RAD51AP1

Summary

RAD51AP1 (RAD51 associated protein 1, HGNC:16956) is a protein-coding gene on chromosome 12p13.32, encoding RAD51-associated protein 1 (Q96B01). Structure-specific DNA-binding protein involved in DNA repair by promoting RAD51-mediated homologous recombination.

Enables DNA binding activity and RNA binding activity. Involved in DNA repair; cellular response to ionizing radiation; and positive regulation of DNA recombination. Located in chromatin and nucleus. Part of protein-containing complex.

Source: NCBI Gene 10635 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 60 total
• MANE Select transcript: NM_006479

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16956
Approved symbol	RAD51AP1
Name	RAD51 associated protein 1
Location	12p13.32
Locus type	gene with protein product
Status	Approved
Aliases	PIR51
Ensembl gene	ENSG00000111247
Ensembl biotype	protein_coding
OMIM	603070
Entrez	10635

Gene structure

Transcript identifiers

Ensembl transcripts: 20 — 10 protein_coding, 8 nonsense_mediated_decay, 1 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000228843, ENST00000352618, ENST00000398012, ENST00000442992, ENST00000535558, ENST00000536117, ENST00000536346, ENST00000536886, ENST00000538817, ENST00000544029, ENST00000544110, ENST00000544173, ENST00000544927, ENST00000544931, ENST00000872153, ENST00000872154, ENST00000925583, ENST00000925584, ENST00000925585, ENST00000925586

RefSeq mRNA: 3 — MANE Select: NM_006479 NM_001130862, NM_001410959, NM_006479

CCDS: CCDS44805, CCDS8529, CCDS91640

Canonical transcript exons

ENST00000352618 — 9 exons

Exon	Start	End
ENSE00001101283	4558857	4560047
ENSE00001783203	4543763	4543904
ENSE00002237384	4538890	4538956
ENSE00003506778	4552983	4553147
ENSE00003512362	4548092	4548178
ENSE00003543393	4556353	4556502
ENSE00003552828	4546309	4546418
ENSE00003588697	4541884	4541933
ENSE00003651559	4548687	4548836

Expression profiles

Bgee: expression breadth ubiquitous, 219 present calls, max score 95.02.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 11.2678 / max 435.9345, expressed in 1389 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
123567	11.2678	1389

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	95.02	gold quality
ventricular zone	UBERON:0003053	92.19	gold quality
embryo	UBERON:0000922	90.76	gold quality
ganglionic eminence	UBERON:0004023	89.98	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	88.40	gold quality
oocyte	CL:0000023	87.71	gold quality
bone marrow	UBERON:0002371	87.12	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	86.29	gold quality
rectum	UBERON:0001052	83.67	gold quality
bone marrow cell	CL:0002092	82.40	gold quality
trabecular bone tissue	UBERON:0002483	82.00	gold quality
colonic epithelium	UBERON:0000397	81.65	gold quality
right testis	UBERON:0004534	80.52	gold quality
testis	UBERON:0000473	80.29	gold quality
left testis	UBERON:0004533	80.22	gold quality
epithelium of nasopharynx	UBERON:0001951	79.54	gold quality
nasopharynx	UBERON:0001728	79.53	gold quality
vermiform appendix	UBERON:0001154	79.24	gold quality
amniotic fluid	UBERON:0000173	77.40	gold quality
tibia	UBERON:0000979	77.40	gold quality
esophagus squamous epithelium	UBERON:0006920	76.62	gold quality
adrenal tissue	UBERON:0018303	76.34	gold quality
stromal cell of endometrium	CL:0002255	76.29	gold quality
duodenum	UBERON:0002114	75.86	gold quality
lymph node	UBERON:0000029	75.77	gold quality
mucosa of transverse colon	UBERON:0004991	75.59	gold quality
tonsil	UBERON:0002372	75.52	gold quality
endometrium	UBERON:0001295	75.43	gold quality
endometrium epithelium	UBERON:0004811	74.99	gold quality
caecum	UBERON:0001153	74.73	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-MTAB-6108	yes	145.69
E-MTAB-6379	no	388.04
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): E2F6, MEN1

miRNA regulators (miRDB)

