PRPF40A

Summary

PRPF40A (pre-mRNA processing factor 40A, HGNC:16463) is a protein-coding gene on chromosome 2q23.3, encoding Pre-mRNA-processing factor 40 homolog A (O75400). Binds to WASL/N-WASP and suppresses its translocation from the nucleus to the cytoplasm, thereby inhibiting its cytoplasmic function. It is a common-essential gene (DepMap: required in 97.8% of cancer cell lines).

Enables RNA binding activity. Involved in several processes, including cytoskeleton organization; regulation of cell shape; and regulation of cytokinesis. Located in nuclear matrix and nuclear speck.

Source: NCBI Gene 55660 — RefSeq curated summary.

At a glance

• GWAS associations: 5
• Clinical variants (ClinVar): 78 total
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 97.8% of screened cell lines (common-essential)
• MANE Select transcript: NM_001365597

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16463
Approved symbol	PRPF40A
Name	pre-mRNA processing factor 40A
Location	2q23.3
Locus type	gene with protein product
Status	Approved
Aliases	FLJ20585, FBP11, HYPA, NY-REN-6, HIP10, FBP-11, FLAF1, Prp40
Ensembl gene	ENSG00000196504
Ensembl biotype	protein_coding
OMIM	612941
Entrez	55660

Gene structure

Transcript identifiers

Ensembl transcripts: 23 — 15 protein_coding, 6 retained_intron, 1 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000354363, ENST00000410080, ENST00000448428, ENST00000450303, ENST00000467114, ENST00000471167, ENST00000471701, ENST00000472760, ENST00000486100, ENST00000489741, ENST00000493468, ENST00000545856, ENST00000696381, ENST00000696382, ENST00000698772, ENST00000698773, ENST00000903550, ENST00000924542, ENST00000924543, ENST00000924544, ENST00000968844, ENST00000968845, ENST00000968846

RefSeq mRNA: 25 — MANE Select: NM_001365597 NM_001354431, NM_001354432, NM_001365596, NM_001365597, NM_001365598, NM_001365599, NM_001365600, NM_001365601, NM_001365602, NM_001365603, NM_001365604, NM_001365605, NM_001395472, NM_001395473, NM_001395475, NM_001395476, NM_001395477, NM_001395478, NM_001395479, NM_001395480, NM_001395481, NM_001395482, NM_001395483, NM_001395488, NM_017892

CCDS: CCDS92876, CCDS92877, CCDS92878, CCDS92879

Canonical transcript exons

ENST00000545856 — 26 exons

Exon	Start	End
ENSE00000778284	152662603	152662698
ENSE00000778286	152663035	152663172
ENSE00000778288	152663655	152663771
ENSE00000778322	152672459	152672623
ENSE00000840615	152664138	152664252
ENSE00000840616	152669137	152669270
ENSE00000924621	152657889	152658020
ENSE00001035357	152659270	152659356
ENSE00001165908	152663876	152663967
ENSE00001167373	152670231	152670381
ENSE00001368991	152671273	152671381
ENSE00002503476	152694542	152694622
ENSE00003460849	152679352	152679472
ENSE00003494437	152677451	152677475
ENSE00003527600	152690962	152690978
ENSE00003534001	152681226	152681336
ENSE00003553062	152659093	152659189
ENSE00003568230	152693038	152693068
ENSE00003580707	152715995	152716126
ENSE00003597491	152676405	152676779
ENSE00003620694	152658948	152659009
ENSE00003643489	152672978	152673042
ENSE00003673098	152673598	152673706
ENSE00003790161	152679056	152679109
ENSE00003974707	152651732	152656398
ENSE00003974709	152717230	152717461

Expression profiles

Bgee: expression breadth ubiquitous, 295 present calls, max score 99.72.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 72.7541 / max 571.0167, expressed in 1826 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
31318	38.7126	1820
31319	12.5547	1746
31317	11.9189	1774
31322	5.6021	1714
31320	3.4414	1448
31321	0.5245	293

