ENSDARG00000076529
danio_rerio	mn1b	ENSDARG00000079248
mus_musculus	Mn1	ENSMUSG00000070576
rattus_norvegicus	Mn1	ENSRNOG00000027489

Protein

Protein identifiers

Transcriptional activator MN1 — Q10571 (reviewed: Q10571)

Alternative names: Probable tumor suppressor protein MN1

All UniProt accessions (2): Q10571, H7C105

UniProt curated annotations — full annotation on UniProt →

Function. Transcriptional activator which specifically regulates expression of TBX22 in the posterior region of the developing palate. Required during later stages of palate development for growth and medial fusion of the palatal shelves. Promotes maturation and normal function of calvarial osteoblasts, including expression of the osteoclastogenic cytokine TNFSF11/RANKL. Necessary for normal development of the membranous bones of the skull. May play a role in tumor suppression.

Subunit / interactions. Interacts with PBX1, PKNOX1, ZBTB24, E2F7, RING1.

Subcellular location. Nucleus.

Tissue specificity. Widely expressed in fetal and adult tissues. Highest expression is observed in fetal brain and skeletal muscle, and adult skeletal muscle.

Disease relevance. CEBALID syndrome (CEBALID) [MIM:618774] An autosomal dominant developmental disorder characterized by global developmental delay, intellectual disability with severe expressive language delay, craniofacial dysmorphism, and structural brain abnormalities. Most patients have an atypical form of rhombencephalosynapsis, a distinctive brain malformation characterized by partial or complete loss of the cerebellar vermis with fusion of the cerebellar hemispheres. Other frequent features include perisylvian polymicrogyria, abnormal posterior clinoid processes, cerebellar hypoplasia or dysplasia, and persistent trigeminal artery. The disease is caused by variants affecting the gene represented in this entry. A chromosomal aberration involving MN1 may be a cause of acute myeloid leukemia (AML). Translocation t(12;22)(p13;q11) with ETV6. Defects in MN1 involved in the development of meningiomas, slowly growing benign tumors derived from the arachnoidal cap cells of the leptomeninges, the soft coverings of the brain and spinal cord. Meningiomas are believed to be the most common primary tumors of the central nervous system in man.

RefSeq proteins (1): NP_002421* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR037644	MN1	Family

UniProt features (40 total): compositionally biased region 17, region of interest 9, sequence variant 8, modified residue 5, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q10571-F1	42.47	0.02

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 (5): 1, 950, 954, 1007, 1081

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 303 (showing top): VERHAAK_AML_WITH_NPM1_MUTATED_DN, YAATNRNNNYNATT_UNKNOWN, BROWNE_HCMV_INFECTION_6HR_DN, YAGI_AML_WITH_INV_16_TRANSLOCATION, GOBP_CELLULAR_RESPONSE_TO_LIPID, LI_WILMS_TUMOR, GOBP_CELL_CYCLE_PHASE_TRANSITION, GGGTGGRR_PAX4_03, MYLLYKANGAS_AMPLIFICATION_HOT_SPOT_22, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, CHANDRAN_METASTASIS_DN, SP1_Q2_01, SENESE_HDAC1_AND_HDAC2_TARGETS_DN, WATANABE_ULCERATIVE_COLITIS_WITH_CANCER_UP, KRASNOSELSKAYA_ILF3_TARGETS_DN

GO Biological Process (5): intramembranous ossification (GO:0001957), regulation of DNA-templated transcription (GO:0006355), negative regulation of osteoblast proliferation (GO:0033689), positive regulation of vitamin D receptor signaling pathway (GO:0070564), regulation of cell cycle G1/S phase transition (GO:1902806)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (1): nucleus (GO:0005634)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
direct ossification	1
DNA-templated transcription	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
negative regulation of cell population proliferation	1
osteoblast proliferation	1
regulation of osteoblast proliferation	1
vitamin D receptor signaling pathway	1
regulation of vitamin D receptor signaling pathway	1
positive regulation of intracellular signal transduction	1
cell cycle G1/S phase transition	1
regulation of cell cycle phase transition	1
binding	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

