PLRG1

Summary

PLRG1 (pleiotropic regulator 1, HGNC:9089) is a protein-coding gene on chromosome 4q31.3, encoding Pleiotropic regulator 1 (O43660). Involved in pre-mRNA splicing as component of the spliceosome. It is a common-essential gene (DepMap: required in 97.7% of cancer cell lines).

This gene encodes a core component of the cell division cycle 5-like (CDC5L) complex. The CDC5L complex is part of the spliceosome and is required for pre-mRNA splicing. The encoded protein plays a critical role in alternative splice site selection. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene.

Source: NCBI Gene 5356 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 65 total
• Cancer dependency (DepMap): dependent in 97.7% of screened cell lines (common-essential)
• MANE Select transcript: NM_002669

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9089
Approved symbol	PLRG1
Name	pleiotropic regulator 1
Location	4q31.3
Locus type	gene with protein product
Status	Approved
Aliases	PRL1, Prp46, PRPF46, Cwc1, TANGO4
Ensembl gene	ENSG00000171566
Ensembl biotype	protein_coding
OMIM	605961
Entrez	5356

Gene structure

Transcript identifiers

Ensembl transcripts: 19 — 10 protein_coding, 6 retained_intron, 3 nonsense_mediated_decay

ENST00000302078, ENST00000499023, ENST00000503251, ENST00000503751, ENST00000504341, ENST00000506192, ENST00000506627, ENST00000506918, ENST00000507125, ENST00000509975, ENST00000512719, ENST00000512773, ENST00000515520, ENST00000905729, ENST00000928812, ENST00000928813, ENST00000928814, ENST00000951250, ENST00000951251

RefSeq mRNA: 2 — MANE Select: NM_002669 NM_001201564, NM_002669

CCDS: CCDS34083, CCDS56341

Canonical transcript exons

ENST00000499023 — 15 exons

Exon	Start	End
ENSE00001127352	154537969	154538108
ENSE00001127361	154539105	154539213
ENSE00001127369	154539951	154540053
ENSE00001127376	154540594	154540695
ENSE00001127402	154546123	154546213
ENSE00001968181	154535005	154536744
ENSE00002029342	154550300	154550400
ENSE00003484099	154547711	154547853
ENSE00003486762	154545836	154545923
ENSE00003528184	154547011	154547064
ENSE00003593179	154540785	154540934
ENSE00003597012	154542187	154542279
ENSE00003616019	154548829	154548935
ENSE00003624555	154544445	154544546
ENSE00003693512	154537286	154537479

Expression profiles

Bgee: expression breadth ubiquitous, 262 present calls, max score 98.26.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 39.5303 / max 709.1135, expressed in 1811 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
54450	39.5303	1811

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	98.26	gold quality
calcaneal tendon	UBERON:0003701	97.28	gold quality
islet of Langerhans	UBERON:0000006	96.48	gold quality
smooth muscle tissue	UBERON:0001135	96.37	gold quality
oocyte	CL:0000023	96.09	gold quality
body of uterus	UBERON:0009853	96.03	gold quality
left lobe of thyroid gland	UBERON:0001120	95.87	gold quality
palpebral conjunctiva	UBERON:0001812	95.86	gold quality
right lobe of thyroid gland	UBERON:0001119	95.80	gold quality
rectum	UBERON:0001052	95.78	gold quality
kidney epithelium	UBERON:0004819	95.77	gold quality
right uterine tube	UBERON:0001302	95.72	gold quality
gall bladder	UBERON:0002110	95.61	gold quality
mucosa of stomach	UBERON:0001199	95.60	gold quality
thyroid gland	UBERON:0002046	95.58	gold quality
esophagus mucosa	UBERON:0002469	95.58	gold quality
minor salivary gland	UBERON:0001830	95.53	gold quality
right ovary	UBERON:0002118	95.50	gold quality
metanephros cortex	UBERON:0010533	95.41	gold quality
left ovary	UBERON:0002119	95.30	gold quality
endocervix	UBERON:0000458	95.20	gold quality
vermiform appendix	UBERON:0001154	95.17	gold quality
esophagus	UBERON:0001043	95.09	gold quality
small intestine Peyer’s patch	UBERON:0003454	95.03	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	95.02	gold quality
descending thoracic aorta	UBERON:0002345	94.99	gold quality
tonsil	UBERON:0002372	94.94	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	94.94	gold quality
embryo	UBERON:0000922	94.92	gold quality
ganglionic eminence	UBERON:0004023	94.92	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	8.19
E-GEOD-124858	no	620.41
E-MTAB-6058	no	388.49

