RFC2

Summary

RFC2 (replication factor C subunit 2, HGNC:9970) is a protein-coding gene on chromosome 7q11.23, encoding Replication factor C subunit 2 (P35250). 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 99.8% of cancer cell lines).

This gene encodes a member of the activator 1 small subunits family. The elongation of primed DNA templates by DNA polymerase delta and epsilon requires the action of the accessory proteins, proliferating cell nuclear antigen (PCNA) and replication factor C (RFC). Replication factor C, also called activator 1, is a protein complex consisting of five distinct subunits. This gene encodes the 40 kD subunit, which has been shown to be responsible for binding ATP and may help promote cell survival. Disruption of this gene is associated with Williams syndrome. Alternatively spliced transcript variants encoding distinct isoforms have been described. A pseudogene of this gene has been defined on chromosome 2.

Source: NCBI Gene 5982 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 81 total
• GTEx eGene: eQTL in 19 tissues, sQTL in 17 (q < 0.05)
• Phenotypes (HPO): 186
• ChEMBL bioactivity: 1 clinical-phase molecule tested; no curated mechanism-of-action drug
• Cancer dependency (DepMap): dependent in 99.8% of screened cell lines (common-essential)
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 1.39 (unconstrained)
• MANE Select transcript: NM_181471
• Notable: 81 clinical variants but no curated precision-oncology (CIViC) evidence yet

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9970
Approved symbol	RFC2
Name	replication factor C subunit 2
Location	7q11.23
Locus type	gene with protein product
Status	Approved
Aliases	A1, RFC40
Ensembl gene	ENSG00000049541
Ensembl biotype	protein_coding
OMIM	600404
Entrez	5982

Gene structure

Transcript identifiers

Ensembl transcripts: 53 — 28 protein_coding, 24 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

MANE Select: ENST00000055077

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 2, TSL 3: 7, TSL 5: 4

ENST00000055077, ENST00000352131, ENST00000463194, ENST00000470266, ENST00000473493, ENST00000479105, ENST00000480432, ENST00000485545, ENST00000491206, ENST00000493156, ENST00000494019, ENST00000497430, ENST00000621097, ENST00000858309, ENST00000858310, ENST00000858311, ENST00000858312, ENST00000858313, ENST00000858314, ENST00000858315, ENST00000858316, ENST00000858317, ENST00000927354, ENST00000927355, ENST00000927356, ENST00000927357, ENST00000927358, ENST00000927359, ENST00000927360, ENST00000927361, ENST00000927362, ENST00000927363, ENST00000982782, ENST00000982783, ENST00000982784, ENST00000982785, ENST00000982786, ENST00001040651, ENST00001040652, ENST00001040653, ENST00001040654, ENST00001040655, ENST00001040658, ENST00001065366, ENST00001065368, ENST00001065369, ENST00001065370, ENST00001065371, ENST00001065372, ENST00001065373, ENST00001065374, ENST00001127852, ENST00001142870

RefSeq mRNA: 5 — MANE Select: NM_181471 NM_001278791, NM_001278792, NM_001278793, NM_002914, NM_181471

CCDS: CCDS5567, CCDS5568, CCDS75618

Canonical transcript exons

ENST00000055077 — 11 exons

Exon	Start	End
ENSE00001837004	74254271	74254399
ENSE00001873689	74231502	74232216
ENSE00003495915	74249012	74249118
ENSE00003513261	74235532	74235645
ENSE00003530063	74238923	74238988
ENSE00003598539	74249739	74249780
ENSE00003604148	74246662	74246763
ENSE00003613494	74243146	74243246
ENSE00003620709	74252429	74252498
ENSE00003622754	74237362	74237442
ENSE00003651712	74239938	74240095

Expression profiles

Bgee: expression breadth ubiquitous, 233 present calls, max score 93.67.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 13.7993 / max 180.7340, expressed in 1772 samples.

Highest expression (Bgee): ventricular zone, ganglionic eminence, embryo, primordial germ cell in gonad, monocyte.

Genetic regulation across tissues (GTEx eQTL / sQTL)

RFC2 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 19 tissues and its splicing (sQTL) in 17 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 36 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Cells EBV-transformed lymphocytes	sqtl	7.9e-31	+2.30	7:74249032:T:C
Skin Sun Exposed Lower leg	sqtl	4.9e-26	+1.45	7:74249032:T:C
Adipose Subcutaneous	sqtl	2.2e-25	+1.52	7:74249032:T:C
Cells Cultured fibroblasts	sqtl	1.6e-23	+1.41	7:74249032:T:C
Whole Blood	eqtl	6.8e-23	-0.35	7:74266047:AT:A
Nerve Tibial	sqtl	1.2e-19	+1.46	7:74249032:T:C
Skin Not Sun Exposed Suprapubic	sqtl	3.9e-18	+1.38	7:74249032:T:C
Testis	sqtl	2.0e-16	+1.76	7:74249032:T:C
Adipose Visceral Omentum	sqtl	4.2e-14	+1.30	7:74249032:T:C
Brain Cortex	sqtl	1.3e-13	+1.81	7:74249032:T:C
Lung	sqtl	2.0e-11	+1.11	7:74249032:T:C
Breast Mammary Tissue	sqtl	9.2e-11	+1.38	7:74249032:T:C
Brain Frontal Cortex BA9	sqtl	2.1e-10	+1.88	7:74249032:T:C
Cells Cultured fibroblasts	eqtl	2.8e-10	-0.25	7:74249032:T:C
Muscle Skeletal	eqtl	2.5e-08	-0.41	7:74249032:T:C
Brain Cerebellar Hemisphere	sqtl	5.5e-08	+1.60	7:74249032:T:C
Skin Sun Exposed Lower leg	eqtl	7.0e-08	-0.26	7:74249032:T:C
Brain Nucleus accumbens basal ganglia	sqtl	5.5e-07	+1.44	7:74249032:T:C
Cells EBV-transformed lymphocytes	eqtl	4.7e-06	-0.35	7:74249032:T:C
Esophagus Mucosa	eqtl	8.1e-06	-0.25	7:74249032:T:C

