RFC5

Summary

RFC5 (replication factor C subunit 5, HGNC:9973) is a protein-coding gene on chromosome 12q24.23, encoding Replication factor C subunit 5 (P40937). Subunit of the replication factor C (RFC) complex which acts during elongation of primed DNA templates by DNA polymerases delta and epsilon, and is necessary for ATP-dependent loading of proliferating cell nuclear antigen (PCNA) onto primed DNA. It is a common-essential gene (DepMap: required in 98.4% of cancer cell lines).

This gene encodes the smallest subunit of the replication factor C complex, which consists of five distinct subunits (140, 40, 38, 37, and 36 kDa) and is required for DNA replication. This subunit interacts with the C-terminal region of proliferating cell nuclear antigen and is required to open and load proliferating cell nuclear antigen onto DNA during S phase. It is a member of the AAA+ (ATPases associated with various cellular activities) ATPase family and forms a core complex with the 38 and 40 kDa subunits that possesses DNA-dependent ATPase activity. A related pseudogene has been identified on chromosome 9. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 5985 — RefSeq curated summary.

At a glance

• GWAS associations: 6
• Clinical variants (ClinVar): 91 total
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 98.4% of screened cell lines (common-essential)
• MANE Select transcript: NM_007370

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9973
Approved symbol	RFC5
Name	replication factor C subunit 5
Location	12q24.23
Locus type	gene with protein product
Status	Approved
Aliases	RFC36
Ensembl gene	ENSG00000111445
Ensembl biotype	protein_coding
OMIM	600407
Entrez	5985

Gene structure

Transcript identifiers

Ensembl transcripts: 17 — 15 protein_coding, 1 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000392542, ENST00000420967, ENST00000449641, ENST00000454402, ENST00000472603, ENST00000484086, ENST00000535092, ENST00000537315, ENST00000543153, ENST00000900836, ENST00000900837, ENST00000900838, ENST00000900839, ENST00000900840, ENST00000900841, ENST00000913933, ENST00000913934

RefSeq mRNA: 6 — MANE Select: NM_007370 NM_001130112, NM_001130113, NM_001206801, NM_001346815, NM_007370, NM_181578

CCDS: CCDS41843, CCDS9185

Canonical transcript exons

ENST00000454402 — 11 exons

Exon	Start	End
ENSE00001254231	118026889	118027018
ENSE00001254246	118024851	118025010
ENSE00001254253	118022286	118022359
ENSE00001254261	118020906	118020985
ENSE00001676720	118031182	118032234
ENSE00001893429	118016703	118016892
ENSE00003501648	118025747	118025828
ENSE00003510262	118019072	118019136
ENSE00003512778	118029771	118029825
ENSE00003604380	118019632	118019768
ENSE00003641073	118027953	118028030

Expression profiles

Bgee: expression breadth ubiquitous, 295 present calls, max score 98.65.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 33.8173 / max 296.3196, expressed in 1804 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
128256	33.8173	1804

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
pons	UBERON:0000988	98.65	gold quality
superior vestibular nucleus	UBERON:0007227	97.82	gold quality
body of tongue	UBERON:0011876	97.61	gold quality
medial globus pallidus	UBERON:0002477	97.51	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	97.22	gold quality
biceps brachii	UBERON:0001507	97.07	gold quality
globus pallidus	UBERON:0001875	97.02	gold quality
endothelial cell	CL:0000115	96.84	gold quality
inferior vagus X ganglion	UBERON:0005363	96.67	gold quality
Brodmann (1909) area 23	UBERON:0013554	96.65	gold quality
subthalamic nucleus	UBERON:0001906	96.53	gold quality
heart right ventricle	UBERON:0002080	96.30	gold quality
trigeminal ganglion	UBERON:0001675	96.13	gold quality
tongue	UBERON:0001723	95.88	gold quality
substantia nigra pars compacta	UBERON:0001965	95.65	gold quality
jejunal mucosa	UBERON:0000399	95.48	gold quality
dorsal plus ventral thalamus	UBERON:0001897	95.41	gold quality
superior surface of tongue	UBERON:0007371	95.25	gold quality
entorhinal cortex	UBERON:0002728	95.22	gold quality
lateral nuclear group of thalamus	UBERON:0002736	95.10	gold quality
orbitofrontal cortex	UBERON:0004167	95.10	gold quality
epithelium of nasopharynx	UBERON:0001951	95.00	gold quality
parietal lobe	UBERON:0001872	94.95	gold quality
dorsal root ganglion	UBERON:0000044	94.81	gold quality
substantia nigra pars reticulata	UBERON:0001966	94.70	gold quality
amniotic fluid	UBERON:0000173	94.67	gold quality
ventral tegmental area	UBERON:0002691	94.49	gold quality
pharyngeal mucosa	UBERON:0000355	94.32	gold quality
postcentral gyrus	UBERON:0002581	94.30	gold quality
CA1 field of hippocampus	UBERON:0003881	94.24	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.90

