GRSF1

Summary

GRSF1 (G-rich RNA sequence binding factor 1, HGNC:4610) is a protein-coding gene on chromosome 4q13.3, encoding G-rich sequence factor 1 (Q12849). Regulator of post-transcriptional mitochondrial gene expression, required for assembly of the mitochondrial ribosome and for recruitment of mRNA and lncRNA. It is a selective cancer dependency (DepMap: 22.7% of cell lines).

The protein encoded by this gene is a cellular protein that binds RNAs containing the G-rich element. The protein is localized in the cytoplasm, and has been shown to stimulate translation of viral mRNAs in vitro. Multiple transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 2926 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 100 total
• Cancer dependency (DepMap): dependent in 22.7% of screened cell lines
• MANE Select transcript: NM_002092

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4610
Approved symbol	GRSF1
Name	G-rich RNA sequence binding factor 1
Location	4q13.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000132463
Ensembl biotype	protein_coding
OMIM	604851
Entrez	2926

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 9 protein_coding, 1 retained_intron, 1 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000254799, ENST00000499044, ENST00000502323, ENST00000505068, ENST00000506453, ENST00000508091, ENST00000514161, ENST00000908528, ENST00000908529, ENST00000908530, ENST00000912405, ENST00000912406

RefSeq mRNA: 2 — MANE Select: NM_002092 NM_001098477, NM_002092

CCDS: CCDS47069, CCDS47070

Canonical transcript exons

ENST00000254799 — 10 exons

Exon	Start	End
ENSE00001977981	70815783	70820861
ENSE00002081628	70839471	70839890
ENSE00003560575	70831539	70831674
ENSE00003566502	70824294	70824368
ENSE00003568508	70826124	70826245
ENSE00003579800	70825296	70825431
ENSE00003582714	70832307	70832450
ENSE00003625286	70833118	70833273
ENSE00003635330	70827852	70828036
ENSE00003680597	70836158	70836314

Expression profiles

Bgee: expression breadth ubiquitous, 299 present calls, max score 98.02.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 100.0127 / max 775.5929, expressed in 1828 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
52443	89.2077	1828
52442	5.8800	1722
52438	2.0332	1174
52444	1.9609	1277
52439	0.3465	148
52440	0.2934	119
52441	0.2910	120

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
parotid gland	UBERON:0001831	98.02	gold quality
gastrocnemius	UBERON:0001388	97.96	gold quality
islet of Langerhans	UBERON:0000006	97.92	gold quality
muscle of leg	UBERON:0001383	97.88	gold quality
choroid plexus epithelium	UBERON:0003911	97.65	gold quality
muscle organ	UBERON:0001630	97.60	gold quality
skeletal muscle organ	UBERON:0014892	97.60	gold quality
adrenal tissue	UBERON:0018303	97.36	gold quality
hindlimb stylopod muscle	UBERON:0004252	97.21	gold quality
skeletal muscle tissue	UBERON:0001134	97.12	gold quality
rectum	UBERON:0001052	97.02	gold quality
biceps brachii	UBERON:0001507	97.02	gold quality
vastus lateralis	UBERON:0001379	96.81	gold quality
right adrenal gland cortex	UBERON:0035827	96.73	gold quality
quadriceps femoris	UBERON:0001377	96.66	gold quality
muscle tissue	UBERON:0002385	96.63	gold quality
deltoid	UBERON:0001476	96.58	gold quality
right adrenal gland	UBERON:0001233	96.52	gold quality
Brodmann (1909) area 23	UBERON:0013554	96.48	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	96.46	gold quality
ventricular zone	UBERON:0003053	96.45	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	96.44	gold quality
stromal cell of endometrium	CL:0002255	96.37	gold quality
pancreas	UBERON:0001264	96.35	gold quality
triceps brachii	UBERON:0001509	96.28	gold quality
left adrenal gland	UBERON:0001234	96.26	gold quality
mucosa of transverse colon	UBERON:0004991	96.26	gold quality
body of pancreas	UBERON:0001150	96.20	gold quality
left adrenal gland cortex	UBERON:0035825	96.05	gold quality
gluteal muscle	UBERON:0002000	96.04	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-CURD-46	yes	20.41
E-CURD-88	yes	4.23
E-ANND-3	no	0.00

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

1 targets.

