FAM98B

Summary

FAM98B (family with sequence similarity 98 member B, HGNC:26773) is a protein-coding gene on chromosome 15q14, encoding tRNA-splicing ligase complex subunit FAM98B (Q52LJ0). Accessory subunit of the tRNA-splicing ligase complex that acts by directly joining spliced tRNA halves to mature-sized tRNAs by incorporating the precursor-derived splice junction phosphate into the mature tRNA as a canonical 3’,5’-phosphodiester. It is a selective cancer dependency (DepMap: 33.6% of cell lines).

Enables identical protein binding activity and protein methyltransferase activity. Involved in positive regulation of cell population proliferation; positive regulation of gene expression; and protein methylation. Located in cytoplasm and nucleoplasm. Part of tRNA-splicing ligase complex.

Source: NCBI Gene 283742 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 71 total
• Cancer dependency (DepMap): dependent in 33.6% of screened cell lines
• MANE Select transcript: NM_173611

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:26773
Approved symbol	FAM98B
Name	family with sequence similarity 98 member B
Location	15q14
Locus type	gene with protein product
Status	Approved
Aliases	FLJ38426
Ensembl gene	ENSG00000171262
Ensembl biotype	protein_coding
OMIM	616142
Entrez	283742

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 3 protein_coding, 1 retained_intron

ENST00000305752, ENST00000397609, ENST00000491535, ENST00000559431

RefSeq mRNA: 1 — MANE Select: NM_173611 NM_173611

CCDS: CCDS10047

Canonical transcript exons

ENST00000397609 — 8 exons

Exon	Start	End
ENSE00001529389	38484255	38487710
ENSE00001529390	38481292	38481459
ENSE00001529405	38454127	38454232
ENSE00002098603	38470227	38470405
ENSE00002104013	38474182	38474298
ENSE00002126422	38473505	38473585
ENSE00002126985	38464032	38464177
ENSE00003464602	38465269	38465403

Expression profiles

Bgee: expression breadth ubiquitous, 255 present calls, max score 96.08.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 33.1480 / max 527.0253, expressed in 1808 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
145868	33.1480	1808

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
upper arm skin	UBERON:0004263	96.08	gold quality
left ventricle myocardium	UBERON:0006566	95.65	gold quality
cerebellar vermis	UBERON:0004720	95.50	gold quality
cardiac muscle of right atrium	UBERON:0003379	95.22	gold quality
thymus	UBERON:0002370	94.76	gold quality
ganglionic eminence	UBERON:0004023	94.67	gold quality
ventricular zone	UBERON:0003053	94.13	gold quality
myocardium	UBERON:0002349	94.06	gold quality
germinal epithelium of ovary	UBERON:0001304	94.00	gold quality
esophagus squamous epithelium	UBERON:0006920	93.81	gold quality
saphenous vein	UBERON:0007318	93.38	gold quality
palpebral conjunctiva	UBERON:0001812	93.35	gold quality
pons	UBERON:0000988	93.25	gold quality
visceral pleura	UBERON:0002401	93.18	gold quality
kidney epithelium	UBERON:0004819	93.11	gold quality
parietal pleura	UBERON:0002400	93.07	gold quality
cortical plate	UBERON:0005343	92.75	gold quality
cauda epididymis	UBERON:0004360	92.56	gold quality
subthalamic nucleus	UBERON:0001906	92.27	gold quality
mucosa of paranasal sinus	UBERON:0005030	92.20	gold quality
pigmented layer of retina	UBERON:0001782	92.02	gold quality
deltoid	UBERON:0001476	91.88	gold quality
vastus lateralis	UBERON:0001379	91.81	gold quality
dorsal plus ventral thalamus	UBERON:0001897	91.72	gold quality
nipple	UBERON:0002030	91.70	gold quality
penis	UBERON:0000989	91.68	gold quality
layer of synovial tissue	UBERON:0007616	91.64	gold quality
mammary duct	UBERON:0001765	91.57	gold quality
heart right ventricle	UBERON:0002080	91.57	gold quality
ventral tegmental area	UBERON:0002691	91.56	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

143 targeting FAM98B, 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-3163	100.00	77.23	8605
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-4673	100.00	66.64	1490
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-4645-5P	99.98	65.81	1284
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-485-3P	99.98	70.68	1585
HSA-MIR-539-3P	99.98	70.74	1616
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-146A-5P	99.96	68.93	988
HSA-MIR-146B-5P	99.96	69.13	977
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-7153-5P	99.94	68.89	1006
HSA-MIR-548A-5P	99.94	71.27	3482
HSA-MIR-548AD-5P	99.94	71.23	3502
HSA-MIR-548AE-5P	99.94	71.23	3502
HSA-MIR-548AK	99.94	71.24	3488
HSA-MIR-548AM-5P	99.94	71.24	3488
HSA-MIR-548AP-5P	99.94	71.14	3489

