RPA3

Summary

RPA3 (replication protein A3, HGNC:10291) is a protein-coding gene on chromosome 7p21.3, encoding Replication protein A 14 kDa subunit (P35244). As part of the heterotrimeric replication protein A complex (RPA/RP-A), binds and stabilizes single-stranded DNA intermediates that form during DNA replication or upon DNA stress. It is a common-essential gene (DepMap: required in 99.8% of cancer cell lines).

Enables damaged DNA binding activity and single-stranded DNA binding activity. Involved in DNA metabolic process. Part of DNA replication factor A complex.

Source: NCBI Gene 6119 — RefSeq curated summary.

At a glance

• GWAS associations: 7
• Clinical variants (ClinVar): 22 total — 1 pathogenic
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 99.8% of screened cell lines (common-essential)
• MANE Select transcript: NM_002947

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10291
Approved symbol	RPA3
Name	replication protein A3
Location	7p21.3
Locus type	gene with protein product
Status	Approved
Aliases	REPA3
Ensembl gene	ENSG00000106399
Ensembl biotype	protein_coding
OMIM	179837
Entrez	6119

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 7 protein_coding, 3 retained_intron

ENST00000223129, ENST00000396682, ENST00000401447, ENST00000406109, ENST00000462723, ENST00000463632, ENST00000483031, ENST00000853923, ENST00000853924, ENST00000935607

RefSeq mRNA: 1 — MANE Select: NM_002947 NM_002947

CCDS: CCDS5356

Canonical transcript exons

ENST00000223129 — 8 exons

Exon	Start	End
ENSE00000671279	7637864	7637972
ENSE00001019351	7640320	7641175
ENSE00001019352	7715175	7715226
ENSE00001019353	7685830	7685998
ENSE00001019354	7718515	7718607
ENSE00001277129	7687228	7687328
ENSE00001553346	7636518	7637082
ENSE00003620461	7639070	7639144

Expression profiles

Bgee: expression breadth ubiquitous, 287 present calls, max score 98.04.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 34.5065 / max 754.7523, expressed in 1814 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
82686	15.9718	1780
82685	14.4389	1716
82687	2.5765	1336
82689	1.0122	618
82688	0.3646	202
82684	0.1426	50

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
bronchial epithelial cell	CL:0002328	98.04	gold quality
epithelium of bronchus	UBERON:0002031	97.82	gold quality
bronchus	UBERON:0002185	97.42	gold quality
type B pancreatic cell	CL:0000169	97.01	gold quality
endometrium epithelium	UBERON:0004811	96.56	gold quality
trabecular bone tissue	UBERON:0002483	93.93	gold quality
embryo	UBERON:0000922	93.67	gold quality
adult organism	UBERON:0007023	93.58	gold quality
ventricular zone	UBERON:0003053	93.49	gold quality
bone marrow	UBERON:0002371	93.38	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	93.18	gold quality
nasal cavity epithelium	UBERON:0005384	92.98	gold quality
ganglionic eminence	UBERON:0004023	92.78	gold quality
mucosa of transverse colon	UBERON:0004991	92.76	gold quality
islet of Langerhans	UBERON:0000006	92.75	gold quality
thymus	UBERON:0002370	92.44	gold quality
right uterine tube	UBERON:0001302	92.27	gold quality
oocyte	CL:0000023	92.22	gold quality
adult mammalian kidney	UBERON:0000082	91.62	gold quality
palpebral conjunctiva	UBERON:0001812	91.48	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	91.44	gold quality
lymph node	UBERON:0000029	91.40	gold quality
mucosa of paranasal sinus	UBERON:0005030	91.36	gold quality
nasal cavity mucosa	UBERON:0001826	91.30	gold quality
eye	UBERON:0000970	91.27	gold quality
pituitary gland	UBERON:0000007	91.24	gold quality
corpus epididymis	UBERON:0004359	91.17	gold quality
adenohypophysis	UBERON:0002196	91.16	gold quality
right adrenal gland	UBERON:0001233	91.01	gold quality
nephron tubule	UBERON:0001231	90.88	gold quality

Single-cell (SCXA)

Detected in 7 experiment(s), a significant marker in 5.