FANTOM5 promoters

1 alternative TSS:

Promoter ID	TPM avg	Samples expressed
84356	13.7993	1772

Top tissues by expression

showing 100 of 274 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
ventricular zone	UBERON:0003053	93.67	gold quality
ganglionic eminence	UBERON:0004023	93.27	gold quality
embryo	UBERON:0000922	92.27	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	88.59	gold quality
monocyte	CL:0000576	88.49	gold quality
granulocyte	CL:0000094	88.21	gold quality
leukocyte	CL:0000738	87.99	gold quality
mononuclear cell	CL:0000842	87.99	gold quality
hindlimb stylopod muscle	UBERON:0004252	87.75	gold quality
cortical plate	UBERON:0005343	87.52	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	87.44	gold quality
skin of leg	UBERON:0001511	87.35	gold quality
mucosa of transverse colon	UBERON:0004991	87.01	gold quality
skin of abdomen	UBERON:0001416	86.50	gold quality
gastrocnemius	UBERON:0001388	86.11	gold quality
stromal cell of endometrium	CL:0002255	86.06	gold quality
esophagus mucosa	UBERON:0002469	85.96	gold quality
muscle of leg	UBERON:0001383	85.80	gold quality
blood	UBERON:0000178	85.76	gold quality
endometrium epithelium	UBERON:0004811	85.61	gold quality
zone of skin	UBERON:0000014	85.55	gold quality
right lobe of liver	UBERON:0001114	85.28	gold quality
rectum	UBERON:0001052	85.21	gold quality
islet of Langerhans	UBERON:0000006	84.45	gold quality
prefrontal cortex	UBERON:0000451	84.45	gold quality
ectocervix	UBERON:0012249	84.31	gold quality
tibial artery	UBERON:0007610	84.23	gold quality
popliteal artery	UBERON:0002250	84.22	gold quality
lymph node	UBERON:0000029	84.19	gold quality
esophagus	UBERON:0001043	84.18	gold quality
body of stomach	UBERON:0001161	83.93	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	83.57	gold quality
minor salivary gland	UBERON:0001830	83.30	gold quality
aorta	UBERON:0000947	83.11	gold quality
descending thoracic aorta	UBERON:0002345	83.00	gold quality
left ovary	UBERON:0002119	82.93	gold quality
lower esophagus mucosa	UBERON:0035834	82.86	gold quality
vermiform appendix	UBERON:0001154	82.83	gold quality
upper lobe of left lung	UBERON:0008952	82.79	gold quality
bone marrow	UBERON:0002371	82.78	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	82.70	gold quality
stomach	UBERON:0000945	82.61	gold quality
muscle layer of sigmoid colon	UBERON:0035805	82.57	gold quality
right ovary	UBERON:0002118	82.50	gold quality
right frontal lobe	UBERON:0002810	82.47	gold quality
left coronary artery	UBERON:0001626	82.46	gold quality
tibial nerve	UBERON:0001323	82.41	gold quality
spleen	UBERON:0002106	82.34	gold quality
body of pancreas	UBERON:0001150	82.31	gold quality
mouth mucosa	UBERON:0003729	82.31	gold quality
lower esophagus muscularis layer	UBERON:0035833	82.27	gold quality
lower esophagus	UBERON:0013473	82.26	gold quality
tonsil	UBERON:0002372	82.22	gold quality
upper lobe of lung	UBERON:0008948	82.19	gold quality
transverse colon	UBERON:0001157	82.16	gold quality
metanephros cortex	UBERON:0010533	81.97	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	81.92	gold quality
endocervix	UBERON:0000458	81.90	gold quality
right coronary artery	UBERON:0001625	81.90	gold quality
pancreas	UBERON:0001264	81.88	gold quality
thoracic aorta	UBERON:0001515	81.88	gold quality
omental fat pad	UBERON:0010414	81.81	gold quality
ascending aorta	UBERON:0001496	81.80	gold quality
peritoneum	UBERON:0002358	81.76	gold quality
body of uterus	UBERON:0009853	81.75	gold quality
bone marrow cell	CL:0002092	81.65	gold quality
right adrenal gland	UBERON:0001233	81.63	gold quality
left uterine tube	UBERON:0001303	81.59	gold quality
left adrenal gland	UBERON:0001234	81.54	gold quality
gall bladder	UBERON:0002110	81.47	gold quality
coronary artery	UBERON:0001621	81.43	gold quality
ovary	UBERON:0000992	81.38	gold quality
right lung	UBERON:0002167	81.38	gold quality
vagina	UBERON:0000996	81.30	gold quality
calcaneal tendon	UBERON:0003701	81.29	gold quality
cerebellar hemisphere	UBERON:0002245	81.23	gold quality
cerebellar cortex	UBERON:0002129	81.16	gold quality
adipose tissue of abdominal region	UBERON:0007808	81.10	gold quality
small intestine Peyer’s patch	UBERON:0003454	81.04	gold quality
skeletal muscle organ	UBERON:0014892	81.03	gold quality
muscle organ	UBERON:0001630	81.02	gold quality
left adrenal gland cortex	UBERON:0035825	81.00	gold quality
sigmoid colon	UBERON:0001159	80.96	gold quality
subcutaneous adipose tissue	UBERON:0002190	80.91	gold quality
saliva-secreting gland	UBERON:0001044	80.88	gold quality
right adrenal gland cortex	UBERON:0035827	80.87	gold quality
colon	UBERON:0001155	80.82	gold quality
mucosa of stomach	UBERON:0001199	80.76	gold quality
adrenal gland	UBERON:0002369	80.74	gold quality
large intestine	UBERON:0000059	80.70	gold quality
apex of heart	UBERON:0002098	80.64	gold quality
intestine	UBERON:0000160	80.59	gold quality
right hemisphere of cerebellum	UBERON:0014890	80.57	gold quality
spinal cord	UBERON:0002240	80.53	gold quality
liver	UBERON:0002107	80.42	gold quality
smooth muscle tissue	UBERON:0001135	80.41	gold quality
colonic epithelium	UBERON:0000397	80.31	gold quality
Brodmann (1909) area 9	UBERON:0013540	80.27	gold quality
anatomical system	UBERON:0000467	80.22	gold quality
small intestine	UBERON:0002108	80.19	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ENAD-17	no	6875.61
E-ANND-3	no	0.00

