FNDC3B

Summary

FNDC3B (fibronectin type III domain containing 3B, HGNC:24670) is a protein-coding gene on chromosome 3q26.31, encoding Fibronectin type III domain-containing protein 3B (Q53EP0). May be a positive regulator of adipogenesis.

Enables RNA binding activity. Predicted to act upstream of or within several processes, including negative regulation of osteoblast differentiation; substrate adhesion-dependent cell spreading; and type II pneumocyte differentiation. Predicted to be located in endoplasmic reticulum.

Source: NCBI Gene 64778 — RefSeq curated summary.

At a glance

• GWAS associations: 105
• Clinical variants (ClinVar): 178 total — 2 likely-pathogenic
• Cancer driver (intOGen): loss-of-function (tumor-suppressor-like) across 1 cancer types
• MANE Select transcript: NM_022763

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:24670
Approved symbol	FNDC3B
Name	fibronectin type III domain containing 3B
Location	3q26.31
Locus type	gene with protein product
Status	Approved
Aliases	FAD104, DKFZp762K137, FLJ23399, PRO4979, YVTM2421
Ensembl gene	ENSG00000075420
Ensembl biotype	protein_coding
OMIM	611909
Entrez	64778

Gene structure

Transcript identifiers

Ensembl transcripts: 56 — 50 protein_coding, 5 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000336824, ENST00000415807, ENST00000416957, ENST00000421757, ENST00000423424, ENST00000443501, ENST00000469491, ENST00000476794, ENST00000478016, ENST00000483344, ENST00000490832, ENST00000494000, ENST00000899158, ENST00000899159, ENST00000899160, ENST00000899161, ENST00000899162, ENST00000899163, ENST00000899164, ENST00000899165, ENST00000899166, ENST00000899167, ENST00000899168, ENST00000899169, ENST00000899170, ENST00000899171, ENST00000899172, ENST00000899173, ENST00000899174, ENST00000899175, ENST00000899176, ENST00000899177, ENST00000899178, ENST00000899179, ENST00000899180, ENST00000899181, ENST00000899182, ENST00000899183, ENST00000899184, ENST00000899185, ENST00000899186, ENST00000899187, ENST00000899188, ENST00000926636, ENST00000926637, ENST00000947473, ENST00000947474, ENST00000947475, ENST00000947476, ENST00000947477, ENST00000947478, ENST00000947479, ENST00000947480, ENST00000947481, ENST00000947482, ENST00000947483

RefSeq mRNA: 2 — MANE Select: NM_022763 NM_001135095, NM_022763

CCDS: CCDS3217

Canonical transcript exons

ENST00000415807 — 26 exons

Exon	Start	End
ENSE00000780521	172380966	172381093
ENSE00000780522	172378270	172378436
ENSE00000780523	172362633	172362845
ENSE00000780525	172352803	172353083
ENSE00000780527	172346327	172346440
ENSE00000826246	172343011	172343116
ENSE00000826247	172344086	172344258
ENSE00000968103	172341113	172341231
ENSE00001211922	172337330	172337401
ENSE00001919747	172397164	172401669
ENSE00003469931	172347212	172347361
ENSE00003494912	172295363	172295514
ENSE00003520920	172310828	172310881
ENSE00003524120	172307363	172307501
ENSE00003531446	172328952	172329076
ENSE00003547557	172333089	172333175
ENSE00003575847	172251260	172251541
ENSE00003622762	172330541	172330715
ENSE00003629013	172226871	172226947
ENSE00003655827	172334944	172335082
ENSE00003656770	172112452	172112590
ENSE00003658189	172285926	172285984
ENSE00003666241	172133471	172133546
ENSE00003669054	172298728	172298787
ENSE00003692446	172247533	172247776
ENSE00003843799	172039578	172039771

Expression profiles

Bgee: expression breadth ubiquitous, 275 present calls, max score 99.30.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 67.0343 / max 834.4671, expressed in 1823 samples.