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 33.6% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 2)

• hCLE/C14orf166 associates with DDX1, HSPC117, and FAM98B in a novel transcription-dependent shuttling RNA-transporting complex. (PMID:24608264)
• the two structural homologs FAM98A and FAM98B included in a novel complex with DDX1 and C14orf166 are required for PRMT1 expression in colorectal cancer cell lines (PMID:28040436)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	fam98b	ENSDARG00000060068
mus_musculus	Fam98b	ENSMUSG00000027349
rattus_norvegicus	Fam98b	ENSRNOG00000005366
rattus_norvegicus	Fam98b-ps1	ENSRNOG00000069394
drosophila_melanogaster	CG5913	FBGN0039385
caenorhabditis_elegans		WBGENE00044326

Paralogs (2): FAM98A (ENSG00000119812), FAM98C (ENSG00000130244)

Protein

Protein identifiers

tRNA-splicing ligase complex subunit FAM98B — Q52LJ0 (reviewed: Q52LJ0)

All UniProt accessions (2): Q52LJ0, H0YNA1

UniProt curated annotations — full annotation on UniProt →

Function. Accessory subunit of the tRNA-splicing ligase complex that acts by directly joining spliced tRNA halves to mature-sized tRNAs by incorporating the precursor-derived splice junction phosphate into the mature tRNA as a canonical 3’,5’-phosphodiester. May act as an RNA ligase with broad substrate specificity and may function toward other RNAs. Could regulate the expression of PRMT1, a protein arginine N-methyltransferase.

Subunit / interactions. Homodimer. Component of the tRNA-splicing ligase core complex composed of the catalytic subunit RTCB and the accessory proteins DDX1, C2orf49/Ashwin/ASW, FAM98B and RTRAF/CGI-99. Interacts with FAM98A.

Subcellular location. Nucleus. Cytoplasm.

Tissue specificity. Expressed strongly in colorectal cancer tissues compared to wild-type colon samples (at protein level). Expressed strongly in colorectal cancer tissues compared to wild-type colon samples.

Miscellaneous. Dubious isoform due to intron retention.

Similarity. Belongs to the FAM98 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q52LJ0-2	2	yes
Q52LJ0-1	1

RefSeq proteins (1): NP_775882* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR018797	FAM98	Family

Pfam: PF10239

UniProt features (7 total): compositionally biased region 2, splice variant 2, chain 1, region of interest 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q52LJ0-F1	75.11	0.39

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-6784531	tRNA processing in the nucleus

MSigDB gene sets: 161 (showing top): GOBP_TRNA_METABOLIC_PROCESS, chr15q14, GOBP_RNA_SPLICING_VIA_ENDONUCLEOLYTIC_CLEAVAGE_AND_LIGATION, GOBP_RNA_SPLICING, YRTCANNRCGC_UNKNOWN, JAATINEN_HEMATOPOIETIC_STEM_CELL_UP, GOBP_METHYLATION, GOBP_TRNA_PROCESSING, REACTOME_METABOLISM_OF_RNA, MOREAUX_MULTIPLE_MYELOMA_BY_TACI_DN, MARSON_BOUND_BY_FOXP3_STIMULATED, MARSON_BOUND_BY_FOXP3_UNSTIMULATED, GOMF_PROTEIN_METHYLTRANSFERASE_ACTIVITY, GOMF_TRANSFERASE_ACTIVITY_TRANSFERRING_ONE_CARBON_GROUPS, ELK1_02

GO Biological Process (4): tRNA splicing, via endonucleolytic cleavage and ligation (GO:0006388), protein methylation (GO:0006479), positive regulation of cell population proliferation (GO:0008284), positive regulation of gene expression (GO:0010628)

GO Molecular Function (4): RNA binding (GO:0003723), protein methyltransferase activity (GO:0008276), identical protein binding (GO:0042802), protein binding (GO:0005515)

GO Cellular Component (4): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), tRNA-splicing ligase complex (GO:0072669)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
tRNA processing	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
RNA splicing, via endonucleolytic cleavage and ligation	1
tRNA processing	1
protein alkylation	1
macromolecule methylation	1
cell population proliferation	1
regulation of cell population proliferation	1
positive regulation of cellular process	1
gene expression	1
regulation of gene expression	1
positive regulation of macromolecule biosynthetic process	1
nucleic acid binding	1
methyltransferase activity	1
catalytic activity, acting on a protein	1
protein binding	1
binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
intracellular anatomical structure	1
intracellular protein-containing complex	1
catalytic complex	1