860 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MN1	HSPB8	Q9UJY1	763
MN1	BEND2	Q8NDZ0	687
MN1	GARS1	P41250	685
MN1	IGHMBP2	P38935	649
MN1	ETV6	P41212	615
MN1	AP1B1	P78436	614
MN1	ACSL6	Q9UKU0	571
MN1	ACSL5	Q9ULC5	559
MN1	CXCL11	O14625	549
MN1	DCTN1	Q14203	549
MN1	HSPB3	Q12988	547
MN1	NPM1	P06748	544
MN1	KANSL3	Q9P2N6	512
MN1	FLT3	P36888	506
MN1	BSCL2	Q96G97	505

IntAct

8 interactions, top by confidence:

A	B	Type	Score
LMO1	ZBTB43	psi-mi:“MI:0914”(association)	0.830
LMO3	ZBTB43	psi-mi:“MI:0914”(association)	0.550
Dlg4	MN1	psi-mi:“MI:0407”(direct interaction)	0.440
MN1	PADI6	psi-mi:“MI:0915”(physical association)	0.400
Prdm16	ESYT2	psi-mi:“MI:0914”(association)	0.350
LMO2	APBB1	psi-mi:“MI:0914”(association)	0.350
LMO2	POLR2D	psi-mi:“MI:0914”(association)	0.350

BioGRID (34): EP300 (Reconstituted Complex), NCOA3 (Reconstituted Complex), MN1 (Affinity Capture-MS), MN1 (Affinity Capture-RNA), DDX39A (Affinity Capture-MS), TPM3 (Affinity Capture-MS), PBX1 (Affinity Capture-MS), PKNOX1 (Affinity Capture-MS), PRKDC (Affinity Capture-MS), EEF1A1P5 (Affinity Capture-MS), TNPO1 (Affinity Capture-MS), ZBTB24 (Affinity Capture-MS), PRC1 (Affinity Capture-MS), TOP2A (Affinity Capture-MS), KRT10 (Affinity Capture-MS)

ESM2 similar proteins: A1YFU7, A2AJK6, A2BH40, B2RWS6, D3YWE6, E9Q4N7, M9NEY8, O00512, O14497, O35126, O42368, O43365, O57401, P02831, P02833, P22810, P23441, P23512, P25822, P32182, P34545, P35582, P35583, P43698, P43699, P50220, P50901, P54258, P54259, P54269, P55317, Q06A37, Q08DG7, Q08E31, Q09472, Q0VCT9, Q10571, Q1KKX7, Q24248, Q24645

Diamond homologs: D3YWE6, Q10571

SIGNOR signaling

5 interactions.

A	Effect	B	Mechanism
EP300	up-regulates	MN1	binding
MN1	up-regulates	Proliferation
MN1	down-regulates	Differentiation
MN1	“up-regulates activity”	EP300	binding
MN1	“up-regulates activity”	MYBBP1A	binding

Disease & clinical

Cancer significance

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	13
Likely pathogenic	15
Uncertain significance	355
Likely benign	73
Benign	14

Top pathogenic / likely-pathogenic (28)