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CDC5L

miRNA regulators (miRDB)

66 targeting PLRG1, 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-4668-3P	100.00	68.74	2635
HSA-MIR-3925-3P	100.00	69.95	1237
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-499A-5P	99.98	70.79	1323
HSA-MIR-485-3P	99.98	70.68	1585
HSA-MIR-539-3P	99.98	70.74	1616
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-497-5P	99.92	71.83	2674
HSA-MIR-8063	99.91	69.76	3146
HSA-MIR-15A-5P	99.90	72.80	2787
HSA-MIR-15B-5P	99.90	72.78	2798
HSA-MIR-16-5P	99.90	72.80	2780
HSA-MIR-195-5P	99.90	72.81	2805
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-8087	99.90	69.55	1351
HSA-MIR-424-5P	99.89	71.90	2641
HSA-MIR-6838-5P	99.89	71.94	2690
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-5582-3P	99.86	72.48	4221
HSA-MIR-548AR-3P	99.85	71.26	3889
HSA-MIR-576-5P	99.84	70.46	2582
HSA-MIR-4698	99.84	71.41	4303
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-3133	99.81	70.92	3506
HSA-MIR-548A-3P	99.76	70.58	3524

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 97.7% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 6)

• the interaction between CDC5L and PLRG1 is essential for pre-mRNA splicing (PMID:14576297)
• A central region in hnRNP-M is required for interaction with CDC5L/PLRG1. (PMID:20467437)
• Crystal structure of the WD40 domain of human PLRG1. (PMID:33239170)
• RNA Helicase DHX37 Facilitates Liver Cancer Progression by Cooperating with PLRG1 to Drive Superenhancer-Mediated Transcription of Cyclin D1. (PMID:35290436)
• YBX1 promotes epithelial-mesenchymal transition in hepatocellular carcinoma via transcriptional regulation of PLRG1. (PMID:39400789)
• Study includes the isolation of a cDNA encoding the human PRL1 homolog. (PMID:9765207)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	plrg1	ENSDARG00000037283
mus_musculus	Plrg1	ENSMUSG00000027998
rattus_norvegicus	Plrg1	ENSRNOG00000006655
drosophila_melanogaster	Tango4	FBGN0030365
caenorhabditis_elegans		WBGENE00006481

Protein

Protein identifiers

Pleiotropic regulator 1 — O43660 (reviewed: O43660)

All UniProt accessions (6): O43660, B7Z982, D6RA26, D6RE04, H0YA24, H0YAA2

UniProt curated annotations — full annotation on UniProt →

Function. Involved in pre-mRNA splicing as component of the spliceosome. Component of the PRP19-CDC5L complex that forms an integral part of the spliceosome and is required for activating pre-mRNA splicing. As a component of the minor spliceosome, involved in the splicing of U12-type introns in pre-mRNAs.

Subunit / interactions. Identified in the spliceosome C complex. Component of the PRP19-CDC5L splicing complex composed of a core complex comprising a homotetramer of PRPF19, CDC5L, PLRG1 and BCAS2, and at least three less stably associated proteins CTNNBL1, CWC15 and HSPA8. Interacts (via its WD40 repeat domain) directly with CDC5L (via its C-terminal); the interaction is required for mRNA splicing but not for spliceosome assembly. Component of the minor spliceosome, which splices U12-type introns. Within this complex, interacts with CRIPT. Also interacts directly in the complex with BCAS2 and PRPF19. Interacts with USB1.

Subcellular location. Nucleus. Nucleus speckle.

Miscellaneous. May be due to a competing donor splice site.

Similarity. Belongs to the WD repeat PRL1/PRL2 family.