Target	Regulation
FASTKD5	Repression

miRNA regulators (miRDB)

162 targeting GRSF1, 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-3613-3P	100.00	76.36	7965
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-3667-3P	99.99	67.17	1636
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-485-3P	99.98	70.68	1585
HSA-MIR-539-3P	99.98	70.74	1616
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-493-5P	99.96	72.47	2382
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-4487	99.96	64.58	1252
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-1236-3P	99.94	68.04	1695
HSA-MIR-144-3P	99.94	73.98	2698

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 22.7% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 17)

• GRSF-1 functions by selectively recruiting cellular and viral mRNAs containing 5’ UTR GRSF-1 binding sites to polyribosomes, which is mediated through interactions with cellular proteins (PMID:12239318)
• The mitochondrial RNA-binding protein GRSF1 localizes to RNA granules and is required for posttranscriptional mitochondrial gene expression. (PMID:23473033)
• GRSF1 regulates RNA processing in mitochondrial RNA granules. (PMID:23473034)
• Grsf1 controls translation of the protein Use1, possibly by positioning the 40S ribosomal subunit and associated translation factors in front of the translation start site. (PMID:25184340)
• MiR-346 depends on GRSF1 to upregulate another target gene. (PMID:26507454)
• HuR and GRSF1 govern the cytoplasmic and mitochondrial localization of the lncRNA RMRP, which is encoded by nuclear DNA but has key functions in mitochondria. (PMID:27198227)
• Deletion of either of the three GRSF1 quasi-RNA-recognition motifs (qRRMs) severely impairs RNA-binding. (PMID:29288125)
• Data show that some of the naturally occurring guanine-rich RNA sequence binding factor 1 (GRSF1) mutants exhibited a strongly reduced RNA-binding activity although the general protein structure was hardly affected. (PMID:29366917)
• GRSF1 positively regulates degradosome-dependent decay of non-coding mitochondrial transcripts that form G4 structures. Comprehensive molecular analyses revealed that GRSF1 melts G4 RNA structures in mtRNAs, which facilitates their degradation by the hSuv3-PNPase complex both in vitro and in vivo. (PMID:29967381)
• These findings indicate that the decline in GRSF1 levels during cellular senescence contributes to impairing mitochondrial function, elevating ROS and DNA damage, suppressing growth, and implementing a pro-inflammatory program. (PMID:30086537)
• These findings suggest that Twinkle is essential for RNA organization in granules, and that mtSSB is involved in the recently proposed GRSF1-mtRNA degradosome pathway, a route suggested to be particularly aimed at degradation of G-quadruplex prone long non-coding mtRNAs. (PMID:30715486)
• our results indicate that GRSF1 helps preserve mitochondrial homeostasis, in turn preventing oxidative DNA damage and the activation of mTOR and NF-kappaB, and suppressing a transcriptional pro-inflammatory program leading to increased IL6 production. (PMID:30753671)
• GRSF1 is an age-related regulator of senescence. (PMID:30944385)
• Identification of the COMM-domain containing protein 1 as specific binding partner for the guanine-rich RNA sequence binding factor 1. (PMID:32645484)
• GRSF1 promotes tumorigenesis and EMT-mediated metastasis through PI3K/AKT pathway in gastric cancer. (PMID:33813277)
• GRSF1 antagonizes age-associated hypercoagulability via modulation of fibrinogen mRNA stability. (PMID:37923734)
• GRSF1 deficiency attenuates mitochondrial function in aging granulosa cells. (PMID:38819377)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
mus_musculus	Grsf1	ENSMUSG00000044221
rattus_norvegicus	Grsf1	ENSRNOG00000003392
drosophila_melanogaster	fus	FBGN0023441
drosophila_melanogaster	glo	FBGN0259139
caenorhabditis_elegans		WBGENE00006367
caenorhabditis_elegans	rbm-12	WBGENE00013703
caenorhabditis_elegans		WBGENE00022253

