PPP1R8

Summary

PPP1R8 (protein phosphatase 1 regulatory subunit 8, HGNC:9296) is a protein-coding gene on chromosome 1p35.3, encoding Nuclear inhibitor of protein phosphatase 1 (Q12972). Inhibitor subunit of the major nuclear protein phosphatase-1 (PP-1). It is a common-essential gene (DepMap: required in 98.5% of cancer cell lines).

This gene, through alternative splicing, encodes three different isoforms. Two of the protein isoforms encoded by this gene are specific inhibitors of type 1 serine/threonine protein phosphatases and can bind but not cleave RNA. The third protein isoform lacks the phosphatase inhibitory function but is a single-strand endoribonuclease comparable to RNase E of E. coli. This isoform requires magnesium for its function and cleaves specific sites in A+U-rich regions of RNA.

Source: NCBI Gene 5511 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 23 total
• Cancer dependency (DepMap): dependent in 98.5% of screened cell lines (common-essential)
• MANE Select transcript: NM_014110

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9296
Approved symbol	PPP1R8
Name	protein phosphatase 1 regulatory subunit 8
Location	1p35.3
Locus type	gene with protein product
Status	Approved
Aliases	ard-1, NIPP-1, PRO2047, ARD1, NIPP1
Ensembl gene	ENSG00000117751
Ensembl biotype	protein_coding
OMIM	602636
Entrez	5511

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 6 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000236412, ENST00000311772, ENST00000373931, ENST00000431586, ENST00000486634, ENST00000876353, ENST00000929766

RefSeq mRNA: 3 — MANE Select: NM_014110 NM_002713, NM_014110, NM_138558

CCDS: CCDS311, CCDS312, CCDS313

Canonical transcript exons

ENST00000311772 — 7 exons

Exon	Start	End
ENSE00001435421	27830782	27830891
ENSE00001949814	27850093	27851676
ENSE00003461118	27847028	27847092
ENSE00003574066	27841014	27841234
ENSE00003613106	27832756	27832816
ENSE00003676902	27843186	27843330
ENSE00003693617	27838699	27838852

Expression profiles

Bgee: expression breadth ubiquitous, 288 present calls, max score 92.92.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 9.6769 / max 68.3181, expressed in 1795 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
1747	9.6769	1795

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
calcaneal tendon	UBERON:0003701	92.92	gold quality
ventricular zone	UBERON:0003053	92.74	gold quality
islet of Langerhans	UBERON:0000006	92.33	gold quality
ganglionic eminence	UBERON:0004023	91.99	gold quality
stromal cell of endometrium	CL:0002255	91.96	gold quality
embryo	UBERON:0000922	91.70	gold quality
cortical plate	UBERON:0005343	91.69	gold quality
smooth muscle tissue	UBERON:0001135	91.01	gold quality
lymph node	UBERON:0000029	90.22	gold quality
endometrium	UBERON:0001295	90.08	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	90.06	gold quality
granulocyte	CL:0000094	90.05	gold quality
leukocyte	CL:0000738	89.81	gold quality
mucosa of sigmoid colon	UBERON:0004993	89.75	gold quality
bone marrow	UBERON:0002371	89.73	gold quality
rectum	UBERON:0001052	89.71	gold quality
mononuclear cell	CL:0000842	89.66	gold quality
spinal cord	UBERON:0002240	89.65	gold quality
monocyte	CL:0000576	89.64	gold quality
placenta	UBERON:0001987	89.40	gold quality
palpebral conjunctiva	UBERON:0001812	89.34	gold quality
esophagus squamous epithelium	UBERON:0006920	89.16	gold quality
penis	UBERON:0000989	89.12	gold quality
gall bladder	UBERON:0002110	89.05	gold quality
hair follicle	UBERON:0002073	88.98	gold quality
popliteal artery	UBERON:0002250	88.98	gold quality
uterus	UBERON:0000995	88.97	gold quality
tibial artery	UBERON:0007610	88.97	gold quality
fallopian tube	UBERON:0003889	88.93	gold quality
oviduct epithelium	UBERON:0004804	88.90	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-3929	yes	127.06
E-ANND-3	yes	3.33

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): POU5F1

miRNA regulators (miRDB)