82 targeting RAD51AP1, 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-3163	100.00	77.23	8605
HSA-MIR-518D-5P	100.00	67.51	979
HSA-MIR-518E-5P	100.00	67.66	954
HSA-MIR-518F-5P	100.00	67.51	979
HSA-MIR-519A-5P	100.00	67.66	954
HSA-MIR-519B-5P	100.00	67.66	954
HSA-MIR-519C-5P	100.00	67.66	954
HSA-MIR-520C-5P	100.00	67.51	979
HSA-MIR-522-5P	100.00	67.66	954
HSA-MIR-523-5P	100.00	67.66	954
HSA-MIR-526A-5P	100.00	67.51	979
HSA-MIR-4682	100.00	68.89	1258
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163
HSA-MIR-23C	99.95	73.92	3192
HSA-MIR-6744-5P	99.93	66.82	748
HSA-MIR-205-3P	99.92	69.92	3165
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-548AR-3P	99.85	71.26	3889
HSA-MIR-548AZ-3P	99.82	70.56	3549
HSA-MIR-548BC	99.82	70.61	3524
HSA-MIR-548E-3P	99.82	70.59	3514
HSA-MIR-548F-3P	99.82	70.59	3540
HSA-MIR-4799-5P	99.82	70.60	2663
HSA-MIR-944	99.82	70.85	3042
HSA-MIR-3133	99.81	70.92	3506
HSA-MIR-4713-5P	99.78	67.80	1794

Literature-anchored findings (GeneRIF, showing 24)

• expression of three (Beclin 1, RbAp48 and Pir51) were increased and one (aldolase b) was decreased in liver tumor tissues (PMID:14966907)
• RAD51AP1 has a selective affinity for branched-DNA structures that are obligatory intermediates during joint molecule formation. (PMID:17996710)
• RAD51AP1 helps maintain genomic integrity via RAD51 recombinase enhancement. (PMID:17996711)
• Enhanced expression of RAD51 associating protein-1 is involved in the growth of intrahepatic cholangiocarcinoma (PMID:18316552)
• Although PALB2 alone stimulates D-loop formation, it has a cooperative effect with RAD51AP1, an enhancer of RAD51. (PMID:20871616)
• RAD51AP1 foci colocalize with a subset of DMC1 foci in spermatocytes. (PMID:21307306)
• RAD51-associated protein 1 (RAD51AP1) interacts with the meiotic recombinase DMC1 through a conserved motif. (PMID:21903585)
• We have finely mapped the two DNA binding domains in RAD51AP1 and using mutant variants, reveal that both domains are indispensable for RAD51AP1 function in cells. (PMID:22375013)
• Data suggest that microRNA/mRNA pairs in hsa-miR-140-3p/RAD51AP1/, hsa-miR-145/E2F3, hsa-miR-139-5p/TOP2A, and hsa-miR-133a/GCLC were correlated with ovarian tumorigenesis. (PMID:22452920)
• RAD51AP1 is required for the maintenance of DNA replication fork progression. (PMID:25288561)
• USP1-UAF1 complex promotes homologous recombination repair via multiple mechanisms: through FANCD2 deubiquitination, as well as by interacting with RAD51AP1. (PMID:27463890)
• The current understanding of the biochemical and biological functions of RAD51AP1 as HR factor is reviewed. It is also discussed how RAD51AP1 may help to promote cancer development and potentially be a promising new target for therapeutic intervention. [REVIEW] (PMID:28963981)
• RAD51AP1 upregulation is described in both tissue and matching blood from patients with ovarian and lung cancer compared with healthy controls. (PMID:29126163)
• High RAD51AP1 expression is associated with epithelial-mesenchymal transition and metastasis in non-small cell lung cancer. (PMID:31317661)
• RAD51AP1 is an essential mediator of the alternative lengthening of telomeres (ALT) mechanism and is co-opted by post-translational mechanisms to maintain telomere length and ensure proliferation of ALT+ cancer cells. (PMID:31400850)
• NUCKS1 promotes RAD54 activity in homologous recombination DNA repair. (PMID:32876692)
• A Novel Neoplastic Fusion Transcript, RAD51AP1-DYRK4, Confers Sensitivity to the MEK Inhibitor Trametinib in Aggressive Breast Cancers. (PMID:33172895)
• RAD51AP1 promotes progression of ovarian cancer via TGF-beta/Smad signalling pathway. (PMID:33314567)
• RAD51AP1 mediates RAD51 activity through nucleosome interaction. (PMID:34058198)
• ZEB1 induces non-small cell lung cancer development by targeting microRNA-320a to increase the expression of RAD51AP1. (PMID:34097859)
• RAD51AP1 Loss Attenuates Colorectal Cancer Stem Cell Renewal and Sensitizes to Chemotherapy. (PMID:34099522)
• Identification of the E2F1-RAD51AP1 axis as a key factor in MGMT-methylated GBM TMZ resistance. (PMID:37283490)
• The gene RAD51AP1 promotes the progression of pancreatic cancer via the PI3K/Akt/NF-kappaB signaling pathway. (PMID:37962862)
• Pre-rRNA facilitates the recruitment of RAD51AP1 to DNA double-strand breaks. (PMID:38403248)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	rad51ap1	ENSDARG00000045853
mus_musculus	Rad51ap1	ENSMUSG00000030346
rattus_norvegicus	Rad51ap1	ENSRNOG00000059878