FANTOM5 promoters (10 alternative TSS)

Promoter ID	TPM avg	Samples expressed
39802	40.4005	1822
39805	13.4980	1651
39803	7.3254	1632
39829	4.0256	296
39807	0.4634	285
39804	0.3877	232
39806	0.3841	197
39808	0.2713	112
39838	0.2710	110
39819	0.0073	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cartilage tissue	UBERON:0002418	99.30	gold quality
calcaneal tendon	UBERON:0003701	98.81	gold quality
tibia	UBERON:0000979	98.41	gold quality
colonic epithelium	UBERON:0000397	98.34	gold quality
secondary oocyte	CL:0000655	97.84	gold quality
decidua	UBERON:0002450	97.79	gold quality
placenta	UBERON:0001987	97.20	gold quality
corpus epididymis	UBERON:0004359	97.13	gold quality
adrenal tissue	UBERON:0018303	97.00	gold quality
pericardium	UBERON:0002407	96.69	gold quality
cauda epididymis	UBERON:0004360	96.50	gold quality
caput epididymis	UBERON:0004358	96.49	gold quality
skin of hip	UBERON:0001554	96.47	gold quality
synovial joint	UBERON:0002217	96.13	gold quality
oocyte	CL:0000023	95.74	gold quality
visceral pleura	UBERON:0002401	95.66	gold quality
stromal cell of endometrium	CL:0002255	95.46	gold quality
cardia of stomach	UBERON:0001162	95.22	gold quality
vena cava	UBERON:0004087	95.20	gold quality
layer of synovial tissue	UBERON:0007616	95.09	gold quality
tendon	UBERON:0000043	95.03	gold quality
heart right ventricle	UBERON:0002080	94.95	gold quality
saphenous vein	UBERON:0007318	94.64	gold quality
islet of Langerhans	UBERON:0000006	94.58	gold quality
mammary duct	UBERON:0001765	94.28	gold quality
parietal pleura	UBERON:0002400	94.21	gold quality
trabecular bone tissue	UBERON:0002483	94.21	gold quality
superficial temporal artery	UBERON:0001614	94.16	gold quality
lower lobe of lung	UBERON:0008949	93.92	gold quality
pylorus	UBERON:0001166	93.83	gold quality

Single-cell (SCXA)

Detected in 8 experiment(s), a significant marker in 6.

Experiment	Marker?	Max mean expression
E-CURD-119	yes	46.64
E-CURD-122	yes	46.06
E-MTAB-10287	yes	45.66
E-MTAB-9067	yes	14.73
E-HCAD-35	yes	7.03
E-MTAB-7037	no	293.35
E-MTAB-10290	no	232.28
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): GATA3, NFKB

miRNA regulators (miRDB)

298 targeting FNDC3B, 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-3613-3P	100.00	76.36	7965
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-5692A	100.00	74.40	6850
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997

Literature-anchored findings (GeneRIF, showing 30)

