FTSJ3

Summary

FTSJ3 (FtsJ RNA 2’-O-methyltransferase 3, HGNC:17136) is a protein-coding gene on chromosome 17q23.3, encoding pre-rRNA 2’-O-ribose RNA methyltransferase FTSJ3 (Q8IY81). RNA 2’-O-methyltransferase involved in the processing of the 34S pre-rRNA to 18S rRNA and in 40S ribosomal subunit formation. It is a common-essential gene (DepMap: required in 91.4% of cancer cell lines).

Although the function of this gene is not known, the existence of this gene is supported by mRNA and EST data. A possible function of the encoded protein can be inferred from amino acid sequence similarity to the E.coli FtsJ protein and to a mouse protein possibly involved in embryogenesis.

Source: NCBI Gene 117246 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 195 total — 1 pathogenic
• Cancer dependency (DepMap): dependent in 91.4% of screened cell lines (common-essential)
• MANE Select transcript: NM_017647

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17136
Approved symbol	FTSJ3
Name	FtsJ RNA 2’-O-methyltransferase 3
Location	17q23.3
Locus type	gene with protein product
Status	Approved
Aliases	SPB1
Ensembl gene	ENSG00000108592
Ensembl biotype	protein_coding
OMIM	618411
Entrez	117246

Gene structure

Transcript identifiers

Ensembl transcripts: 17 — 7 retained_intron, 6 protein_coding, 3 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000427159, ENST00000577263, ENST00000579569, ENST00000579831, ENST00000580129, ENST00000580272, ENST00000580290, ENST00000580295, ENST00000580376, ENST00000581209, ENST00000582476, ENST00000583202, ENST00000583901, ENST00000584193, ENST00000584574, ENST00000585145, ENST00000914549

RefSeq mRNA: 1 — MANE Select: NM_017647 NM_017647

CCDS: CCDS11644

Canonical transcript exons

ENST00000427159 — 21 exons

Exon	Start	End
ENSE00000742098	63819433	63819994
ENSE00000742100	63820079	63820173
ENSE00000742102	63820255	63820438
ENSE00000742104	63820839	63820938
ENSE00000742112	63821984	63822168
ENSE00000742114	63823817	63823952
ENSE00000742117	63824331	63824411
ENSE00000742118	63824637	63824737
ENSE00000948145	63825242	63825436
ENSE00001047314	63825048	63825163
ENSE00001047330	63824825	63824929
ENSE00001347899	63827052	63827663
ENSE00003470558	63821723	63821843
ENSE00003544376	63821354	63821643
ENSE00003544775	63826056	63826135
ENSE00003566665	63826836	63826928
ENSE00003572579	63826258	63826304
ENSE00003604307	63826567	63826672
ENSE00003625896	63821030	63821115
ENSE00003636801	63824084	63824239
ENSE00003660595	63825536	63825635

Expression profiles

Bgee: expression breadth ubiquitous, 261 present calls, max score 93.72.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 19.6714 / max 178.9283, expressed in 1803 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
167489	16.0288	1793
167486	1.7712	918
167488	0.7930	391
167487	0.5588	320
167490	0.5195	274

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
metanephros cortex	UBERON:0010533	93.72	gold quality
granulocyte	CL:0000094	92.94	gold quality
sural nerve	UBERON:0015488	92.58	gold quality
tendon of biceps brachii	UBERON:0008188	92.55	gold quality
stromal cell of endometrium	CL:0002255	92.26	gold quality
cervix squamous epithelium	UBERON:0006922	92.20	gold quality
mucosa of stomach	UBERON:0001199	92.02	gold quality
right ovary	UBERON:0002118	91.90	gold quality
right adrenal gland	UBERON:0001233	91.60	gold quality
right lobe of thyroid gland	UBERON:0001119	91.51	gold quality
body of uterus	UBERON:0009853	91.39	gold quality
endocervix	UBERON:0000458	91.31	gold quality
left ovary	UBERON:0002119	91.29	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	91.27	gold quality
right adrenal gland cortex	UBERON:0035827	91.26	gold quality
lower esophagus muscularis layer	UBERON:0035833	91.14	gold quality
lower esophagus	UBERON:0013473	91.10	gold quality
left adrenal gland cortex	UBERON:0035825	91.03	gold quality
left adrenal gland	UBERON:0001234	90.96	gold quality
left lobe of thyroid gland	UBERON:0001120	90.86	gold quality
muscle layer of sigmoid colon	UBERON:0035805	90.84	gold quality
left uterine tube	UBERON:0001303	90.54	gold quality
small intestine Peyer’s patch	UBERON:0003454	90.52	gold quality
skin of leg	UBERON:0001511	90.44	gold quality
spleen	UBERON:0002106	90.39	gold quality
body of stomach	UBERON:0001161	90.35	gold quality
transverse colon	UBERON:0001157	90.32	gold quality
tibial nerve	UBERON:0001323	90.30	gold quality
adrenal cortex	UBERON:0001235	90.23	gold quality
minor salivary gland	UBERON:0001830	90.23	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-CURD-112	yes	7.12
E-ANND-3	yes	6.30