Variant ID	HGVS	Classification
1027391	NM_002430.3(MN1):c.3555C>A (p.Cys1185Ter)	Pathogenic
1709292	NM_002430.3(MN1):c.2464C>T (p.Gln822Ter)	Pathogenic
2443358	NM_002430.3(MN1):c.3794del (p.Pro1265fs)	Pathogenic
3179664	NM_002430.3(MN1):c.1627C>T (p.Gln543Ter)	Pathogenic
3397250	NM_002430.3(MN1):c.922C>T (p.Gln308Ter)	Pathogenic
4527027	NM_002430.3(MN1):c.2301del (p.Ser768fs)	Pathogenic
4625130	NM_002430.3(MN1):c.1827del (p.Ser609fs)	Pathogenic
4818986	NM_002430.3(MN1):c.176dup (p.Ile60fs)	Pathogenic
812559	NM_002430.3(MN1):c.3817C>T (p.Gln1273Ter)	Pathogenic
812563	NM_002430.3(MN1):c.3835C>T (p.Gln1279Ter)	Pathogenic
812564	NM_002430.3(MN1):c.3846_3849del (p.Val1283fs)	Pathogenic
978210	NM_002430.3(MN1):c.1415C>A (p.Ser472Ter)	Pathogenic
984651	NM_002430.3(MN1):c.3900del (p.Trp1301fs)	Pathogenic
1333278	NM_002430.3(MN1):c.3680G>A (p.Trp1227Ter)	Likely pathogenic
1699334	NM_002430.3(MN1):c.3953C>A (p.Ala1318Asp)	Likely pathogenic
2443066	NM_002430.3(MN1):c.3822del (p.Gly1275fs)	Likely pathogenic
2572388	NM_002430.3(MN1):c.1363A>T (p.Lys455Ter)	Likely pathogenic
2572438	NM_002430.3(MN1):c.487G>T (p.Glu163Ter)	Likely pathogenic
2576072	NM_002430.3(MN1):c.2063del (p.Gly688fs)	Likely pathogenic
4292252	NM_002430.3(MN1):c.3474_3484del (p.Gln1159fs)	Likely pathogenic
4294434	NM_002430.3(MN1):c.736_737del (p.Met246fs)	Likely pathogenic
812558	NM_002430.3(MN1):c.3745G>T (p.Glu1249Ter)	Likely pathogenic
979028	Single allele	Likely pathogenic
979061	NM_002430.3(MN1):c.3730_3731insAAGAC (p.Thr1244fs)	Likely pathogenic
979062	NM_002430.3(MN1):c.3849_3850delinsA (p.His1284fs)	Likely pathogenic
979063	NM_002430.3(MN1):c.3893_3894dup (p.Pro1299fs)	Likely pathogenic
979064	NM_002430.3(MN1):c.536del (p.Ser178_Ser179insTer)	Likely pathogenic
979065	NM_002430.3(MN1):c.1091dup (p.Pro365fs)	Likely pathogenic

SpliceAI

685 predictions. Top by Δscore:

Variant	Effect	Δscore
22:27751092:GTGGG:G	acceptor_gain	0.9900
22:27751093:TGGG:T	acceptor_gain	0.9900
22:27751094:GGG:G	acceptor_gain	0.9900
22:27751095:GG:G	acceptor_gain	0.9900
22:27751095:GGCT:G	acceptor_loss	0.9900
22:27751096:GC:G	acceptor_loss	0.9900
22:27751097:C:CC	acceptor_gain	0.9900
22:27751099:G:C	acceptor_gain	0.9900
22:27796762:CCTT:C	donor_gain	0.9900
22:27796758:TATA:T	donor_loss	0.9800
22:27796759:ATACC:A	donor_loss	0.9800
22:27796760:TACCT:T	donor_loss	0.9800
22:27796761:A:T	donor_loss	0.9800
22:27796762:C:CG	donor_loss	0.9800
22:27796765:T:A	donor_gain	0.9800
22:27751099:G:GC	acceptor_gain	0.9700
22:27795234:C:CT	acceptor_gain	0.9600
22:27801121:T:TA	donor_gain	0.9600
22:27795234:C:T	acceptor_gain	0.9500
22:27801155:AGGCT:A	donor_gain	0.9500
22:27795121:G:A	donor_gain	0.9000
22:27801149:C:A	donor_gain	0.9000
22:27795241:C:CT	acceptor_gain	0.8900
22:27796759:ATAC:A	donor_gain	0.8700
22:27801121:TC:T	donor_gain	0.8700
22:27801122:CC:C	donor_gain	0.8700
22:27801123:C:CT	donor_gain	0.8700
22:27796761:A:AC	donor_gain	0.8500
22:27796762:C:CC	donor_gain	0.8500
22:27796763:C:G	donor_loss	0.8500