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

75 targeting RFC5, 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-656-3P	100.00	72.15	2788
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-103A-3P	99.98	69.14	1595
HSA-MIR-107	99.98	69.14	1595
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-559	99.95	72.28	3609
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-548I	99.94	71.25	3481
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
HSA-MIR-548AQ-5P	99.94	71.34	3426
HSA-MIR-548AR-5P	99.94	71.28	3515
HSA-MIR-548AS-5P	99.94	71.22	3482
HSA-MIR-548AU-5P	99.94	71.24	3488
HSA-MIR-548AY-5P	99.94	71.23	3502
HSA-MIR-548B-5P	99.94	71.23	3502
HSA-MIR-548BB-5P	99.94	71.27	3509
HSA-MIR-548C-5P	99.94	71.24	3488
HSA-MIR-548D-5P	99.94	71.23	3502
HSA-MIR-548H-5P	99.94	71.24	3488
HSA-MIR-548J-5P	99.94	71.14	3489
HSA-MIR-548O-5P	99.94	71.24	3488
HSA-MIR-548W	99.94	71.24	3488

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 98.4% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 3)

• AEG-1 Knockdown Sensitizes Glioma Cells to Radiation Through Impairing Homologous Recombination Via Targeting RFC5. (PMID:34042508)
• Prognostic biomarker replication factor C subunit 5 and its correlation with immune infiltrates in acute myeloid leukemia. (PMID:35544695)
• RFC5, regulated by circ_0038985/miR-3614-5p, functions as an oncogene in the progression of colorectal cancer. (PMID:36988339)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	rfc5	ENSDARG00000035634
mus_musculus	Rfc5	ENSMUSG00000029363
rattus_norvegicus	Rfc5	ENSRNOG00000001134
drosophila_melanogaster	RfC3	FBGN0032244
caenorhabditis_elegans		WBGENE00018409

Paralogs (3): RFC2 (ENSG00000049541), RFC3 (ENSG00000133119), RFC4 (ENSG00000163918)

Protein

Protein identifiers

Replication factor C subunit 5 — P40937 (reviewed: P40937)

Alternative names: Activator 1 36 kDa subunit, Activator 1 subunit 5, Replication factor C 36 kDa subunit

All UniProt accessions (6): P40937, C9JH72, E9PEP3, F5H0U6, F5H304, F5H5S0

UniProt curated annotations — full annotation on UniProt →

Function. Subunit of the replication factor C (RFC) complex which acts during elongation of primed DNA templates by DNA polymerases delta and epsilon, and is necessary for ATP-dependent loading of proliferating cell nuclear antigen (PCNA) onto primed DNA.

Subunit / interactions. Subunit of the RFC complex, an heteropentameric complex consisting of a large subunit RFC1 and four small subunits RFC2, RFC3, RFC4 and RFC5; the RFC complex interacts with PCNA. Forms an heterotetrameric complex with RFC2, RFC3 and RFC4; this complex has ATPase activity but is not stimulated by PCNA. The heterotetramer of subunits RFC2, RFC3, RFC4 and RFC5 interacts with RAD17.

Subcellular location. Nucleus.

Similarity. Belongs to the activator 1 small subunits family.

Isoforms (2)

UniProt ID	Names	Canonical?
P40937-1	1	yes
P40937-2	2

RefSeq proteins (6): NP_001123584, NP_001123585, NP_001193730, NP_001333744, NP_031396, NP_853556 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003593	AAA+_ATPase	Domain
IPR003959	ATPase_AAA_core	Domain
IPR008921	DNA_pol3_clamp-load_cplx_C	Homologous_superfamily
IPR013748	Rep_factorC_C	Domain
IPR027417	P-loop_NTPase	Homologous_superfamily
IPR047854	RFC_lid	Domain
IPR050238	DNA_Rep/Repair_Clamp_Loader	Family

Pfam: PF00004, PF08542, PF21960

Enzyme classification (BRENDA):

• EC 3.6.4.B8 — (BRENDA: organisms, substrates, inhibitors, Km, kcat entries)

UniProt features (39 total): helix 21, strand 9, turn 4, chain 1, binding site 1, modified residue 1, splice variant 1, sequence variant 1

Structure

Experimental structures (PDB)

16 structures.