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 80 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Hypothalamus	tissue	95.4
Pons	tissue	86.8
Midbrain	tissue	86.8
Corpus callosum	tissue	83.0
Thalamus	tissue	80.7
Medulla oblongata	tissue	79.2
Spinal cord	tissue	77.2
Substantia nigra	tissue	75.8
Periaqueductal gray	tissue	73.9
Superior colliculi	tissue	72.9
Septum	tissue	70.8
Putamen	tissue	67.0
Ventral forebrain	tissue	61.5
Basal ganglia	tissue	60.0	low
Hippocampal formation	tissue	53.5
Cerebral cortex	tissue	52.5	medium
Somatosensory cortex	tissue	52.5
Motor cortex	tissue	49.4
Prefrontal cortex	tissue	48.5
Occipital cortex	tissue	47.9
Retrosplenial cortex	tissue	46.7
Temporal cortex	tissue	45.7
Entorhinal cortex	tissue	45.3
Retrosplenial and cingulate cortex	tissue	45.3
Amygdala	tissue	44.7
Olfactory bulb	tissue	43.4
Insular cortex	tissue	40.8
Cerebellum	tissue	40.0	medium
Tonsil	tissue	28.8	medium
Bone marrow	tissue	25.5	high
Lymph node	tissue	21.9	medium
Thymus	tissue	18.8
Liver	tissue	18.7	not detected
Skin 1	tissue	17.9	high
Placenta	tissue	17.2	high
Breast	tissue	14.5	medium
Rectum	tissue	14.0	high
Esophagus	tissue	13.7	medium
Ovary	tissue	12.9	high
Appendix	tissue	12.6	high
Colon	tissue	12.4	medium
Vagina	tissue	12.2	medium
Smooth muscle	tissue	11.8	not detected
Pancreas	tissue	11.7	medium
Skeletal muscle	tissue	11.6	not detected
Tongue	tissue	11.4
Parathyroid gland	tissue	11.1	not detected
Urinary bladder	tissue	10.7	medium
Spleen	tissue	10.6	not detected
Lung	tissue	10.3	low
Choroid plexus	tissue	10.1
Prostate	tissue	9.8	medium
Fallopian tube	tissue	9.4	medium
Small intestine	tissue	8.8	high
Locus coeruleus	tissue	8.7
Nucleus accumbens	tissue	8.6
Thyroid gland	tissue	8.6	medium
Duodenum	tissue	8.5	medium
Endometrium 1	tissue	8.4	high
Testis	tissue	8.2	medium

Brain sub-regions (HPA Brain Atlas): detected in 192; highest nTPM — White matter (83.0), Dorsal spinal cord (77.2), Ventral spinal cord (76.1), Dorsal hippocampus (53.5), Subiculum (52.4).

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): E2F1, E2F4, MYC

miRNA regulators (miRDB)

Targeting RFC2 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

17 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4425	100.00	67.59	1049
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-4446-5P	99.72	69.19	2544
HSA-MIR-3679-3P	99.64	69.88	1599
HSA-MIR-4708-3P	99.51	67.99	870
HSA-MIR-504-3P	99.30	67.18	1745
HSA-MIR-7151-3P	99.04	69.72	2370
HSA-MIR-2355-5P	98.83	65.51	1589
HSA-MIR-5089-5P	98.45	66.06	1388
HSA-MIR-4252	98.45	66.37	987
HSA-MIR-6849-3P	97.25	64.57	1371
HSA-MIR-122-5P	97.23	64.92	1024
HSA-MIR-4256	96.22	67.70	669
HSA-MIR-11181-5P	96.12	67.46	665
HSA-MIR-744-5P	93.78	65.29	230
HSA-MIR-10396A-5P	93.49	65.54	172

Functional genomics

gnomAD constraint: pLI 0.00081, LOEUF 1.39, missense Z 0.236 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000055077 — one region, missense o/e 0.88. DepMap (CRISPR cell-line fitness): dependent in 99.8% of screened cell lines, common-essential.

Most-dependent cell lines (DepMap gene-effect, lower = stronger; ≤ −0.5 shown): LN382 (-3.049), D341 Med (-3.038), SNU-398 (-2.969), PA-TU-8988S (-2.855), HCC1143 (-2.851), OCUM-1 (-2.743), SNU-5 (-2.699), NB-4 (-2.676), HCC-95 (-2.671), NCI-H520 (-2.669), SK-HEP-1 (-2.631), Lu-65 (-2.604), KARPAS-422 (-2.583), OAW28 (-2.576), NCI-H1666 (-2.551).

