FBLL1

Summary

FBLL1 (fibrillarin like rRNA 2’-O-methyltransferase 1, HGNC:35458) is a protein-coding gene on chromosome 5q34, encoding RNA 2’-O-methyltransferase FBLL1 (A6NHQ2). S-adenosyl-L-methionine-dependent RNA methyltransferase that catalyzes 2’-hydroxyl ribose methylation in RNAs.

Predicted to enable RNA binding activity; histone H2A Q104 methyltransferase activity; and rRNA methyltransferase activity. Predicted to be involved in box C/D sno(s)RNA 3’-end processing and rRNA methylation. Predicted to act upstream of or within blastocyst hatching. Located in fibrillar center and nucleoplasm.

Source: NCBI Gene 345630 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 3 total
• MANE Select transcript: NM_001355274

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:35458
Approved symbol	FBLL1
Name	fibrillarin like rRNA 2’-O-methyltransferase 1
Location	5q34
Locus type	gene with protein product
Status	Approved
Aliases	LOC345630
Ensembl gene	ENSG00000188573
Ensembl biotype	protein_coding
Entrez	345630

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000338333

RefSeq mRNA: 1 — MANE Select: NM_001355274 NM_001355274

CCDS: CCDS87345

Canonical transcript exons

ENST00000338333 — 1 exons

Exon	Start	End
ENSE00003379479	168529305	168530634

Expression profiles

Bgee: expression breadth ubiquitous, 168 present calls, max score 91.05.

FANTOM5 (CAGE): breadth broad, TPM avg 0.9593 / max 43.0608, expressed in 286 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
60081	0.9593	286

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
prefrontal cortex	UBERON:0000451	91.05	gold quality
cortical plate	UBERON:0005343	90.66	gold quality
hypothalamus	UBERON:0001898	89.83	gold quality
Brodmann (1909) area 9	UBERON:0013540	89.80	gold quality
frontal cortex	UBERON:0001870	89.40	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	89.33	gold quality
anterior cingulate cortex	UBERON:0009835	89.21	gold quality
neocortex	UBERON:0001950	89.15	gold quality
superior frontal gyrus	UBERON:0002661	88.92	gold quality
primary visual cortex	UBERON:0002436	88.47	gold quality
right frontal lobe	UBERON:0002810	88.32	gold quality
cerebral cortex	UBERON:0000956	88.27	gold quality
postcentral gyrus	UBERON:0002581	88.14	gold quality
middle temporal gyrus	UBERON:0002771	87.47	gold quality
Brodmann (1909) area 23	UBERON:0013554	87.17	gold quality
parietal lobe	UBERON:0001872	86.06	gold quality
entorhinal cortex	UBERON:0002728	86.04	gold quality
forebrain	UBERON:0001890	85.80	gold quality
brain	UBERON:0000955	85.29	gold quality
Ammon’s horn	UBERON:0001954	85.27	gold quality
nucleus accumbens	UBERON:0001882	85.22	gold quality
right hemisphere of cerebellum	UBERON:0014890	85.16	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	85.00	gold quality
temporal lobe	UBERON:0001871	84.90	gold quality
amygdala	UBERON:0001876	84.89	gold quality
pancreatic ductal cell	CL:0002079	84.87	silver quality
occipital lobe	UBERON:0002021	84.70	gold quality
cerebellum	UBERON:0002037	84.69	gold quality
cerebellar cortex	UBERON:0002129	84.67	gold quality
cerebellar hemisphere	UBERON:0002245	84.60	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.30

Regulation

Is transcription factor: no

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	fbl	ENSDARG00000053912
mus_musculus	Fbll1	ENSMUSG00000051062
rattus_norvegicus	Fbll1	ENSRNOG00000015303
drosophila_melanogaster	Fib	FBGN0003062
drosophila_melanogaster	CG10909	FBGN0038090
caenorhabditis_elegans		WBGENE00001423

Paralogs (1): FBL (ENSG00000105202)

Protein

Protein identifiers

RNA 2’-O-methyltransferase FBLL1 — A6NHQ2 (reviewed: A6NHQ2)

Alternative names: Fibrillarin like 1

All UniProt accessions (1): A6NHQ2

UniProt curated annotations — full annotation on UniProt →

Function. S-adenosyl-L-methionine-dependent RNA methyltransferase that catalyzes 2’-hydroxyl ribose methylation in RNAs. Functions as part of box C/D small nucleolar ribonucleoprotein (snoRNP) complexes, where guide snoRNAs ensure methylation specificity through base pairing with RNA substrates. Exhibits broad substrate specificity, methylating multiple sites on ribosomal RNAs (rRNAs) and messenger RNAs (mRNAs) depending on the guide snoRNA incorporated in the complex. Specifically expressed in brain, it regulates the expression of GAP43 by stabilizing its mRNA through methylation and thereby plays an indirect role in neuronal differentiation.