Paralogs (1): NUCKS1 (ENSG00000069275)

Protein

Protein identifiers

RAD51-associated protein 1 — Q96B01 (reviewed: Q96B01)

Alternative names: RAD51-interacting protein

All UniProt accessions (7): Q96B01, F5H031, F5H1Y0, F5H4V6, F5H710, H0YFK6, H0YGT5

UniProt curated annotations — full annotation on UniProt →

Function. Structure-specific DNA-binding protein involved in DNA repair by promoting RAD51-mediated homologous recombination. Acts by stimulating D-Loop formation by RAD51: specifically enhances joint molecule formation through its structure-specific DNA interaction and its interaction with RAD51. Binds single-stranded DNA (ssDNA), double-stranded DNA (dsDNA) and secondary DNA structures, such as D-loop structures: has a strong preference for branched-DNA structures that are obligatory intermediates during joint molecule formation. Cooperates with WDR48/UAF1 to stimulate RAD51-mediated homologous recombination: both WDR48/UAF1 and RAD51AP1 have coordinated role in DNA-binding during homologous recombination and DNA repair. WDR48/UAF1 and RAD51AP1 also have a coordinated role in DNA-binding to promote USP1-mediated deubiquitination of FANCD2. Also involved in meiosis by promoting DMC1-mediated homologous meiotic recombination. Key mediator of alternative lengthening of telomeres (ALT) pathway, a homology-directed repair mechanism of telomere elongation that controls proliferation in aggressive cancers, by stimulating homologous recombination. May also bind RNA; additional evidences are however required to confirm RNA-binding in vivo.

Subunit / interactions. Monomer; elongated monodisperse monomer. Interacts (via C-terminal region) with RAD51; the interaction is direct. Interacts (via SIM motif) with WDR48/UAF1; WDR48/UAF1 and RAD51AP1 cooperate together to stimulate RAD51-mediated homologous recombination (HR). Interacts (via WVPP motif) with DMC1; the interaction is direct. Interacts with PALB2. Interacts with RAD52. Does not interact with DMC1; lack of interaction is caused by the absence of the WVPP motif in this isoform.

Subcellular location. Chromosome. Nucleus. Telomere.

Tissue specificity. Highly expressed in testis and thymus. Lower levels in colon and small intestine. Little or no expression in spleen, prostate, ovary and peripheral blood leukocytes.

Post-translational modifications. Sumoylation with SUMO2/3 by NSMCE2/MMS21 promotes stabilization, possibly by preventing ubiquitination. Sumoylation is required for alternative lengthening of telomeres (ALT) pathway.