Literature-anchored findings (GeneRIF, showing 8)

• Upregulation by BCR/ABL requires activation of STAT5 and plays a key role in the BCR/ABL-mediated cell protection from apoptosis. (PMID:12036885)
• evidence is presented for a novel interaction between RFC40 and the RIalpha subunit of PKA; findings indicate that modulation in the formation of the RFC40-RIa complex is associated with decreased cell survival (PMID:15655353)
• The cAMP functions as an upstream modulator that regulates the expression and nuclear translocation of RFC40 protein. (PMID:16413017)
• RPA plays a regulatory role in DNA damage responses via repression of RFC2 ubiquitylation in human cells. (PMID:18245774)
• Up-regulated RFC2 predicts unfavorable progression in hepatocellular carcinoma. (PMID:34022962)
• RFC2: a prognosis biomarker correlated with the immune signature in diffuse lower-grade gliomas. (PMID:35210438)
• CircCOL1A2 Sponges MiR-1286 to Promote Cell Invasion and Migration of Gastric Cancer by Elevating Expression of USP10 to Downregulate RFC2 Ubiquitination Level. (PMID:35791074)
• RFC2 promotes aerobic glycolysis and progression of colorectal cancer. (PMID:37821801)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	rfc2	ENSDARG00000014274
mus_musculus	Rfc2	ENSMUSG00000023104
rattus_norvegicus	Rfc2	ENSRNOG00000001457
drosophila_melanogaster	RfC4	FBGN0260985
caenorhabditis_elegans		WBGENE00004338

Paralogs (3): RFC5 (ENSG00000111445), RFC3 (ENSG00000133119), RFC4 (ENSG00000163918)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:1341868) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 2 distinct phenotype terms.

Mouse phenotype (MP)	Records
preweaning lethality, complete penetrance	1
embryonic lethality prior to organogenesis	1

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Halobacterium salinarum R1	B0R7H7	100.0%	Diamond
Halobacterium salinarum NRC-1	Q9HN27	100.0%	Diamond
Methanococcus maripaludis C5	A4FZ74	99.0%	Diamond
Methanococcus maripaludis C6	A9A6K6	99.0%	Diamond
Bos taurus	Q2TBV1	98.6%	Diamond
Methanococcus maripaludis S2	Q6M044	98.4%	Diamond
Methanococcus maripaludis C7	A6VJ61	97.5%	Diamond
Gallus gallus	P53033	93.6%	Diamond
Pyrobaculum arsenaticum DSM 13514	A4WLY0	91.5%	Diamond
Pyrobaculum aerophilum str. IM2	Q8ZWS2	91.5%	Diamond
Methanococcus vannielii SB	A6US36	91.1%	Diamond
Methanosarcina mazei Go1	Q8PVY4	90.8%	Diamond
Methanosarcina acetivorans C2A	Q8TSX5	90.8%	Diamond
Pyrobaculum islandicum DSM 4184	A1RV38	89.9%	Diamond
Methanosarcina barkeri str. Fusaro	Q46C63	88.8%	Diamond
Thermoplasma volcanium GSS1	Q977Z9	88.3%	Diamond
Thermoplasma acidophilum DSM 1728	Q9HI47	88.3%	Diamond
Pyrococcus abyssi GE5	Q9V2G3	87.5%	Diamond
Pyrobaculum calidifontis JCM 11548	A3MS28	86.9%	Diamond
Sulfolobus acidocaldarius DSM 639	Q4JAB0	85.5%	Diamond
Oryza sativa Japonica Group	Q7XRX1	85.5%	Diamond
Sulfurisphaera tokodaii str. 7	Q975D3	85.5%	Diamond
Arabidopsis thaliana	Q9CAM7	85.5%	Diamond
Saccharolobus solfataricus P2	Q9UXF5	83.4%	Diamond
Pyrococcus horikoshii OT3	O57852	82.8%	Diamond
Pyrococcus furiosus DSM 3638	Q8U4J3	82.8%	Diamond
Thermococcus kodakarensis KOD1	Q5JHP2	80.8%	Diamond
Methanoculleus marisnigri JR1	A3CUX9	77.6%	Diamond
Methanoregula boonei 6A8	A7I8Y0	77.6%	Diamond
Escherichia phage RB69	O64301	77.5%	Diamond
Haloquadratum walsbyi DSM 16790	Q18E75	76.1%	Diamond
Natronomonas pharaonis DSM 2160	Q3ITJ2	76.1%	Diamond
Haloarcula marismortui ATCC 43049	Q5UZE5	76.0%	Diamond
Methanocaldococcus jannaschii DSM 2661	Q58817	73.2%	Diamond
Methanospirillum hungatei JF-1	Q2FQT9	72.8%	Diamond
Methanobrevibacter smithii ATCC 35061	A5UMF3	72.4%	Diamond
Methanothermobacter thermautotrophicus str. Delta H	O26343	72.4%	Diamond
Staphylothermus marinus F1	A3DNV9	71.0%	Diamond
Aeropyrum pernix K1	Q9YBS7	70.7%	Diamond
Methanocorpusculum labreanum Z	A2SQT3	69.9%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
CLIP2	protein-coding	7461
LAT2	protein-coding	7462
GTF2IRD1	protein-coding	9569
WBSCR23	ncRNA	107986810
LIMK1	protein-coding	3984
MIR590	ncRNA	693175
EIF4H	protein-coding	7458
ELN-AS1	ncRNA	107986809
ELN	protein-coding	2006

Protein

Protein identifiers

Replication factor C subunit 2 — P35250 (reviewed: P35250)

Alternative names: Activator 1 40 kDa subunit, Activator 1 subunit 2, Replication factor C 40 kDa subunit

All UniProt accessions (12): A0A087WVY3, P35250, F8WC37, F8WDC9, H7C596, H7C5A0, H7C5G4, H7C5P1, H7C5P4, H7C5Q7, H7C5S7, Q75MT5

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. This subunit binds ATP.