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

16 targeting FTSJ3, 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-4692	100.00	67.32	2066
HSA-MIR-5193	100.00	67.26	1744
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-204-5P	99.79	71.62	2439
HSA-MIR-211-5P	99.79	71.65	2440
HSA-MIR-4499	99.62	67.29	1470
HSA-MIR-12123	99.52	71.79	2990
HSA-MIR-1324	99.46	66.57	1302
HSA-MIR-2392	99.43	67.50	708
HSA-MIR-4291	99.20	68.88	2969
HSA-MIR-892C-5P	99.16	70.56	2116
HSA-MIR-506-5P	98.02	67.41	1065
HSA-MIR-22-5P	97.67	68.92	1355
HSA-MIR-663B	97.40	62.91	664
HSA-MIR-4513	95.04	67.06	727
HSA-MIR-6855-3P	95.04	66.57	725

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 91.4% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 5)

• The results presented in this work indicate a close functional interaction between NIP7 and FTSJ3 during pre-rRNA processing and show that FTSJ3 participates in ribosome synthesis in human cells. (PMID:22195017)
• Components of the FTSJ3 interactome identified by coimmunoprecipitation. (PMID:22540864)
• identification of an unexpected mechanism used by HIV-1 to evade innate immune recognition: the recruitment of the TRBP-FTSJ3 complex to viral RNA and its 2’-O-methylation (PMID:30626973)
• Pan-cancer analysis of RNA methyltransferases identifies FTSJ3 as a potential regulator of breast cancer progression. (PMID:31957540)
• RNA Methyltransferase FTSJ3 Regulates the Type I Interferon Pathway to Promote Hepatocellular Carcinoma Immune Evasion. (PMID:37963197)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	ftsj3	ENSDARG00000104938
mus_musculus	Ftsj3	ENSMUSG00000020706
rattus_norvegicus	Ftsj3	ENSRNOG00000009857
drosophila_melanogaster	CG8939	FBGN0030720
caenorhabditis_elegans		WBGENE00019168

Paralogs (2): FTSJ1 (ENSG00000068438), MRM2 (ENSG00000122687)

Protein

Protein identifiers

pre-rRNA 2’-O-ribose RNA methyltransferase FTSJ3 — Q8IY81 (reviewed: Q8IY81)

Alternative names: Protein ftsJ homolog 3, Putative rRNA methyltransferase 3

All UniProt accessions (8): Q8IY81, J3KRY4, J3KS36, J3KS74, J3QKT6, J3QR05, J3QRS5, J3QSE2

UniProt curated annotations — full annotation on UniProt →

Function. RNA 2’-O-methyltransferase involved in the processing of the 34S pre-rRNA to 18S rRNA and in 40S ribosomal subunit formation. (Microbial infection) In case of infection by HIV-1 virus, recruited to HIV-1 RNA and catalyzes 2’-O-methylation of the viral genome, allowing HIV-1 virus to escape the innate immune system. RNA 2’-O-methylation provides a molecular signature for discrimination of self from non-self and is used by HIV-1 to evade innate immune recognition by IFIH1/MDA5. Mediates methylation of internal residues of HIV-1 RNA, with a strong preference for adenosine. Recruited to HIV-1 RNA via interaction with TARBP2/TRBP.

Subunit / interactions. Interacts with NIP7. (Microbial infection) Interacts with TARBP2/TRBP in case of infection by HIV-1; leading to recruitment to HIV-1 TAR RNA. The complex formed with TARBP2/TRBP is independent of DICER.

Subcellular location. Nucleus. Nucleolus.

Post-translational modifications. Citrullinated by PADI4.

Similarity. Belongs to the class I-like SAM-binding methyltransferase superfamily. RNA methyltransferase RlmE family. SPB1 subfamily.