Protein interactions and networks

STRING

1023 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
FAM98B	RTRAF	Q9Y224	996
FAM98B	DDX1	Q92499	988
FAM98B	RTCB	Q9Y3I0	950
FAM98B	C2orf49	Q9BVC5	909
FAM98B	ZBTB8OS	Q8IWT0	640
FAM98B	HNRNPDL	O14979	603
FAM98B	CDIN1	Q9Y2V0	582
FAM98B	KHSRP	Q92945	546
FAM98B	USP17L19	D6RCP7	507
FAM98B	USP17L15	C9J2P7	506
FAM98B	PRMT1	Q99873	470
FAM98B	ELAVL4	P26378	456
FAM98B	TRPT1	Q86TN4	448
FAM98B	RTCA	O00442	430
FAM98B	FBXW11	Q9UKB1	407

IntAct

76 interactions, top by confidence:

A	B	Type	Score
DDX1	FAM98B	psi-mi:“MI:0915”(physical association)	0.670
RTRAF	FAM98B	psi-mi:“MI:0915”(physical association)	0.560
MAPT	KIF2A	psi-mi:“MI:0914”(association)	0.530
N	RBM47	psi-mi:“MI:0914”(association)	0.530
DDX1	FAM98C	psi-mi:“MI:0914”(association)	0.530
FAM98B	PRMT1	psi-mi:“MI:0915”(physical association)	0.400
FAM98B	FAM98B	psi-mi:“MI:0915”(physical association)	0.400
FAM98A	FAM98B	psi-mi:“MI:0915”(physical association)	0.400
JUN	TPM3	psi-mi:“MI:0914”(association)	0.350
Xpo1	IFT56	psi-mi:“MI:0914”(association)	0.350
ZBTB8OS	FAM98B	psi-mi:“MI:0914”(association)	0.350
DLD	NFKBIE	psi-mi:“MI:0914”(association)	0.350
MAPT	MEX3A	psi-mi:“MI:0914”(association)	0.350
RTCB	NSA2	psi-mi:“MI:0914”(association)	0.350
CAND1	GTPBP10	psi-mi:“MI:0914”(association)	0.350
COPS5	FBLL1	psi-mi:“MI:0914”(association)	0.350
CUL3	PXDNL	psi-mi:“MI:0914”(association)	0.350
LRRK2		psi-mi:“MI:0914”(association)	0.350
RTRAF	DNAJB6	psi-mi:“MI:0914”(association)	0.350
PAK4	SNRPE	psi-mi:“MI:0914”(association)	0.350
N	MRPL45	psi-mi:“MI:0914”(association)	0.350
N	RBM47	psi-mi:“MI:0914”(association)	0.350
MAPT	SHTN1	psi-mi:“MI:0914”(association)	0.350

BioGRID (156): FAM98B (Affinity Capture-RNA), FAM98B (Affinity Capture-RNA), FAM98B (Affinity Capture-MS), FAM98B (Affinity Capture-MS), C14orf166 (Co-fractionation), FAM98B (Co-fractionation), FAM98B (Co-fractionation), FAM98B (Co-fractionation), FAM98B (Co-fractionation), FAM98B (Co-fractionation), FAM98B (Co-fractionation), FAM98B (Co-fractionation), FAM98B (Co-fractionation), FAM98B (Co-fractionation), FAM98B (Co-fractionation)

ESM2 similar proteins: A4IFB1, A6H7H1, A9ULY7, B1H1X4, B5DDX6, B5DF93, B5X165, D3Z8X7, O60308, P70501, Q05AW9, Q28HX4, Q3TC46, Q3TJZ6, Q52LJ0, Q5EA95, Q5FWT1, Q5R4R4, Q5R539, Q5R679, Q5R8Q4, Q5RHQ8, Q60520, Q62418, Q66I22, Q6A0A9, Q6DEZ2, Q6IVW0, Q80V31, Q80VD1, Q86TB9, Q8BH43, Q8BXG3, Q8CBY3, Q8CDG3, Q8CF97, Q8K2L8, Q8NCA5, Q8ND56, Q8R3P2

Diamond homologs: Q17RN3, Q3TJZ6, Q52LJ0, Q5FWT1, Q5R679, Q80VD1, Q8NCA5

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 65 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
tRNA processing in the nucleus	5	21.9×	1e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	64
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1025 predictions. Top by Δscore:

Variant	Effect	Δscore
15:38454230:GGG:G	donor_gain	1.0000
15:38454231:GG:G	donor_gain	1.0000
15:38454231:GGG:G	donor_gain	1.0000
15:38454231:GGGTG:G	donor_loss	1.0000
15:38454232:GG:G	donor_gain	1.0000
15:38454232:GGTG:G	donor_loss	1.0000
15:38454233:G:GG	donor_gain	1.0000
15:38464111:C:G	donor_gain	1.0000
15:38464160:A:T	donor_gain	1.0000
15:38465265:A:AG	acceptor_gain	1.0000
15:38465265:AAAG:A	acceptor_gain	1.0000
15:38465266:A:G	acceptor_gain	1.0000
15:38465267:A:AG	acceptor_gain	1.0000
15:38465268:G:GG	acceptor_gain	1.0000
15:38465268:GGAA:G	acceptor_gain	1.0000
15:38465400:CTAT:C	donor_gain	1.0000
15:38465400:CTATG:C	donor_loss	1.0000
15:38465401:TAT:T	donor_gain	1.0000
15:38465402:AT:A	donor_gain	1.0000
15:38465403:TG:T	donor_loss	1.0000
15:38465404:G:GG	donor_gain	1.0000
15:38465404:GTAAG:G	donor_loss	1.0000
15:38465405:TAAGT:T	donor_loss	1.0000
15:38465406:AAG:A	donor_loss	1.0000
15:38470225:A:AG	acceptor_gain	1.0000
15:38470226:G:GA	acceptor_gain	1.0000
15:38470226:GT:G	acceptor_gain	1.0000
15:38470226:GTA:G	acceptor_gain	1.0000
15:38470226:GTATT:G	acceptor_gain	1.0000
15:38470401:CAAAG:C	donor_loss	1.0000

AlphaMissense

2749 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
15:38474281:T:A	W238R	1.000
15:38474281:T:C	W238R	1.000
15:38484280:G:C	R308T	1.000
15:38484280:G:T	R308M	1.000
15:38484281:G:C	R308S	1.000
15:38484281:G:T	R308S	1.000
15:38484283:G:A	G309E	1.000
15:38484330:T:A	W325R	1.000
15:38484330:T:C	W325R	1.000
15:38484332:G:C	W325C	1.000
15:38484332:G:T	W325C	1.000
15:38474230:C:A	R221S	0.999
15:38474231:G:C	R221P	0.999
15:38474234:G:C	R222P	0.999
15:38474272:T:C	S235P	0.999
15:38474275:T:C	F236L	0.999
15:38474277:T:A	F236L	0.999
15:38474277:T:G	F236L	0.999
15:38474283:G:C	W238C	0.999
15:38474283:G:T	W238C	0.999
15:38481332:G:C	R257P	0.999
15:38484262:T:C	M302T	0.999
15:38484276:G:C	D307H	0.999
15:38484277:A:T	D307V	0.999
15:38484282:G:A	G309R	0.999
15:38484282:G:C	G309R	0.999
15:38484283:G:T	G309V	0.999
15:38484285:G:C	G310R	0.999
15:38484322:T:C	M322T	0.999
15:38484322:T:G	M322R	0.999

dbSNP variants (sampled 300 via entrez): RS1000148454 (15:38477550 C>T), RS1000252264 (15:38483092 T>C), RS1000283317 (15:38482739 A>T), RS1000473904 (15:38459450 CT>C), RS1000504963 (15:38462812 A>G,T), RS1000598571 (15:38475682 A>G), RS1000635545 (15:38468830 C>T), RS1000665215 (15:38468514 T>C), RS1000752458 (15:38475955 C>T), RS1000864789 (15:38464448 T>A,C), RS1001002887 (15:38457123 A>G), RS1001057025 (15:38476864 G>A,T), RS1001117066 (15:38456818 A>G), RS1001126439 (15:38469638 A>G), RS1001135819 (15:38477361 G>A)

Disease associations

OMIM: gene MIM:616142 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST002211_9	Psychosis (atypical)	4.000000e-06
GCST002463_20	Systemic lupus erythematosus	1.000000e-14

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

29 total (human), top 29 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases expression, increases expression	2
sodium arsenite	increases abundance, increases expression, increases activity	2
Air Pollutants	affects expression, increases abundance, decreases expression	2
Benzo(a)pyrene	affects methylation, increases expression	2
aristolochic acid I	decreases expression	1
FR900359	increases phosphorylation	1
triphenyl phosphate	affects expression	1
pirinixic acid	affects binding, increases activity, increases expression	1
beta-lapachone	increases expression	1
methylparaben	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	increases reaction, affects binding	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
abrine	decreases expression	1
LDN 193189	affects cotreatment, increases expression	1
Arsenic	increases abundance, increases expression	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Ivermectin	decreases expression	1
Methyl Methanesulfonate	decreases expression	1
Ozone	affects expression, increases abundance	1
Quercetin	decreases expression	1
Ribonucleotides	affects binding	1
Tetrachlorodibenzodioxin	affects expression	1
Tretinoin	decreases expression	1
Valproic Acid	decreases expression	1
Vanadates	decreases expression	1
Aflatoxin M1	decreases expression	1
Antirheumatic Agents	increases expression	1
Particulate Matter	decreases expression, increases abundance	1

Clinical trials (associated diseases)

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