Paralogs (8): HNRNPH3 (ENSG00000096746), ESRP2 (ENSG00000103067), ESRP1 (ENSG00000104413), HNRNPH2 (ENSG00000126945), HNRNPH1 (ENSG00000169045), HNRNPF (ENSG00000169813), RBM12B (ENSG00000183808), RBM12 (ENSG00000244462)

Protein

Protein identifiers

G-rich sequence factor 1 — Q12849 (reviewed: Q12849)

All UniProt accessions (4): Q12849, H0Y8R1, H0YAK1, H0YAM1

UniProt curated annotations — full annotation on UniProt →

Function. Regulator of post-transcriptional mitochondrial gene expression, required for assembly of the mitochondrial ribosome and for recruitment of mRNA and lncRNA. Binds RNAs containing the 14 base G-rich element. Preferentially binds RNAs transcribed from three contiguous genes on the light strand of mtDNA, the ND6 mRNA, and the long non-coding RNAs for MT-CYB and MT-ND5, each of which contains multiple consensus binding sequences. Involved in the degradosome-mediated decay of non-coding mitochondrial transcripts (MT-ncRNA) and tRNA-like molecules. Acts by unwinding G-quadruplex RNA structures in MT-ncRNA, thus facilitating their degradation by the degradosome. G-quadruplexes (G4) are non-canonical 4 stranded structures formed by transcripts from the light strand of mtDNA.

Subunit / interactions. Monomer. Found in a complex with DDX28, DHX30, FASTKD2 and FASTKD5. Interacts with the mitochondrial RNase P complex subunit TRMT10C/MRPP1. Interacts with the 2 components of the mitochondrial degradosome complex, PNPT1 and SUPV3L1, in an RNA-dependent manner.

Subcellular location. Mitochondrion matrix Cytoplasm.

Domain organisation. The RRM domains mediate RNA-binding.

Miscellaneous. Depletion of GRSF1 by siRNA results in a combined OXPHOS assembly defect, with the prominent loss of complexes I, III, IV, and V. It also leads to altered steady-state levels of mitochondrial rRNAs and mRNAs.

Isoforms (2)

UniProt ID	Names	Canonical?
Q12849-1	1	yes
Q12849-5	2

RefSeq proteins (2): NP_001091947, NP_002083* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000504	RRM_dom	Domain
IPR012677	Nucleotide-bd_a/b_plait_sf	Homologous_superfamily
IPR034424	GRSF-1_RRM2	Domain
IPR034425	GRSF1_RRM1	Domain
IPR034426	GRSF1_RRM3	Domain
IPR035979	RBD_domain_sf	Homologous_superfamily
IPR050666	ESRP	Family

Pfam: PF00076

UniProt features (38 total): mutagenesis site 9, strand 9, helix 7, domain 3, sequence conflict 2, turn 2, modified residue 2, transit peptide 1, chain 1, splice variant 1, sequence variant 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
4QU6	X-RAY DIFFRACTION	1.75
4QU7	X-RAY DIFFRACTION	2.5
2LMI	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q12849-F1	66.72	0.19

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 (2): 244, 335

Mutagenesis-validated functional residues (9):