Experiment	Marker?	Max mean expression
E-HCAD-1	yes	38.69
E-GEOD-125970	yes	21.83
E-CURD-46	yes	20.96
E-HCAD-13	yes	20.72
E-ANND-3	yes	9.71
E-MTAB-6819	no	574.27
E-MTAB-9388	no	12.34

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): E2F4

miRNA regulators (miRDB)

32 targeting RPA3, 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-450A-1-3P	100.00	69.33	1837
HSA-MIR-6740-5P	100.00	65.64	932
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-146A-5P	99.96	68.93	988
HSA-MIR-146B-5P	99.96	69.13	977
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-7153-5P	99.94	68.89	1006
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-218-5P	99.93	72.22	2103
HSA-MIR-3121-3P	99.82	71.96	3630
HSA-MIR-636	99.80	69.58	1500
HSA-MIR-5002-5P	99.76	70.84	1763
HSA-MIR-6505-5P	99.73	69.25	1595
HSA-MIR-3120-3P	99.54	70.28	2669
HSA-MIR-203A-3P	99.49	70.56	2806
HSA-MIR-584-3P	99.35	67.69	1082
HSA-MIR-329-5P	99.27	68.11	1597
HSA-MIR-4477A	98.83	69.75	2952
HSA-MIR-7705	98.69	67.47	543
HSA-MIR-4469	97.93	65.81	1319
HSA-MIR-3074-3P	97.83	67.26	922
HSA-MIR-3059-3P	96.71	67.08	606
HSA-MIR-4256	96.22	67.70	669

Functional genomics

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

Literature-anchored findings (GeneRIF, showing 13)

• RPA3 interacts directly with ssDNA on the 3’-side on a 31 nt ssDNA. (PMID:19010961)
• Data indicate taht candidate genes ACTB, BZW, OCM, MACC1, NXPH1, PRPS1L1, RAC1 and RPA3, which lie within the DFNB90 region, were sequenced and no potentially causal variants were identified. (PMID:21734401)
• The allele “T” of rs6947203 in the RPA3 gene acts as a protective allele in glioma. (PMID:23573956)
• RPA, best known for its role in DNA replication and repair, recruits HIRA to promoters and enhancers and regulates deposition of newly synthesized H3.3 to these regulatory elements for gene regulation. (PMID:28107649)
• RPA3 is a potential marker of prognosis, radioresistance and survival in nasopharyngeal carcinoma. (PMID:28557284)
• Up-regulation of RPA3 is involved in gastric cancer tumorigenesis and is associated with poorer patient survival. (PMID:28766245)
• MiR-146a-5p could lead to the restriction of proliferation and the promotion of radiosensitivity and apoptosis in HCC cells through activation of DNA repair pathway and inhibition of RPA3. (PMID:30462539)
• A four-gene signature in the tumor microenvironment that significantly associates with the prognosis of patients with breast cancer. (PMID:32791092)
• Dynamic elements of replication protein A at the crossroads of DNA replication, recombination, and repair. (PMID:32856505)
• Variants of FOXO3 and RPA3 genes affecting IGF-1 levels alter the risk of development of primary osteoarthritis. (PMID:33112260)
• Overexpression of replication protein A3 is associated with unfavorable outcome in bladder urothelial carcinoma. (PMID:34269312)
• Knockdown of replication protein A 3 induces protective autophagy and enhances cisplatin sensitivity in lung adenocarcinoma by inhibiting AKT/mTOR signaling via binding to cyclin-dependent kinases regulatory subunit 2. (PMID:35903032)
• RPA3 promotes the proliferation, migration, and invasion of gliomas by activating the PI3K-AKT-mTOR pathway. (PMID:37571896)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	rpa3	ENSDARG00000002613
mus_musculus	Rpa3	ENSMUSG00000012483
rattus_norvegicus	Rpa3l1	ENSRNOG00000037481