73 targeting PPP1R8, 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-4533	100.00	69.48	2758
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-4775	99.98	75.00	6394
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-10523-5P	99.91	69.22	2038
HSA-MIR-4493	99.90	66.48	977
HSA-MIR-380-3P	99.89	70.18	1978
HSA-MIR-4496	99.88	68.89	2236
HSA-MIR-3941	99.86	70.54	2735
HSA-MIR-629-3P	99.85	67.99	1875
HSA-MIR-3180-5P	99.82	69.12	2422
HSA-MIR-4713-5P	99.78	67.80	1794
HSA-MIR-3934-3P	99.76	65.51	1351
HSA-MIR-4766-5P	99.75	69.23	2662
HSA-MIR-4802-3P	99.72	70.13	1273
HSA-MIR-548M	99.70	68.87	1749
HSA-MIR-466	99.67	70.85	2863
HSA-MIR-3158-5P	99.65	67.51	1763
HSA-MIR-1260A	99.61	66.67	1098
HSA-MIR-1260B	99.61	66.67	1098
HSA-MIR-6861-3P	99.60	68.46	444
HSA-MIR-4762-5P	99.57	68.54	1424
HSA-MIR-12122	99.56	69.33	1672
HSA-MIR-4276	99.56	67.66	2514
HSA-MIR-4672	99.50	71.58	2893
HSA-MIR-136-5P	99.50	67.26	1153

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 98.5% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 13)

• The protein phosphatase-1 regulator NIPP1 is also a splicing factor involved in a late step of spliceosome assembly (PMID:11909864)
• NIPP1 has a role in the nuclear targeting and/or retention of PP1 (PMID:15501817)
• We demonstrate that interaction with NIPP1 mediates decreased PP1gamma activity in hypoxia, an event which may constitute an inherent part of the cellular oxygen-sensing machinery and may play a role in physiologic adaptation to hypoxia. (PMID:16826568)
• Required for the global trimethylation of histone3 at lysine27 and is implicated in gene silencing by enhancer of zeste homolog (EZH)2. (PMID:17724462)
• NIPP1 is present in a complex with EED and EZH2 in vivo and has distinct binding sites for these proteins. (PMID:17804093)
• NMR structure of the NIPP1 FHA domain. (PMID:18253837)
• NIPP1 works as a molecular sensor for PP1 to recognize phosphorylated Sap155. (PMID:18842582)
• PP1/NIPP1 is a novel molecular compass that controls directed cell migration. (PMID:22815811)
• The molecular basis by which NIPP1 directs PP1 substrate specificity in the nucleus. (PMID:22940584)
• Data suggest overexpression of NIPP1 in HeLa cells causes induction of genes of mesenchymal lineage with reduction in cell proliferation; thus, key dephosphorylation events may be involved in epithelial-mesenchymal transition or transdifferentiation. (PMID:25907536)
• NIPP1 could be activated by hypoxia and contributed to hypoxia-induced invasive and metastatic potential in hepatocellular carcinoma. (PMID:27644248)
• PP1-NIPP1 expression resulted in the build up of RNA-DNA hybrids (R-loops), enhanced chromatin compaction and a diminished repair of DNA double-strand breaks. (PMID:29898919)
• PP1 regulatory subunit NIPP1 regulates transcription of E2F1 target genes following DNA damage. (PMID:33939241)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	ppp1r8a	ENSDARG00000007186
danio_rerio	ppp1r8b	ENSDARG00000022430
mus_musculus	Ppp1r8	ENSMUSG00000028882
rattus_norvegicus	Ppp1r8	ENSRNOG00000059550
drosophila_melanogaster	NiPp1	FBGN0026402
caenorhabditis_elegans	sut-6	WBGENE00015233

Paralogs (2): SLC4A1AP (ENSG00000163798), SNIP1 (ENSG00000163877)

Protein

Protein identifiers

Nuclear inhibitor of protein phosphatase 1 — Q12972 (reviewed: Q12972)

Alternative names: Protein phosphatase 1 regulatory inhibitor subunit 8

All UniProt accessions (3): A0A0A0MT09, Q12972, Q6ICT4

UniProt curated annotations — full annotation on UniProt →

Function. Inhibitor subunit of the major nuclear protein phosphatase-1 (PP-1). It has RNA-binding activity but does not cleave RNA and may target PP-1 to RNA-associated substrates. May also be involved in pre-mRNA splicing. Binds DNA and might act as a transcriptional repressor. Seems to be required for cell proliferation. Isoform Gamma is a site-specific single-strand endoribonuclease that cleaves single strand RNA 3’ to purines and pyrimidines in A+U-rich regions. It generates 5’-phosphate termini at the site of cleavage. This isoform does not inhibit PP-1. May be implicated in mRNA splicing.