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 RFC3, RFC4 and RFC5; this complex has ATPase activity but is not stimulated by PCNA. The heterotetramer of subunits RFC2, RFC3, RFC4 and RFC5 interacts with RAD17. RFC2 also interacts with PRKAR1A; the complex may be involved in cell survival. Interacts with DDX11.

Subcellular location. Nucleus.

Disease relevance. RFC2 is located in the Williams-Beuren syndrome (WBS) critical region. WBS results from a hemizygous deletion of several genes on chromosome 7q11.23, thought to arise as a consequence of unequal crossing over between highly homologous low-copy repeat sequences flanking the deleted region.

Similarity. Belongs to the activator 1 small subunits family.

Isoforms (2)

UniProt ID	Names	Canonical?
P35250-1	1	yes
P35250-2	2

RefSeq proteins (5): NP_001265720, NP_001265721, NP_001265722, NP_002905, NP_852136* (*=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

Enzyme classification (BRENDA)

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

UniProt features (43 total): helix 22, strand 7, modified residue 5, turn 3, chain 1, region of interest 1, sequence conflict 1, binding site 1, splice variant 1, sequence variant 1

Structure

Experimental structures (PDB)

16 structures by resolution:

PDB	Title	Method	Resolution (Å)
8UMV	Atomic model of the human CTF18-RFC-PCNA-DNA ternary complex with narrow PCNA opening …	ELECTRON MICROSCOPY	2.75
8UMY	Atomic model of the human CTF18-RFC-PCNA-DNA ternary complex with narrow PCNA opening …	ELECTRON MICROSCOPY	2.83
8UMW	Atomic model of the human CTF18-RFC-PCNA-DNA ternary complex in the five-subunit binding …	ELECTRON MICROSCOPY	2.93
8ZWO	Structure of CTF18-PCNA with ATP	ELECTRON MICROSCOPY	2.99
8UN0	Atomic model of the human CTF18-RFC-PCNA-DNA ternary complex with cracked and closed PCNA …	ELECTRON MICROSCOPY	3
8UII	Cryo-EM map of human clamp-clamp loader ATAD5-RFC-closed PCNA complex in intermediate …	ELECTRON MICROSCOPY	3.04
8UI8	Cryo-EM map of human clamp-clamp loader ATAD5-RFC-two PCNAs complex in intermediate state …	ELECTRON MICROSCOPY	3.1
8UMU	Atomic model of the human CTF18-RFC-PCNA binary complex in the four-subunit binding state …	ELECTRON MICROSCOPY	3.16
9IIN	Structure of CTF18-PCNA with ATP and Mg2+	ELECTRON MICROSCOPY	3.2
9UIQ	Structure of CTF18-PCNA with ATP	ELECTRON MICROSCOPY	3.2
8UMT	Atomic model of the human CTF18-RFC-PCNA binary complex in the three-subunit binding …	ELECTRON MICROSCOPY	3.33
8UNJ	Atomic model of the human CTF18-RFC alone in the apo state (State 1)	ELECTRON MICROSCOPY	3.35
6VVO	Structure of the human clamp loader (Replication Factor C, RFC) bound to the sliding …	ELECTRON MICROSCOPY	3.4
8UI9	Cryo-EM map of human clamp-clamp loader ATAD5-RFC-cracked PCNA complex in intermediate …	ELECTRON MICROSCOPY	3.5
7Z6H	Structure of DNA-bound human RAD17-RFC clamp loader and 9-1-1 checkpoint clamp	ELECTRON MICROSCOPY	3.59
8UI7	Cryo-EM map of human clmap-clamp loader ATAD5-RFC-gapped PCNA complex in intermediate …	ELECTRON MICROSCOPY	4.2

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P35250-F1	87.63	0.77

Human Protein Atlas

Protein class: Predicted intracellular proteins, Plasma proteins, Disease related genes, Human disease related genes, Other congenital disorders, Chromosomal abnormalities, Essential proteins

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): nucleoplasm; golgi apparatus

Antibody reliability (HPA): IH approved · IF supported

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)

Position	Role
76–83	ATP

Post-translational modifications (5)

Type	Positions
N-acetylmethionine	1
Phosphoserine	18, 30
N6-acetyllysine	163, 304

Function

Pathways and Gene Ontology

Reactome pathways

22 curated (TAS) of 59; 5 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

59 pathways:

ID	Pathway	Evidence
R-HSA-9709570	Impaired BRCA2 binding to RAD51 ⚕	curated
R-HSA-176187	Activation of ATR in response to replication stress	curated
R-HSA-5696400	Dual Incision in GG-NER	curated
R-HSA-6782135	Dual incision in TC-NER	curated
R-HSA-69473	G2/M DNA damage checkpoint	curated
R-HSA-5696397	Gap-filling DNA repair synthesis and ligation in GG-NER	curated
R-HSA-6782210	Gap-filling DNA repair synthesis and ligation in TC-NER	curated
R-HSA-5685942	HDR through Homologous Recombination (HRR)	curated
R-HSA-5685938	HDR through Single Strand Annealing (SSA)	curated
R-HSA-5651801	PCNA-Dependent Long Patch Base Excision Repair	curated
R-HSA-69091	Polymerase switching	curated
R-HSA-174411	Polymerase switching on the C-strand of the telomere	curated
R-HSA-5693616	Presynaptic phase of homologous DNA pairing and strand exchange	curated
R-HSA-5693607	Processing of DNA double-strand break ends	curated
R-HSA-110314	Recognition of DNA damage by PCNA-containing replication complex	curated
R-HSA-6804756	Regulation of TP53 Activity through Phosphorylation	curated
R-HSA-9968295	Somatic hypermutation of immunoglobulin genes by error-prone mismatch repair (MMR)	curated
R-HSA-5656169	Termination of translesion DNA synthesis	curated
R-HSA-110320	Translesion Synthesis by POLH	curated
R-HSA-5656121	Translesion synthesis by POLI	curated
R-HSA-5655862	Translesion synthesis by POLK	curated
R-HSA-110312	Translesion synthesis by REV1	curated
R-HSA-9701190	Defective homologous recombination repair (HRR) due to BRCA2 loss of function ⚕	—
R-HSA-1643685	Disease ⚕	—
R-HSA-9675136	Diseases of DNA Double-Strand Break Repair ⚕	—
R-HSA-9675135	Diseases of DNA repair ⚕	—
R-HSA-73884	Base Excision Repair	—
R-HSA-1640170	Cell Cycle	—
R-HSA-69620	Cell Cycle Checkpoints	—
R-HSA-69278	Cell Cycle, Mitotic	—
R-HSA-73886	Chromosome Maintenance	—
R-HSA-73893	DNA Damage Bypass	—
R-HSA-5693532	DNA Double-Strand Break Repair	—
R-HSA-73894	DNA Repair	—
R-HSA-69306	DNA Replication	—
R-HSA-69190	DNA strand elongation	—
R-HSA-180786	Extension of Telomeres	—
R-HSA-69481	G2/M Checkpoints	—
R-HSA-74160	Gene expression (Transcription)	—
R-HSA-212436	Generic Transcription Pathway	—
R-HSA-5696399	Global Genome Nucleotide Excision Repair (GG-NER)	—
R-HSA-5693567	HDR through Homologous Recombination (HRR) or Single Strand Annealing (SSA)	—
R-HSA-5693579	Homologous DNA Pairing and Strand Exchange	—
R-HSA-5693538	Homology Directed Repair	—
R-HSA-69186	Lagging Strand Synthesis	—
R-HSA-69109	Leading Strand Synthesis	—
R-HSA-5696398	Nucleotide Excision Repair	—
R-HSA-73857	RNA Polymerase II Transcription	—
R-HSA-5633007	Regulation of TP53 Activity	—
R-HSA-110373	Resolution of AP sites via the multiple-nucleotide patch replacement pathway	—
R-HSA-73933	Resolution of Abasic Sites (AP sites)	—
R-HSA-69242	S Phase	—
R-HSA-9968297	Somatic hypermutation of immunoglobulin genes by error-prone base excision repair (BER)	electronic
R-HSA-69239	Synthesis of DNA	—
R-HSA-174417	Telomere C-strand (Lagging Strand) Synthesis	—
R-HSA-157579	Telomere Maintenance	—
R-HSA-6781827	Transcription-Coupled Nucleotide Excision Repair (TC-NER)	—
R-HSA-3700989	Transcriptional Regulation by TP53	—
R-HSA-110313	Translesion synthesis by Y family DNA polymerases bypasses lesions on DNA template	—

MSigDB gene sets: 735 (showing top): PID_FANCONI_PATHWAY, REACTOME_DNA_REPLICATION, BORCZUK_MALIGNANT_MESOTHELIOMA_UP, GOBP_POSITIVE_REGULATION_OF_DNA_BIOSYNTHETIC_PROCESS, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, FISCHER_G1_S_CELL_CYCLE, ENK_UV_RESPONSE_KERATINOCYTE_UP, REACTOME_G2_M_DNA_DAMAGE_CHECKPOINT, GOBP_CELL_CYCLE_PHASE_TRANSITION, REACTOME_ACTIVATION_OF_ATR_IN_RESPONSE_TO_REPLICATION_STRESS, DACOSTA_UV_RESPONSE_VIA_ERCC3_UP, FRASOR_RESPONSE_TO_SERM_OR_FULVESTRANT_DN, GOBP_REGULATION_OF_TRANSFERASE_ACTIVITY, KAUFFMANN_DNA_REPAIR_GENES, GOBP_POSITIVE_REGULATION_OF_CATALYTIC_ACTIVITY

GO Biological Process (5): DNA replication checkpoint signaling (GO:0000076), 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

12 top-level categories:

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

30 GO namespaces:

Category	Terms
DNA metabolic process	2
DNA integrity checkpoint signaling	1
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
anion 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

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 5 of 18 annotations. The rest are phylogenetic / computational / electronic (IEA).

5 experimentally-supported GO terms:

GO term	NS	Evidence
DNA-templated DNA replication	BP	direct assay
positive regulation of DNA-directed DNA polymerase activity	BP	direct assay
Ctf18 RFC-like complex	CC	direct assay
DNA replication factor C complex	CC	direct assay
nucleoplasm	CC	direct assay

Protein interactions and networks

IntAct

Human interaction partners of RFC2 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

6 partners by confidence:

Partner	Interaction type	MIscore	Records
RFC4	association	0.810	8
RFC1	physical association	0.640	1
PRKAR1A	physical association	0.520	7
E6	physical association	0.490	6
PHLDA3	physical association	0.000	1
PITX2	physical association	0.000	1

BioGRID (271 interactions; top human partners by supporting records): RFC5 (Co-fractionation; 11 records), RFC4 (Co-fractionation; 9 records), PCNA (Affinity Capture-MS; 6 records), BRD4 (Affinity Capture-Western; 5 records), RAD17 (Affinity Capture-MS; 4 records), RFC1 (Co-fractionation; 4 records), RPA1 (Affinity Capture-MS; 4 records), CHTF18 (Affinity Capture-MS; 3 records), DSCC1 (Affinity Capture-MS; 3 records), MYC (Affinity Capture-MS; 3 records), RFC3 (Co-fractionation; 3 records), RPA2 (Affinity Capture-MS; 3 records), RPA3 (Affinity Capture-MS; 3 records), BRCA1 (Affinity Capture-MS; 2 records), BRD3 (Affinity Capture-MS; 2 records)

SIGNOR signaling

1 signaling interactions:

A	Effect	B	Mechanism
RFC2	“form complex”	“RF-C complex”	binding

Protein complexes (CORUM) (22)

Experimentally-characterized complexes this protein is a subunit of (★ = the complex contains a known drug target).