Protein

Protein identifiers

Replication protein A 14 kDa subunit — P35244 (reviewed: P35244)

Alternative names: Replication factor A protein 3

All UniProt accessions (3): P35244, A4D105, B5MC59

UniProt curated annotations — full annotation on UniProt →

Function. As part of the heterotrimeric replication protein A complex (RPA/RP-A), binds and stabilizes single-stranded DNA intermediates that form during DNA replication or upon DNA stress. It prevents their reannealing and in parallel, recruits and activates different proteins and complexes involved in DNA metabolism. Thereby, it plays an essential role both in DNA replication and the cellular response to DNA damage. In the cellular response to DNA damage, the RPA complex controls DNA repair and DNA damage checkpoint activation. Through recruitment of ATRIP activates the ATR kinase a master regulator of the DNA damage response. It is required for the recruitment of the DNA double-strand break repair factors RAD51 and RAD52 to chromatin, in response to DNA damage. Also recruits to sites of DNA damage proteins like XPA and XPG that are involved in nucleotide excision repair and is required for this mechanism of DNA repair. Also plays a role in base excision repair (BER), probably through interaction with UNG. RPA stimulates 5’-3’ helicase activity of BRIP1/FANCJ. Also recruits SMARCAL1/HARP, which is involved in replication fork restart, to sites of DNA damage. May also play a role in telomere maintenance. RPA3 has its own single-stranded DNA-binding activity and may be responsible for polarity of the binding of the complex to DNA. As part of the alternative replication protein A complex, aRPA, binds single-stranded DNA and probably plays a role in DNA repair. Compared to the RPA2-containing, canonical RPA complex, may not support chromosomal DNA replication and cell cycle progression through S-phase. The aRPA may not promote efficient priming by DNA polymerase alpha but could support DNA synthesis by polymerase delta in presence of PCNA and replication factor C (RFC), the dual incision/excision reaction of nucleotide excision repair and RAD51-dependent strand exchange.

Subunit / interactions. Component of the canonical replication protein A complex (RPA), a heterotrimer composed of RPA1, RPA2 and RPA3. Also a component of the aRPA, the alternative replication protein A complex, a trimeric complex similar to the replication protein A complex/RPA but where RPA1 and RPA3 are associated with RPA4 instead of RPA2. Interacts with BRIP1/FANCJ via the RPA1 subunit; following DNA damage they colocalize in foci in the nucleus.

Subcellular location. Nucleus.

Post-translational modifications. Ubiquitinated by RFWD3 at stalled replication forks in response to DNA damage: ubiquitination by RFWD3 does not lead to degradation by the proteasome and promotes removal of the RPA complex from stalled replication forks, promoting homologous recombination.

Similarity. Belongs to the replication factor A protein 3 family.

RefSeq proteins (1): NP_002938* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR012340	NA-bd_OB-fold	Homologous_superfamily
IPR013970	Rfa2	Family

Pfam: PF08661

UniProt features (18 total): strand 8, helix 4, cross-link 3, initiator methionine 1, chain 1, modified residue 1

Structure

Experimental structures (PDB)

10 structures.