Subunit / interactions. Interacts with phosphorylated CDC5L, SF3B1 and MELK. Interacts with EED, in a nucleic acid-stimulated manner. Part of a complex consisting of PPP1R8, EED, HDAC2 and PP-1. Part of the spliceosome. Interacts with PPP1CA, PPP1CB and PPP1CC.

Subcellular location. Nucleus. Nucleus speckle Cytoplasm.

Tissue specificity. Ubiquitously expressed, with highest levels in heart and skeletal muscle, followed by brain, placenta, lung, liver and pancreas. Less abundant in kidney. The concentration and ratio between isoforms is cell-type dependent. Isoform Alpha (>90%) and isoform Beta were found in brain, heart and kidney. Isoform Gamma is mainly found in B-cells and T-lymphocytes, and has been found in 293 embryonic kidney cells.

Post-translational modifications. May be inactivated by phosphorylation on Ser-199 or Ser-204. Phosphorylated by Lyn in vitro on Tyr-264, and also on Tyr-335 in the presence of RNA.

Cofactor. Endoribonuclease function is magnesium-dependent.

Domain organisation. Has a basic N- and C-terminal and an acidic central domain. The FHA domain mediates interactions with threonine-phosphorylated MELK.

Miscellaneous. A synthetic peptide, NIPP-1(330-351), is able to inhibit PP-1. Phosphorylation of Tyr-335 reduces PP-1 inhibition, whereas phosphorylation of Thr-346 or Ser-348 has no effect.

Isoforms (3)

UniProt ID	Names	Canonical?
Q12972-1	Alpha	yes
Q12972-2	Beta, Delta
Q12972-3	Gamma, ARD-1

RefSeq proteins (3): NP_002704, NP_054829, NP_612568 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000253	FHA_dom	Domain
IPR008984	SMAD_FHA_dom_sf	Homologous_superfamily
IPR050923	Cell_Proc_Reg/RNA_Proc	Family

Pfam: PF00498

UniProt features (35 total): mutagenesis site 12, region of interest 8, modified residue 7, short sequence motif 2, splice variant 2, chain 1, domain 1, helix 1, strand 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
3V4Y	X-RAY DIFFRACTION	2.1

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q12972-F1	68.40	0.31

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 (7): 161, 178, 199, 204, 249, 264, 335

Mutagenesis-validated functional residues (12):

Position	Phenotype
68–71	abolishes interaction with cdc5l, sf3b1 and melk, and localization in nuclear speckles. no effect on repressor activity.
193–197	no effect on interaction with eed.
195–197	abolishes nuclear import; when associated with a-234–237-a.
199	no change in subcellular location, no effect on interaction with eed or repressor activity; when associated with a-204 o
201	reduces pp-1 binding, no effect on subcellular location or repressor activity and prevents retargeting of ppp1ca and ppp
203	reduces pp-1 binding, no effect on subcellular location or repressor activity and prevents retargeting of ppp1ca and ppp
204	no change in subcellular location, no effect on interaction with eed or repressor activity; when associated with a-199 o
234–237	abolishes nuclear import; when associated with a-195-197-a.
264	abolishes in vitro phosphorylation of isoform gamma by lyn.
335	decreases the ability of isoform gamma to bind and inhibit pp-1.
346	no effect on the ability of isoform gamma to inhibit pp-1.
348	no effect on the ability of isoform gamma to inhibit pp-1.

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: 164 (showing top): E2F_Q4, E2F_Q4_01, MULLIGHAN_NPM1_SIGNATURE_3_UP, GOMF_ENDONUCLEASE_ACTIVITY, GOMF_RNA_NUCLEASE_ACTIVITY, GOMF_NUCLEASE_ACTIVITY, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, WEIGEL_OXIDATIVE_STRESS_BY_TBH_AND_H2O2, PUJANA_CHEK2_PCC_NETWORK, HOFMANN_MYELODYSPLASTIC_SYNDROM_RISK_DN, GCM_PPP1CC, MCBRYAN_PUBERTAL_BREAST_4_5WK_DN, E2F_Q3, GOMF_RNA_ENDONUCLEASE_ACTIVITY, REACTOME_MRNA_3_END_PROCESSING