AlphaMissense

8613 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
22:27750922:A:G	L1319P	1.000
22:27750942:A:C	F1312L	1.000
22:27750942:A:T	F1312L	1.000
22:27750943:A:G	F1312S	1.000
22:27750944:A:G	F1312L	1.000
22:27797043:G:C	F1167L	1.000
22:27797043:G:T	F1167L	1.000
22:27797044:A:C	F1167C	1.000
22:27797044:A:G	F1167S	1.000
22:27797045:A:G	F1167L	1.000
22:27797052:C:A	R1164S	1.000
22:27797052:C:G	R1164S	1.000
22:27797053:C:A	R1164M	1.000
22:27797053:C:G	R1164T	1.000
22:27797059:A:G	L1162P	1.000
22:27797065:A:C	I1160S	1.000
22:27797065:A:G	I1160T	1.000
22:27797065:A:T	I1160N	1.000
22:27797068:T:G	Q1159P	1.000
22:27797072:C:G	A1158P	1.000
22:27797077:A:G	L1156P	1.000
22:27797077:A:T	L1156H	1.000
22:27797080:A:C	I1155S	1.000
22:27797086:A:G	L1153P	1.000
22:27798000:G:C	F848L	1.000
22:27798000:G:T	F848L	1.000
22:27798001:A:C	F848C	1.000
22:27798001:A:G	F848S	1.000
22:27798002:A:G	F848L	1.000
22:27798007:A:T	V846E	1.000

dbSNP variants (sampled 300 via entrez): RS1000062591 (22:27793664 A>G), RS1000089883 (22:27786730 T>C), RS1000148363 (22:27755723 C>A,T), RS1000200537 (22:27754604 G>A), RS1000245608 (22:27761761 G>A,C), RS1000297692 (22:27760110 G>C), RS1000319768 (22:27761555 A>G), RS1000320328 (22:27788165 G>A), RS1000329567 (22:27759892 C>A,G), RS1000335573 (22:27772328 A>C,G), RS1000366819 (22:27802070 C>A,T), RS1000422618 (22:27801804 T>G), RS1000439306 (22:27764938 G>A), RS1000482443 (22:27789296 C>T), RS1000616481 (22:27796234 G>A,T)

Disease associations

OMIM: gene MIM:156100 | disease phenotypes: MIM:618774, MIM:607174, MIM:142340, MIM:108800

GenCC curated gene-disease

Disease	Classification	Inheritance
CEBALID syndrome	Strong	Autosomal dominant
familial meningioma	Limited	Autosomal dominant

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
CEBALID syndrome	Definitive	AD

Mondo (5): CEBALID syndrome (MONDO:0032908), familial meningioma (MONDO:0011789), hepatoblastoma (MONDO:0018666), congenital diaphragmatic hernia (MONDO:0005711), atrial septal defect (MONDO:0006664)

Orphanet (5): Facial dysmorphism-Intellectual disability-rhombencephalosynapsis syndrome (Orphanet:693549), Familial multiple meningioma (Orphanet:263662), Hepatoblastoma (Orphanet:449), Interatrial communication (Orphanet:1478), Congenital diaphragmatic hernia (Orphanet:2140)