Isoforms (3)

UniProt ID	Names	Canonical?
Q96B01-1	1	yes
Q96B01-2	2
Q96B01-3	3

RefSeq proteins (3): NP_001124334, NP_001397888, NP_006470* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR031419	RAD51_interact	Domain
IPR052003	HR_DNA-Binding_Protein	Family

Pfam: PF15696

UniProt features (48 total): mutagenesis site 20, compositionally biased region 7, modified residue 7, region of interest 6, cross-link 2, splice variant 2, short sequence motif 2, chain 1, sequence variant 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
9QNC	ELECTRON MICROSCOPY	2.98
9QN8	ELECTRON MICROSCOPY	3.14

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96B01-F1	59.01	0.05

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 (9): 19, 21, 66, 120, 124, 280, 327, 251, 269

Mutagenesis-validated functional residues (20):

Position	Phenotype
34–47	in k6ra; impaired dna-binding.
34–37	in k2ra; impaired dna-binding.
44	does not affect sumoylation.
150–153	abolished interaction with wdr48/uaf1.
154–159	reduced sumoylation. reduced ubiquitination.
154–157	decreased interaction with wdr48/uaf1.
156	does not affect interaction with wdr48/uaf1.
157–159	decreased interaction with wdr48/uaf1.
240	does not affect sumoylation.
248–253	in k4a; reduced dna-binding. in k7wa; strongly decreased dna-binding; when associated with 300-a–a-304.
269	strongly reduced sumoylation. strongly reduced ubiquitination.
300–304	in k3wa; reduced dna-binding. in k7wa; strongly decreased dna-binding; when associated with 248-a–a-253.
304	abolished interaction with dmc1 without affecting interaction with rad51.
326	does not affect sumoylation.
327–352	abolished interaction with rad51.
328–352	in mutant delta25; abolished interaction with rad51.
333	strongly decreases interaction with rad51; when associated with q-336, a-345 and a-346.
336	strongly decreases interaction with rad51; when associated with a-333, a-345 and a-346. decreased interacting with rad51
345–346	strongly decreases interaction with rad51; when associated with a-333; and q-336.
346	decreased interacting with rad51 and ability to stimulate rad51-mediated homologous recombination. does not affect inter

Function

Pathways and Gene Ontology

Reactome pathways

8 pathways

ID	Pathway
R-HSA-5685942	HDR through Homologous Recombination (HRR)
R-HSA-5693554	Resolution of D-loop Structures through Synthesis-Dependent Strand Annealing (SDSA)
R-HSA-5693568	Resolution of D-loop Structures through Holliday Junction Intermediates
R-HSA-5693579	Homologous DNA Pairing and Strand Exchange
R-HSA-9701192	Defective homologous recombination repair (HRR) due to BRCA1 loss of function
R-HSA-9704331	Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA1 binding function
R-HSA-9704646	Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA2/RAD51/RAD51C binding function
R-HSA-9709603	Impaired BRCA2 binding to PALB2

MSigDB gene sets: 396 (showing top): GOBP_REGULATION_OF_DOUBLE_STRAND_BREAK_REPAIR, GOBP_REGULATION_OF_DNA_RECOMBINATION, GOBP_POSITIVE_REGULATION_OF_REPRODUCTIVE_PROCESS, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, GNF2_MSH2, GOBP_RESPONSE_TO_IONIZING_RADIATION, HORIUCHI_WTAP_TARGETS_DN, KANG_DOXORUBICIN_RESISTANCE_UP, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, GOBP_REGULATION_OF_NUCLEAR_DIVISION, GOBP_REGULATION_OF_MEIOTIC_NUCLEAR_DIVISION, CHIANG_LIVER_CANCER_SUBCLASS_UNANNOTATED_DN, GOBP_REGULATION_OF_DOUBLE_STRAND_BREAK_REPAIR_VIA_HOMOLOGOUS_RECOMBINATION, GOBP_POSITIVE_REGULATION_OF_ORGANELLE_ORGANIZATION, GOBP_REGULATION_OF_MEIOTIC_CELL_CYCLE

GO Biological Process (10): double-strand break repair via homologous recombination (GO:0000724), DNA repair (GO:0006281), DNA damage response (GO:0006974), regulation of double-strand break repair via homologous recombination (GO:0010569), positive regulation of reciprocal meiotic recombination (GO:0010845), interstrand cross-link repair (GO:0036297), meiotic cell cycle (GO:0051321), cellular response to ionizing radiation (GO:0071479), positive regulation of double-strand break repair via homologous recombination (GO:1905168), DNA recombination (GO:0006310)