Position	Phenotype
159	impairs rna-binding and melting of g-quadruplex rna structures; when associated with a-155; a-223; a-255; a-259; a-320;
223	impairs rna-binding and melting of g-quadruplex rna structures; when associated with a-155; a-159; a-255; a-259; a-320;
255	impairs rna-binding and melting of g-quadruplex rna structures; when associated with a-155; a-159; a-223; a-259; a-320;
259	impairs rna-binding and melting of g-quadruplex rna structures; when associated with a-155; a-159; a-223; a-255; a-320;
320	impairs rna-binding and melting of g-quadruplex rna structures; when associated with a-155; a-159; a-223; a-255; a-259;
406	impairs rna-binding and melting of g-quadruplex rna structures; when associated with a-155; a-159; a-223; a-255; a-259;
410	impairs rna-binding and melting of g-quadruplex rna structures; when associated with a-155; a-159; a-223; a-255; a-259;
470	impairs rna-binding and melting of g-quadruplex rna structures; when associated with a-155; a-159; a-223; a-255; a-259;
155	impairs rna-binding and melting of g-quadruplex rna structures; when associated with a-159; a-223; a-255; a-259; a-320;

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-192823	Viral mRNA Translation
R-HSA-9836573	Mitochondrial RNA degradation

MSigDB gene sets: 212 (showing top): GOBP_MORPHOGENESIS_OF_AN_EPITHELIUM, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_TRNA_METABOLIC_PROCESS, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, SHAFFER_IRF4_TARGETS_IN_ACTIVATED_B_LYMPHOCYTE, GOBP_MORPHOGENESIS_OF_EMBRYONIC_EPITHELIUM, chr4q13, GTGCCTT_MIR506, SCHUHMACHER_MYC_TARGETS_UP, RUTELLA_RESPONSE_TO_CSF2RB_AND_IL4_UP, GOBP_REGULATION_OF_CATABOLIC_PROCESS, GOBP_ANTERIOR_POSTERIOR_PATTERN_SPECIFICATION, GOBP_POSITIVE_REGULATION_OF_CATABOLIC_PROCESS, TGTGTGA_MIR377, GNF2_XRCC5

GO Biological Process (7): mitochondrial RNA catabolic process (GO:0000957), positive regulation of mitochondrial RNA catabolic process (GO:0000962), mRNA processing (GO:0006397), tRNA processing (GO:0008033), anterior/posterior pattern specification (GO:0009952), morphogenesis of embryonic epithelium (GO:0016331), regulation of RNA splicing (GO:0043484)

GO Molecular Function (5): G-quadruplex RNA binding (GO:0002151), RNA binding (GO:0003723), mRNA binding (GO:0003729), nucleic acid binding (GO:0003676), protein binding (GO:0005515)

GO Cellular Component (7): nucleoplasm (GO:0005654), cytoplasm (GO:0005737), mitochondrion (GO:0005739), mitochondrial matrix (GO:0005759), ribonucleoprotein granule (GO:0035770), mitochondrial nucleoid (GO:0042645), ribonucleoprotein complex (GO:1990904)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Influenza Viral RNA Transcription and Replication	1
Metabolism of RNA	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
mitochondrion	3
RNA processing	2
RNA binding	2
binding	2
cellular anatomical structure	2
intracellular membraneless organelle	2
mitochondrial RNA metabolic process	1
RNA catabolic process	1
mitochondrial RNA catabolic process	1
regulation of mitochondrial RNA catabolic process	1
positive regulation of catabolic process	1
positive regulation of RNA metabolic process	1
mRNA metabolic process	1
tRNA metabolic process	1
regionalization	1
morphogenesis of an epithelium	1
embryonic morphogenesis	1
RNA splicing	1
regulation of gene expression	1
regulation of primary metabolic process	1
nucleic acid binding	1
nuclear lumen	1
intracellular anatomical structure	1
cytoplasm	1
intracellular membrane-bounded organelle	1
intracellular organelle lumen	1
supramolecular complex	1
mitochondrial matrix	1
nucleoid	1
protein-containing complex	1