PDB	Method	Resolution (Å)
3KDF	X-RAY DIFFRACTION	1.98
2PI2	X-RAY DIFFRACTION	2
1QUQ	X-RAY DIFFRACTION	2.5
2PQA	X-RAY DIFFRACTION	2.5
1L1O	X-RAY DIFFRACTION	2.8
2Z6K	X-RAY DIFFRACTION	3
8RK2	ELECTRON MICROSCOPY	3.2
9PD3	ELECTRON MICROSCOPY	3.3
9PD4	ELECTRON MICROSCOPY	3.4
9MJ5	ELECTRON MICROSCOPY	3.5

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P35244-F1	93.01	0.84

Functional residue map

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

Post-translational modifications (4): 2, 23, 39, 88

Function

Pathways and Gene Ontology

Reactome pathways

29 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-174437	Removal of the Flap Intermediate from the C-strand
R-HSA-176187	Activation of ATR in response to replication stress
R-HSA-3371453	Regulation of HSF1-mediated heat shock response
R-HSA-3371511	HSF1 activation
R-HSA-5358565	Mismatch repair (MMR) directed by MSH2:MSH6 (MutSalpha)
R-HSA-5358606	Mismatch repair (MMR) directed by MSH2:MSH3 (MutSbeta)
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-5696395	Formation of Incision Complex in GG-NER
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-6783310	Fanconi Anemia Pathway
R-HSA-6804756	Regulation of TP53 Activity through Phosphorylation
R-HSA-68962	Activation of the pre-replicative complex
R-HSA-69166	Removal of the Flap Intermediate
R-HSA-69473	G2/M DNA damage checkpoint
R-HSA-912446	Meiotic recombination
R-HSA-9709570	Impaired BRCA2 binding to RAD51

MSigDB gene sets: 384 (showing top): REACTOME_FORMATION_OF_INCISION_COMPLEX_IN_GG_NER, GNF2_CKS1B, REACTOME_MEIOTIC_RECOMBINATION, RNGTGGGC_UNKNOWN, GOBP_CHROMOSOME_ORGANIZATION, REACTOME_DNA_REPLICATION, MODULE_52, YAATNRNNNYNATT_UNKNOWN, REACTOME_G2_M_DNA_DAMAGE_CHECKPOINT, GCANCTGNY_MYOD_Q6, CHIANG_LIVER_CANCER_SUBCLASS_UNANNOTATED_DN, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, REACTOME_ACTIVATION_OF_ATR_IN_RESPONSE_TO_REPLICATION_STRESS, GOBP_TELOMERE_ORGANIZATION, RACCACAR_AML_Q6

GO Biological Process (11): telomere maintenance (GO:0000723), double-strand break repair via homologous recombination (GO:0000724), DNA replication (GO:0006260), DNA repair (GO:0006281), base-excision repair (GO:0006284), nucleotide-excision repair (GO:0006289), mismatch repair (GO:0006298), regulation of mitotic cell cycle (GO:0007346), regulation of cell population proliferation (GO:0042127), DNA recombination (GO:0006310), DNA damage response (GO:0006974)

GO Molecular Function (4): damaged DNA binding (GO:0003684), single-stranded DNA binding (GO:0003697), DNA binding (GO:0003677), protein binding (GO:0005515)

GO Cellular Component (5): nucleoplasm (GO:0005654), DNA replication factor A complex (GO:0005662), site of double-strand break (GO:0035861), nucleus (GO:0005634), nuclear lumen (GO:0031981)

Reactome top-level categories

Rollup of top-10 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
Global Genome Nucleotide Excision Repair (GG-NER)	3
Cellular response to heat stress	2
Mismatch Repair	2
DNA Damage Bypass	1
Processive synthesis on the C-strand of the telomere	1
G2/M Checkpoints	1
Resolution of AP sites via the multiple-nucleotide patch replacement pathway	1
Homologous DNA Pairing and Strand Exchange	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
DNA metabolic process	4
DNA repair	3
DNA binding	2
telomere organization	1
recombinational repair	1
double-strand break repair	1
DNA biosynthetic process	1
DNA damage response	1
mitotic cell cycle	1
regulation of cell cycle	1
cell population proliferation	1
regulation of cellular process	1
cellular response to stress	1
nucleic acid binding	1
binding	1
nuclear lumen	1
cellular anatomical structure	1
nuclear replisome	1
nuclear protein-containing complex	1
site of DNA damage	1
intracellular membrane-bounded organelle	1
nucleus	1
intracellular organelle lumen	1