Isoforms (2)

UniProt ID	Names	Canonical?
O43660-1	1	yes
O43660-2	2

RefSeq proteins (2): NP_001188493, NP_002660* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001680	WD40_rpt	Repeat
IPR015943	WD40/YVTN_repeat-like_dom_sf	Homologous_superfamily
IPR019775	WD40_repeat_CS	Conserved_site
IPR020472	WD40_PAC1	Repeat
IPR036322	WD40_repeat_dom_sf	Homologous_superfamily
IPR045241	Prp46/PLRG1-like	Family

Pfam: PF00400

UniProt features (55 total): strand 31, turn 9, repeat 7, modified residue 4, chain 1, splice variant 1, helix 1, region of interest 1

Structure

Experimental structures (PDB)

36 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
4YVD	X-RAY DIFFRACTION	1.7
7DH6	X-RAY DIFFRACTION	2.58
8C6J	ELECTRON MICROSCOPY	2.8
6ID1	ELECTRON MICROSCOPY	2.86
7DVQ	ELECTRON MICROSCOPY	2.89
6ID0	ELECTRON MICROSCOPY	2.9
6ICZ	ELECTRON MICROSCOPY	3
8I0R	ELECTRON MICROSCOPY	3
8I0T	ELECTRON MICROSCOPY	3
8I0V	ELECTRON MICROSCOPY	3
7QTT	ELECTRON MICROSCOPY	3.1
6QDV	ELECTRON MICROSCOPY	3.3
8I0U	ELECTRON MICROSCOPY	3.3
9FMD	ELECTRON MICROSCOPY	3.3
6FF4	ELECTRON MICROSCOPY	3.4
6ZYM	ELECTRON MICROSCOPY	3.4
8I0P	ELECTRON MICROSCOPY	3.4
8I0W	ELECTRON MICROSCOPY	3.4
8RO2	ELECTRON MICROSCOPY	3.5
5XJC	ELECTRON MICROSCOPY	3.6
7W59	ELECTRON MICROSCOPY	3.6
7W5A	ELECTRON MICROSCOPY	3.6
7ABF	ELECTRON MICROSCOPY	3.9
5YZG	ELECTRON MICROSCOPY	4.1
7AAV	ELECTRON MICROSCOPY	4.2
8I0S	ELECTRON MICROSCOPY	4.2
7W5B	ELECTRON MICROSCOPY	4.3
6FF7	ELECTRON MICROSCOPY	4.5
5Z58	ELECTRON MICROSCOPY	4.9
5Z56	ELECTRON MICROSCOPY	5.1

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O43660-F1	77.74	0.58

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): 119, 201, 391, 1

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-72163	mRNA Splicing - Major Pathway
R-HSA-9918481	Dengue Virus-Host Interactions

MSigDB gene sets: 137 (showing top): GOBP_CELL_CYCLE_PHASE_TRANSITION, GOBP_POSITIVE_REGULATION_OF_MITOTIC_CELL_CYCLE, GOBP_POSITIVE_REGULATION_OF_G1_S_TRANSITION_OF_MITOTIC_CELL_CYCLE, NKX61_01, GOCC_NUCLEAR_REPLICATION_FORK, WANG_LMO4_TARGETS_DN, REACTOME_PROCESSING_OF_CAPPED_INTRON_CONTAINING_PRE_MRNA, GOBP_REGULATION_OF_CELL_CYCLE, GOBP_REGULATION_OF_CELL_CYCLE_G1_S_PHASE_TRANSITION, GOBP_POSITIVE_REGULATION_OF_CELL_CYCLE_PROCESS, GOBP_CELL_CYCLE_G1_S_PHASE_TRANSITION, GOBP_RNA_SPLICING, GOBP_MITOTIC_CELL_CYCLE, REACTOME_MRNA_SPLICING, NKX22_01

GO Biological Process (5): mRNA splicing, via spliceosome (GO:0000398), protein localization to nucleus (GO:0034504), positive regulation of G1/S transition of mitotic cell cycle (GO:1900087), mRNA processing (GO:0006397), RNA splicing (GO:0008380)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (11): Prp19 complex (GO:0000974), fibrillar center (GO:0001650), nucleus (GO:0005634), nucleoplasm (GO:0005654), nuclear speck (GO:0016607), nuclear membrane (GO:0031965), U2-type catalytic step 2 spliceosome (GO:0071007), catalytic step 2 spliceosome (GO:0071013), DNA replication factor A complex (GO:0005662), spliceosomal complex (GO:0005681), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
mRNA Splicing	1
Dengue Virus Infection	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
RNA processing	2
nuclear protein-containing complex	2
RNA splicing, via transesterification reactions with bulged adenosine as nucleophile	1
mRNA processing	1
protein localization to organelle	1
G1/S transition of mitotic cell cycle	1
positive regulation of mitotic cell cycle phase transition	1
positive regulation of cell cycle G1/S phase transition	1
regulation of G1/S transition of mitotic cell cycle	1
mRNA metabolic process	1
binding	1
protein-containing complex	1
nucleolus	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
nuclear ribonucleoprotein granule	1
nucleus	1
nuclear envelope	1
organelle membrane	1
U2-type spliceosomal complex	1
U2 snRNP	1
U6 snRNP	1
catalytic step 2 spliceosome	1
Prp19 complex	1
spliceosomal complex	1
U5 snRNP	1
catalytic complex	1
nuclear replisome	1
ribonucleoprotein complex	1