GO Molecular Function (7): DNA secondary structure binding (GO:0000217), DNA binding (GO:0003677), double-stranded DNA binding (GO:0003690), single-stranded DNA binding (GO:0003697), RNA binding (GO:0003723), D-loop DNA binding (GO:0062037), protein binding (GO:0005515)

GO Cellular Component (6): chromosome, telomeric region (GO:0000781), chromatin (GO:0000785), nucleus (GO:0005634), nucleoplasm (GO:0005654), chromosome (GO:0005694), protein-containing complex (GO:0032991)

Reactome top-level categories

Rollup of top-6 pathways:

Category	Pathways
Resolution of D-Loop Structures	2
Defective homologous recombination repair (HRR) due to PALB2 loss of function	2
HDR through Homologous Recombination (HRR) or Single Strand Annealing (SSA)	1
HDR through Homologous Recombination (HRR)	1
Diseases of DNA Double-Strand Break Repair	1
Defective homologous recombination repair (HRR) due to BRCA2 loss of function	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
DNA binding	3
DNA metabolic process	2
double-strand break repair via homologous recombination	2
positive regulation of DNA recombination	2
nucleic acid binding	2
cellular anatomical structure	2
recombinational repair	1
double-strand break repair	1
DNA damage response	1
cellular response to stress	1
regulation of DNA recombination	1
regulation of double-strand break repair	1
reciprocal meiotic recombination	1
regulation of reciprocal meiotic recombination	1
positive regulation of meiotic nuclear division	1
DNA repair	1
cell cycle	1
sexual reproduction	1
reproductive process	1
meiotic nuclear division	1
response to ionizing radiation	1
cellular response to radiation	1
regulation of double-strand break repair via homologous recombination	1
positive regulation of double-strand break repair	1
DNA secondary structure binding	1
binding	1
chromosomal region	1
chromosome	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
intracellular membraneless organelle	1
cellular_component	1

Protein interactions and networks

STRING

1223 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RAD51AP1	WDR48	Q8TAF3	969
RAD51AP1	RAD51	Q06609	933
RAD51AP1	RAB22A	Q9UL26	845
RAD51AP1	USP1	O94782	708
RAD51AP1	RAD54L	Q92698	655
RAD51AP1	ATRX	P46100	653
RAD51AP1	BRCA1	P38398	640
RAD51AP1	PALB2	Q86YC2	639
RAD51AP1	EXO1	Q9UQ84	627
RAD51AP1	NCAPG	Q9BPX3	607
RAD51AP1	CHEK1	O14757	590
RAD51AP1	KIF4A	O95239	579
RAD51AP1	DSCC1	Q9BVC3	574
RAD51AP1	TTK	P33981	573
RAD51AP1	KIF20A	O95235	568

IntAct

26 interactions, top by confidence:

A	B	Type	Score
USP12	PHLPP1	psi-mi:“MI:0914”(association)	0.570
SIAH1	RAD51AP1	psi-mi:“MI:0915”(physical association)	0.560
RAD51AP1	USP12	psi-mi:“MI:0914”(association)	0.530
RAD51AP1	LRRK2	psi-mi:“MI:0407”(direct interaction)	0.440
RAD51AP1	MANF	psi-mi:“MI:0915”(physical association)	0.400
USP46	PJA2	psi-mi:“MI:0914”(association)	0.350
WDR48	UNC13B	psi-mi:“MI:0914”(association)	0.350
RAD51AP1	VPS26B	psi-mi:“MI:0914”(association)	0.350
RAD51AP1	USP1	psi-mi:“MI:0914”(association)	0.350
	EBAG9	psi-mi:“MI:0914”(association)	0.350
H2BC10	SMCHD1	psi-mi:“MI:2364”(proximity)	0.270
FBXW7	RAD51AP1	psi-mi:“MI:2364”(proximity)	0.270
RAD51AP1	FBXW7	psi-mi:“MI:2364”(proximity)	0.270
RAD51AP1	SMARCA4	psi-mi:“MI:2364”(proximity)	0.270
SMARCA4	RAD51AP1	psi-mi:“MI:2364”(proximity)	0.270
RAD51AP1	TP53	psi-mi:“MI:2364”(proximity)	0.270
RAD51AP1	SIAH1	psi-mi:“MI:0915”(physical association)	0.000
Map3k1	UBA1	psi-mi:“MI:0220”(ubiquitination reaction)	0.000