Subunit / interactions. Component of a box C/D small nucleolar ribonucleoprotein (snoRNP) complex composed of FBLL1, SNU13/NHP2L1, NOP56 and NOP58 and a guide snoRNA which mediates 2’-hydroxyl ribose methylation in RNAs.

Subcellular location. Nucleus. Nucleolus.

Similarity. Belongs to the methyltransferase superfamily. Fibrillarin family.

RefSeq proteins (1): NP_001342203* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000692	Fibrillarin	Family
IPR020813	Fibrillarin_CS	Conserved_site
IPR029063	SAM-dependent_MTases_sf	Homologous_superfamily

Pfam: PF01269

Catalyzed reactions (Rhea), 1 shown:

• a ribonucleotide in RNA + S-adenosyl-L-methionine = a 2’-O-methylribonucleotide in RNA + S-adenosyl-L-homocysteine + H(+) (RHEA:58956)

UniProt features (11 total): binding site 4, modified residue 3, chain 1, region of interest 1, mutagenesis site 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-A6NHQ2-F1	77.91	0.51

Functional residue map

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

Ligand- & substrate-binding residues (4): 184–185; 203–204; 228–229; 248–251

Post-translational modifications (3): 8, 15, 27

Mutagenesis-validated functional residues (1):

Position	Phenotype
248	decreased rna 2’-o-methyltransferase activity.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 95 (showing top): GOBP_RIBOSOME_BIOGENESIS, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, GOBP_REGULATION_OF_MRNA_CATABOLIC_PROCESS, GOBP_SNO_S_RNA_METABOLIC_PROCESS, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_NEUROGENESIS, GOBP_RNA_METHYLATION, GOBP_MRNA_MODIFICATION, GOBP_POST_TRANSCRIPTIONAL_REGULATION_OF_GENE_EXPRESSION, GOBP_IN_UTERO_EMBRYONIC_DEVELOPMENT, GOBP_RNA_MODIFICATION, GOBP_REGULATION_OF_CATABOLIC_PROCESS, GOBP_BLASTOCYST_DEVELOPMENT, GOBP_EMBRYO_DEVELOPMENT, GOBP_CHROMATIN_REMODELING

GO Biological Process (7): box C/D sno(s)RNA 3’-end processing (GO:0000494), blastocyst hatching (GO:0001835), rRNA methylation (GO:0031167), mRNA stabilization (GO:0048255), chromatin remodeling (GO:0006338), rRNA processing (GO:0006364), methylation (GO:0032259)

GO Molecular Function (6): RNA binding (GO:0003723), rRNA methyltransferase activity (GO:0008649), RNA 2’-O-methyltransferase activity (GO:0062105), histone H2AQ104 methyltransferase activity (GO:1990259), methyltransferase activity (GO:0008168), transferase activity (GO:0016740)

GO Cellular Component (8): fibrillar center (GO:0001650), nucleoplasm (GO:0005654), nucleolus (GO:0005730), Cajal body (GO:0015030), box C/D methylation guide snoRNP complex (GO:0031428), small-subunit processome (GO:0032040), nucleus (GO:0005634), ribonucleoprotein complex (GO:1990904)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
RNA methyltransferase activity	2
nucleolus	2
cellular anatomical structure	2
nuclear lumen	2
sno(s)RNA 3’-end processing	1
box C/D sno(s)RNA processing	1
blastocyst development	1
hatching	1
rRNA modification	1
RNA methylation	1
regulation of mRNA stability	1
RNA stabilization	1
negative regulation of mRNA catabolic process	1
chromatin organization	1
RNA processing	1
rRNA metabolic process	1
ribosome biogenesis	1
metabolic process	1
nucleic acid binding	1
S-adenosylmethionine-dependent methyltransferase activity	1
catalytic activity, acting on a rRNA	1
O-methyltransferase activity	1
protein-glutamine N-methyltransferase activity	1
histone H2A methyltransferase activity	1
transferase activity, transferring one-carbon groups	1
catalytic activity	1
intracellular membraneless organelle	1
nuclear ribonucleoprotein granule	1
box C/D RNP complex	1
preribosome	1
t-UTP complex	1
nuclear protein-containing complex	1
intracellular membrane-bounded organelle	1
protein-containing complex	1