PDB	Method	Resolution (Å)
8UMV	ELECTRON MICROSCOPY	2.75
8UMY	ELECTRON MICROSCOPY	2.83
8UMW	ELECTRON MICROSCOPY	2.93
8ZWO	ELECTRON MICROSCOPY	2.99
8UN0	ELECTRON MICROSCOPY	3
8UII	ELECTRON MICROSCOPY	3.04
8UI8	ELECTRON MICROSCOPY	3.1
8UMU	ELECTRON MICROSCOPY	3.16
9IIN	ELECTRON MICROSCOPY	3.2
9UIQ	ELECTRON MICROSCOPY	3.2
8UMT	ELECTRON MICROSCOPY	3.33
8UNJ	ELECTRON MICROSCOPY	3.35
6VVO	ELECTRON MICROSCOPY	3.4
8UI9	ELECTRON MICROSCOPY	3.5
7Z6H	ELECTRON MICROSCOPY	3.59
8UI7	ELECTRON MICROSCOPY	4.2

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P40937-F1	90.52	0.78

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 (1): 60–67

Post-translational modifications (1): 1

Function

Pathways and Gene Ontology

Reactome pathways

21 pathways

ID	Pathway
R-HSA-110312	Translesion synthesis by REV1
R-HSA-110314	Recognition of DNA damage by PCNA-containing replication complex
R-HSA-110320	Translesion Synthesis by POLH
R-HSA-174411	Polymerase switching on the C-strand of the telomere
R-HSA-176187	Activation of ATR in response to replication stress
R-HSA-5651801	PCNA-Dependent Long Patch Base Excision Repair
R-HSA-5655862	Translesion synthesis by POLK
R-HSA-5656121	Translesion synthesis by POLI
R-HSA-5656169	Termination of translesion DNA synthesis
R-HSA-5685938	HDR through Single Strand Annealing (SSA)
R-HSA-5685942	HDR through Homologous Recombination (HRR)
R-HSA-5693607	Processing of DNA double-strand break ends
R-HSA-5693616	Presynaptic phase of homologous DNA pairing and strand exchange
R-HSA-5696397	Gap-filling DNA repair synthesis and ligation in GG-NER
R-HSA-5696400	Dual Incision in GG-NER
R-HSA-6782135	Dual incision in TC-NER
R-HSA-6782210	Gap-filling DNA repair synthesis and ligation in TC-NER
R-HSA-6804756	Regulation of TP53 Activity through Phosphorylation
R-HSA-69091	Polymerase switching
R-HSA-69473	G2/M DNA damage checkpoint
R-HSA-9709570	Impaired BRCA2 binding to RAD51

MSigDB gene sets: 344 (showing top): PID_FANCONI_PATHWAY, GSE18804_SPLEEN_MACROPHAGE_VS_TUMORAL_MACROPHAGE_DN, REACTOME_DNA_REPLICATION, HORIUCHI_WTAP_TARGETS_DN, GOBP_POSITIVE_REGULATION_OF_DNA_BIOSYNTHETIC_PROCESS, PAL_PRMT5_TARGETS_UP, REACTOME_G2_M_DNA_DAMAGE_CHECKPOINT, MORF_BRCA1, CHIANG_LIVER_CANCER_SUBCLASS_UNANNOTATED_DN, MORF_ATRX, GOBP_CELL_CYCLE_PHASE_TRANSITION, DITTMER_PTHLH_TARGETS_UP, REACTOME_ACTIVATION_OF_ATR_IN_RESPONSE_TO_REPLICATION_STRESS, DACOSTA_UV_RESPONSE_VIA_ERCC3_UP, FRASOR_RESPONSE_TO_SERM_OR_FULVESTRANT_DN

GO Biological Process (4): DNA replication (GO:0006260), DNA-templated DNA replication (GO:0006261), DNA repair (GO:0006281), positive regulation of DNA-directed DNA polymerase activity (GO:1900264)

GO Molecular Function (8): DNA binding (GO:0003677), ATP binding (GO:0005524), ATP hydrolysis activity (GO:0016887), enzyme binding (GO:0019899), nucleotide binding (GO:0000166), DNA clamp loader activity (GO:0003689), protein binding (GO:0005515), single-stranded DNA helicase activity (GO:0017116)

