PRPF40B

Summary

PRPF40B (pre-mRNA processing factor 40B, HGNC:25031) is a protein-coding gene on chromosome 12q13.12, encoding Pre-mRNA-processing factor 40 homolog B (Q6NWY9). May be involved in pre-mRNA splicing.

This gene encodes a WW-domain containing protein similar to yeast splicing factor PRP40. This protein has been shown to interact with Huntingtin and methyl CpG binding protein 2 (MeCP2). Alternative splicing results in different transcript variants.

Source: NCBI Gene 25766 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 95 total
• MANE Select transcript: NM_001031698

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25031
Approved symbol	PRPF40B
Name	pre-mRNA processing factor 40B
Location	12q13.12
Locus type	gene with protein product
Status	Approved
Aliases	HYPC
Ensembl gene	ENSG00000110844
Ensembl biotype	protein_coding
OMIM	621019
Entrez	25766

Gene structure

Transcript identifiers

Ensembl transcripts: 28 — 16 protein_coding, 7 retained_intron, 4 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000261897, ENST00000380281, ENST00000508736, ENST00000527253, ENST00000546626, ENST00000547764, ENST00000548399, ENST00000548436, ENST00000548825, ENST00000549547, ENST00000551063, ENST00000551111, ENST00000551269, ENST00000551320, ENST00000551418, ENST00000552301, ENST00000853189, ENST00000853190, ENST00000853191, ENST00000853192, ENST00000853193, ENST00000853194, ENST00000922971, ENST00000922972, ENST00000922973, ENST00000960369, ENST00000960370, ENST00000960371

RefSeq mRNA: 11 — MANE Select: NM_001031698 NM_001031698, NM_001363607, NM_001379030, NM_001379031, NM_001379032, NM_001379033, NM_001379034, NM_001379035, NM_001379036, NM_001379037, NM_012272

CCDS: CCDS31796, CCDS86298

Canonical transcript exons

ENST00000548825 — 26 exons

Exon	Start	End
ENSE00000919724	49637733	49637824
ENSE00000919726	49642235	49642372
ENSE00000919727	49642580	49642675
ENSE00000919731	49643861	49644004
ENSE00001657313	49634538	49634602
ENSE00001708376	49637470	49637584
ENSE00001717286	49635843	49635993
ENSE00001766738	49635365	49635473
ENSE00001785349	49636716	49636849
ENSE00001797999	49635099	49635263
ENSE00002342804	49623561	49623593
ENSE00003266590	49644100	49644665
ENSE00003472454	49634332	49634455
ENSE00003491270	49631860	49631925
ENSE00003499371	49632855	49632880
ENSE00003499593	49633637	49633661
ENSE00003522127	49643691	49643752
ENSE00003526235	49642930	49643016
ENSE00003535598	49630545	49630625
ENSE00003574341	49633886	49634092
ENSE00003583241	49641908	49642024
ENSE00003598961	49632596	49632623
ENSE00003608827	49633427	49633547
ENSE00003626581	49633014	49633124
ENSE00003640707	49643223	49643397
ENSE00003759647	49631401	49631544

Expression profiles

Bgee: expression breadth ubiquitous, 196 present calls, max score 94.47.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 4.6888 / max 57.4145, expressed in 1463 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
125344	2.8698	1158
125343	1.1958	760
125342	0.6231	360

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right lobe of thyroid gland	UBERON:0001119	94.47	gold quality
left lobe of thyroid gland	UBERON:0001120	94.12	gold quality
adenohypophysis	UBERON:0002196	93.48	gold quality
left testis	UBERON:0004533	93.29	gold quality
sural nerve	UBERON:0015488	93.29	gold quality
right testis	UBERON:0004534	93.28	gold quality
left ovary	UBERON:0002119	93.08	gold quality
right uterine tube	UBERON:0001302	92.98	gold quality
endocervix	UBERON:0000458	92.83	gold quality
right ovary	UBERON:0002118	92.83	gold quality
thyroid gland	UBERON:0002046	92.74	gold quality
metanephros cortex	UBERON:0010533	92.28	gold quality
body of uterus	UBERON:0009853	91.95	gold quality
mucosa of stomach	UBERON:0001199	91.87	gold quality
pituitary gland	UBERON:0000007	91.81	gold quality
ectocervix	UBERON:0012249	91.29	gold quality
right hemisphere of cerebellum	UBERON:0014890	90.87	gold quality
apex of heart	UBERON:0002098	90.78	gold quality
testis	UBERON:0000473	90.51	gold quality
right adrenal gland cortex	UBERON:0035827	90.46	gold quality
left uterine tube	UBERON:0001303	90.33	gold quality
right frontal lobe	UBERON:0002810	90.30	gold quality
gastrocnemius	UBERON:0001388	90.29	gold quality
right adrenal gland	UBERON:0001233	90.12	gold quality
descending thoracic aorta	UBERON:0002345	90.00	gold quality
cerebellar hemisphere	UBERON:0002245	89.98	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	89.93	gold quality
ascending aorta	UBERON:0001496	89.89	gold quality
thoracic aorta	UBERON:0001515	89.88	gold quality
muscle of leg	UBERON:0001383	89.83	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	3.17