• Up-regulation of miR-143 expression transcribed by NF-kappaB in hepatitis B virus-related hepatocellular carcinoma promotes cancer cell invasion/migration and tumor metastasis by repression of FNDC3B expression. (PMID:19472311)
• FNDC3B amplification is involved in tumor maintenance in addition to its ability to promote cancer. (PMID:22510613)
• Central corneal thickness-associated loci FNDC3B confers a relatively large risk for keratoconus and is also associated with primary open-angle glaucoma. (PMID:23291589)
• fad104 suppressed the invasion and metastasis of melanoma cells by inhibiting activation of the STAT3 signaling pathway (PMID:25671570)
• fad104 suppressed anchorage-independent growth of melanoma cells, and the N-terminal region of FAD104 is essential for inhibiting malignant transformation and STAT3 activity (PMID:26948083)
• FNDC3B and ANXA2 expression correlate negatively with patient survival in hepatocellular carcinoma (PMID:27385217)
• we report the first two patients with de novo 3q26.31 microdeletions. Both have dysmorphic features, consistent with the phenotypes seen in fndc3b-deficient mice in animal studies, which imply a critical role of FNDC3B in human craniofacial development. (PMID:27541078)
• findings together indicate that NS5ABP37 inhibits cancer cell proliferation and promotes apoptosis, by altering SREBP-dependent lipogenesis and cholesterogenesis in HepG2 and L02 cells and inducing oxidative stress and endoplasmic reticulum stress (PMID:27862769)
• MiR-129-5p could directly suppress FNDC3B. (PMID:28068630)
• These findings demonstrate that FAD104 is a novel suppressor of TGF-beta signalling and represses TGF-beta-mediated EMT in cervical cancer cells. (PMID:29180690)
• we found that knockdown of FNDC3B could suppress the migratory and invasive abilities of OTSCC cells. In addition, treating OTSCC cells with CoCl2 (a hypoxia mimetic agent) upregulated the mRNA and protein expression of FNDC3B via HIF-1alpha (PMID:29393475)
• we identified an invasion-related circFNDC3B that was downregulated in human BC tissues and cells, and we found that decreased circFNDC3B expression was associated with poor prognosis of BC patients. (PMID:30458784)
• Findings highlight a physiological role for circRNAs in cardiac repair and indicate that modulation of circFndc3b expression may represent a potential strategy to promote cardiac function and remodeling after MI. (PMID:31541092)
• results suggested that the 3’-UTR shortening of FNDC3B mRNA mediated its overexpression in nasopharyngeal carcinoma and promoted its progression by targeting MYH9 (PMID:32232887)
• Association between hsa_circ_0006156 expression and incidence of gastric cancer. (PMID:32271420)
• CircFNDC3B sequestrates miR-937-5p to derepress TIMP3 and inhibit colorectal cancer progression. (PMID:32896063)
• The Interaction of the Tumor Suppressor FAM46C with p62 and FNDC3 Proteins Integrates Protein and Secretory Homeostasis. (PMID:32966780)
• Novel lncRNA XLOC_032768 protects against renal tubular epithelial cells apoptosis in renal ischemia-reperfusion injury by regulating FNDC3B/TGF-beta1. (PMID:32972270)
• MicroRNA-363-3p promote the development of acute myeloid leukemia with RUNX1 mutation by targeting SPRYD4 and FNDC3B. (PMID:33950983)
• CircSOS2 promotes cervical squamous cell carcinoma by regulation of proliferation, cell cycle, apoptosis, migration, invasion, and glycolysis by targeting miR-543/FNDC3B axis. (PMID:34023283)
• Identification of Circ-FNDC3B, an Overexpressed circRNA in Abdominal Aortic Aneurysm, as a Regulator of Vascular Smooth Muscle Cells. (PMID:34789642)
• Hsa_circRNA_0001971 contributes to oral squamous cell carcinoma progression via miR-186-5p/Fibronectin type III domain containing 3B axis. (PMID:35060189)
• Long Non-Coding RNA DUXAP8 Acts as an Oncogene in Sinonasal Squamous Cell Carcinoma Through miR-584-5p/FNDC3B Pathway. (PMID:35695194)
• Overexpression of circFNDC3B promotes the progression of oral tongue squamous cell carcinoma through the miR-1322/MED1 axis. (PMID:35916453)
• Integrated machine learning methods identify FNDC3B as a potential prognostic biomarker and correlated with immune infiltrates in glioma. (PMID:36275754)
• m[6]A-modified circFNDC3B inhibits colorectal cancer stemness and metastasis via RNF41-dependent ASB6 degradation. (PMID:36446779)
• Circ_0000285 regulates nasopharyngeal carcinoma progression through miR-1278/FNDC3B axis. (PMID:36738165)
• Lack of Association of Polymorphism Located Upstream of ABCA1 (rs2472493), in FNDC3B (rs7636836), and Near ANKRD55-MAP3K1 Genes (rs61275591) in Primary Open-Angle Glaucoma Patients of Saudi Origin. (PMID:36980976)
• circFNDC3B promotes esophageal squamous cell carcinoma progression by targeting MYO5A via miR-370-3p/miR-136-5p. (PMID:37667251)
• Identification of fibronectin type III domain containing 3B as a potential prognostic and therapeutic target for pancreatic cancer: a preliminary analysis. (PMID:38581008)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	fndc3bb	ENSDARG00000062023
danio_rerio	fndc3ba	ENSDARG00000078179
mus_musculus	Fndc3b	ENSMUSG00000039286
rattus_norvegicus	Fndc3b	ENSRNOG00000024089
drosophila_melanogaster	mtgo	FBGN0259735
caenorhabditis_elegans		WBGENE00007944