GO Cellular Component (5): nucleus (GO:0005634), nucleoplasm (GO:0005654), DNA replication factor C complex (GO:0005663), Ctf18 RFC-like complex (GO:0031390), chromosome (GO:0005694)

Reactome top-level categories

Rollup of top-12 pathways:

Category	Pathways
Translesion synthesis by Y family DNA polymerases bypasses lesions on DNA template	5
HDR through Homologous Recombination (HRR) or Single Strand Annealing (SSA)	3
G2/M Checkpoints	2
Global Genome Nucleotide Excision Repair (GG-NER)	2
Transcription-Coupled Nucleotide Excision Repair (TC-NER)	2
DNA Damage Bypass	1
Telomere C-strand (Lagging Strand) Synthesis	1
Resolution of AP sites via the multiple-nucleotide patch replacement pathway	1
Homologous DNA Pairing and Strand Exchange	1
Regulation of TP53 Activity	1
Leading Strand Synthesis	1
Lagging Strand Synthesis	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
DNA metabolic process	2
DNA biosynthetic process	1
DNA replication	1
DNA damage response	1
DNA-directed DNA polymerase activity	1
positive regulation of catalytic activity	1
regulation of transferase activity	1
positive regulation of DNA biosynthetic process	1
nucleic acid binding	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
ribonucleoside triphosphate phosphatase activity	1
ATP-dependent activity	1
protein binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
DNA binding	1
ATP-dependent activity, acting on DNA	1
binding	1
DNA helicase activity	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
cellular anatomical structure	1
replication fork	1
protein-containing complex	1
chromosome	1
nuclear protein-containing complex	1
intracellular membraneless organelle	1

Protein interactions and networks

STRING

2870 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RFC5	RFC3	P40938	992
RFC5	RFC2	P32846	989
RFC5	RFC4	P35249	989
RFC5	DSCC1	Q9BVC3	980
RFC5	CHTF8	P0CG13	978
RFC5	RAD17	O75943	961
RFC5	CHTF18	Q8WVB6	949
RFC5	ATAD5	Q96QE3	922
RFC5	RFC1	P35251	833
RFC5	SMC3	Q9UQE7	817
RFC5	WAPL	Q7Z5K2	787
RFC5	ESCO1	Q5FWF5	782
RFC5	ESCO2	Q56NI9	759
RFC5	PDS5A	Q29RF7	749
RFC5	MCM3	P25205	695

IntAct

246 interactions, top by confidence:

A	B	Type	Score
RFC5	RFC4	psi-mi:“MI:0915”(physical association)	0.950
RFC4	RFC5	psi-mi:“MI:0915”(physical association)	0.950
RFC4	RFC5	psi-mi:“MI:0914”(association)	0.950
HUS1	RAD1	psi-mi:“MI:0914”(association)	0.840
TRIM38	RFC5	psi-mi:“MI:0915”(physical association)	0.830
XIAP	RFC5	psi-mi:“MI:0915”(physical association)	0.830
NAB2	RFC5	psi-mi:“MI:0915”(physical association)	0.830
RFC5	XIAP	psi-mi:“MI:0915”(physical association)	0.830
RFC5	NAB2	psi-mi:“MI:0915”(physical association)	0.830

BioGRID (310): RFC5 (Affinity Capture-MS), RFC5 (Two-hybrid), RFC5 (Two-hybrid), RFC5 (Two-hybrid), TRIM38 (Two-hybrid), RFC5 (Affinity Capture-MS), RFC5 (Affinity Capture-MS), RFC5 (Affinity Capture-MS), RFC5 (Affinity Capture-MS), RFC5 (Two-hybrid), RFC2 (Co-fractionation), RFC5 (Co-fractionation), RFC5 (Co-fractionation), RFC5 (Co-fractionation), RFC5 (Co-fractionation)

ESM2 similar proteins: A2SQT3, A5UMF3, A7I8Y0, B4F6J6, D0FH76, F6QV99, O13984, O14003, O34528, O74111, O94697, P0C7N7, P25847, P34429, P38251, P38629, P40339, P40348, P40937, P53016, P53720, P54609, Q09803, Q09843, Q0W037, Q2FQT9, Q2NH89, Q4P7Z8, Q503W7, Q505J9, Q54BN3, Q54MD4, Q54ST4, Q5UP47, Q6CJU1, Q6FIL3, Q6YZ54, Q75C39, Q793F9, Q7KN62