22 complexes by size:

Complex	Subunits	Members
★ RC complex, S-phase-specific	23	POLD4, POLE2, POLE4, CCNA2, CDK2, POLD2, POLD3, RFC2, POLE, RFC1, RFC5, RPA3, LIG1, PARP1, POLA1, POLD1, RFC3, RPA2, POLA2, POLE3, RFC4, RPA1, TOP1
★ DNA synthesome complex, breast cancer MCF7 cells	23	POLA2, POLD3, POLE4, PRIM1, RFC1, RPA1, PCNA, POLD4, POLE2, POLE3, RFC4, TOP1, POLA1, RFC2, RFC3, RFC5, RPA2, RPA3, TOP2A, POLD1, POLD2, POLE, PRIM2
★ DNA synthesome complex, breast cancer cells	20	POLD3, POLE4, RFC2, RFC3, POLA2, POLE3, LIG1, PARP1, PCNA, POLD2, PRIM1, PRIM2, RFC1, RFC4, POLD4, POLE, POLE2, RFC5, POLA1, POLD1
★ RC complex, G2/M-phase-specific	19	CCNB1, POLA1, POLA2, POLD2, RPA1, RPA2, CDK1, POLD3, RFC1, RFC2, RPA3, POLD1, POLD4, POLE, POLE3, PARP1, POLE2, POLE4, TOP1
★ DNA synthesome complex, leukemia cells	19	PCNA, POLD1, RFC5, TOP2A, POLD4, PRIM1, PRIM2, RFC2, RPA2, TOP1, POLD2, POLD3, RPA1, POLA1, POLA2, RFC1, RFC3, RFC4, RPA3
★ DNA synthesome core complex	14	PCNA, POLA2, POLD1, POLD2, POLD3, POLD4, PRIM2, RFC1, POLA1, PRIM1, RFC2, RFC3, RFC4, RFC5
BASC complex (BRCA1-associated genome surveillance complex)	12	MRE11, MSH2, MSH6, NBN, RFC1, ATM, RAD50, RFC2, RFC4, BLM, BRCA1, MLH1
★ RC sub-complex	9	RFC1, RFC3, CCNA2, POLA1, RFC2, RFC4, RFC5, CDK2, POLA2
9-1-1-RAD17-RFC complex	8	RAD17, RAD9A, RFC2, RFC3, RFC4, RFC5, HUS1, RAD1
CTF18-cohesion-RFC-POLH complex	8	DSCC1, POLH, RFC2, RFC3, RFC4, RFC5, CHTF18, CHTF8
BASC (Ab 80) complex (BRCA1-associated genome surveillance complex)	8	RFC2, RFC4, BLM, BRCA1, MLH1, MSH2, MSH6, RFC1
CTF18-cohesion-RFC complex	7	RFC5, CHTF18, CHTF8, DSCC1, RFC2, RFC3, RFC4
BRD4-RFC complex	6	BRD4, RFC1, RFC2, RFC3, RFC4, RFC5
PCNA-CHL12-RFC2-5 complex	6	CHTF18, PCNA, RFC2, RFC3, RFC4, RFC5
BASC (Ab 81) complex (BRCA1-associated genome surveillance complex)	6	RFC4, ATM, BRCA1, MLH1, RFC1, RFC2
CHTF18-RFC2-5 complex	5	CHTF18, RFC2, RFC3, RFC4, RFC5
PCNA-RFC2-5 complex	5	RFC4, RFC5, PCNA, RFC2, RFC3
RAD17-RFC complex	5	RFC5, RAD17, RFC2, RFC3, RFC4
RFC complex	5	RFC1, RFC2, RFC3, RFC4, RFC5
RFC2-5 subcomplex	4	RFC2, RFC3, RFC4, RFC5
RFC core complex	3	RFC4, RFC5, RFC2
RFC2-RIalpha complex	2	PPP2R1A, RFC2

Disease & clinical

Genetic variants

Variant evidence for RFC2: 81 ClinVar records (0 pathogenic / likely pathogenic).

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	39
Likely benign	18
Benign	8

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 40 predictions of 912):

Position(s)	Effect	Δscore	Sites
7:74232217–74232218	acceptor_loss	1.0000	5
7:74237443–74237444	acceptor_loss	1.0000	5
7:74237448–74237449	acceptor_gain	1.0000	2
7:74239936–74239937	donor_loss	1.0000	3
7:74240096–74240097	acceptor_loss	1.0000	5
7:74243144–74243145	donor_loss	1.0000	5
7:74243247–74243248	acceptor_loss	1.0000	4
7:74249010–74249011	donor_loss	1.0000	5
7:74232217	acceptor_loss	0.9900
7:74235530–74235531	donor_loss	0.9900	5