GO Biological Process (4): mRNA processing (GO:0006397), RNA catabolic process (GO:0006401), cell population proliferation (GO:0008283), RNA splicing (GO:0008380)

GO Molecular Function (13): DNA binding (GO:0003677), RNA binding (GO:0003723), mRNA binding (GO:0003729), RNA endonuclease activity (GO:0004521), protein serine/threonine phosphatase inhibitor activity (GO:0004865), ribonuclease E activity (GO:0008995), molecular function inhibitor activity (GO:0140678), nuclease activity (GO:0004518), endonuclease activity (GO:0004519), protein phosphatase inhibitor activity (GO:0004864), protein binding (GO:0005515), hydrolase activity (GO:0016787), protein phosphatase regulator activity (GO:0019888)

GO Cellular Component (5): nucleus (GO:0005634), nucleoplasm (GO:0005654), spliceosomal complex (GO:0005681), cytoplasm (GO:0005737), nuclear speck (GO:0016607)

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
RNA processing	2
nucleic acid binding	2
phosphoprotein phosphatase activity	2
cellular anatomical structure	2
mRNA metabolic process	1
RNA metabolic process	1
nucleic acid catabolic process	1
cellular process	1
RNA binding	1
endonuclease activity	1
RNA nuclease activity	1
protein serine/threonine phosphatase activity	1
protein phosphatase inhibitor activity	1
RNA endonuclease activity producing 5’-phosphomonoesters, hydrolytic mechanism	1
molecular function regulator activity	1
catalytic activity, acting on a nucleic acid	1
nuclease activity	1
phosphatase inhibitor activity	1
protein phosphatase regulator activity	1
binding	1
catalytic activity	1
phosphatase regulator activity	1
protein phosphatase binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
nuclear protein-containing complex	1
ribonucleoprotein complex	1
intracellular anatomical structure	1
nuclear ribonucleoprotein granule	1

Protein interactions and networks

STRING

1782 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PPP1R8	PNPT1	Q8TCS8	952
PPP1R8	SF3B1	O75533	913
PPP1R8	PPP1R3B	Q86XI6	863
PPP1R8	PPP1R3C	Q9UQK1	848
PPP1R8	PPP1R3A	Q16821	774
PPP1R8	PPP1CC	P36873	760
PPP1R8	PPP1R10	Q96QC0	755
PPP1R8	PPP1CB	P37140	734
PPP1R8	PPP1CA	P08129	733
PPP1R8	CDC5L	Q99459	646
PPP1R8	PPP1R7	Q15435	620
PPP1R8	PPP1R12A	O14974	594
PPP1R8	MELK	Q14680	539
PPP1R8	PPP1R15A	O75807	520
PPP1R8	PPP1R11	O60927	507

IntAct

81 interactions, top by confidence:

A	B	Type	Score
PPP1R8	PPP1CA	psi-mi:“MI:0914”(association)	0.910
PPP1CA	PPP1R8	psi-mi:“MI:0915”(physical association)	0.910
PPP1R8	PPP1CA	psi-mi:“MI:0915”(physical association)	0.910
HSPA8	GAK	psi-mi:“MI:0914”(association)	0.760
PPP1CB	CCDC85C	psi-mi:“MI:0914”(association)	0.750
PPP1CB	CCDC85C	psi-mi:“MI:2364”(proximity)	0.750
PPP1CC	CCDC85C	psi-mi:“MI:0914”(association)	0.740
PPP1CC	CCDC85C	psi-mi:“MI:2364”(proximity)	0.740
PPP1CA	CCDC85C	psi-mi:“MI:0914”(association)	0.670
PPP1CA	CCDC85C	psi-mi:“MI:2364”(proximity)	0.670
PPP1R8	LRRK2	psi-mi:“MI:0407”(direct interaction)	0.590
PPP1R8	APPBP2	psi-mi:“MI:0915”(physical association)	0.560
APPBP2	PPP1R8	psi-mi:“MI:0915”(physical association)	0.560
SNRNP27	UBA6	psi-mi:“MI:0914”(association)	0.530
CYP1A1	SNX3	psi-mi:“MI:0914”(association)	0.530
WASHC3	WASH3P	psi-mi:“MI:0914”(association)	0.530
PPP1CA	PQBP1	psi-mi:“MI:0914”(association)	0.510
CDC5L	PPP1R8	psi-mi:“MI:0915”(physical association)	0.510
PPP1R8	CDC5L	psi-mi:“MI:0915”(physical association)	0.510
CPSF6	DDX39A	psi-mi:“MI:0914”(association)	0.480
Cep72		psi-mi:“MI:0915”(physical association)	0.400
PPP1R8	SF3A2	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (165): APPBP2 (Two-hybrid), PPP1R8 (Affinity Capture-MS), PPP1R8 (Affinity Capture-MS), PPP1R8 (Affinity Capture-MS), PPP1R8 (Affinity Capture-MS), DDX1 (Co-fractionation), FAM98B (Co-fractionation), PPP1CA (Co-fractionation), PPP1CC (Co-fractionation), PPP1R8 (Co-fractionation), PPP1R8 (Co-fractionation), SHC1 (Co-fractionation), SHMT2 (Co-fractionation), SNUPN (Co-fractionation), VPS4B (Co-fractionation)