Diamond homologs: A0B6D7, A1RSA2, A1RSA3, A1RV38, A1RWU6, A1RWU7, A2BL93, A2SQR6, A2SQT3, A3CTR4, A3CUX9, A3DNV8, A3DNV9, A3MS27, A3MS28, A4FZL6, A4WGV2, A4WGV3, A4WLY0, A5UMF3, A5UMF4, A6URV8, A6US36, A6UWR5, A6VIW1, A6VJ61, A7I781, A7I8Y0, A8AC24, A9A6N2, B0R601, B0R7H7, B1YC69, B9LPV1, C3MQ13, C3MVD2, C3N5N1, C3NE95, C3NHF4, C4KHA7

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
RFC5	“form complex”	“RF-C complex”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 128 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
Translesion synthesis by REV1	5	43.5×	5e-06
Translesion synthesis by POLI	5	41.0×	6e-06
Translesion synthesis by POLK	5	38.7×	7e-06
Translesion Synthesis by POLH	5	36.6×	9e-06
PCNA-Dependent Long Patch Base Excision Repair	5	31.6×	2e-05
Impaired BRCA2 binding to RAD51	8	30.1×	5e-08
Activation of ATR in response to replication stress	8	29.3×	5e-08
HDR through Single Strand Annealing (SSA)	8	28.6×	5e-08

GO biological processes:

GO term	Partners	Fold	FDR
telomere maintenance	6	14.7×	7e-04
cytoplasmic translation	6	10.2×	3e-03
double-strand break repair via homologous recombination	7	10.0×	9e-04
DNA repair	13	7.6×	1e-05
DNA damage response	13	6.4×	6e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	53
Likely benign	3
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

1752 predictions. Top by Δscore:

Variant	Effect	Δscore
12:118016881:G:GT	donor_gain	1.0000
12:118016882:A:T	donor_gain	1.0000
12:118016889:CCTG:C	donor_loss	1.0000
12:118016890:CTG:C	donor_loss	1.0000
12:118016891:TG:T	donor_loss	1.0000
12:118016892:GG:G	donor_loss	1.0000
12:118016900:G:GT	donor_gain	1.0000
12:118019070:AG:A	acceptor_gain	1.0000
12:118019071:GG:G	acceptor_gain	1.0000
12:118019132:TACCA:T	donor_gain	1.0000
12:118019134:CCAGT:C	donor_loss	1.0000
12:118019135:CA:C	donor_gain	1.0000
12:118019135:CAGTA:C	donor_loss	1.0000
12:118019136:AG:A	donor_loss	1.0000
12:118019137:G:GG	donor_gain	1.0000
12:118019137:GTAA:G	donor_loss	1.0000
12:118019138:T:G	donor_loss	1.0000
12:118019139:AA:A	donor_loss	1.0000
12:118019622:T:A	acceptor_gain	1.0000
12:118019627:CTCAG:C	acceptor_loss	1.0000
12:118019628:TCAGT:T	acceptor_loss	1.0000
12:118019629:CAG:C	acceptor_loss	1.0000
12:118019630:A:AG	acceptor_gain	1.0000
12:118019630:AG:A	acceptor_loss	1.0000
12:118019631:G:GG	acceptor_gain	1.0000
12:118019631:GTTCA:G	acceptor_gain	1.0000
12:118019766:G:GT	donor_gain	1.0000
12:118019766:GAGG:G	donor_loss	1.0000
12:118019768:GGTAA:G	donor_loss	1.0000
12:118019769:G:T	donor_loss	1.0000

AlphaMissense

2234 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:118019688:G:T	G63W	1.000
12:118019679:G:C	G60R	0.999
12:118019680:G:A	G60D	0.999
12:118019688:G:A	G63R	0.999
12:118019688:G:C	G63R	0.999
12:118019689:G:A	G63E	0.999
12:118019695:G:A	G65D	0.999
12:118019697:A:C	K66Q	0.999
12:118019698:A:T	K66M	0.999
12:118019699:G:C	K66N	0.999
12:118019699:G:T	K66N	0.999
12:118020964:C:A	A109D	0.999
12:118022312:A:C	D125A	0.999
12:118022312:A:T	D125V	0.999
12:118022315:A:C	E126A	0.999
12:118022315:A:T	E126V	0.999
12:118022316:A:C	E126D	0.999
12:118022316:A:T	E126D	0.999
12:118022343:G:C	Q135H	0.999
12:118022343:G:T	Q135H	0.999
12:118024880:T:C	F151L	0.999
12:118024882:C:A	F151L	0.999
12:118024882:C:G	F151L	0.999
12:118024883:T:C	C152R	0.999
12:118024894:T:G	C155W	0.999
12:118024897:C:A	N156K	0.999
12:118024897:C:G	N156K	0.999
12:118024936:C:G	C169W	0.999
12:118025799:G:C	D212H	0.999
12:118026889:A:C	S222R	0.999