AlphaMissense

1,233 missense substitutions predicted likely pathogenic (of 2,342 scored), across 276 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
D141	8	0.998	0.999
D144	8	0.997	0.999
D294	8	0.993	0.999
D228	8	0.991	0.998
F167	8	0.983	0.999
D256	8	0.978	0.993
N172	8	0.974	0.999
N106	8	0.967	0.998
F123	8	0.952	0.997
M158	8	0.910	0.997
N53	8	0.901	0.995
F63	8	0.852	0.969
H135	8	0.744	0.953
E142	7	0.999	1.000
R155	7	0.997	1.000
R230	7	0.995	0.999
R117	7	0.993	1.000
R111	7	0.991	0.999
R43	7	0.990	0.999
K82	7	0.989	0.999

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

2 prognostic cancer types:

Cancer	Prognostic	p-value
Liver Hepatocellular Carcinoma (TCGA)	unfavorable	2.96e-05
Liver Hepatocellular Carcinoma (validation)	unfavorable	5.2e-05

Disease associations

OMIM: gene MIM:600404 | disease phenotypes:

HPO phenotypes

showing 60 of 186 phenotypes (HPO-id order):

HPO	Term
HP:0000010	Recurrent urinary tract infections
HP:0000014	Abnormality of the bladder
HP:0000015	Bladder diverticulum
HP:0000023	Inguinal hernia
HP:0000025	Functional abnormality of male internal genitalia
HP:0000028	Cryptorchidism
HP:0000044	Hypogonadotropic hypogonadism
HP:0000075	Renal duplication
HP:0000076	Vesicoureteral reflux
HP:0000083	Renal insufficiency
HP:0000089	Renal hypoplasia
HP:0000093	Proteinuria
HP:0000121	Nephrocalcinosis
HP:0000125	Pelvic kidney
HP:0000147	Polycystic ovaries
HP:0000154	Wide mouth
HP:0000158	Macroglossia
HP:0000179	Thick lower lip vermilion
HP:0000212	Gingival overgrowth
HP:0000232	Everted lower lip vermilion
HP:0000252	Microcephaly
HP:0000275	Narrow face
HP:0000280	Coarse facial features
HP:0000286	Epicanthus
HP:0000307	Pointed chin
HP:0000337	Broad forehead
HP:0000343	Long philtrum
HP:0000347	Micrognathia
HP:0000348	High forehead
HP:0000358	Posteriorly rotated ears
HP:0000389	Chronic otitis media
HP:0000400	Macrotia
HP:0000407	Sensorineural hearing impairment
HP:0000411	Protruding ear
HP:0000431	Wide nasal bridge
HP:0000464	Abnormality of the neck
HP:0000485	Megalocornea
HP:0000486	Strabismus
HP:0000501	Glaucoma
HP:0000505	Visual impairment
HP:0000518	Cataract
HP:0000545	Myopia
HP:0000581	Blepharophimosis
HP:0000627	Posterior embryotoxon
HP:0000632	Lacrimation abnormality
HP:0000635	Blue irides
HP:0000668	Hypodontia
HP:0000670	Carious teeth
HP:0000682	Abnormal dental enamel morphology
HP:0000689	Dental malocclusion
HP:0000691	Microdontia
HP:0000716	Depression
HP:0000717	Autism
HP:0000722	Compulsive behaviors
HP:0000739	Anxiety
HP:0000767	Pectus excavatum
HP:0000787	Kidney stone
HP:0000821	Hypothyroidism
HP:0000822	Hypertension
HP:0000826	Precocious puberty

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5725141 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

Phase ≥1, by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 1,601 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

1 molecules by phase:

Molecule	Name	Phase	Patents
CHEMBL1232461	MOLIBRESIB	2	1,601

PharmGKB: 1 entry (CPIC guideline: no)

ChEMBL bioactivities

2 potent at pChembl≥5 of 2 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.46	Kd	35	nM	MOLIBRESIB
7.05	IC50	90	nM	MOLIBRESIB

PubChem BioAssay actives

2 with measured affinity, of 7 total; 1 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	2179095: Binding affinity against RFC2 (unknown origin) assessed as apparent dissociation constant incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	kd	0.0350	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases abundance, increases expression, decreases expression	6
bisphenol A	affects expression, decreases expression	3
Cyclosporine	decreases expression	3
cobaltous chloride	decreases expression	2
Arsenic	increases expression, decreases expression, increases abundance	2
Tretinoin	decreases expression	2
lasiocarpine	increases metabolic processing, decreases expression	1
triphenyl phosphate	affects expression	1
2,2’-methylenebis(4-methyl-6-tert-butylphenol)	affects expression, affects response to substance	1
riddelliine	decreases expression, increases metabolic processing	1
beta-lapachone	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
perfluorooctanoic acid	decreases expression	1
zinc chromate	decreases expression, increases abundance	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, increases expression	1
coumarin	increases phosphorylation	1
2,3-dimethoxy-1,4-naphthoquinone	increases expression	1
chromium hexavalent ion	decreases expression, increases abundance	1
CGP 52608	affects binding, increases reaction	1
K 7174	decreases expression	1
nutlin 3	affects cotreatment, increases secretion	1
abrine	increases expression	1
NSC 689534	affects binding, decreases expression	1
(+)-JQ1 compound	decreases expression	1
Dasatinib	decreases expression	1
Resveratrol	affects cotreatment, increases expression	1
Sunitinib	decreases expression	1
Arsenic Trioxide	increases expression	1
Troglitazone	decreases expression	1
Acetaminophen	increases expression	1

ChEMBL screening assays

7 unique, capped per target: 7 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5697130	Binding	Inhibition of RFC2 (unknown origin) assessed as fold change at 10 uM incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	Inhibition of BET recruitment to chromatin as an effective treatment for MLL-fusion leukaemia. — *Nature*

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for RFC2 across ~30M SureChEMBL compounds — explore on Sugi Predict.