Paralogs (11): MYOM2 (ENSG00000036448), MYBPC2 (ENSG00000086967), MYOM1 (ENSG00000101605), FNDC3A (ENSG00000102531), OBSL1 (ENSG00000124006), MYBPH (ENSG00000133055), MYBPC3 (ENSG00000134571), MYOM3 (ENSG00000142661), IGSF22 (ENSG00000179057), MYBPC1 (ENSG00000196091), MYBPHL (ENSG00000221986)

Protein

Protein identifiers

Fibronectin type III domain-containing protein 3B — Q53EP0 (reviewed: Q53EP0)

Alternative names: Factor for adipocyte differentiation 104, HCV NS5A-binding protein 37

All UniProt accessions (2): Q53EP0, C9JKH7

UniProt curated annotations — full annotation on UniProt →

Function. May be a positive regulator of adipogenesis.

Subcellular location. Membrane.

Tissue specificity. Predominantly expressed in white adipose tissue (WAT) especially in the stromal vascular cells. Expressed in adipocyte differentiable 3T3-L1 cells but not in the non-adipogenic cell line NIH-3T3. Expression increased in the early stage of adipogenesis.

Similarity. Belongs to the FNDC3 family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q53EP0-1	1	yes
Q53EP0-2	2
Q53EP0-3	3

RefSeq proteins (2): NP_001128567, NP_073600* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003961	FN3_dom	Domain
IPR013783	Ig-like_fold	Homologous_superfamily
IPR036116	FN3_sf	Homologous_superfamily
IPR050617	E3_ligase_FN3/SPRY	Family

Pfam: PF00041

UniProt features (38 total): sequence conflict 13, domain 9, splice variant 4, modified residue 3, sequence variant 3, region of interest 2, compositionally biased region 2, chain 1, transmembrane region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q53EP0-F1	75.78	0.41

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 (3): 208, 393, 1163

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 339 (showing top): AAGTCCA_MIR422B_MIR422A, YANG_BREAST_CANCER_ESR1_LASER_DN, IVANOVA_HEMATOPOIESIS_LATE_PROGENITOR, TATTATA_MIR374, ATGCAGT_MIR217, chr3q26, TONKS_TARGETS_OF_RUNX1_RUNX1T1_FUSION_ERYTHROCYTE_UP, CTAGGAA_MIR384, CHEN_LVAD_SUPPORT_OF_FAILING_HEART_UP, GGGCATT_MIR365, KINSEY_TARGETS_OF_EWSR1_FLII_FUSION_DN, SCHAEFFER_PROSTATE_DEVELOPMENT_12HR_UP, ACATTCC_MIR1_MIR206, ATTCTTT_MIR186, LIAO_METASTASIS

GO Biological Process (0):

GO Molecular Function (2): RNA binding (GO:0003723), protein binding (GO:0005515)

GO Cellular Component (3): cytoplasm (GO:0005737), endomembrane system (GO:0012505), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
nucleic acid binding	1
binding	1
intracellular anatomical structure	1
vacuole	1
plasma membrane	1

Protein interactions and networks

STRING

1344 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
FNDC3B	ZNF469	Q96JG9	621
FNDC3B	TMCO1	Q9UM00	581
FNDC3B	MPDZ	O75970	538
FNDC3B	GMDS	O60547	531
FNDC3B	GAS7	O60861	515
FNDC3B	ARPC1B	O15143	507
FNDC3B	AFAP1	Q8N556	493
FNDC3B	VSX1	Q9NZR4	484
FNDC3B	BANP	Q8N9N5	483
FNDC3B	LNX1	Q8TBB1	480
FNDC3B	SIX6	O95475	474
FNDC3B	AGTR2	P50052	470
FNDC3B	NABP1	Q96AH0	448
FNDC3B	LCN12	Q6JVE5	443
FNDC3B	NFIB	O00712	431