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

25 targeting PRPF40B, 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-340-5P	100.00	72.50	4437
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-185-3P	99.95	67.01	1743
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-6745	99.74	65.33	1321
HSA-MIR-4690-5P	99.65	66.24	813
HSA-MIR-6715B-5P	99.64	69.63	1420
HSA-MIR-1827	99.63	68.57	3265
HSA-MIR-4649-3P	99.56	66.90	1783
HSA-MIR-4269	99.55	69.89	1373
HSA-MIR-766-5P	99.47	67.91	2225
HSA-MIR-4716-5P	98.82	68.57	1168
HSA-MIR-12125	98.59	67.54	1044
HSA-MIR-6764-3P	98.44	67.64	1153
HSA-MIR-6824-3P	98.44	67.62	1154
HSA-MIR-1910-3P	98.44	67.51	1695
HSA-MIR-6804-5P	98.39	65.77	1084
HSA-MIR-6511A-5P	98.13	67.47	1770
HSA-MIR-6880-5P	98.08	65.59	1282
HSA-MIR-6742-3P	97.95	64.50	1490
HSA-MIR-7113-5P	97.88	67.33	1735
HSA-MIR-4521	97.73	67.64	684
HSA-MIR-335-5P	97.10	68.12	1022
HSA-MIR-342-3P	96.44	67.48	1344
HSA-MIR-554	95.20	66.98	341

Literature-anchored findings (GeneRIF, showing 2)

• Placing our data in a functional context, we also show that PRPF40B depletion increased Fas/CD95 receptor number and cell apoptosis, which suggests the ability of PRPF40B to alter the alternative splicing of key apoptotic genes to regulate cell survival (PMID:25605964)
• Study characterizes the transcriptomic regulation of PRPF40B in K562 cells upon knockout (KO) and rescue with MDS mutations, to reveal a set of targets with weak splice sites and A-rich motifs. Importantly, PRPF40B KO up-regulated a hypoxia signature which, together with its low expression in AML, suggests a role of PRPF40B in myeloid leukemias. (PMID:31088860)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
mus_musculus	Prpf40b	ENSMUSG00000023007
rattus_norvegicus	Prpf40b	ENSRNOG00000052539
drosophila_melanogaster	Prp40	FBGN0031492
caenorhabditis_elegans		WBGENE00014218

Paralogs (1): PRPF40A (ENSG00000196504)

Protein

Protein identifiers

Pre-mRNA-processing factor 40 homolog B — Q6NWY9 (reviewed: Q6NWY9)

Alternative names: Huntingtin yeast partner C, Huntingtin-interacting protein C

All UniProt accessions (4): A0A8Z5ADK7, Q6NWY9, F8VU11, H0YII7

UniProt curated annotations — full annotation on UniProt →

Function. May be involved in pre-mRNA splicing.

Subunit / interactions. Interacts with the N-terminus of HD.

Subcellular location. Nucleus speckle.

Tissue specificity. Expressed in the striatum and cortex of the brain (at protein level). Highly expressed in testis, fetal kidney and fetal brain. Moderately expressed in pancreas, skeletal muscle, placenta, brain and heart. Weakly expressed in colon, ileum, ovary, prostate, spleen, kidney and fetal lung.

Similarity. Belongs to the PRPF40 family.

Isoforms (4)

UniProt ID	Names	Canonical?
Q6NWY9-1	1	yes
Q6NWY9-2	2
Q6NWY9-3	3
Q6NWY9-4	4

RefSeq proteins (11): NP_001026868, NP_001350536, NP_001365959, NP_001365960, NP_001365961, NP_001365962, NP_001365963, NP_001365964, NP_001365965, NP_001365966, NP_036404 (=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 (31 total): domain 8, compositionally biased region 8, splice variant 6, modified residue 4, region of interest 2, cross-link 2, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6NWY9-F1	69.16	0.35

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 (6): 148, 764, 832, 852, 175, 838

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 95 (showing top): GAUSSMANN_MLL_AF4_FUSION_TARGETS_C_UP, GOBP_RNA_SPLICING, GOBP_MRNA_CIS_SPLICING_VIA_SPLICEOSOME, GOCC_U1_SNRNP, GOCC_U2_TYPE_SPLICEOSOMAL_COMPLEX, GOCC_NUCLEAR_SPECK, GOCC_NUCLEAR_BODY, GOCC_RIBONUCLEOPROTEIN_GRANULE, GOCC_PRESPLICEOSOME, GOCC_SPLICEOSOMAL_COMPLEX, GOCC_RIBONUCLEOPROTEIN_COMPLEX, KEGG_SPLICEOSOME, GOBP_MRNA_PROCESSING, GOCC_SUPRAMOLECULAR_COMPLEX, GOCC_SM_LIKE_PROTEIN_FAMILY_COMPLEX