ESM2 similar proteins: A0AVK6, D4A4D7, E1BE02, F1LMN3, F1QZ88, F7EA39, O94885, P0C6C1, P59808, P70121, Q08AZ1, Q12972, Q28147, Q2HNT1, Q2HNT2, Q3UG20, Q3UH68, Q3UUF8, Q58FA4, Q5R7F2, Q5RIX9, Q5RJ80, Q5ZJ69, Q63028, Q69ZW3, Q6P2L6, Q6S7F2, Q6ZQ03, Q6ZSZ6, Q80Z38, Q86UP3, Q8BLB8, Q8NDI1, Q8R3G1, Q8R515, Q8TEW0, Q92870, Q96AV8, Q96DT7, Q99NH2

Diamond homologs: A0JM08, B7SY83, Q12972, Q28147, Q498L0, Q4JVU0, Q80U49, Q8R3G1, Q9BWU0, Q9FIK2, Q9Y4F5, P34648, Q54VU4, A0QNG6, Q5M9G6, Q5SW79, Q6A065, Q8BIZ6, Q8TAD8, Q8W4D8, Q6NHD4

SIGNOR signaling

11 interactions.

A	Effect	B	Mechanism
PPP1R8	“up-regulates activity”	EZH2	binding
PRKACA	“down-regulates activity”	PPP1R8	phosphorylation
CSNK2A1	“up-regulates activity”	PPP1R8	phosphorylation
CSNK2A2	“up-regulates activity”	PPP1R8	phosphorylation
LYN	“down-regulates activity”	PPP1R8	phosphorylation
PPP1R8	“down-regulates activity”	PPP1CA	binding
PPP1R8	“down-regulates activity”	PP1	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 81 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 Polyadenylation	11	15.6×	1e-08
mRNA Splicing	8	14.2×	7e-06
mRNA Splicing - Major Pathway	16	14.1×	4e-12
Processing of Capped Intron-Containing Pre-mRNA	8	10.6×	4e-05
CHD1 and CHD2 subfamily	5	8.8×	8e-03
Dengue Virus-Host Interactions	11	8.1×	7e-06
Metabolism of RNA	11	7.4×	1e-05

GO biological processes:

GO term	Partners	Fold	FDR
spliceosomal snRNP assembly	5	38.2×	5e-05
mRNA splicing, via spliceosome	16	19.3×	8e-14

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	19
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1063 predictions. Top by Δscore:

Variant	Effect	Δscore
1:27832754:AG:A	acceptor_gain	1.0000
1:27832755:GG:G	acceptor_gain	1.0000
1:27838697:A:AG	acceptor_gain	1.0000
1:27838698:G:GG	acceptor_gain	1.0000
1:27838698:GA:G	acceptor_gain	1.0000
1:27838848:CAGTA:C	donor_gain	1.0000
1:27838850:GTA:G	donor_gain	1.0000
1:27838853:G:GG	donor_gain	1.0000
1:27841158:GAGA:G	donor_gain	1.0000
1:27841220:GAAAC:G	donor_gain	1.0000
1:27841221:A:T	donor_gain	1.0000
1:27843170:AT:A	acceptor_gain	1.0000
1:27843171:T:G	acceptor_gain	1.0000
1:27843171:T:TA	acceptor_gain	1.0000
1:27843174:ACCCT:A	acceptor_gain	1.0000
1:27843178:T:A	acceptor_gain	1.0000
1:27843179:G:A	acceptor_gain	1.0000
1:27843184:A:AG	acceptor_gain	1.0000
1:27843185:G:GG	acceptor_gain	1.0000
1:27847023:TGCA:T	acceptor_loss	1.0000
1:27847024:GCA:G	acceptor_loss	1.0000
1:27847025:CA:C	acceptor_loss	1.0000
1:27847026:A:AG	acceptor_gain	1.0000
1:27847026:AGAG:A	acceptor_gain	1.0000
1:27847027:G:GG	acceptor_gain	1.0000
1:27847027:GA:G	acceptor_gain	1.0000
1:27847027:GAGG:G	acceptor_gain	1.0000
1:27850061:A:AG	acceptor_gain	1.0000
1:27850062:A:G	acceptor_gain	1.0000
1:27850079:ATCGT:A	acceptor_gain	1.0000