RefSeq proteins (1): NP_060117* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002877	RNA_MeTrfase_FtsJ_dom	Domain
IPR012920	rRNA_MeTfrase_SPB1-like_C	Domain
IPR015507	rRNA-MeTfrase_E	Family
IPR024576	rRNA_MeTfrase_Spb1_DUF3381	Domain
IPR028589	SPB1-like	Family
IPR029063	SAM-dependent_MTases_sf	Homologous_superfamily
IPR050082	RNA_methyltr_RlmE	Family

Pfam: PF01728, PF07780, PF11861

Catalyzed reactions (Rhea), 2 shown:

• a ribonucleotide in rRNA + S-adenosyl-L-methionine = a 2’-O-methylribonucleotide in rRNA + S-adenosyl-L-homocysteine + H(+) (RHEA:48628)
• a ribonucleotide in RNA + S-adenosyl-L-methionine = a 2’-O-methylribonucleotide in RNA + S-adenosyl-L-homocysteine + H(+) (RHEA:58956)

UniProt features (45 total): modified residue 13, compositionally biased region 7, cross-link 6, binding site 5, region of interest 4, mutagenesis site 3, sequence variant 2, coiled-coil region 2, chain 1, active site 1, sequence conflict 1

Structure

Experimental structures (PDB)

11 structures.

PDB	Method	Resolution (Å)
8FKV	ELECTRON MICROSCOPY	2.47
8FKW	ELECTRON MICROSCOPY	2.5
8FKX	ELECTRON MICROSCOPY	2.59
8FKY	ELECTRON MICROSCOPY	2.67
8FKQ	ELECTRON MICROSCOPY	2.76
8FKT	ELECTRON MICROSCOPY	2.81
8FKU	ELECTRON MICROSCOPY	2.82
8FKP	ELECTRON MICROSCOPY	2.85
8FKS	ELECTRON MICROSCOPY	2.88
8FKR	ELECTRON MICROSCOPY	2.89
8IR1	ELECTRON MICROSCOPY	3.3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8IY81-F1	71.56	0.28

Functional residue map

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

Catalytic / active sites (1): 157 (proton acceptor)

Ligand- & substrate-binding residues (5): 56; 58; 76; 92; 117

Post-translational modifications (19): 333, 335, 336, 347, 356, 392, 549, 573, 584, 644, 676, 688, 783, 357, 579, 643, 659, 678, 710

Mutagenesis-validated functional residues (3):

Position	Phenotype
31	abolishes rna 2’-o-methyltransferase activity; when associated with a-117 and a-157.
117	abolishes rna 2’-o-methyltransferase activity; when associated with a-31 and a-157.
157	abolishes rna 2’-o-methyltransferase activity; when associated with a-31 and a-117.

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-6791226	Major pathway of rRNA processing in the nucleolus and cytosol
R-HSA-72312	rRNA processing
R-HSA-8868773	rRNA processing in the nucleus and cytosol
R-HSA-8953854	Metabolism of RNA

MSigDB gene sets: 136 (showing top): GSE45365_NK_CELL_VS_CD11B_DC_DN, GOBP_RIBOSOME_BIOGENESIS, SHEPARD_CRASH_AND_BURN_MUTANT_UP, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GOBP_RNA_METHYLATION, MONNIER_POSTRADIATION_TUMOR_ESCAPE_UP, GOBP_RNA_MODIFICATION, GOBP_MATURATION_OF_5_8S_RRNA_FROM_TRICISTRONIC_RRNA_TRANSCRIPT_SSU_RRNA_5_8S_RRNA_LSU_RRNA, GOBP_MATURATION_OF_LSU_RRNA, NRF2_Q4, STONER_ESOPHAGEAL_CARCINOGENESIS_UP, WANG_TARGETS_OF_MLL_CBP_FUSION_DN, GOBP_MATURATION_OF_5_8S_RRNA, GOBP_RRNA_MODIFICATION, BURTON_ADIPOGENESIS_2

GO Biological Process (7): maturation of LSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA) (GO:0000463), maturation of 5.8S rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA) (GO:0000466), RNA methylation (GO:0001510), rRNA methylation (GO:0031167), rRNA processing (GO:0006364), methylation (GO:0032259), ribosome biogenesis (GO:0042254)

GO Molecular Function (8): RNA binding (GO:0003723), rRNA (uridine-2’-O-ribose)-methyltransferase activity (GO:0008650), rRNA (guanine) methyltransferase activity (GO:0016435), RNA 2’-O-methyltransferase activity (GO:0062105), protein binding (GO:0005515), methyltransferase activity (GO:0008168), rRNA methyltransferase activity (GO:0008649), transferase activity (GO:0016740)