HPO phenotypes

40 total (30 of 40 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000218	High palate
HP:0000248	Brachycephaly
HP:0000262	Turricephaly
HP:0000268	Dolichocephaly
HP:0000316	Hypertelorism
HP:0000341	Narrow forehead
HP:0000358	Posteriorly rotated ears
HP:0000365	Hearing impairment
HP:0000369	Low-set ears
HP:0000377	Abnormal pinna morphology
HP:0000457	Depressed nasal ridge
HP:0000463	Anteverted nares
HP:0000486	Strabismus
HP:0000494	Downslanted palpebral fissures
HP:0000574	Thick eyebrow
HP:0000639	Nystagmus
HP:0000750	Delayed speech and language development
HP:0000776	Congenital diaphragmatic hernia
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001270	Motor delay
HP:0001290	Generalized hypotonia
HP:0001357	Plagiocephaly
HP:0002126	Polymicrogyria
HP:0002167	Abnormal speech pattern
HP:0002553	Highly arched eyebrow
HP:0002591	Polyphagia
HP:0002858	Meningioma
HP:0003196	Short nose

GWAS associations

31 associations (top):

Study	Trait	p-value
GCST002587_33	Blood pressure (smoking interaction)	2.000000e-08
GCST002587_34	Blood pressure (smoking interaction)	1.000000e-08
GCST002619_3	Age-related cataracts	6.000000e-06
GCST002828_9	Urate levels in obese individuals	4.000000e-06
GCST003094_4	Mitral valve prolapse	1.000000e-08
GCST003818_43	Resting heart rate	5.000000e-07
GCST004183_18	Lung function (FEV1)	3.000000e-11
GCST004602_243	Mean corpuscular volume	9.000000e-10
GCST004603_149	Platelet count	3.000000e-11
GCST004607_191	Plateletcrit	6.000000e-16
GCST004630_36	Mean corpuscular hemoglobin	7.000000e-11
GCST006629_27	Pulse pressure	2.000000e-10
GCST007430_12	Peak expiratory flow	3.000000e-08
GCST007431_79	Lung function (FEV1/FVC)	4.000000e-19
GCST007432_206	FEV1	2.000000e-15
GCST008480_13	Lung function (FEV1)	3.000000e-09
GCST008482_10	Lung function (FVC)	4.000000e-06
GCST009545_5	Moderate or severe prolonged lymphopenia in dimethyl fumarate-treated relapsing-remitting multiple sclerosis	4.000000e-06
GCST010002_79	Refractive error	2.000000e-11
GCST010485_4	Platelet reactivity in response to clopidogrel treatment	3.000000e-06
GCST011947_37	White matter hyperintensity volume	3.000000e-08
GCST011950_2	White matter hyperintensity volume (adjusted for hypertension)	2.000000e-08
GCST011953_4	White matter hyperintensity volume x hypertension interaction (2df)	1.000000e-07
GCST90002390_313	Mean corpuscular hemoglobin	6.000000e-17
GCST90002392_131	Mean corpuscular volume	8.000000e-18
GCST90002396_82	Mean reticulocyte volume	6.000000e-20
GCST90002397_594	Mean spheric corpuscular volume	9.000000e-13
GCST90002400_500	Plateletcrit	3.000000e-26
GCST90002402_642	Platelet count	3.000000e-16
GCST90002403_697	Red blood cell count	1.000000e-09

EFO canonical traits (15, from GWAS)

EFO ID	Trait name
EFO:0006335	systolic blood pressure
EFO:0006525	cigarettes per day measurement
EFO:0006526	pack-years measurement
EFO:0004531	urate measurement
EFO:0004314	forced expiratory volume
EFO:0004309	platelet count
EFO:0007985	platelet crit
EFO:0004527	mean corpuscular hemoglobin
EFO:0005763	pulse pressure measurement
EFO:0009718	peak expiratory flow
EFO:0004713	FEV/FVC ratio
EFO:0004312	vital capacity
EFO:0005665	white matter hyperintensity measurement
EFO:0010701	mean reticulocyte volume
EFO:0004305	erythrocyte count

MeSH disease descriptors (4)