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	99.72	gold quality
caput epididymis	UBERON:0004358	99.02	gold quality
corpus epididymis	UBERON:0004359	98.86	gold quality
cauda epididymis	UBERON:0004360	98.78	gold quality
calcaneal tendon	UBERON:0003701	98.60	gold quality
epithelium of nasopharynx	UBERON:0001951	98.58	gold quality
trabecular bone tissue	UBERON:0002483	98.51	gold quality
mucosa of paranasal sinus	UBERON:0005030	98.33	gold quality
oral cavity	UBERON:0000167	98.18	gold quality
oocyte	CL:0000023	98.15	gold quality
visceral pleura	UBERON:0002401	98.07	gold quality
sural nerve	UBERON:0015488	97.91	gold quality
cranial nerve II	UBERON:0000941	97.82	gold quality
skin of hip	UBERON:0001554	97.65	gold quality
jejunal mucosa	UBERON:0000399	97.59	gold quality
mammary duct	UBERON:0001765	97.56	gold quality
gingiva	UBERON:0001828	97.51	gold quality
bronchial epithelial cell	CL:0002328	97.48	gold quality
palpebral conjunctiva	UBERON:0001812	97.44	gold quality
gingival epithelium	UBERON:0001949	97.42	gold quality
parietal pleura	UBERON:0002400	97.35	gold quality
mucosa of sigmoid colon	UBERON:0004993	97.26	gold quality
epithelium of mammary gland	UBERON:0003244	97.20	gold quality
superficial temporal artery	UBERON:0001614	97.09	gold quality
germinal epithelium of ovary	UBERON:0001304	97.07	gold quality
colonic mucosa	UBERON:0000317	96.99	gold quality
mammalian vulva	UBERON:0000997	96.91	gold quality
adrenal tissue	UBERON:0018303	96.89	gold quality
tongue squamous epithelium	UBERON:0006919	96.86	gold quality
pleura	UBERON:0000977	96.85	gold quality

Single-cell (SCXA)

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

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

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

263 targeting PRPF40A, 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-3613-3P	100.00	76.36	7965
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-3064-3P	100.00	70.09	1254
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-6748-5P	100.00	65.81	1057
HSA-MIR-1193	100.00	65.93	529
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-10401-5P	99.99	65.79	948
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-1184	99.99	68.19	1458
HSA-MIR-6759-5P	99.99	66.54	785
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 97.8% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 10)

• Data describe the structure of an FF domain from HYPA/FBP11, which differs from those of other phosphopeptide-binding domains and represents a novel phosphopeptide-binding fold. (PMID:12381297)
• Results suggest an essential role of WW/FF domain-containing factors such as FBP11 and CA150 in pre-mRNA splicing that likely occurs in concert with transcription in vivo. (PMID:15456888)
• NAKAP-HypA scaffold is a potential nuclear docking site for huntingtin protein and may contribute to the nuclear accumulation of huntingtin observed in HD. (PMID:16391387)
• FBP11 binding mechanism underlies the molecular pathology of severe neurological disorders, e.g., Rett syndrome and Huntington disease. (PMID:17065151)
• an atomic-resolution structure of an “invisible” folding intermediate of a small protein module: the FF domain; structure reveals non-native elements preventing formation of native conformation in the carboxyl-terminal part of the protein (PMID:20829478)
• Interaction with polyglutamine-expanded huntingtin alters cellular distribution and RNA processing of huntingtin yeast two-hybrid protein A (HYPA). (PMID:21566141)
• Study of native domain FF3-71 from human HYPA/FBP11 and the truncated version FF3-60 with C-terminal helix being deleted by molecular dynamics simulations. (PMID:22408419)
• our data revealed that COL1A1, UCP2, and PRPF40A are novel players implicated in the complex network of hypoxia response in non-small cell lung cancer (PMID:28258342)
• Multidisciplinary approach showed that HsPrp40Ap interacts with centrin in vitro, supporting a coupled functional role for these proteins in pre-mRNA splicing. (PMID:28636910)
• Intramolecular autoinhibition regulates the selectivity of PRPF40A tandem WW domains for proline-rich motifs. (PMID:38719828)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	prpf40a	ENSDARG00000058467
mus_musculus	Prpf40a	ENSMUSG00000061136
rattus_norvegicus	Prpf40a	ENSRNOG00000004864
drosophila_melanogaster	Prp40	FBGN0031492
caenorhabditis_elegans		WBGENE00014218