IntAct

63 interactions, top by confidence:

A	B	Type	Score
CENPH	NDC80	psi-mi:“MI:0914”(association)	0.800
SLC1A1	AGPAT2	psi-mi:“MI:0914”(association)	0.640
FNDC3B	TRIP13	psi-mi:“MI:0915”(physical association)	0.550
TRIP13	FNDC3B	psi-mi:“MI:0915”(physical association)	0.550
KLRG2	GXYLT2	psi-mi:“MI:0914”(association)	0.530
SPINT2	UPK3BL1	psi-mi:“MI:0914”(association)	0.530
CENPH	PSMD11	psi-mi:“MI:0914”(association)	0.530
SLCO1B3	LGALS3	psi-mi:“MI:0914”(association)	0.530
LPAR1	TMEM223	psi-mi:“MI:0914”(association)	0.530
SLC25A6	HRAS	psi-mi:“MI:0914”(association)	0.530
SDC1	ILVBL	psi-mi:“MI:0915”(physical association)	0.400
FNDC3B	VAC14	psi-mi:“MI:0915”(physical association)	0.370
TENT5A	GOLGA8R	psi-mi:“MI:0914”(association)	0.350
		psi-mi:“MI:0914”(association)	0.350
	ESYT2	psi-mi:“MI:0914”(association)	0.350
	HAX1	psi-mi:“MI:0914”(association)	0.350
BVLF1	VWA8	psi-mi:“MI:0914”(association)	0.350
	KPNA4	psi-mi:“MI:0914”(association)	0.350
CAMK2D	DVL2	psi-mi:“MI:0914”(association)	0.350
ESR1	ESYT2	psi-mi:“MI:0914”(association)	0.350
TENT5A	TMEM131L	psi-mi:“MI:0914”(association)	0.350
FAM189B	KLRG2	psi-mi:“MI:0914”(association)	0.350
RBFOX2	PRMT5	psi-mi:“MI:0914”(association)	0.350
DISC1	AGRN	psi-mi:“MI:0914”(association)	0.350
ATG16L1	ESYT2	psi-mi:“MI:0914”(association)	0.350
PCDH10	TMEM223	psi-mi:“MI:0914”(association)	0.350

BioGRID (231): FNDC3B (Two-hybrid), FNDC3B (Two-hybrid), FNDC3B (Two-hybrid), FNDC3B (Two-hybrid), FNDC3B (Two-hybrid), FNDC3B (Affinity Capture-MS), FNDC3B (Affinity Capture-MS), TRIP13 (Two-hybrid), FNDC3B (Affinity Capture-MS), FNDC3B (Affinity Capture-MS), FNDC3B (Affinity Capture-MS), FNDC3B (Affinity Capture-MS), FNDC3B (Affinity Capture-MS), FNDC3B (Affinity Capture-MS), FNDC3B (Affinity Capture-MS)

ESM2 similar proteins: A2ABU4, A7MBL8, O08874, O70468, P10894, P16419, P29074, P39447, P52179, P53666, P54296, P56741, P70175, Q00872, Q02173, Q14324, Q14896, Q15835, Q16513, Q32L23, Q3TZZ7, Q53EP0, Q5RBN1, Q5VTT5, Q5XKE0, Q5ZJP5, Q62234, Q62936, Q63518, Q63651, Q6NWW9, Q6R005, Q6ZN16, Q8BPM2, Q8BWW9, Q8BX90, Q8IVH8, Q8N9C0, Q90233, Q90688

Diamond homologs: A8JAM0, D3ZN95, G5EC23, P38853, P51610, P51611, Q10AZ7, Q4V8F4, Q53EP0, Q5RDA9, Q5RKG2, Q61191, Q6AYI2, Q6NWW9, Q6P3S6, Q7M3S9, Q8H4D4, Q8VEM9, Q93XW5, Q9BQ90, Q9D968, Q9V4C8, Q9Y5Z7, Q5EA50, A2AAJ9, P08922, Q5RBN1, Q5ZJP5, Q63132, Q6DFV6, Q78DX7, Q8BX90, Q9Y2H6, A3KN33, P29294, P29317, Q03145, Q15746, Q1KL86, Q505D9

SIGNOR signaling

0 interactions.