Protein interactions and networks

STRING

2435 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PLRG1	BCAS2	O75934	997
PLRG1	CDC5L	Q99459	996
PLRG1	PRPF19	Q9UMS4	989
PLRG1	CWC15	Q9P013	924
PLRG1	HSPA8	P11142	886
PLRG1	RBM22	Q9NW64	856
PLRG1	SNW1	Q13573	804
PLRG1	PRKCG	P05129	765
PLRG1	BUD31	P41223	760
PLRG1	CTNNBL1	Q8WYA6	747
PLRG1	SYF2	O95926	737
PLRG1	XAB2	Q9HCS7	709
PLRG1	YJU2	Q9BW85	680
PLRG1	TXNL4A	P83876	676
PLRG1	ECM2	O94769	666

IntAct

136 interactions, top by confidence:

A	B	Type	Score
CDC5L	PLRG1	psi-mi:“MI:0915”(physical association)	0.860
PLRG1	CDC5L	psi-mi:“MI:0915”(physical association)	0.860
CDC5L	PLRG1	psi-mi:“MI:2364”(proximity)	0.860
BCAS2	PLRG1	psi-mi:“MI:0914”(association)	0.790
PLRG1	BCAS2	psi-mi:“MI:0407”(direct interaction)	0.790
PLRG1	BCAS2	psi-mi:“MI:0914”(association)	0.790
PLRG1	PRPF19	psi-mi:“MI:0407”(direct interaction)	0.770
PRPF19	PLRG1	psi-mi:“MI:0914”(association)	0.770
SF3B1	PLRG1	psi-mi:“MI:0915”(physical association)	0.660
SF3B1	SAP18	psi-mi:“MI:0914”(association)	0.640
PLRG1	HNRNPM	psi-mi:“MI:0915”(physical association)	0.610
PLRG1	HNRNPM	psi-mi:“MI:2364”(proximity)	0.610
PLRG1	HNRNPM	psi-mi:“MI:0407”(direct interaction)	0.610
PLRG1	SF3A2	psi-mi:“MI:0915”(physical association)	0.560
N	RBM47	psi-mi:“MI:0914”(association)	0.530
PLRG1	AQR	psi-mi:“MI:0914”(association)	0.530
CHD8	ACOT7	psi-mi:“MI:0914”(association)	0.500
CUL3	ACOT7	psi-mi:“MI:0914”(association)	0.500
FMR1	ACOT7	psi-mi:“MI:0914”(association)	0.500
CPSF6	DDX39A	psi-mi:“MI:0914”(association)	0.480
P/V/C	PLRG1	psi-mi:“MI:0914”(association)	0.430
P/V/C	PLRG1	psi-mi:“MI:0403”(colocalization)	0.430
DNAH17	PLRG1	psi-mi:“MI:0915”(physical association)	0.400
Prpf8		psi-mi:“MI:0915”(physical association)	0.400

BioGRID (332): PLRG1 (Affinity Capture-MS), PLRG1 (Affinity Capture-MS), PLRG1 (Affinity Capture-MS), PLRG1 (Affinity Capture-MS), HNRNPM (Affinity Capture-Western), PLRG1 (Affinity Capture-Western), CDC5L (FRET), PLRG1 (FRET), HNRNPM (Reconstituted Complex), PLRG1 (Affinity Capture-MS), AP2M1 (Co-fractionation), BCAS2 (Co-fractionation), CDC5L (Co-fractionation), ISY1-RAB43 (Co-fractionation), ISY1 (Co-fractionation)