GO Biological Process (4): mRNA splicing, via spliceosome (GO:0000398), mRNA cis splicing, via spliceosome (GO:0045292), mRNA processing (GO:0006397), RNA splicing (GO:0008380)

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

GO Cellular Component (5): U1 snRNP (GO:0005685), nuclear matrix (GO:0016363), nuclear speck (GO:0016607), U2-type prespliceosome (GO:0071004), nucleus (GO:0005634)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
RNA processing	2
RNA splicing, via transesterification reactions with bulged adenosine as nucleophile	1
mRNA processing	1
mRNA splicing, via spliceosome	1
mRNA metabolic process	1
nucleic acid binding	1
binding	1
spliceosomal snRNP complex	1
nuclear lumen	1
cellular anatomical structure	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

862 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PRPF40B	FICD	Q9BVA6	833
PRPF40B	U2AF2	P26368	830
PRPF40B	SF3A1	Q15459	783
PRPF40B	SETD2	Q9BYW2	664
PRPF40B	ZRSR2	Q15696	641
PRPF40B	U2AF1	Q01081	610
PRPF40B	SRSF2	Q01130	605
PRPF40B	A0A0A6YYJ8	A0A0A6YYJ8	544
PRPF40B	LUC7L2	Q9Y383	535
PRPF40B	MAGEA3	P43357	529
PRPF40B	ZDHHC17	Q8IUH5	512
PRPF40B	MECP2	P51608	510
PRPF40B	HTT	P42858	500
PRPF40B	BCORL1	Q5H9F3	494
PRPF40B	SF1	Q15637	471

IntAct

9 interactions, top by confidence:

A	B	Type	Score
PRPF40B	FUBP1	psi-mi:“MI:0915”(physical association)	0.560
PRPF40B	P4HA1	psi-mi:“MI:0915”(physical association)	0.400
rep	TAF4	psi-mi:“MI:0914”(association)	0.350
PRPF40B	GNB5	psi-mi:“MI:0914”(association)	0.350
PRPF40B	RBM25	psi-mi:“MI:0914”(association)	0.350
ARGLU1	PIAS2	psi-mi:“MI:2364”(proximity)	0.270
PRPF40B	FUBP1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (44): PRPF40B (Co-fractionation), PRPF40B (Co-fractionation), PRPF40B (Co-fractionation), SRRM2 (Co-fractionation), PRPF40B (Affinity Capture-MS), PRPF40B (Affinity Capture-MS), PRPF40B (Affinity Capture-MS), RGS9 (Affinity Capture-MS), GNB5 (Affinity Capture-MS), RBM25 (Affinity Capture-MS), PRPF40B (Two-hybrid), HTT (Reconstituted Complex), FUBP1 (Two-hybrid), PRPF40B (Affinity Capture-MS), PRPF40B (Proximity Label-MS)

ESM2 similar proteins: A0JMV4, A4IFB1, A4IGK4, B6EUA9, D3ZTQ1, E6ZGB4, F1QLR3, O14776, O70523, O75376, O75400, P21127, P24788, P25440, P34600, P35922, P51114, P51115, Q12872, Q15059, Q2T9I5, Q2TBT7, Q3USH5, Q4KKX4, Q5BJ56, Q5R539, Q5T8P6, Q5TJG6, Q5XI81, Q60974, Q61584, Q6DDU9, Q6INA9, Q6MGA9, Q6NWY9, Q6NZN0, Q6P949, Q6PFK1, Q7JJ13, Q7ZTQ5

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

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	82
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

5343 predictions. Top by Δscore:

Variant	Effect	Δscore
12:49588635:A:T	acceptor_gain	1.0000
12:49598749:GCCCA:G	donor_loss	1.0000
12:49598751:CCACC:C	donor_loss	1.0000
12:49598752:CA:C	donor_loss	1.0000
12:49598753:A:T	donor_loss	1.0000
12:49598943:CTTGC:C	acceptor_gain	1.0000
12:49598944:TTGC:T	acceptor_gain	1.0000
12:49598945:TGC:T	acceptor_gain	1.0000
12:49598946:GC:G	acceptor_gain	1.0000
12:49598947:CC:C	acceptor_gain	1.0000
12:49598948:C:CC	acceptor_gain	1.0000
12:49598948:C:CG	acceptor_loss	1.0000
12:49598949:T:G	acceptor_loss	1.0000
12:49599464:CCTA:C	donor_loss	1.0000
12:49599465:CTACC:C	donor_loss	1.0000
12:49599504:A:AC	donor_gain	1.0000
12:49599504:ATGG:A	donor_gain	1.0000
12:49599505:T:C	donor_gain	1.0000
12:49603181:CTA:C	donor_loss	1.0000
12:49603182:TA:T	donor_loss	1.0000
12:49603184:C:CA	donor_loss	1.0000
12:49603184:CCTTG:C	donor_gain	1.0000
12:49603186:TTGTG:T	donor_gain	1.0000
12:49603364:TCAC:T	acceptor_gain	1.0000
12:49603365:CACC:C	acceptor_gain	1.0000
12:49603367:CCT:C	acceptor_loss	1.0000
12:49603368:C:CC	acceptor_gain	1.0000
12:49603369:T:C	acceptor_loss	1.0000
12:49604309:TCA:T	donor_loss	1.0000
12:49604310:CACC:C	donor_loss	1.0000