Protein interactions and networks

STRING

1905 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RPA3	RPA2	P15927	997
RPA3	RPA1	P27694	997
RPA3	RPA4	Q13156	996
RPA3	STN1	Q9H668	996
RPA3	POLR1F	Q3B726	911
RPA3	ATRIP	Q8WXE1	747
RPA3	POLD2	P49005	687
RPA3	SOHLH1	Q5JUK2	683
RPA3	LPAR3	Q9UBY5	662
RPA3	RAD17	O75943	643
RPA3	XRCC6	P12956	609
RPA3	POLR2D	O15514	608
RPA3	CHEK1	O14757	606
RPA3	RAD51	Q06609	604
RPA3	XRCC5	P13010	601

IntAct

177 interactions, top by confidence:

A	B	Type	Score
RPA2	RPA1	psi-mi:“MI:0914”(association)	0.960
RPA1	RPA2	psi-mi:“MI:0915”(physical association)	0.960
RPA1	RPA2	psi-mi:“MI:0914”(association)	0.960
RPA1	RPA2	psi-mi:“MI:0407”(direct interaction)	0.960
RPA3	RPA2	psi-mi:“MI:0914”(association)	0.930
RPA3	RPA2	psi-mi:“MI:0407”(direct interaction)	0.930
RPA2	RPA3	psi-mi:“MI:0915”(physical association)	0.930
RPA3	RPA2	psi-mi:“MI:0915”(physical association)	0.930
RPA1	RPA3	psi-mi:“MI:0914”(association)	0.920
RPA1	RPA3	psi-mi:“MI:0915”(physical association)	0.920
RPA4	RPA1	psi-mi:“MI:0914”(association)	0.740
RPA3	RPA4	psi-mi:“MI:0915”(physical association)	0.660
BLM	RPA2	psi-mi:“MI:0914”(association)	0.640
RAD52	RPA3	psi-mi:“MI:0915”(physical association)	0.620
RIF1	RPA2	psi-mi:“MI:0914”(association)	0.550
PRIMPOL	RPA2	psi-mi:“MI:0914”(association)	0.510
POLL	BCKDHA	psi-mi:“MI:0914”(association)	0.510
AIFM1	HAX1	psi-mi:“MI:0914”(association)	0.420

BioGRID (3308): RPA3 (Affinity Capture-MS), RPA3 (Affinity Capture-MS), RPA3 (Affinity Capture-RNA), LTN1 (Co-fractionation), RPA2 (Co-fractionation), RPA3 (Co-fractionation), RPA3 (Co-fractionation), RPA3 (Co-fractionation), RPA3 (Affinity Capture-MS), RPA3 (Affinity Capture-MS), RPA3 (Affinity Capture-MS), RPA3 (Affinity Capture-MS), RPA3 (Affinity Capture-MS), RPA3 (Proximity Label-MS), RPA3 (Affinity Capture-MS)

ESM2 similar proteins: A1L4Y1, A2QCJ2, B8A5I7, F1QR43, F4JP46, P09380, P09381, P27694, P28042, P32445, P35244, P41345, P59931, P59933, P78586, Q01217, Q04837, Q0JJS8, Q28EX9, Q2KJD7, Q32PB0, Q40089, Q4IBU4, Q4X0Z7, Q5AZT7, Q5FW17, Q5FWT7, Q5R4C4, Q5R7Q4, Q5R8R4, Q5RDQ0, Q5ZJJ8, Q641F1, Q69YN2, Q6DI37, Q6NLG7, Q6NWD4, Q6P4T2, Q6STH5, Q7S8C4

Diamond homologs: P35244, Q9CQ71

SIGNOR signaling

4 interactions.