Protein interactions and networks

STRING

1816 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GRSF1	GPX4	P36969	964
GRSF1	FASTKD2	Q9NYY8	763
GRSF1	DDX28	Q9NUL7	758
GRSF1	SUPV3L1	Q8IYB8	748
GRSF1	MT-ND6	P03923	738
GRSF1	DHX30	Q7L2E3	692
GRSF1	FASTKD5	Q7L8L6	672
GRSF1	FASTK	Q14296	653
GRSF1	SLIRP	Q9GZT3	627
GRSF1	ELAVL1	Q15717	596
GRSF1	MT-ND5	P03915	575
GRSF1	PNPT1	Q8TCS8	573
GRSF1	LRPPRC	P42704	558
GRSF1	TRMT10C	Q7L0Y3	553
GRSF1	PTCD1	O75127	541

IntAct

76 interactions, top by confidence:

A	B	Type	Score
RPS6KA2	MAPK1	psi-mi:“MI:0914”(association)	0.910
PSMD10	CLIC1	psi-mi:“MI:0914”(association)	0.650
RPS6KA3	ROCK2	psi-mi:“MI:0914”(association)	0.640
GRSF1	PSMD10	psi-mi:“MI:0915”(physical association)	0.560
IGHMBP2	THAP12	psi-mi:“MI:0914”(association)	0.530
RPS3	ZNF316	psi-mi:“MI:0914”(association)	0.530
PSMD10	DDAH1	psi-mi:“MI:0914”(association)	0.460
steC	SCD	psi-mi:“MI:0914”(association)	0.460
BDKRB2	GRSF1	psi-mi:“MI:0915”(physical association)	0.370
BCAR1	MYO1C	psi-mi:“MI:0914”(association)	0.350
ESR1	ESYT2	psi-mi:“MI:0914”(association)	0.350
CAND1	GTPBP10	psi-mi:“MI:0914”(association)	0.350
CUL1	LGALS8	psi-mi:“MI:0914”(association)	0.350
CUL2	ANXA2P2	psi-mi:“MI:0914”(association)	0.350
CUL3	PXDNL	psi-mi:“MI:0914”(association)	0.350
CUL5	DDX3X	psi-mi:“MI:0914”(association)	0.350
CHCHD2	POLRMT	psi-mi:“MI:0914”(association)	0.350
CISD3	POLRMT	psi-mi:“MI:0914”(association)	0.350
NDUFA4	NUDT19	psi-mi:“MI:0914”(association)	0.350
NDUFS3	ACOT7	psi-mi:“MI:0914”(association)	0.350
NMES1	COX7A2L	psi-mi:“MI:0914”(association)	0.350
CISD3	TIMM44	psi-mi:“MI:0914”(association)	0.350
Arhgap30	ARHGAP6	psi-mi:“MI:0914”(association)	0.350
IMMP2L	ANKHD1-EIF4EBP3	psi-mi:“MI:0914”(association)	0.350
MAPK3	HMMR	psi-mi:“MI:0914”(association)	0.350

BioGRID (774): GRSF1 (Affinity Capture-Western), GRSF1 (Reconstituted Complex), GRSF1 (Affinity Capture-RNA), GRSF1 (Affinity Capture-MS), GRSF1 (Co-fractionation), GRSF1 (Affinity Capture-MS), GRSF1 (Affinity Capture-MS), GRSF1 (Affinity Capture-MS), GRSF1 (Affinity Capture-MS), GRSF1 (Affinity Capture-MS), GRSF1 (Affinity Capture-MS), GRSF1 (Affinity Capture-MS), GRSF1 (Affinity Capture-RNA), GRSF1 (Affinity Capture-RNA), GRSF1 (Affinity Capture-RNA)