GO Cellular Component (6): nucleoplasm (GO:0005654), chromosome (GO:0005694), nucleolus (GO:0005730), preribosome, large subunit precursor (GO:0030687), preribosome, small subunit precursor (GO:0030688), nucleus (GO:0005634)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
rRNA processing in the nucleus and cytosol	1
Metabolism of RNA	1
rRNA processing	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
RNA methyltransferase activity	2
nuclear lumen	2
intracellular membraneless organelle	2
preribosome	2
maturation of LSU-rRNA	1
maturation of 5.8S rRNA	1
RNA modification	1
macromolecule methylation	1
rRNA modification	1
RNA methylation	1
RNA processing	1
rRNA metabolic process	1
ribosome biogenesis	1
metabolic process	1
ribonucleoprotein complex biogenesis	1
nucleic acid binding	1
rRNA (uridine) methyltransferase activity	1
RNA 2’-O-methyltransferase activity	1
rRNA methyltransferase activity	1
O-methyltransferase activity	1
binding	1
transferase activity, transferring one-carbon groups	1
S-adenosylmethionine-dependent methyltransferase activity	1
catalytic activity, acting on a rRNA	1
catalytic activity	1
cellular anatomical structure	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

3318 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
FTSJ3	NIP7	Q9Y221	838
FTSJ3	NOP2	P46087	813
FTSJ3	WDR74	Q6RFH5	699
FTSJ3	NOP58	Q9Y2X3	683
FTSJ3	FBL	P22087	657
FTSJ3	GNL2	Q13823	654
FTSJ3	NSA2	O95478	651
FTSJ3	EBNA1BP2	Q99848	602
FTSJ3	RSL24D1	Q9UHA3	596
FTSJ3	RPF2	Q9H7B2	591
FTSJ3	WDR12	Q9GZL7	559
FTSJ3	ZZEF1	O43149	557
FTSJ3	RRP8	O43159	550
FTSJ3	RBM8A	Q9Y5S9	546
FTSJ3	SFTPB	P07988	543

IntAct

349 interactions, top by confidence:

A	B	Type	Score
CDK8	MED19	psi-mi:“MI:2364”(proximity)	0.850
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
FTSJ3	H1-4	psi-mi:“MI:0915”(physical association)	0.670
RPL14	RRP8	psi-mi:“MI:0914”(association)	0.640
NOP53	RRP8	psi-mi:“MI:0914”(association)	0.640
NOL12	RRP8	psi-mi:“MI:0914”(association)	0.640
AURKB	SEC16A	psi-mi:“MI:2364”(proximity)	0.570
RPL36	FTSJ3	psi-mi:“MI:0915”(physical association)	0.560
FTSJ3	H1-2	psi-mi:“MI:0915”(physical association)	0.560
FTSJ3	SSX2	psi-mi:“MI:0915”(physical association)	0.560
SSX2	FTSJ3	psi-mi:“MI:0915”(physical association)	0.560
PLEKHO1	UBA6	psi-mi:“MI:0914”(association)	0.530
ZNF512	ZNF724	psi-mi:“MI:0914”(association)	0.530
RBM34	NVL	psi-mi:“MI:0914”(association)	0.530
RRP8	NVL	psi-mi:“MI:0914”(association)	0.530
H1-4	IGF2BP3	psi-mi:“MI:0914”(association)	0.530
WDR55	PES1	psi-mi:“MI:0914”(association)	0.530
RPL37A	MPHOSPH10	psi-mi:“MI:0914”(association)	0.530
RPL18	NOP56	psi-mi:“MI:0914”(association)	0.530
PRR11	NVL	psi-mi:“MI:0914”(association)	0.530
MAK16	NVL	psi-mi:“MI:0914”(association)	0.530
ZNF71	NVL	psi-mi:“MI:0914”(association)	0.530
KNOP1	DHX15	psi-mi:“MI:0914”(association)	0.530
RPL30	RRP8	psi-mi:“MI:0914”(association)	0.530
RPL8	RRP8	psi-mi:“MI:0914”(association)	0.530
RPL18A	RRP8	psi-mi:“MI:0914”(association)	0.530