Descriptor	Name	Tree numbers
D006344	Heart Septal Defects, Atrial	C14.240.400.560.375; C14.280.400.560.375; C16.131.240.400.560.375
D018197	Hepatoblastoma	C04.557.435.380
D065630	Hernias, Diaphragmatic, Congenital	C16.131.433; C23.300.707.960.500.116
C537443	Meningioma, familial (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression, decreases expression	6
methylmercuric chloride	increases expression, affects cotreatment	3
Benzo(a)pyrene	increases methylation, affects methylation, increases expression	3
Calcitriol	decreases reaction, increases expression	2
Aflatoxin B1	increases expression, increases methylation	2
Particulate Matter	increases expression, decreases expression, increases abundance	2
pirinixic acid	affects binding, decreases expression, increases activity	1
bisphenol A	decreases methylation	1
terbufos	increases methylation	1
trichostatin A	increases expression	1
sodium arsenite	affects cotreatment, decreases expression, increases abundance	1
manganese chloride	affects cotreatment, decreases expression, increases abundance	1
benzo(e)pyrene	decreases methylation	1
S-(1,2-dichlorovinyl)cysteine	decreases expression	1
seocalcitol	increases expression	1
monomethylarsonous acid	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
licochalcone B	decreases expression	1
jinfukang	affects cotreatment, decreases expression	1
fatostatin	decreases expression	1
(+)-JQ1 compound	decreases expression	1
PCI 5002	affects cotreatment, increases expression	1
Valsartan	decreases expression, decreases reaction	1
Sunitinib	increases expression	1
Troglitazone	increases expression	1
Vorinostat	decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Arsenic	affects cotreatment, decreases expression, increases abundance	1
Cadmium	decreases expression, increases abundance	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT04081701	PHASE4	RECRUITING	68-Ga DOTATATE PET/MRI in the Diagnosis and Management of Somatostatin Receptor Positive CNS Tumors.
NCT04386642	PHASE4	UNKNOWN	Tranexamic Acid Reduce Blood Loss in Meningioma Resection
NCT06377371	PHASE4	RECRUITING	Feasibility of Intraoperative Tracing of Meningioma Using [Cu64]DOTATATE
NCT00517959	PHASE3	UNKNOWN	SCRT Versus Conventional RT in Children and Young Adults With Low Grade and Benign Brain Tumors
NCT01655927	PHASE3	UNKNOWN	Efficacy of Tranexamic Acid in Brain Tumor Resections
NCT03015701	PHASE3	COMPLETED	S9005 Mifepristone in Meningioma
NCT03558516	PHASE3	COMPLETED	Magnesium and Intraoperative Blood Loss in Meningioma Surgery
NCT04305470	PHASE3	COMPLETED	Gleolan for Visualization of Newly Diagnosed or Recurrent Meningioma
NCT00003483	PHASE2	TERMINATED	Antineoplaston Therapy in Treating Patients With Meningioma
NCT00589784	PHASE2	COMPLETED	Phase II Trial of Sunitinib (SU011248) in Patients With Recurrent or Inoperable Meningioma
NCT00706810	PHASE2	COMPLETED	Combination of Hydroxyurea and Verapamil for Refractory Meningiomas
NCT00859040	PHASE2	COMPLETED	Monthly SOM230C for Recurrent or Progressive Meningioma
NCT01967823	PHASE2	COMPLETED	T Cell Receptor Immunotherapy Targeting NY-ESO-1 for Patients With NY-ESO-1 Expressing Cancer