BioGRID (83): RAD51AP1 (Two-hybrid), RAD51AP1 (Biochemical Activity), JUP (Affinity Capture-MS), WDR48 (Affinity Capture-MS), IGHG2 (Affinity Capture-MS), IGHG3 (Affinity Capture-MS), IGHG4 (Affinity Capture-MS), USP1 (Affinity Capture-MS), USP46 (Affinity Capture-MS), RAD51AP1 (Reconstituted Complex), RAD51AP1 (Two-hybrid), RAD51AP1 (Proximity Label-MS), RAD51AP1 (Affinity Capture-MS), RAD51AP1 (Affinity Capture-Western), RAD51AP1 (Affinity Capture-Western)

ESM2 similar proteins: A0A1B0GTU1, A2AUY4, B7ZS37, D3Z8Y2, D4A4L4, D4A666, E1B7L7, O46385, O60293, O75152, O95425, P0DQW0, Q08AZ1, Q3KQW7, Q3U1C4, Q3UH68, Q3ZC82, Q4G0F8, Q4V9H5, Q5F3Z9, Q5NBX1, Q5REG6, Q5ZJJ1, Q5ZM88, Q61464, Q62394, Q68FE9, Q6NZF1, Q6PJT7, Q6ZQ03, Q6ZU65, Q76L83, Q7TMD5, Q8BHZ4, Q8BJ05, Q8BLG0, Q8BZ32, Q8C9B9, Q8CCJ9, Q8K298

Diamond homologs: A0A3Q2UEI8, Q29S11, Q80XU3, Q8C551, Q96B01, Q9EPJ0, Q9H1E3

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
RAD51AP1	up-regulates	DNA_repair
RAD51AP1	“up-regulates activity”	RAD51	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	42
Likely benign	4
Benign	5

Top pathogenic / likely-pathogenic (0)

SpliceAI

1513 predictions. Top by Δscore:

Variant	Effect	Δscore
12:4541072:A:AG	acceptor_gain	1.0000
12:4541875:T:TA	acceptor_gain	1.0000
12:4541882:A:AG	acceptor_gain	1.0000
12:4541883:G:GG	acceptor_gain	1.0000
12:4541883:GAC:G	acceptor_gain	1.0000
12:4543739:T:TA	acceptor_gain	1.0000
12:4543746:A:AG	acceptor_gain	1.0000
12:4543747:A:G	acceptor_gain	1.0000
12:4543751:A:AG	acceptor_gain	1.0000
12:4543753:A:AG	acceptor_gain	1.0000
12:4543753:ACAT:A	acceptor_gain	1.0000
12:4543755:A:AG	acceptor_gain	1.0000
12:4543755:AT:A	acceptor_gain	1.0000
12:4543756:T:G	acceptor_gain	1.0000
12:4543756:T:TA	acceptor_gain	1.0000
12:4543760:TA:T	acceptor_loss	1.0000
12:4543761:A:T	acceptor_loss	1.0000
12:4543779:A:AG	acceptor_gain	1.0000
12:4546413:A:G	donor_gain	1.0000
12:4546419:G:GG	donor_gain	1.0000
12:4548087:TTTA:T	acceptor_loss	1.0000
12:4548088:TTAG:T	acceptor_loss	1.0000
12:4548089:TAGG:T	acceptor_loss	1.0000
12:4548672:A:AG	acceptor_gain	1.0000
12:4548672:AT:A	acceptor_gain	1.0000
12:4548673:T:TA	acceptor_gain	1.0000
12:4548682:T:A	acceptor_gain	1.0000
12:4548834:CTGG:C	donor_loss	1.0000
12:4548836:GGT:G	donor_loss	1.0000
12:4548837:G:GA	donor_loss	1.0000