A	Effect	B	Mechanism
POT1	“down-regulates activity”	RPA3	binding
ACD	“down-regulates activity”	RPA3	binding
RAD23B	“up-regulates activity”	RPA3	binding
RPA3	up-regulates	Nucleotide-excision_repair

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 159 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
HDR through Single Strand Annealing (SSA)	7	17.4×	9e-05
Impaired BRCA2 binding to RAD51	6	15.7×	7e-04
Presynaptic phase of homologous DNA pairing and strand exchange	6	13.8×	1e-03
Dual Incision in GG-NER	5	11.0×	7e-03
Formation of Incision Complex in GG-NER	5	10.8×	7e-03
HDR through Homologous Recombination (HRR)	6	9.7×	4e-03
SUMOylation of DNA damage response and repair proteins	7	8.7×	2e-03
Transcriptional activation of mitochondrial biogenesis	5	8.6×	1e-02

GO biological processes:

GO term	Partners	Fold	FDR
branching involved in ureteric bud morphogenesis	6	16.0×	3e-04
telomere maintenance	8	15.6×	1e-05
double-strand break repair via nonhomologous end joining	5	15.4×	2e-03
negative regulation of extrinsic apoptotic signaling pathway in absence of ligand	5	15.0×	2e-03
nucleotide-excision repair	5	14.0×	2e-03
DNA recombination	5	12.3×	4e-03
mRNA transcription by RNA polymerase II	5	12.1×	4e-03
double-strand break repair	8	11.9×	7e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	13
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
154993	GRCh38/hg38 7p22.3-15.2(chr7:1698124-27207295)x3	Pathogenic

SpliceAI

1322 predictions. Top by Δscore:

Variant	Effect	Δscore
7:7637859:TTTAC:T	donor_loss	1.0000
7:7637860:TTACC:T	donor_loss	1.0000
7:7637861:TACCA:T	donor_loss	1.0000
7:7637862:A:AG	donor_loss	1.0000
7:7637863:CCA:C	donor_loss	1.0000
7:7637968:TCAAG:T	acceptor_gain	1.0000
7:7637969:CAAG:C	acceptor_gain	1.0000
7:7637969:CAAGC:C	acceptor_gain	1.0000
7:7637971:AGCTA:A	acceptor_loss	1.0000
7:7637973:C:CC	acceptor_gain	1.0000
7:7637973:CTAAG:C	acceptor_loss	1.0000
7:7639052:A:AC	donor_gain	1.0000
7:7639061:TAA:T	donor_gain	1.0000
7:7639062:A:AC	donor_gain	1.0000
7:7639062:AAA:A	donor_gain	1.0000
7:7639068:A:AC	donor_gain	1.0000
7:7639069:C:CC	donor_gain	1.0000
7:7718513:A:AC	donor_gain	1.0000
7:7718514:C:CC	donor_gain	1.0000
7:7718514:CA:C	donor_gain	1.0000
7:7718514:CAA:C	donor_gain	1.0000
7:7718514:CAAA:C	donor_gain	1.0000
7:7718514:CAAAA:C	donor_gain	1.0000
7:7637858:ATTT:A	donor_loss	0.9900
7:7637862:A:AC	donor_gain	0.9900
7:7637863:C:CC	donor_gain	0.9900
7:7637970:AAG:A	acceptor_gain	0.9900
7:7637971:AG:A	acceptor_gain	0.9900
7:7637979:C:CT	acceptor_gain	0.9900
7:7637981:C:CT	acceptor_gain	0.9900