dbSNP variants (sampled 300 via entrez): RS1000471544 (12:118015586 T>C), RS1000654564 (12:118020722 T>C), RS1000828457 (12:118040722 G>A), RS1000854068 (12:118035570 G>A,T), RS1001032612 (12:118034017 A>G), RS1001063098 (12:118033768 A>C), RS1001291494 (12:118041163 A>G), RS1001384573 (12:118016206 T>C), RS1001397061 (12:118034458 G>A,T), RS1001541129 (12:118016248 T>C), RS1001613366 (12:118015958 G>C), RS1001901015 (12:118014753 C>A,T), RS1001927687 (12:118023215 G>A), RS1002236049 (12:118039362 A>G,T), RS1002260353 (12:118027092 C>A,T)

Disease associations

OMIM: gene MIM:600407 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST001762_129	Obesity-related traits	5.000000e-06
GCST006940_65	Neurociticism	6.000000e-11
GCST009391_1289	Metabolite levels	7.000000e-06
GCST009391_959	Metabolite levels	3.000000e-06
GCST010063_5	Physiological traits	8.000000e-07
GCST012015_5	Chronic rhinosinusitis	2.000000e-06

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0004626	IGFBP-3 measurement
EFO:0007660	neuroticism measurement
EFO:0010548	xanthine measurement
EFO:0010444	triacylglycerol 60:12 measurement
EFO:0004338	body weight

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4296000 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 1,538 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1232461	MOLIBRESIB	2	1,538

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

ChEMBL bioactivities

4 potent at pChembl≥5 of 4 total, top 4 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.43	Kd	37	nM	MOLIBRESIB
7.05	IC50	90	nM	MOLIBRESIB
6.23	Kd	584.1	nM	CHEMBL3752910
6.23	ED50	584.1	nM	CHEMBL3752910

PubChem BioAssay actives

3 with measured affinity, of 10 total; 2 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
2-[(4S)-6-(4-chlorophenyl)-8-methoxy-1-methyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-4-yl]-N-ethylacetamide	2179103: Binding affinity against RFC5 (unknown origin) assessed as apparent dissociation constant incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	kd	0.0370	uM
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149221: Binding affinity to human RFC5 incubated for 45 mins by Kinobead based pull down assay	kd	0.5841	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	decreases expression, increases expression, increases methylation	5
bisphenol A	affects expression, decreases expression	3
sodium arsenite	increases expression, decreases expression	3
Cisplatin	decreases expression, decreases reaction, increases expression	3
Cyclosporine	decreases expression	3
Resveratrol	affects cotreatment, increases expression	2
Air Pollutants	decreases expression, increases abundance	2
Doxorubicin	decreases expression, affects response to substance	2
Rotenone	decreases expression, increases expression	2
Tretinoin	decreases expression	2
lasiocarpine	decreases expression, increases metabolic processing	1
2,2’-methylenebis(4-methyl-6-tert-butylphenol)	affects response to substance, affects expression	1
methylselenic acid	decreases expression	1
riddelliine	decreases expression, increases metabolic processing	1
beta-lapachone	increases expression	1
arsenite	affects binding, increases reaction	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
cobaltous chloride	decreases expression	1
perfluorooctanoic acid	decreases expression	1
manganese chloride	decreases expression	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, increases expression	1
tamibarotene	affects expression	1
microcystin RR	increases expression	1
AM 251	decreases expression	1
2-palmitoylglycerol	increases expression	1
K 7174	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
erucylphospho-N,N,N-trimethylpropylammonium	decreases expression	1
trans-10,cis-12-conjugated linoleic acid	decreases expression	1
palbociclib	decreases expression	1

ChEMBL screening assays

9 unique, capped per target: 9 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4118982	Binding	Binding affinity to RFC5 in human NCI-H358 cells at 1 uM by mass spectrometry based pull down assay	Studies of TAK1-centered polypharmacology with novel covalent TAK1 inhibitors. — Bioorg Med Chem

Clinical trials (associated diseases)

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