BioGRID (538): FTSJ3 (Affinity Capture-MS), FTSJ3 (Affinity Capture-MS), FTSJ3 (Affinity Capture-MS), FTSJ3 (Affinity Capture-MS), FTSJ3 (Affinity Capture-MS), FTSJ3 (Affinity Capture-MS), FTSJ3 (Affinity Capture-MS), FTSJ3 (Affinity Capture-MS), FTSJ3 (Affinity Capture-MS), FTSJ3 (Affinity Capture-MS), FTSJ3 (Affinity Capture-MS), FTSJ3 (Affinity Capture-MS), FTSJ3 (Affinity Capture-MS), FTSJ3 (Affinity Capture-MS), FTSJ3 (Affinity Capture-MS)

ESM2 similar proteins: A1A5P2, A6QNR1, A8WY26, D3ZND0, O15213, O59678, P27672, P78316, Q0V8M0, Q15050, Q24K12, Q28IV8, Q2KIH4, Q2KII6, Q3T0Q8, Q3T0Z5, Q3UFY0, Q4KLC4, Q5M985, Q5RAS1, Q5RJT2, Q5TAP6, Q5TJE7, Q5ZKM1, Q640M1, Q6EJB6, Q6P0I6, Q6PFJ1, Q8BK35, Q8IY81, Q8N9T8, Q8NEJ9, Q8R3N1, Q8VDQ9, Q96BZ8, Q96EU6, Q9BRP8, Q9BRR8, Q9BVJ6, Q9C086

Diamond homologs: A0B8A1, A0LGZ0, A0RV28, A1K598, A1KT57, A1RGW7, A1S454, A1TXM4, A2SSW7, A4FYM2, A4IYP4, A4VNP3, A4XYE8, A4Y9C8, A5IHX0, A5UKI5, A5VUZ8, A5W995, A5WCU8, A6USA0, A6UUK5, A6VCK9, A6VJR0, A9A3M9, A9A6B9, A9KGE6, A9M3N1, A9MBW8, A9N8M5, B0KHY6, B0R7G3, B0TZQ8, B1J262, B2FKA1, B2SAY0, B2SF85, B3PLQ4, B4RK82, B4SRA0, B6IZD5

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 225 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
Peptide chain elongation	22	18.9×	2e-20
Viral mRNA Translation	22	18.9×	2e-20
PELO:HBS1L and ABCE1 dissociate a ribosome on a non-stop mRNA	22	18.6×	2e-20
Selenocysteine synthesis	22	17.9×	4e-20
Eukaryotic Translation Termination	22	17.9×	4e-20
Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC)	22	17.5×	6e-20
ZNF598 and the Ribosome-associated Quality Trigger (RQT) complex dissociate a ribosome stalled on a no-go mRNA	22	17.5×	6e-20
SRP-dependent cotranslational protein targeting to membrane	25	16.9×	1e-21

GO biological processes:

GO term	Partners	Fold	FDR
cytoplasmic translation	25	23.5×	1e-24
ribosomal large subunit biogenesis	9	20.3×	1e-07
positive regulation of viral genome replication	5	14.8×	2e-03
rRNA processing	20	14.4×	3e-15
translation	25	13.0×	3e-18
negative regulation of proteasomal ubiquitin-dependent protein catabolic process	6	12.2×	1e-03
regulation of signal transduction by p53 class mediator	6	11.7×	1e-03
ribosomal small subunit biogenesis	10	11.6×	3e-06

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	153
Likely benign	6
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
253549	GRCh37/hg19 17q22-23.3(chr17:56321134-62080001)x3	Pathogenic

SpliceAI

3234 predictions. Top by Δscore:

Variant	Effect	Δscore
17:63819990:AGAGA:A	acceptor_gain	1.0000
17:63819991:GAGA:G	acceptor_gain	1.0000
17:63819992:AGA:A	acceptor_gain	1.0000
17:63819993:GA:G	acceptor_gain	1.0000
17:63819995:C:CC	acceptor_gain	1.0000
17:63819996:T:G	acceptor_loss	1.0000
17:63819998:C:CT	acceptor_gain	1.0000
17:63820075:TTA:T	donor_loss	1.0000
17:63820076:TACC:T	donor_loss	1.0000
17:63820077:AC:A	donor_loss	1.0000
17:63820078:C:A	donor_loss	1.0000
17:63820098:T:A	donor_gain	1.0000
17:63820169:AGCAT:A	acceptor_gain	1.0000
17:63820170:GCAT:G	acceptor_gain	1.0000
17:63820171:CAT:C	acceptor_gain	1.0000
17:63820171:CATC:C	acceptor_gain	1.0000
17:63820172:AT:A	acceptor_gain	1.0000
17:63820174:C:CA	acceptor_loss	1.0000
17:63820174:C:CC	acceptor_gain	1.0000
17:63820252:TA:T	donor_loss	1.0000
17:63820253:AC:A	donor_gain	1.0000
17:63820253:ACCCT:A	donor_gain	1.0000
17:63820254:CC:C	donor_gain	1.0000
17:63820254:CCCT:C	donor_gain	1.0000
17:63820254:CCCTC:C	donor_gain	1.0000
17:63820257:T:A	donor_gain	1.0000
17:63820276:AG:A	donor_gain	1.0000
17:63820438:CCT:C	acceptor_loss	1.0000
17:63820935:TTCG:T	acceptor_gain	1.0000
17:63820936:TCG:T	acceptor_gain	1.0000