Paralogs (1): PRPF40B (ENSG00000110844)

Protein

Protein identifiers

Pre-mRNA-processing factor 40 homolog A — O75400 (reviewed: O75400)

Alternative names: Fas ligand-associated factor 1, Formin-binding protein 11, Formin-binding protein 3, Huntingtin yeast partner A, Huntingtin-interacting protein 10, Huntingtin-interacting protein A, Renal carcinoma antigen NY-REN-6

All UniProt accessions (9): A0A7N4I394, A0A8Q3SIG7, A0A8V8TM61, A0A8V8TM87, O75400, F5H578, H0YG38, H7BXZ7, H7C2N3

UniProt curated annotations — full annotation on UniProt →

Function. Binds to WASL/N-WASP and suppresses its translocation from the nucleus to the cytoplasm, thereby inhibiting its cytoplasmic function. Plays a role in the regulation of cell morphology and cytoskeletal organization. Required in the control of cell shape and migration. May play a role in cytokinesis. May be involved in pre-mRNA splicing.

Subunit / interactions. Interacts with the N-terminus of HTT. Interacts with the phosphorylated C-terminal domain of POLR2A. Interacts with AKAP8L, SF1, SRPK1, ENAH, ATBF1 and MECP2. Interacts through the WW domains with formin proline-rich regions and with WASL/N-WASP.

Subcellular location. Nucleus speckle. Nucleus matrix.

Tissue specificity. Expressed in the brain cortex (at protein level). Widely expressed.

Domain organisation. The WW domains are essential for localization to nuclear speckles.

Miscellaneous. Probable target of nonsense-mediated mRNA decay.

Similarity. Belongs to the PRPF40 family.

Isoforms (4)

UniProt ID	Names	Canonical?
O75400-1	1	yes
O75400-2	2
O75400-3	3
O75400-5	5

RefSeq proteins (25): NP_001341360, NP_001341361, NP_001352525, NP_001352526, NP_001352527, NP_001352528, NP_001352529, NP_001352530, NP_001352531, NP_001352532, NP_001352533, NP_001352534, NP_001382401, NP_001382402, NP_001382404, NP_001382405, NP_001382406, NP_001382407, NP_001382408, NP_001382409, NP_001382410, NP_001382411, NP_001382412, NP_001382417, NP_060362 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001202	WW_dom	Domain
IPR002713	FF_domain	Domain
IPR036020	WW_dom_sf	Homologous_superfamily
IPR036517	FF_domain_sf	Homologous_superfamily
IPR039726	Prp40-like	Family

Pfam: PF00397, PF01846, PF25432

UniProt features (78 total): modified residue 21, helix 12, strand 10, domain 8, compositionally biased region 5, splice variant 5, turn 5, region of interest 4, cross-link 4, sequence conflict 3, chain 1

Structure

Experimental structures (PDB)

12 structures.

PDB	Method	Resolution (Å)
1UZC	SOLUTION NMR
1YWI	SOLUTION NMR
1YWJ	SOLUTION NMR
1ZR7	SOLUTION NMR
2CQN	SOLUTION NMR
2DYF	SOLUTION NMR
2KZG	SOLUTION NMR
2L5F	SOLUTION NMR
2L9V	SOLUTION NMR
2LKS	SOLUTION NMR
8PXW	SOLUTION NMR
8PXX	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O75400-F1	68.14	0.36

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 (25): 9, 34, 151, 196, 345, 373, 723, 787, 883, 885, 888, 932, 933, 935, 938, 191, 241, 375, 376, 17 …

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-72163	mRNA Splicing - Major Pathway
R-HSA-9770562	mRNA Polyadenylation

MSigDB gene sets: 251 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_DN, GSE45365_CTRL_VS_MCMV_INFECTION_NK_CELL_DN, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, YAGI_AML_WITH_INV_16_TRANSLOCATION, GOBP_REGULATION_OF_CELL_MORPHOGENESIS, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, SHAFFER_IRF4_TARGETS_IN_ACTIVATED_B_LYMPHOCYTE, CHANDRAN_METASTASIS_DN, WEI_MYCN_TARGETS_WITH_E_BOX, WANG_LMO4_TARGETS_DN, MILI_PSEUDOPODIA_HAPTOTAXIS_UP, GOBP_CYTOKINESIS, BLALOCK_ALZHEIMERS_DISEASE_UP, REACTOME_MRNA_3_END_PROCESSING, REACTOME_PROCESSING_OF_CAPPED_INTRON_CONTAINING_PRE_MRNA