Protein interactions and networks

STRING

2756 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
FBLL1	SNU13	P55769	647
FBLL1	NOP58	Q9Y2X3	643
FBLL1	NOP56	O00567	643
FBLL1	ADAD2	Q8NCV1	510
FBLL1	GAR1	Q9NY12	502
FBLL1	MCCD1	P59942	465
FBLL1	HENMT1	Q5T8I9	464
FBLL1	NSUN7	Q8NE18	460
FBLL1	DKC1	O60832	458
FBLL1	ADAD1	Q96M93	457
FBLL1	SSRP1	Q08945	453
FBLL1	TRIQK	Q629K1	452
FBLL1	MAGEB6B	A0A0J9YX57	439
FBLL1	TSEN34	Q9BSV6	420
FBLL1	YBX1	P16990	407

IntAct

25 interactions, top by confidence:

A	B	Type	Score
ESR2	FBLL1	psi-mi:“MI:0914”(association)	0.460
KSR1	FBLL1	psi-mi:“MI:0914”(association)	0.350
KSR1	FAM168B	psi-mi:“MI:0914”(association)	0.350
Mecom	ESYT2	psi-mi:“MI:0914”(association)	0.350
ESR1	ESYT2	psi-mi:“MI:0914”(association)	0.350
COPS5	FBLL1	psi-mi:“MI:0914”(association)	0.350
BMI1	MEIS3P1	psi-mi:“MI:0914”(association)	0.350
ESR2		psi-mi:“MI:0914”(association)	0.350
MAPT	SHTN1	psi-mi:“MI:0914”(association)	0.350
CEP63	CIBAR1	psi-mi:“MI:0914”(association)	0.350
SRSF5	FBLL1	psi-mi:“MI:0914”(association)	0.350
LIN28A	FBLL1	psi-mi:“MI:0914”(association)	0.350
DGCR8	VWA8	psi-mi:“MI:2364”(proximity)	0.270
FASTKD2	MED19	psi-mi:“MI:2364”(proximity)	0.270
LIN28B	MEX3A	psi-mi:“MI:2364”(proximity)	0.270
RBM15	ILVBL	psi-mi:“MI:2364”(proximity)	0.270
RPS3	ESYT2	psi-mi:“MI:2364”(proximity)	0.270
SBDS	RPSA2	psi-mi:“MI:2364”(proximity)	0.270
ZC3H11A	ESYT2	psi-mi:“MI:2364”(proximity)	0.270
DDX6	RPSA2	psi-mi:“MI:2364”(proximity)	0.270

ESM2 similar proteins: A0A1D5AG16, A4QEZ2, A6NHQ2, A9Q1D5, B1VGC2, B8BDQ4, C3PH19, C8VBH4, F4IF36, O83861, P13567, P15646, P22087, P22232, P22509, P34498, P35549, P35550, P35551, P35901, Q0AK69, Q22053, Q24957, Q27200, Q55CW0, Q5PAJ5, Q68FL4, Q6BQ34, Q6FN88, Q6H442, Q756P0, Q767L0, Q7S9B6, Q7URR0, Q7XTS3, Q80WS3, Q829X3, Q8FPA7, Q8I1F4, Q8SR42

Diamond homologs: A0B6X7, A1RRJ7, A3CSX5, A3DNY7, A3MV65, A4FYN1, A4WKL2, A6NHQ2, A6UV22, A6VJQ1, A9A6C8, B0R515, B1YAJ6, B6YXH6, B9LMQ1, C3MPR8, C3MYR2, C3N5E4, C3NDZ8, C3NHQ5, C4KH10, C5A403, C6A2L3, O27283, O28192, O57811, P0CW08, P0CW09, P15646, P22087, P22232, P22509, P35549, P35550, P35551, P35552, P35553, P58032, Q18H64, Q22053

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	1
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

102 predictions. Top by Δscore:

Variant	Effect	Δscore
5:168529507:G:GT	donor_gain	0.8000
5:168529478:C:G	donor_gain	0.7700
5:168529477:A:AG	donor_gain	0.7600
5:168529840:C:CA	acceptor_gain	0.7000
5:168529472:C:A	donor_gain	0.6900
5:168530083:T:TA	acceptor_gain	0.6900
5:168529841:G:A	acceptor_gain	0.6500
5:168530078:A:AG	acceptor_gain	0.6500
5:168530081:ATT:A	acceptor_gain	0.6300
5:168529470:ACC:A	donor_gain	0.6100
5:168530079:T:G	acceptor_gain	0.5400
5:168529836:ACCGC:A	acceptor_gain	0.4800
5:168529499:C:A	donor_gain	0.4600
5:168530183:G:C	acceptor_gain	0.4600
5:168530175:C:CA	acceptor_gain	0.4400
5:168529491:CCCCG:C	donor_loss	0.4300
5:168529494:CG:C	donor_loss	0.4300
5:168529495:GG:G	donor_loss	0.4300
5:168529496:G:GC	donor_loss	0.4300
5:168529497:T:G	donor_loss	0.4300
5:168529498:G:GT	donor_loss	0.4300
5:168529499:CGTGC:C	donor_loss	0.4300
5:168529500:G:C	donor_loss	0.4300
5:168529501:TGCC:T	donor_gain	0.4300
5:168530074:C:CA	acceptor_gain	0.4300
5:168529469:C:T	donor_gain	0.4200
5:168529494:C:A	donor_gain	0.4100
5:168529496:G:GG	donor_gain	0.4100
5:168530074:CGACA:C	acceptor_gain	0.3900
5:168529501:T:G	donor_loss	0.3800

AlphaMissense

2140 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:168529943:C:A	R147S	1.000
5:168529943:C:G	R147G	1.000
5:168529944:G:C	R147P	1.000
5:168529949:T:A	W149R	1.000
5:168529949:T:C	W149R	1.000
5:168529964:T:C	S154P	1.000
5:168529967:A:G	K155E	1.000
5:168529969:G:C	K155N	1.000
5:168529969:G:T	K155N	1.000
5:168529979:G:C	A159P	1.000
5:168530031:T:C	L176P	1.000
5:168530052:G:A	G183D	1.000
5:168530052:G:T	G183V	1.000
5:168530058:C:T	T185I	1.000
5:168530061:T:A	V186D	1.000
5:168530063:T:C	S187P	1.000
5:168530070:T:A	V189D	1.000
5:168530072:T:C	S190P	1.000
5:168530073:C:T	S190F	1.000
5:168530075:G:C	D191H	1.000
5:168530076:A:T	D191V	1.000
5:168530100:T:A	V199D	1.000
5:168530106:C:A	A201D	1.000
5:168530109:T:A	V202D	1.000
5:168530139:T:C	L212P	1.000
5:168530151:C:A	A216D	1.000
5:168530159:C:A	R219S	1.000
5:168530167:C:A	N221K	1.000
5:168530167:C:G	N221K	1.000
5:168530243:G:C	A247P	1.000

dbSNP variants (sampled 300 via entrez): RS1001354637 (5:168531050 T>G), RS1002062116 (5:168531047 C>T), RS1003069011 (5:168529070 A>G), RS1003429082 (5:168529325 C>A,T), RS1005638430 (5:168530950 T>C), RS1005702199 (5:168529622 G>C), RS1005734759 (5:168529422 G>A,C), RS1006075926 (5:168528585 C>T), RS1006871453 (5:168529921 G>A,C), RS1007592462 (5:168528906 C>T), RS1007875866 (5:168527816 A>C,G), RS1008292345 (5:168531129 A>G), RS1008629381 (5:168529682 G>A,C), RS1009942452 (5:168530684 C>A), RS1010849816 (5:168530119 C>T)

Disease associations

OMIM: gene `` | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

26 total (human), top 26 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
entinostat	increases expression, affects cotreatment, decreases expression	2
Tobacco Smoke Pollution	increases expression	2
Valproic Acid	affects expression, increases methylation	2
aristolochic acid I	increases expression	1
methylmercuric chloride	increases expression	1
perfluorooctanoic acid	increases expression	1
ferrous chloride	decreases expression	1
versicolorin A	increases expression	1
perfluorooctane sulfonic acid	increases expression	1
fipronil	affects cotreatment, increases expression	1
perfluoro-n-nonanoic acid	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
perfluorohexanesulfonic acid	increases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	increases expression	1
dorsomorphin	increases expression, affects cotreatment	1
licochalcone B	increases expression	1
Sunitinib	increases expression	1
Air Pollutants	decreases expression, increases abundance	1
Benzo(a)pyrene	affects methylation	1
DEET	affects cotreatment, increases expression	1
Estradiol	affects expression	1
Ivermectin	decreases expression	1
Ribonucleotides	affects binding	1
1-Methyl-4-phenylpyridinium	increases expression	1
Asbestos, Serpentine	decreases expression	1
Particulate Matter	increases abundance, decreases expression	1

Clinical trials (associated diseases)

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