NCT02523014	PHASE2	RECRUITING	Vismodegib, FAK Inhibitor GSK2256098, Capivasertib, and Abemaciclib in Treating Patients With Progressive Meningiomas
NCT02648997	PHASE2	ACTIVE_NOT_RECRUITING	An Open-Label Phase II Study of Nivolumab or Nivolumab/Ipilimumab in Adult Participants With Progessive/ Recurrent Meningioma
NCT02831257	PHASE2	COMPLETED	AZD2014 In NF2 Patients With Progressive or Symptomatic Meningiomas
NCT02847559	PHASE2	RECRUITING	Optune Delivered Electric Field Therapy and Bevacizumab in Treating Patients With Recurrent or Progressive Grade 2 or 3 Meningioma
NCT03013387	PHASE2	WITHDRAWN	Dosimetry Guided PRRT With 90Y-DOTATOC
NCT03071874	PHASE2	UNKNOWN	Vistusertib (AZD2014) For Recurrent Grade II-III Meningiomas
NCT03095248	PHASE2	TERMINATED	Trial of Selumetinib in Patients With Neurofibromatosis Type II Related Tumors
NCT03273712	PHASE2	COMPLETED	Dosimetry-Guided, Peptide Receptor Radiotherapy (PRRT) With 90Y-DOTA- tyr3-Octreotide (90Y-DOTATOC)
NCT03971461	PHASE2	ACTIVE_NOT_RECRUITING	Phase II Study of 177Lu-DOTATATE Radionuclide in Adults With Progressive or High-risk Meningioma
NCT04082520	PHASE2	RECRUITING	Lutathera for the Treatment of Inoperable, Progressive Meningioma After External Beam Radiation Therapy
NCT04298541	PHASE2	NOT_YET_RECRUITING	Direct Comparison of Ga-68-DOTATATE and Ga-68-DOTATOC
NCT04374305	PHASE2	RECRUITING	Innovative Trial for Understanding the Impact of Targeted Therapies in NF2-Related Schwannomatosis (INTUITT-NF2)
NCT04659811	PHASE2	ACTIVE_NOT_RECRUITING	Stereotactic Radiosurgery and Immunotherapy (Pembrolizumab) for the Treatment of Recurrent Meningioma
NCT05425004	PHASE2	RECRUITING	Cabozantinib for Patients With Recurrent or Progressive Meningioma
NCT05940493	PHASE2	RECRUITING	Abemaciclib in Newly Diagnosed Meningioma Patients
NCT06012929	PHASE2	WITHDRAWN	A Study of ONC201 for Refractory Meningioma
NCT06126588	PHASE2	RECRUITING	Combination of Everolimus and 177Lu-DOTATATE in the Treatment of Grades 2 and 3 Refractory Meningioma: a Phase IIb Clinical Trial
NCT06132685	PHASE2	RECRUITING	Post-Operative Dosing of Dexamethasone in Patients With Brain Tumors After a Craniotomy, PODS Trial
NCT06322342	PHASE2	COMPLETED	Phase 2 Ascending Dose Safety and Efficacy Study of RVP-001, a Manganese-based MRI Contrast Agent
NCT06326190	PHASE2	RECRUITING	177Lu-DOTATATE for Recurrent Meningioma
NCT06439420	PHASE2	COMPLETED	CBT-I in Primary Brain Tumor Patients: Phase IIc Randomized Feasibility Pilot Trial
NCT06684795	PHASE2	RECRUITING	FG001 in Subjects with Meningiomas or Presumed Low-Grade Gliomas Scheduled for Neurosurgery
NCT06710249	PHASE2	RECRUITING	Impact of Salovum® and SPC® Flakes on Brain Tumor Induced Edema
NCT06804655	PHASE2	NOT_YET_RECRUITING	Pharmacoscopy for Patients With Refractory Primary Brain Tumors
NCT07428616	PHASE2	RECRUITING	A Study of Zanzalintinib in Participants With Recurrent or Progressive Meningioma
NCT07533942	PHASE2	NOT_YET_RECRUITING	A Study of JZP3507 (ONC206) in Recurrent Grade 2 or 3 Meningioma
NCT03267836	PHASE1	TERMINATED	Neoadjuvant Avelumab and Hypofractionated Proton Radiation Therapy Followed by Surgery for Recurrent Radiation-refractory Meningioma