GO Biological Process (9): mRNA splicing, via spliceosome (GO:0000398), cytoskeleton organization (GO:0007010), regulation of cell shape (GO:0008360), cell migration (GO:0016477), regulation of cytokinesis (GO:0032465), mRNA cis splicing, via spliceosome (GO:0045292), cell division (GO:0051301), mRNA processing (GO:0006397), RNA splicing (GO:0008380)

GO Molecular Function (2): RNA binding (GO:0003723), protein binding (GO:0005515)

GO Cellular Component (7): nucleoplasm (GO:0005654), U1 snRNP (GO:0005685), membrane (GO:0016020), nuclear matrix (GO:0016363), nuclear speck (GO:0016607), U2-type prespliceosome (GO:0071004), nucleus (GO:0005634)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
mRNA Splicing	1
mRNA 3’-end processing	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
RNA processing	2
nuclear lumen	2
RNA splicing, via transesterification reactions with bulged adenosine as nucleophile	1
mRNA processing	1
organelle organization	1
regulation of cell morphogenesis	1
regulation of biological quality	1
cell motility	1
cytokinesis	1
regulation of cell cycle process	1
regulation of cell division	1
mRNA splicing, via spliceosome	1
cellular process	1
mRNA metabolic process	1
nucleic acid binding	1
binding	1
spliceosomal snRNP complex	1
nuclear ribonucleoprotein granule	1
U2-type spliceosomal complex	1
U1 snRNP	1
U2 snRNP	1
prespliceosome	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

3264 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PRPF40A	HTT	P42858	971
PRPF40A	RBM25	P49756	931
PRPF40A	SNRNP70	P08621	918
PRPF40A	LUC7L	Q9NQ29	888
PRPF40A	SETD2	Q9BYW2	797
PRPF40A	FMN1	Q68DA7	791
PRPF40A	AKAP8L	Q9ULX6	779
PRPF40A	SNRPA	P09012	773
PRPF40A	SNRPC	P09234	727
PRPF40A	SF1	Q15637	724
PRPF40A	DDX46	Q7L014	659
PRPF40A	FICD	Q9BVA6	659
PRPF40A	PRPF8	Q6P2Q9	639
PRPF40A	MAGEA3	P43357	624
PRPF40A	FMNL3	Q8IVF7	619

IntAct

225 interactions, top by confidence:

A	B	Type	Score
HUS1	RAD1	psi-mi:“MI:0914”(association)	0.840
HTT	PRPF40A	psi-mi:“MI:0915”(physical association)	0.740
HTT	PRPF40A	psi-mi:“MI:0407”(direct interaction)	0.740
PRPF40A	HTT	psi-mi:“MI:0407”(direct interaction)	0.740
RAD9A	RAD1	psi-mi:“MI:0914”(association)	0.670
NCBP1	KPNA3	psi-mi:“MI:0914”(association)	0.640
NCBP2	KPNA3	psi-mi:“MI:0914”(association)	0.640
SF3B1	SAP18	psi-mi:“MI:0914”(association)	0.640
SNRPA1	U2SURP	psi-mi:“MI:0914”(association)	0.640
CHEK2	PPM1G	psi-mi:“MI:0914”(association)	0.560
RBM25	PRPF40A	psi-mi:“MI:0915”(physical association)	0.560
RBM25	PRPF40A	psi-mi:“MI:0914”(association)	0.560
PRPF40A	SDCBP2	psi-mi:“MI:0915”(physical association)	0.550
FNBP4	PRPF40A	psi-mi:“MI:0914”(association)	0.550
PRPF40A	UBQLN4	psi-mi:“MI:0915”(physical association)	0.550
FNBP4	PRPF40A	psi-mi:“MI:0915”(physical association)	0.550
PRPF40A	HNRNPUL1	psi-mi:“MI:0915”(physical association)	0.550
NUF2	SPC24	psi-mi:“MI:0914”(association)	0.530
TMEM63B	SLC19A2	psi-mi:“MI:0914”(association)	0.530
HDGFL2	CDC7	psi-mi:“MI:0914”(association)	0.530