AlphaMissense

2292 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:27832756:G:C	W19C	1.000
1:27832756:G:T	W19C	1.000
1:27832775:G:C	G26R	1.000
1:27832776:G:A	G26D	1.000
1:27832781:C:G	H28D	1.000
1:27832783:T:A	H28Q	1.000
1:27832783:T:G	H28Q	1.000
1:27832785:T:A	L29Q	1.000
1:27832785:T:C	L29P	1.000
1:27832785:T:G	L29R	1.000
1:27832791:T:A	V31E	1.000
1:27832796:A:G	K33E	1.000
1:27832797:A:T	K33I	1.000
1:27832798:A:C	K33N	1.000
1:27832798:A:T	K33N	1.000
1:27838699:A:G	K40E	1.000
1:27838701:A:C	K40N	1.000
1:27838701:A:T	K40N	1.000
1:27838703:T:C	L41P	1.000
1:27838709:T:A	I43N	1.000
1:27838712:A:T	D44V	1.000
1:27838726:T:G	Y49D	1.000
1:27838733:T:C	F51S	1.000
1:27838735:G:A	G52R	1.000
1:27838735:G:C	G52R	1.000
1:27838735:G:T	G52W	1.000
1:27838736:G:A	G52E	1.000
1:27838736:G:T	G52V	1.000
1:27838738:A:G	R53G	1.000
1:27838739:G:C	R53T	1.000

dbSNP variants (sampled 300 via entrez): RS1000052398 (1:27842296 C>G,T), RS1000187399 (1:27841887 T>C), RS1000233580 (1:27829527 A>C,G), RS1000325780 (1:27836093 G>A), RS1000452564 (1:27829387 C>A,G), RS1000549268 (1:27842088 C>G), RS1000657850 (1:27840627 A>G), RS1000658436 (1:27834077 A>G), RS1000766647 (1:27835008 A>G,T), RS1000848853 (1:27830527 G>C), RS1000922867 (1:27840329 C>G), RS1000932594 (1:27837666 T>C), RS1000990059 (1:27837304 G>A), RS1001155965 (1:27843699 T>G), RS1001194549 (1:27830735 G>A,T)

Disease associations

OMIM: gene MIM:602636 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression	5
Cadmium Chloride	decreases expression, increases abundance, increases expression	2
2,4,6-tribromophenol	decreases expression	1
bisphenol A	decreases expression	1
nobiletin	decreases expression, decreases reaction	1
sodium arsenate	decreases expression, decreases reaction	1
decabromobiphenyl ether	decreases expression	1
arsenite	affects binding, decreases reaction	1
sodium arsenite	increases abundance, increases expression, affects cotreatment	1
manganese chloride	increases abundance, increases expression, affects cotreatment	1
di-n-butylphosphoric acid	affects expression	1
cylindrospermopsin	increases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
pentabrominated diphenyl ether 100	decreases expression	1
hexabrominated diphenyl ether 153	decreases expression	1
Vorinostat	decreases expression	1
Acetaminophen	decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Arsenic	affects cotreatment, increases abundance, increases expression	1
Atrazine	decreases expression	1
Benzo(a)pyrene	increases methylation, affects methylation	1
Cadmium	increases abundance, increases expression	1
Hydrogen Peroxide	decreases expression	1
Ivermectin	decreases expression	1
Manganese	increases abundance, increases expression, affects cotreatment	1
Rotenone	decreases expression	1
Smoke	decreases expression	1
Tetrachlorodibenzodioxin	affects expression	1
Copper Sulfate	decreases expression	1
tert-Butylhydroperoxide	decreases expression	1

Clinical trials (associated diseases)

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