AlphaMissense

805 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:7640345:A:T	V25D	0.996
7:7637935:C:T	G71E	0.995
7:7640333:C:T	G29E	0.995
7:7637936:C:G	G71R	0.994
7:7637936:C:T	G71R	0.994
7:7640334:C:A	G29W	0.993
7:7637062:C:G	A102P	0.991
7:7639122:A:G	F41S	0.991
7:7639131:C:A	G38V	0.991
7:7640334:C:G	G29R	0.991
7:7640334:C:T	G29R	0.991
7:7639116:A:G	L43P	0.990
7:7637911:A:T	I79N	0.989
7:7637941:A:T	V69E	0.989
7:7637935:C:A	G71V	0.988
7:7639116:A:T	L43H	0.987
7:7637929:A:T	V73E	0.986
7:7639116:A:C	L43R	0.986
7:7639131:C:T	G38E	0.985
7:7637061:G:T	A102D	0.981
7:7637911:A:C	I79S	0.978
7:7639086:A:T	I53N	0.976
7:7637906:A:G	C81R	0.975
7:7637911:A:G	I79T	0.972
7:7639111:C:G	D45H	0.971
7:7640333:C:A	G29V	0.970
7:7637865:A:C	F94L	0.969
7:7637865:A:T	F94L	0.969
7:7637867:A:G	F94L	0.969
7:7637904:A:C	C81W	0.969

dbSNP variants (sampled 300 via entrez): RS1000060916 (7:7669131 G>T), RS1000078765 (7:7668895 A>G), RS1000091289 (7:7650205 C>T), RS1000098337 (7:7700898 C>A), RS1000162636 (7:7689409 T>G), RS1000205516 (7:7685565 C>A), RS1000210099 (7:7691552 G>A), RS1000234043 (7:7652880 G>A), RS1000242601 (7:7658106 C>G,T), RS1000282701 (7:7707216 G>T), RS1000325965 (7:7680477 C>T), RS1000333325 (7:7674317 A>C,G), RS1000352296 (7:7647516 C>T), RS1000375498 (7:7717351 C>T), RS1000394106 (7:7667427 G>A)

Disease associations

OMIM: gene MIM:179837 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

7 associations (top):

Study	Trait	p-value
GCST000937_8	Insulin-like growth factors	4.000000e-07
GCST000942_3	Drug-induced Stevens-Johnson syndrome or toxic epidermal necrolysis (SJS/TEN)	1.000000e-08
GCST002828_5	Urate levels in obese individuals	6.000000e-06
GCST006392_4	Estimated glomerular filtration rate	7.000000e-07
GCST006393_4	Serum creatinine levels	9.000000e-07
GCST007998_25	Intraocular pressure	4.000000e-07
GCST011319_1	Interstitial lung diseases in rheumatoid arthritis	2.000000e-08

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004627	IGF-1 measurement
EFO:0004531	urate measurement
EFO:0004695	intraocular pressure measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6066353 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects expression, affects cotreatment, increases methylation, increases expression	3
sodium arsenite	decreases expression, increases expression	3
Benzo(a)pyrene	decreases methylation, increases expression, affects methylation	3
Cyclosporine	decreases expression	3
Cadmium Chloride	increases expression, decreases expression	3
Cisplatin	decreases response to substance, increases expression	2
Estradiol	increases expression, decreases expression	2
Valproic Acid	affects expression, decreases methylation, increases expression	2
Particulate Matter	decreases expression, increases abundance	2
dicrotophos	decreases expression	1
3,4-dihydroxyphenylethanol	affects cotreatment, increases expression	1
kaempferol	increases expression, affects cotreatment	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
nickel subsulfide	increases expression	1
cobaltous chloride	decreases expression	1
perfluorooctanoic acid	decreases expression	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, increases expression	1
usnic acid	increases expression	1
CGP 52608	affects binding, increases reaction	1
fenpyroximate	increases expression	1
poly(propyleneimine)	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
riccardin D	decreases expression	1
LDN 193189	affects cotreatment, increases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	decreases expression	1
Bortezomib	decreases expression	1
Resveratrol	affects cotreatment, increases expression	1
Arsenic Trioxide	decreases expression	1
Fulvestrant	affects cotreatment, increases methylation	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5652279	Binding	Binding affinity to human RPA3 incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Clinical trials (associated diseases)

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