BioGRID (581): PRPF40A (Two-hybrid), PRPF40A (Two-hybrid), PRPF40A (Two-hybrid), PRPF40A (Affinity Capture-MS), PRPF40A (Affinity Capture-MS), PRPF40A (Affinity Capture-MS), TERF2IP (Affinity Capture-MS), NKAP (Affinity Capture-MS), C17orf85 (Affinity Capture-MS), DDX46 (Affinity Capture-MS), CCDC9 (Affinity Capture-MS), RNPS1 (Affinity Capture-MS), TERF2 (Affinity Capture-MS), JMJD6 (Affinity Capture-MS), CSNK2A2 (Affinity Capture-MS)

ESM2 similar proteins: A0JM64, A0JMV4, A2VDN6, A4IFB1, A4IGK4, D3ZTQ1, O70523, O75400, P35922, P51113, P51114, P51115, P70501, P98175, Q06787, Q12872, Q15459, Q2KHP9, Q2KIA6, Q2NLB0, Q2TBT7, Q3TCX3, Q3USH5, Q5BJ56, Q5R539, Q5R9B4, Q5SFM8, Q5T8P6, Q5XI81, Q61584, Q66I22, Q6DDU9, Q6GLC9, Q6NZ18, Q6NZN0, Q7TN31, Q80TJ7, Q80WE1, Q8CGC4, Q8JZX4

Diamond homologs: B6EUA9, F4JCC1, O14776, O75400, Q3B807, Q5VWI1, Q6NWY9, Q80W14, Q8CGF7, Q9R1C7, P34600, O04425

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 222 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
Transport of Mature Transcript to Cytoplasm	7	16.4×	1e-05
mRNA Splicing	22	14.8×	3e-17
RNA Polymerase II Transcription Termination	9	12.1×	4e-06
Processing of Capped Intron-Containing Pre-mRNA	24	12.1×	3e-17
mRNA Polyadenylation	21	11.3×	2e-14
mRNA 3’-end processing	9	10.9×	9e-06
HIV Transcription Elongation	5	10.3×	4e-03
SUMOylation of intracellular receptors	5	10.3×	4e-03

GO biological processes:

GO term	Partners	Fold	FDR
U2-type prespliceosome assembly	7	21.3×	1e-05
alternative mRNA splicing, via spliceosome	5	16.4×	2e-03
spliceosomal complex assembly	5	14.7×	3e-03
positive regulation of transcription elongation by RNA polymerase II	8	11.7×	1e-04
mRNA splicing, via spliceosome	22	9.8×	9e-13
protein sumoylation	6	9.5×	4e-03
RNA splicing	20	8.6×	1e-10
mRNA processing	14	5.4×	1e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	52
Likely benign	0
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

4144 predictions. Top by Δscore:

Variant	Effect	Δscore
2:152656281:A:AC	donor_gain	1.0000
2:152656282:C:CC	donor_gain	1.0000
2:152656319:T:TA	donor_gain	1.0000
2:152657883:A:AC	donor_gain	1.0000
2:152657883:ACTT:A	donor_loss	1.0000
2:152657884:C:CC	donor_gain	1.0000
2:152657884:CTTA:C	donor_gain	1.0000
2:152657885:TTA:T	donor_loss	1.0000
2:152657887:A:AC	donor_gain	1.0000
2:152657887:ACAG:A	donor_loss	1.0000
2:152657888:C:CA	donor_gain	1.0000
2:152657888:CA:C	donor_gain	1.0000
2:152657888:CAG:C	donor_gain	1.0000
2:152657888:CAGA:C	donor_gain	1.0000
2:152657888:CAGAA:C	donor_gain	1.0000
2:152658016:GAGTC:G	acceptor_gain	1.0000
2:152658017:AGTC:A	acceptor_gain	1.0000
2:152658017:AGTCC:A	acceptor_gain	1.0000
2:152658018:GTC:G	acceptor_gain	1.0000
2:152658018:GTCC:G	acceptor_gain	1.0000
2:152658019:TC:T	acceptor_gain	1.0000
2:152658019:TCC:T	acceptor_gain	1.0000
2:152658020:CCTG:C	acceptor_gain	1.0000
2:152658020:CCTGT:C	acceptor_gain	1.0000
2:152658021:C:A	acceptor_loss	1.0000
2:152658021:C:CC	acceptor_gain	1.0000
2:152658021:C:G	acceptor_gain	1.0000
2:152658021:C:T	acceptor_gain	1.0000
2:152658022:T:A	acceptor_gain	1.0000
2:152658023:G:C	acceptor_gain	1.0000