AlphaMissense

5843 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:49633089:T:A	W120R	1.000
12:49633089:T:C	W120R	1.000
12:49633091:G:C	W120C	1.000
12:49633091:G:T	W120C	1.000
12:49633448:T:A	W139R	1.000
12:49633448:T:C	W139R	1.000
12:49633514:T:A	W161R	1.000
12:49633514:T:C	W161R	1.000
12:49633516:G:C	W161C	1.000
12:49633516:G:T	W161C	1.000
12:49634433:T:C	F283S	1.000
12:49634442:T:C	L286P	1.000
12:49634445:T:C	L287P	1.000
12:49634542:T:A	V292D	1.000
12:49634559:T:A	W298R	1.000
12:49634559:T:C	W298R	1.000
12:49634560:G:C	W298S	1.000
12:49634561:G:C	W298C	1.000
12:49634561:G:T	W298C	1.000
12:49634568:G:C	A301P	1.000
12:49635123:A:C	K320N	1.000
12:49635123:A:T	K320N	1.000
12:49635124:A:G	K321E	1.000
12:49635126:G:C	K321N	1.000
12:49635126:G:T	K321N	1.000
12:49635130:G:C	A323P	1.000
12:49635133:T:C	F324L	1.000
12:49635135:C:A	F324L	1.000
12:49635135:C:G	F324L	1.000
12:49635147:G:C	K328N	1.000

dbSNP variants (sampled 300 via entrez): RS1000016086 (12:49637274 T>G), RS1000016184 (12:49634595 C>G,T), RS1000055983 (12:49641230 G>A), RS1000086690 (12:49641547 C>T), RS1000188901 (12:49627232 C>G), RS1000450063 (12:49640449 A>C,T), RS1000587176 (12:49620945 C>T), RS1000626197 (12:49626837 A>G), RS1000707385 (12:49629166 T>C), RS1001083128 (12:49628883 A>G), RS1001140810 (12:49622181 G>A), RS1001171856 (12:49622594 A>G), RS1001617506 (12:49637829 G>A), RS1001648496 (12:49638271 T>A,G), RS1002007240 (12:49640145 G>T)

Disease associations

OMIM: gene MIM:621019 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST008595_117	Cognitive ability, years of educational attainment or schizophrenia (pleiotropy)	9.000000e-09

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004337	intelligence
EFO:0004784	self reported educational attainment

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

28 total (human), top 28 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
FR900359	affects phosphorylation	1
bisphenol F	affects cotreatment, increases expression	1
TAK-243	decreases sumoylation	1
triphenyl phosphate	affects expression	1
bisphenol A	increases methylation	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
coumarin	increases phosphorylation	1
entinostat	increases expression	1
abrine	increases expression	1
jinfukang	affects cotreatment, increases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Sunitinib	increases expression	1
Air Pollutants	decreases expression, increases abundance	1
Benzo(a)pyrene	affects methylation	1
Caffeine	decreases phosphorylation	1
Cisplatin	increases expression, affects cotreatment	1
Dexamethasone	affects cotreatment, increases expression	1
Doxorubicin	increases expression	1
Indomethacin	affects cotreatment, increases expression	1
Phthalic Acids	increases methylation	1
Plant Extracts	affects cotreatment, decreases expression	1
Tetrachlorodibenzodioxin	affects expression	1
Tobacco Smoke Pollution	decreases expression	1
Valproic Acid	affects expression	1
1-Methyl-3-isobutylxanthine	affects cotreatment, increases expression	1
Cyclosporine	increases expression	1
Acrylamide	decreases expression	1
Particulate Matter	decreases expression, increases abundance	1

Cellosaurus cell lines

3 cell lines: 3 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_E0M1	Ubigene HeLa PRPF40B KO	Cancer cell line	Female
CVCL_TH22	HAP1 PRPF40B (-) 1	Cancer cell line	Male
CVCL_XR93	HAP1 PRPF40B (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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