AlphaMissense

5552 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:63825246:G:C	C197W	1.000
17:63825247:C:T	C197Y	0.999
17:63825312:G:C	F175L	0.999
17:63825312:G:T	F175L	0.999
17:63825314:A:G	F175L	0.999
17:63825360:G:C	F159L	0.999
17:63825360:G:T	F159L	0.999
17:63825362:A:G	F159L	0.999
17:63825366:C:A	K157N	0.999
17:63825366:C:G	K157N	0.999
17:63825370:G:T	T156K	0.999
17:63825586:T:A	D117V	0.999
17:63825586:T:G	D117A	0.999
17:63825592:A:G	L115P	0.999
17:63825592:A:T	L115H	0.999
17:63826568:A:G	W58R	0.999
17:63826568:A:T	W58R	0.999
17:63826647:C:A	K31N	0.999
17:63826647:C:G	K31N	0.999
17:63826650:G:C	F30L	0.999
17:63826650:G:T	F30L	0.999
17:63826652:A:G	F30L	0.999
17:63824398:A:G	W311R	0.998
17:63824398:A:T	W311R	0.998
17:63825255:A:C	F194L	0.998
17:63825255:A:T	F194L	0.998
17:63825257:A:G	F194L	0.998
17:63825262:T:A	E192V	0.998
17:63825289:G:T	P183H	0.998
17:63825291:C:A	K182N	0.998

dbSNP variants (sampled 300 via entrez): RS1000576455 (17:63828367 T>C), RS1000628655 (17:63827929 C>A,G,T), RS1000685753 (17:63823182 G>A,C), RS1000752852 (17:63823343 C>G), RS1000853832 (17:63819374 G>A), RS1000962143 (17:63824584 G>A), RS1001305384 (17:63823469 C>G), RS1001589878 (17:63827193 T>A,C), RS1001759498 (17:63822149 T>C), RS1001802503 (17:63828974 G>A), RS1002123382 (17:63827608 G>A,C), RS1002191329 (17:63829224 A>G,T), RS1002475762 (17:63827984 G>A), RS1002529051 (17:63825831 A>C,G), RS1002537783 (17:63827455 G>A,C)

Disease associations

OMIM: gene MIM:618411 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST010083_356	Hemoglobin levels	5.000000e-12

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004509	hemoglobin measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects cotreatment, decreases expression, increases expression	2
bisphenol S	affects expression, affects cotreatment, decreases expression	2
Valproic Acid	affects expression, decreases methylation	2
Aflatoxin B1	affects cotreatment, decreases expression, increases methylation	2
FR900359	affects phosphorylation	1
TAK-243	increases sumoylation	1
alpha phellandrene	decreases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	decreases expression	1
deoxynivalenol	increases expression	1
beta-lapachone	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
coumarin	decreases phosphorylation	1
nivalenol	increases expression	1
di-n-butylphosphoric acid	affects expression	1
2,3,5-(triglutathion-S-yl)hydroquinone	increases ADP-ribosylation	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
nutlin 3	affects cotreatment, increases secretion	1
LDN 193189	affects cotreatment, decreases expression	1
Resveratrol	affects cotreatment, increases expression	1
Air Pollutants	decreases expression, increases abundance	1
Air Pollutants, Occupational	decreases expression	1
Benzo(a)pyrene	affects methylation	1
Cadmium	increases abundance, increases expression	1
Caffeine	affects phosphorylation	1
Dactinomycin	affects cotreatment, increases secretion	1
Dexamethasone	affects cotreatment, decreases expression	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Indomethacin	affects cotreatment, decreases expression	1

Clinical trials (associated diseases)

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