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): 80 total
• Phenotypes (HPO): 186
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 99.8% of screened cell lines (common-essential)
• MANE Select transcript: NM_181471

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: 32 — 24 protein_coding, 7 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

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

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.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
84356	13.7993	1772

Top tissues by expression

274 total, 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

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

Regulation

Is transcription factor: no

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

miRNA regulators (miRDB)

17 targeting RFC2, 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-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

DepMap (CRISPR cell-line fitness): dependent in 99.8% of screened cell lines, common-essential.

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)

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 (40 total): helix 21, strand 7, modified residue 5, chain 1, region of interest 1, sequence conflict 1, turn 1, binding site 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-P35250-F1	87.63	0.77

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): 76–83

Post-translational modifications (5): 1, 18, 30, 163, 304

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

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 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
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

0 interactions, top by confidence (×1000):

IntAct

134 interactions, top by confidence:

A	B	Type	Score
HUS1	RAD1	psi-mi:“MI:0914”(association)	0.840
RFC4	RFC2	psi-mi:“MI:0914”(association)	0.810
RFC2	RFC4	psi-mi:“MI:0915”(physical association)	0.810
RFC4	RFC2	psi-mi:“MI:0915”(physical association)	0.810
RAD17	RFC4	psi-mi:“MI:0914”(association)	0.730
RFC5	RAD17	psi-mi:“MI:0914”(association)	0.730
RFC4	RAD17	psi-mi:“MI:0914”(association)	0.730
RFC1	RFC4	psi-mi:“MI:0914”(association)	0.710
RFC1	RFC4	psi-mi:“MI:0915”(physical association)	0.710
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
RAD9A	RAD1	psi-mi:“MI:0914”(association)	0.670
RFC2	RFC1	psi-mi:“MI:0915”(physical association)	0.640
CFTR	HAX1	psi-mi:“MI:0914”(association)	0.610
PCNA	POM121C	psi-mi:“MI:0914”(association)	0.550
MAPT	KIF2A	psi-mi:“MI:0914”(association)	0.530

BioGRID (262): RFC2 (Affinity Capture-MS), RFC2 (Affinity Capture-MS), RFC2 (Affinity Capture-MS), RFC2 (Affinity Capture-MS), RFC2 (Affinity Capture-MS), RFC2 (Affinity Capture-MS), GINS3 (Co-fractionation), RFC2 (Co-fractionation), RFC2 (Co-fractionation), RFC2 (Co-fractionation), RFC2 (Co-fractionation), RFC2 (Co-fractionation), RFC2 (Co-fractionation), RFC2 (Affinity Capture-MS), RFC2 (Proximity Label-MS)

ESM2 similar proteins: A0A1L8EV45, C9WPN6, F1QGW6, F6RQL9, O73723, O77676, P00516, P0C605, P20461, P23258, P23330, P31321, P32392, P35250, P41091, P53033, P61157, P61158, P62482, P62483, P81795, P83887, P83888, Q05B83, Q0VCD2, Q13126, Q13303, Q13976, Q27955, Q2KHU8, Q2KJ81, Q2VIR3, Q32KM1, Q4V7C7, Q5R797, Q5R8R1, Q5ZHS1, Q5ZMS3, Q641P0, Q641W4

Diamond homologs: A0B6D7, A1RSA2, A1RV38, A1RWU7, A2SQR6, A2SQT3, A3CTR4, A3CUX9, A3DNV9, A3MS28, A4FZ74, A4WGV2, A4WLY0, A5UMF3, A5UMF4, A6US36, A6VJ61, A7I781, A7I8Y0, A9A6K6, B0R601, B0R7H7, O14003, O26342, O26343, O28219, O29072, O57852, O57853, O74111, O94449, O94697, P0C7N7, P34429, P35249, P35250, P38629, P40339, P40348, P40937

SIGNOR signaling

1 interactions.

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

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 125 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	43.0×	6e-06
Translesion synthesis by POLI	5	40.5×	7e-06
Translesion synthesis by POLK	5	38.2×	9e-06
Translesion Synthesis by POLH	5	36.2×	1e-05
PCNA-Dependent Long Patch Base Excision Repair	5	31.3×	2e-05
Polymerase switching on the C-strand of the telomere	6	30.6×	3e-06
Gap-filling DNA repair synthesis and ligation in GG-NER	5	26.5×	4e-05
Impaired BRCA2 binding to RAD51	7	26.0×	2e-06

GO biological processes:

GO term	Partners	Fold	FDR
DNA damage checkpoint signaling	5	18.7×	8e-04
intrinsic apoptotic signaling pathway	5	17.1×	9e-04
cellular response to UV	6	16.9×	3e-04
positive regulation of miRNA transcription	5	13.8×	2e-03
ribosomal small subunit biogenesis	6	13.0×	8e-04
telomere maintenance	5	12.7×	3e-03
cytoplasmic translation	7	12.3×	3e-04
rRNA processing	7	9.4×	9e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	39
Likely benign	17
Benign	8

Top pathogenic / likely-pathogenic (0)

SpliceAI

2398 predictions. Top by Δscore:

Variant	Effect	Δscore
7:74224187:G:GT	donor_gain	1.0000
7:74224188:A:T	donor_gain	1.0000
7:74224196:GG:G	donor_gain	1.0000
7:74224197:GG:G	donor_gain	1.0000
7:74224553:G:GT	donor_gain	1.0000
7:74232213:TTTCC:T	acceptor_loss	1.0000
7:74232215:TCCTG:T	acceptor_loss	1.0000
7:74232217:C:A	acceptor_loss	1.0000
7:74232218:T:G	acceptor_loss	1.0000
7:74237438:CAGAC:C	acceptor_gain	1.0000
7:74237442:CCTGG:C	acceptor_loss	1.0000
7:74237443:C:CG	acceptor_loss	1.0000
7:74237444:T:G	acceptor_loss	1.0000
7:74237448:C:CT	acceptor_gain	1.0000
7:74237448:C:T	acceptor_gain	1.0000
7:74237449:A:T	acceptor_gain	1.0000
7:74239934:ATACC:A	donor_loss	1.0000
7:74239935:TACCT:T	donor_loss	1.0000
7:74239937:C:CA	donor_loss	1.0000
7:74240091:GGGCT:G	acceptor_gain	1.0000
7:74240092:GGCT:G	acceptor_gain	1.0000
7:74240092:GGCTC:G	acceptor_gain	1.0000
7:74240093:GCTC:G	acceptor_gain	1.0000
7:74240094:CT:C	acceptor_gain	1.0000
7:74240094:CTCT:C	acceptor_gain	1.0000
7:74240096:C:CC	acceptor_gain	1.0000
7:74240096:CT:C	acceptor_loss	1.0000
7:74240101:C:CT	acceptor_gain	1.0000
7:74243142:TCA:T	donor_loss	1.0000
7:74243143:CACCG:C	donor_loss	1.0000

AlphaMissense

2342 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:74243168:A:C	C171W	1.000
7:74243217:C:A	R155M	1.000
7:74246671:T:A	E142V	1.000
7:74246725:G:T	A124D	1.000
7:74246746:C:A	R117M	1.000
7:74249089:G:C	S85R	1.000
7:74249089:G:T	S85R	1.000
7:74249091:T:G	S85R	1.000
7:74232209:C:T	G321E	0.999
7:74235606:C:G	D294H	0.999
7:74237429:G:T	P258H	0.999
7:74238975:A:G	L236P	0.999
7:74239942:C:A	R230M	0.999
7:74239958:C:G	A225P	0.999
7:74240076:A:C	C185W	0.999
7:74240078:A:G	C185R	0.999
7:74240080:C:G	R184P	0.999
7:74240084:A:G	S183P	0.999
7:74240089:A:T	I181N	0.999
7:74243165:A:C	N172K	0.999
7:74243165:A:T	N172K	0.999
7:74243169:C:T	C171Y	0.999
7:74243178:G:T	A168D	0.999
7:74243180:G:C	F167L	0.999
7:74243180:G:T	F167L	0.999
7:74243181:A:G	F167S	0.999
7:74243182:A:G	F167L	0.999
7:74243184:C:G	R166P	0.999
7:74243216:C:A	R155S	0.999
7:74243216:C:G	R155S	0.999

dbSNP variants (sampled 300 via entrez): RS1000034531 (7:74247554 C>T), RS1000134831 (7:74254311 T>C), RS1000217670 (7:74254077 G>A,T), RS1001141045 (7:74234880 A>C), RS1001220356 (7:74255119 C>T), RS1001464819 (7:74235237 A>G), RS1001692718 (7:74231698 T>C), RS1002064537 (7:74236769 C>A), RS1002132263 (7:74238332 C>A,T), RS1002542866 (7:74236376 T>A,C), RS1002643009 (7:74233218 C>A,T), RS1002674176 (7:74232972 T>C), RS1002910839 (7:74245033 T>A,C), RS1003091366 (7:74251309 C>T), RS1003190758 (7:74239477 G>A,T)

Disease associations

OMIM: gene MIM:600404 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

186 total (30 of 186 shown, 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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5725141 (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

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	decreases expression, increases abundance, increases 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	increases expression, affects cotreatment	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)

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