ESM2 similar proteins: A0A0R0IHP4, A2AQW0, A2Y5T7, A7MBL8, F4IV66, G4LTX4, K7MTW9, O08874, O22870, O35099, O48741, O65502, O65693, O81770, P29344, P30957, Q01289, Q12849, Q16513, Q41249, Q43847, Q5KQI6, Q5VQ09, Q5ZBH5, Q67W29, Q6STH5, Q6ZN16, Q75LJ4, Q80VL1, Q8BWW9, Q8C5Q4, Q8GSJ1, Q8LB01, Q8W4D4, Q92736, Q93VC7, Q99683, Q9C5J8, Q9FEB5, Q9FFQ1

Diamond homologs: A1L1G1, A8WPC5, B2RYD2, B2RYJ8, O35737, P31943, P52597, P55795, P70333, Q12849, Q22708, Q3SZF3, Q3US41, Q5E9J1, Q5RD26, Q5ZLR4, Q60HC3, Q6AY09, Q6DEZ7, Q6NXG1, Q794E4, Q7ZVR8, Q7ZY29, Q8C5Q4, Q8K0G8, Q8R3C6, Q8VHV7, Q9BJZ5, Q9H6T0, Q9Z2X1, P31942, Q15020, Q5REG1, Q9JLI8, Q9Y4C8, Q5RBM8, Q8R4X3, Q8SQ27, Q9NTZ6, Q66JV4

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
GRSF1	“down-regulates quantity by repression”	FASTKD5	“transcriptional regulation”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 102 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
MAPK targets/ Nuclear events mediated by MAP kinases	5	37.2×	5e-05
Nuclear Events (kinase and transcription factor activation)	5	23.7×	2e-04
MAP kinase activation	5	21.1×	3e-04
Interleukin-17 signaling	5	17.4×	6e-04
Toll Like Receptor 10 (TLR10) Cascade	5	14.8×	1e-03
Toll Like Receptor 5 (TLR5) Cascade	5	14.8×	1e-03
MyD88 cascade initiated on plasma membrane	5	14.0×	1e-03
Signaling by NTRK1 (TRKA)	5	13.5×	1e-03

GO biological processes:

GO term	Partners	Fold	FDR
intrinsic apoptotic signaling pathway	5	19.7×	2e-03
G1/S transition of mitotic cell cycle	6	13.2×	2e-03
negative regulation of translation	6	12.9×	2e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	69
Likely benign	6
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

1621 predictions. Top by Δscore:

Variant	Effect	Δscore
4:70825289:GACTT:G	donor_loss	1.0000
4:70825290:ACTT:A	donor_loss	1.0000
4:70825291:CTTA:C	donor_loss	1.0000
4:70825294:A:AC	donor_gain	1.0000
4:70825294:A:C	donor_loss	1.0000
4:70825295:C:CG	donor_gain	1.0000
4:70825295:CG:C	donor_gain	1.0000
4:70825295:CGA:C	donor_gain	1.0000
4:70825295:CGAA:C	donor_gain	1.0000
4:70825427:AAAAA:A	acceptor_gain	1.0000
4:70825428:AAAA:A	acceptor_gain	1.0000
4:70825429:AAA:A	acceptor_gain	1.0000
4:70825430:AA:A	acceptor_gain	1.0000
4:70825432:C:CC	acceptor_gain	1.0000
4:70826112:A:AC	donor_gain	1.0000
4:70826113:C:CC	donor_gain	1.0000
4:70826113:CTG:C	donor_gain	1.0000
4:70827846:CCTTA:C	donor_loss	1.0000
4:70827848:TTA:T	donor_loss	1.0000
4:70827849:TA:T	donor_loss	1.0000
4:70827850:A:AC	donor_gain	1.0000
4:70827851:C:CC	donor_gain	1.0000
4:70827854:ATTT:A	donor_gain	1.0000
4:70828032:TGTAT:T	acceptor_gain	1.0000
4:70828034:TAT:T	acceptor_gain	1.0000
4:70828036:TCTA:T	acceptor_loss	1.0000
4:70828037:C:CC	acceptor_gain	1.0000
4:70828039:A:AC	acceptor_gain	1.0000
4:70828039:A:C	acceptor_gain	1.0000
4:70828043:C:CT	acceptor_gain	1.0000