ESM2 similar proteins: A0A1L8I2C5, A0A396ISC0, A6PWY4, A9X1C6, D3Z3I0, D3ZW91, F1M7L9, F4K5R6, O13286, O43660, P43254, P93471, Q12417, Q15291, Q2TAF3, Q39190, Q3E906, Q3UMY5, Q4PSE4, Q4V837, Q5RHI5, Q5ZIU8, Q5ZMV9, Q6DIP5, Q6GPU3, Q6NL34, Q6ZJW8, Q7ZVL2, Q7ZX22, Q86Y33, Q8BG40, Q8BX09, Q8C0M0, Q8CFJ9, Q8GYY7, Q8L3Z8, Q8LPL5, Q8VZS9, Q8VZY7, Q922V4

Diamond homologs: A0JMQ0, A1CF18, A1CQI9, A1D3F5, A2QEV8, A2QPZ4, A3LXF0, A4H6F7, A4HUV2, A4IHS2, A4R0Q1, A4RDD7, A5DBG1, A5DWF4, A6QX61, A6RRD4, A6RUL1, A6ZMA9, A7EF03, A8ID74, A8NWR2, A8PWB6, A8QD31, A8XYW9, A9UZS7, B0R0D7, B0WC36, B0XQ42, B2AY28, B2VR76, B3MHX6, B3NLK7, B4GIU9, B4HN85, B4J9K1, B4KQU8, B4LKS9, B4MYI5, B4P528, B6GZD3

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
PLRG1	“up-regulates activity”	HNRNPM	binding
PLRG1	“form complex”	PRP19-CDC5L	binding
WEE1	“down-regulates activity”	PLRG1	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 126 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
mRNA Splicing	21	27.8×	3e-23
mRNA Splicing - Major Pathway	41	27.0×	2e-47
Processing of Capped Intron-Containing Pre-mRNA	26	25.7×	4e-28
mRNA Polyadenylation	21	22.2×	3e-21
mRNA 3’-end processing	9	21.4×	2e-08
RNA Polymerase II Transcription Termination	7	18.5×	4e-06
Dengue Virus-Host Interactions	29	16.0×	1e-25
Transport of Mature mRNA derived from an Intron-Containing Transcript	8	14.7×	3e-06

GO biological processes:

GO term	Partners	Fold	FDR
regulation of mRNA splicing, via spliceosome	5	41.8×	9e-06
U2-type prespliceosome assembly	6	35.3×	2e-06
mRNA splicing, via spliceosome	38	32.8×	1e-45
regulation of alternative mRNA splicing, via spliceosome	8	18.4×	2e-06
mRNA export from nucleus	6	16.7×	1e-04
RNA splicing	19	15.8×	2e-15
mRNA processing	18	13.4×	2e-13
negative regulation of translation	7	12.9×	9e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	44
Likely benign	2
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

2044 predictions. Top by Δscore:

Variant	Effect	Δscore
4:154537284:A:AC	donor_gain	1.0000
4:154537285:C:CC	donor_gain	1.0000
4:154537285:CGG:C	donor_gain	1.0000
4:154537477:CAG:C	acceptor_gain	1.0000
4:154537478:AGCT:A	acceptor_loss	1.0000
4:154537479:GCT:G	acceptor_loss	1.0000
4:154537480:C:CC	acceptor_gain	1.0000
4:154537481:T:C	acceptor_gain	1.0000
4:154537970:T:TA	donor_gain	1.0000
4:154538051:T:TA	donor_gain	1.0000
4:154538104:TGTAA:T	acceptor_gain	1.0000
4:154538105:GTAA:G	acceptor_gain	1.0000
4:154538106:TAA:T	acceptor_gain	1.0000
4:154538107:AA:A	acceptor_gain	1.0000
4:154538109:C:CC	acceptor_gain	1.0000
4:154539103:A:AC	donor_gain	1.0000
4:154539103:ACTGT:A	donor_gain	1.0000
4:154539104:C:CT	donor_gain	1.0000
4:154539104:CT:C	donor_gain	1.0000
4:154539104:CTGT:C	donor_gain	1.0000
4:154539104:CTGTC:C	donor_gain	1.0000
4:154539945:TCATA:T	donor_loss	1.0000
4:154539946:CATAC:C	donor_loss	1.0000
4:154539947:ATAC:A	donor_loss	1.0000
4:154539948:TA:T	donor_loss	1.0000
4:154539949:A:AG	donor_loss	1.0000
4:154540049:CAAAT:C	acceptor_gain	1.0000
4:154540050:AAAT:A	acceptor_gain	1.0000
4:154540051:AAT:A	acceptor_gain	1.0000
4:154540052:AT:A	acceptor_gain	1.0000