AlphaMissense

2222 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:4558941:T:C	L336S	0.994
12:4558948:A:C	R338S	0.989
12:4558948:A:T	R338S	0.989
12:4546352:G:C	A102P	0.987
12:4558938:G:A	G335D	0.987
12:4556490:T:A	W304R	0.986
12:4556490:T:C	W304R	0.986
12:4558931:C:A	R333S	0.986
12:4558937:G:C	G335R	0.985
12:4558947:G:C	R338T	0.983
12:4558959:T:A	V342D	0.982
12:4546356:T:C	L103P	0.981
12:4558963:A:C	K343N	0.981
12:4558963:A:T	K343N	0.981
12:4558968:T:C	L345S	0.981
12:4546358:G:C	A104P	0.979
12:4558970:C:G	H346D	0.978
12:4558944:C:T	S337F	0.977
12:4546344:T:C	L99S	0.976
12:4543768:T:C	F25L	0.975
12:4543770:T:A	F25L	0.975
12:4543770:T:G	F25L	0.975
12:4546353:C:A	A102E	0.975
12:4558972:T:A	H346Q	0.975
12:4558972:T:G	H346Q	0.975
12:4546339:A:C	R97S	0.973
12:4546339:A:T	R97S	0.973
12:4558961:A:G	K343E	0.973
12:4556492:G:C	W304C	0.972
12:4556492:G:T	W304C	0.972

dbSNP variants (sampled 300 via entrez): RS1000039036 (12:4557503 T>G), RS1000163898 (12:4542534 T>C), RS1000233434 (12:4544566 A>G), RS1000386806 (12:4538048 G>A), RS1000644794 (12:4560408 C>A), RS1000660935 (12:4551923 A>G), RS1000663590 (12:4551577 C>G), RS1000690264 (12:4544896 C>T), RS1000788189 (12:4558494 A>G), RS1000919639 (12:4544589 C>CT), RS1001015527 (12:4537439 T>A), RS1001038996 (12:4537058 C>G), RS1001208914 (12:4550534 C>T), RS1001322723 (12:4557761 G>A), RS1001541087 (12:4538864 T>G)

Disease associations

OMIM: gene MIM:603070 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST000703_5	Phosphorus levels	4.000000e-09
GCST001792_1	Colorectal cancer	3.000000e-08
GCST001792_2	Colorectal cancer	5.000000e-10

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004861	phosphorus measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects expression, decreases expression, increases expression	3
sodium arsenite	decreases expression, increases expression, affects methylation	3
Benzo(a)pyrene	increases expression, decreases expression	3
Estradiol	increases expression	3
Cyclosporine	decreases expression	3
Resveratrol	decreases expression, affects cotreatment, increases expression	2
Acetaminophen	decreases expression, increases expression	2
Tetrachlorodibenzodioxin	decreases expression	2
GSK-J4	decreases expression	1
afuresertib	decreases expression	1
FR900359	affects phosphorylation	1
TAK-243	increases sumoylation	1
dicrotophos	decreases expression	1
apocarotenal	increases expression	1
propionaldehyde	decreases expression	1
pirinixic acid	affects binding, decreases expression, increases activity	1
beta-lapachone	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
perfluorooctanoic acid	decreases expression	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	increases expression, affects cotreatment	1
2-amino-3,8-dimethylimidazo(4,5-f)quinoxaline	increases expression	1
M-VAC protocol	increases response to substance	1
K 7174	decreases expression	1
4-chloro-N-((4-(1,1-dimethylethyl)phenyl)methyl)-3-ethyl-1-methyl-1H-pyrazole-5-carboxamide	increases expression	1
erucylphospho-N,N,N-trimethylpropylammonium	decreases expression	1
trans-10,cis-12-conjugated linoleic acid	decreases expression	1
palbociclib	decreases expression	1
jinfukang	increases expression	1
incobotulinumtoxinA	decreases expression	1
picoxystrobin	increases expression	1

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_F1KP	DT40-RAD51AP1 KO-1 FLAG-HsRAD51AP1	Cancer cell line	Female

Clinical trials (associated diseases)

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