AlphaMissense

3128 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:70825362:C:G	A443P	1.000
4:70825367:C:T	G441E	1.000
4:70826173:A:T	V403D	1.000
4:70831539:C:G	R317P	1.000
4:70831599:A:G	F297S	1.000
4:70831612:C:G	A293P	1.000
4:70831617:C:T	G291E	1.000
4:70832351:A:G	L257P	1.000
4:70832351:A:T	L257H	1.000
4:70832354:C:T	G256E	1.000
4:70832355:C:G	G256R	1.000
4:70832355:C:T	G256R	1.000
4:70832366:A:T	V252D	1.000
4:70833202:C:G	A196P	1.000
4:70833207:C:T	G194D	1.000
4:70836202:A:G	L157P	1.000
4:70836205:C:T	G156E	1.000
4:70836206:C:G	G156R	1.000
4:70836206:C:T	G156R	1.000
4:70824350:A:G	L471P	0.999
4:70825331:G:T	A453D	0.999
4:70825332:C:G	A453P	0.999
4:70825349:A:G	F447S	0.999
4:70825355:A:T	V445E	0.999
4:70825361:G:T	A443D	0.999
4:70825367:C:A	G441V	0.999
4:70825368:C:G	G441R	0.999
4:70825368:C:T	G441R	0.999
4:70826158:A:G	L408S	0.999
4:70826161:C:T	G407E	0.999

dbSNP variants (sampled 300 via entrez): RS1000102523 (4:70831292 T>C), RS1000193248 (4:70826618 T>G), RS1000200954 (4:70818804 C>G), RS1000225733 (4:70826878 T>C), RS10002655 (4:70824762 G>A,C,T), RS10002846 (4:70824965 G>A,T), RS1000595455 (4:70830825 A>C), RS1000667340 (4:70832108 T>A), RS1000671069 (4:70820580 C>A,T), RS1000735511 (4:70821823 G>A), RS1000873680 (4:70821399 T>C), RS1000957752 (4:70825090 AAAAG>A), RS1000983011 (4:70840572 G>T), RS1001111221 (4:70836029 G>A), RS1001127305 (4:70840686 C>A)

Disease associations

OMIM: gene MIM:604851 | 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
GCST007847_102	Type 2 diabetes	3.000000e-09

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Particulate Matter	decreases expression, increases abundance, increases expression	3
bisphenol A	decreases expression	2
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
aristolochic acid I	decreases expression	1
FR900359	affects phosphorylation	1
triphenyl phosphate	affects expression	1
sodium arsenite	increases expression	1
cobaltous chloride	increases expression	1
aflatoxin B2	decreases methylation	1
di-n-butylphosphoric acid	affects expression	1
2,3,5-(triglutathion-S-yl)hydroquinone	increases ADP-ribosylation	1
ICG 001	increases expression	1
abrine	decreases expression	1
dorsomorphin	decreases expression, affects cotreatment	1
bisphenol S	increases expression	1
jinfukang	decreases expression	1
LDN 193189	affects cotreatment, decreases expression	1
NSC 689534	affects binding, decreases expression	1
Air Pollutants	increases abundance, decreases expression	1
Atrazine	decreases expression	1
Vehicle Emissions	increases abundance, decreases expression	1
Benzo(a)pyrene	affects methylation	1
Copper	affects binding, decreases expression	1
Dinitrochlorobenzene	affects binding	1
Doxorubicin	decreases expression	1
Enzyme Inhibitors	increases O-linked glycosylation, decreases activity	1
Formaldehyde	decreases expression	1
Ivermectin	decreases expression	1
Methyl Methanesulfonate	decreases expression	1

Clinical trials (associated diseases)

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