AlphaMissense

3367 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:154537320:T:A	K484I	1.000
4:154537323:T:A	D483V	1.000
4:154537324:C:G	D483H	1.000
4:154537450:A:G	W441R	1.000
4:154537450:A:T	W441R	1.000
4:154537456:A:G	W439R	1.000
4:154537456:A:T	W439R	1.000
4:154537470:C:A	G434V	1.000
4:154537470:C:T	G434D	1.000
4:154538068:A:G	W398R	1.000
4:154538068:A:T	W398R	1.000
4:154538072:C:A	K396N	1.000
4:154538072:C:G	K396N	1.000
4:154538074:T:C	K396E	1.000
4:154538094:G:A	S389F	1.000
4:154538094:G:T	S389Y	1.000
4:154539132:A:T	V375D	1.000
4:154539187:A:G	W357R	1.000
4:154539187:A:T	W357R	1.000
4:154539192:C:G	R355P	1.000
4:154539204:T:A	D351V	1.000
4:154539205:C:G	D351H	1.000
4:154539209:G:C	S349R	1.000
4:154539209:G:T	S349R	1.000
4:154539211:T:G	S349R	1.000
4:154540050:A:G	W315R	1.000
4:154540050:A:T	W315R	1.000
4:154540608:C:G	D309H	1.000
4:154540676:C:T	G286E	1.000
4:154540801:T:A	D274V	1.000

dbSNP variants (sampled 300 via entrez): RS1000038094 (4:154546548 G>T), RS1000055779 (4:154552179 G>A), RS1000320440 (4:154542686 G>A,C), RS1000809974 (4:154535019 CTTTAT>C), RS1000853349 (4:154547935 G>C,T), RS1000855177 (4:154541174 T>A), RS1001113983 (4:154549073 T>C), RS1001125102 (4:154548605 C>T), RS1001187586 (4:154535684 T>C), RS1001261065 (4:154535892 T>C), RS1001409496 (4:154546879 A>G), RS1001418554 (4:154540160 G>A), RS1002025940 (4:154546647 A>G), RS1002263870 (4:154535486 T>C), RS1002356031 (4:154549955 T>C)

Disease associations

OMIM: gene MIM:605961 | 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
GCST001158_4	Fibrinogen	2.000000e-36
GCST004121_27	Fibrinogen levels	1.000000e-142
GCST006015_1	Fibrinogen levels	1.000000e-11

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases expression, decreases methylation	2
Air Pollutants	affects expression, increases abundance, decreases expression	2
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
dicrotophos	decreases expression	1
triphenyl phosphate	affects expression	1
deoxynivalenol	increases expression	1
beta-lapachone	increases expression	1
sodium arsenite	increases expression	1
2-bromopalmitate	decreases reaction, increases abundance, increases palmitoylation	1
cupric oxide	increases expression	1
beta-methylcholine	affects expression	1
nutlin 3	affects cotreatment, increases secretion	1
ICG 001	decreases expression	1
(4-amino-1,4-dihydro-3-(2-pyridyl)-5-thioxo-1,2,4-triazole)copper(II)	increases expression	1
picoxystrobin	increases expression	1
Irinotecan	affects cotreatment, increases expression	1
Sunitinib	increases expression	1
Fulvestrant	increases methylation	1
Atrazine	increases expression	1
Cadmium	increases palmitoylation, decreases reaction, increases abundance	1
Dactinomycin	affects cotreatment, increases secretion	1
Diethylstilbestrol	decreases expression	1
Fluorouracil	increases expression, affects cotreatment	1
Hydralazine	affects cotreatment, increases expression	1
Hydrogen Peroxide	affects expression	1
Ivermectin	decreases expression	1
Ozone	affects expression, increases abundance	1
Ribonucleotides	affects binding	1
Theophylline	increases expression	1
Thiram	increases expression	1

Clinical trials (associated diseases)

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