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: loss-of-function (tumor-suppressor-like) across 1 cancer types — LNM.

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	2
Uncertain significance	128
Likely benign	6
Benign	9

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
155535	GRCh38/hg38 3q26.31(chr3:171960150-172473569)x1	Likely pathogenic
441683	GRCh37/hg19 3q26.31(chr3:171622716-171968102)x1	Likely pathogenic

SpliceAI

6852 predictions. Top by Δscore:

Variant	Effect	Δscore
3:172133467:GCAG:G	acceptor_loss	1.0000
3:172133468:CA:C	acceptor_loss	1.0000
3:172133469:A:AG	acceptor_gain	1.0000
3:172133469:A:C	acceptor_loss	1.0000
3:172133469:AG:A	acceptor_gain	1.0000
3:172133470:G:A	acceptor_loss	1.0000
3:172133470:G:GG	acceptor_gain	1.0000
3:172133470:GG:G	acceptor_gain	1.0000
3:172133470:GGTT:G	acceptor_gain	1.0000
3:172133547:G:GG	donor_gain	1.0000
3:172205620:G:T	donor_gain	1.0000
3:172251276:T:TA	acceptor_gain	1.0000
3:172285916:C:CA	acceptor_gain	1.0000
3:172285919:A:AG	acceptor_gain	1.0000
3:172285920:A:G	acceptor_gain	1.0000
3:172285980:CACAG:C	donor_loss	1.0000
3:172285981:ACAG:A	donor_loss	1.0000
3:172285982:CAGGT:C	donor_loss	1.0000
3:172285984:GGTA:G	donor_loss	1.0000
3:172285985:G:A	donor_loss	1.0000
3:172285986:T:G	donor_loss	1.0000
3:172295504:A:G	donor_gain	1.0000
3:172298726:A:AG	acceptor_gain	1.0000
3:172298726:AGT:A	acceptor_gain	1.0000
3:172298727:G:GC	acceptor_gain	1.0000
3:172298727:GT:G	acceptor_gain	1.0000
3:172298727:GTG:G	acceptor_gain	1.0000
3:172310822:TTTTA:T	acceptor_loss	1.0000
3:172310823:TTTA:T	acceptor_loss	1.0000
3:172310824:TTA:T	acceptor_loss	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000003302 (3:172157201 A>G), RS1000003703 (3:172377309 G>A,C), RS1000003966 (3:172115553 A>C,G), RS1000017992 (3:172290427 A>G), RS1000022053 (3:172247849 T>C), RS1000023509 (3:172330921 C>T), RS1000041271 (3:172038451 A>AAAT), RS1000041793 (3:172294369 G>A), RS1000046320 (3:172209164 C>T), RS1000048882 (3:172386626 G>A), RS1000048947 (3:172129692 C>T), RS1000053609 (3:172172914 A>G), RS1000055562 (3:172372687 A>G), RS1000067148 (3:172133157 T>C), RS1000077532 (3:172208842 G>A)

Disease associations

OMIM: gene MIM:611909 | disease phenotypes: MIM:607174

GenCC curated gene-disease

Mondo (1): familial meningioma (MONDO:0011789)

Orphanet (1): Familial multiple meningioma (Orphanet:263662)

HPO phenotypes

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

GWAS associations

105 associations (top):