AlphaMissense

6456 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000008360 (2:152715675 C>T), RS1000159347 (2:152678131 T>C), RS1000227085 (2:152688291 C>A,T), RS1000313612 (2:152684241 C>A), RS1000318563 (2:152695590 A>G), RS1000353855 (2:152665684 T>C), RS1000358476 (2:152709853 T>C), RS1000405080 (2:152671684 G>A), RS1000426507 (2:152716527 T>A,C), RS1000485436 (2:152699511 G>A), RS1000508542 (2:152653060 T>A,C), RS1000562239 (2:152653458 T>C), RS1000587027 (2:152671613 A>T), RS1000631220 (2:152716372 C>T), RS1000743438 (2:152710981 T>A,C)

Disease associations

OMIM: gene MIM:612941 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST006151_4	Memory dysfunction in frontotemporal lobe dementia	8.000000e-06
GCST006626_22	Pulse pressure	5.000000e-09
GCST006979_41	Heel bone mineral density	9.000000e-12
GCST009391_557	Metabolite levels	5.000000e-06
GCST010002_400	Refractive error	6.000000e-11

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0001072	memory impairment
EFO:0005763	pulse pressure measurement
EFO:0009270	heel bone mineral density
EFO:0009769	histidine measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5725154 (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

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

pChembl	Type	Value	Unit	Molecule
7.87	Kd	13.53	nM	CHEMBL5653589
7.87	ED50	13.53	nM	CHEMBL5653589
7.87	Kd	13.43	nM	CHEMBL3752910
7.87	ED50	13.43	nM	CHEMBL3752910
7.80	Kd	16	nM	MOLIBRESIB
7.52	IC50	30	nM	MOLIBRESIB

PubChem BioAssay actives

4 with measured affinity, of 11 total; 3 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
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149091: Binding affinity to human PRPF40A incubated for 45 mins by Kinobead based pull down assay	kd	0.0134	uM
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149091: Binding affinity to human PRPF40A incubated for 45 mins by Kinobead based pull down assay	kd	0.0135	uM
2-[(4S)-6-(4-chlorophenyl)-8-methoxy-1-methyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-4-yl]-N-ethylacetamide	2179117: Binding affinity against PRPF40A (unknown origin) assessed as apparent dissociation constant incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	kd	0.0160	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases expression, decreases methylation	4
aristolochic acid I	decreases expression	1
FR900359	increases phosphorylation	1
TAK-243	decreases sumoylation	1
dicrotophos	decreases expression	1
daidzein	affects cotreatment, increases expression	1
methylmercuric chloride	decreases expression	1
bisphenol A	affects cotreatment, decreases methylation	1
deoxynivalenol	increases expression	1
kojic acid	decreases expression	1
daidzin	affects cotreatment, increases expression	1
coumarin	affects phosphorylation	1
genistin	affects cotreatment, increases expression	1
hinokiflavone	increases sumoylation	1
tamibarotene	affects expression	1
di-n-butylphosphoric acid	affects expression	1
glycitein	affects cotreatment, increases expression	1
glycitin	affects cotreatment, increases expression	1
bisphenol B	increases expression	1
jinfukang	decreases expression	1
Fulvestrant	decreases methylation, affects cotreatment	1
Air Pollutants	decreases expression, increases abundance	1
Caffeine	decreases phosphorylation	1
Doxorubicin	decreases expression	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Ivermectin	decreases expression	1
Lead	decreases expression	1
Progesterone	increases expression	1
Ribonucleotides	affects binding	1
Selenium	decreases expression	1

ChEMBL screening assays

8 unique, capped per target: 8 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5652133	Binding	Binding affinity to human PRPF40A 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.