Study	Trait	p-value
GCST001806_3	Corneal structure	5.000000e-12
GCST001956_50	Height	4.000000e-16
GCST001969_19	Heart rate	1.000000e-09
GCST002580_3	Intraocular pressure	4.000000e-08
GCST002647_95	Height	3.000000e-39
GCST002702_41	Height	2.000000e-23
GCST003008_15	Triptolide cytotoxicity	7.000000e-06
GCST003059_6	Parkinson’s disease	1.000000e-06
GCST004063_103	Waist circumference adjusted for body mass index	5.000000e-09
GCST004063_165	Waist circumference adjusted for body mass index	8.000000e-10
GCST004067_197	Hip circumference adjusted for BMI	1.000000e-09
GCST004067_85	Hip circumference adjusted for BMI	3.000000e-12
GCST004074_10	Intraocular pressure	7.000000e-13
GCST004074_9	Intraocular pressure	3.000000e-12
GCST004500_16	Waist circumference adjusted for BMI (adjusted for smoking behaviour)	1.000000e-11
GCST004500_2	Waist circumference adjusted for BMI (adjusted for smoking behaviour)	3.000000e-08
GCST004500_96	Waist circumference adjusted for BMI (adjusted for smoking behaviour)	3.000000e-06
GCST004501_49	Waist circumference adjusted for BMI (joint analysis main effects and smoking interaction)	6.000000e-13
GCST004501_50	Waist circumference adjusted for BMI (joint analysis main effects and smoking interaction)	6.000000e-09
GCST004503_4	Waist circumference adjusted for BMI in smokers	9.000000e-06
GCST004503_8	Waist circumference adjusted for BMI in smokers	7.000000e-08
GCST004504_49	Waist circumference adjusted for BMI in non-smokers	2.000000e-07
GCST004562_180	Waist circumference adjusted for body mass index	1.000000e-10
GCST004562_19	Waist circumference adjusted for body mass index	2.000000e-07
GCST004562_220	Waist circumference adjusted for body mass index	2.000000e-07
GCST004562_94	Waist circumference adjusted for body mass index	5.000000e-11
GCST004562_96	Waist circumference adjusted for body mass index	1.000000e-07
GCST004563_183	Waist circumference adjusted for BMI (joint analysis main effects and physical activity interaction)	1.000000e-07
GCST004563_230	Waist circumference adjusted for BMI (joint analysis main effects and physical activity interaction)	3.000000e-10
GCST004563_3	Waist circumference adjusted for BMI (joint analysis main effects and physical activity interaction)	1.000000e-07

EFO canonical traits (20, from GWAS)

EFO ID	Trait name
EFO:0004345	corneal topography
EFO:0004695	intraocular pressure measurement
EFO:0006952	cytotoxicity measurement
EFO:0007789	BMI-adjusted waist circumference
EFO:0008039	BMI-adjusted hip circumference
EFO:0004318	smoking behavior
EFO:0008002	physical activity measurement
EFO:0009188	Red cell distribution width
EFO:0007986	reticulocyte count
EFO:0005213	central corneal thickness
EFO:0004847	age at onset
EFO:0005763	pulse pressure measurement
EFO:0004541	HbA1c measurement
EFO:0010067	corneal resistance factor
EFO:0010066	corneal hysteresis
EFO:0004462	PR interval
EFO:0004327	electrocardiography
EFO:0004980	appendicular lean mass
EFO:0004527	mean corpuscular hemoglobin
EFO:0007788	BMI-adjusted waist-hip ratio

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
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

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases expression, increases methylation	6
Valproic Acid	affects expression, increases expression	5
Estradiol	affects cotreatment, decreases expression, increases expression	3
Fluorouracil	affects response to substance, decreases expression	2
Nickel	increases expression	2
Tretinoin	increases expression	2
Cyclosporine	decreases expression, increases expression	2
Aflatoxin B1	affects cotreatment, decreases expression, increases methylation	2
aristolochic acid I	decreases expression	1
FR900359	increases phosphorylation	1
bisphenol F	affects cotreatment, increases methylation	1
dicrotophos	increases expression	1
methylmercuric chloride	increases expression	1
triphenyl phosphate	affects expression	1
propionaldehyde	increases expression	1
bisphenol A	affects cotreatment, increases expression	1
deoxynivalenol	increases expression	1
cobaltous chloride	affects expression, decreases expression	1
ochratoxin A	decreases expression	1
benzo(e)pyrene	increases methylation	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
chloropicrin	decreases expression	1
entinostat	increases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Vorinostat	increases expression	1
Leflunomide	increases expression	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