CNOT8

Summary

CNOT8 (CCR4-NOT transcription complex subunit 8, HGNC:9207) is a protein-coding gene on chromosome 5q33.2, encoding CCR4-NOT transcription complex subunit 8 (Q9UFF9). Has 3’-5’ poly(A) exoribonuclease activity for synthetic poly(A) RNA substrate.

Enables poly(A)-specific ribonuclease activity. Involved in miRNA-mediated gene silencing by mRNA destabilization and positive regulation of cell population proliferation. Located in nucleus. Part of CCR4-NOT complex.

Source: NCBI Gene 9337 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 34 total
• MANE Select transcript: NM_001301073

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9207
Approved symbol	CNOT8
Name	CCR4-NOT transcription complex subunit 8
Location	5q33.2
Locus type	gene with protein product
Status	Approved
Aliases	CAF1, hCAF1, CALIF
Ensembl gene	ENSG00000155508
Ensembl biotype	protein_coding
OMIM	603731
Entrez	9337

Gene structure

Transcript identifiers

Ensembl transcripts: 91 — 84 protein_coding, 4 protein_coding_CDS_not_defined, 2 nonsense_mediated_decay, 1 retained_intron

ENST00000285896, ENST00000403027, ENST00000517568, ENST00000517876, ENST00000518028, ENST00000518775, ENST00000518782, ENST00000519211, ENST00000519394, ENST00000519404, ENST00000519430, ENST00000519903, ENST00000520472, ENST00000520671, ENST00000521174, ENST00000521402, ENST00000521450, ENST00000521583, ENST00000521729, ENST00000522139, ENST00000522458, ENST00000522644, ENST00000523270, ENST00000523698, ENST00000524105, ENST00000873116, ENST00000873117, ENST00000873118, ENST00000873119, ENST00000873120, ENST00000873121, ENST00000873122, ENST00000873123, ENST00000873124, ENST00000873125, ENST00000873126, ENST00000873127, ENST00000873128, ENST00000873129, ENST00000873130, ENST00000873131, ENST00000873132, ENST00000873133, ENST00000873134, ENST00000873135, ENST00000873136, ENST00000873137, ENST00000873138, ENST00000873139, ENST00000873140, ENST00000873141, ENST00000873142, ENST00000873143, ENST00000873144, ENST00000873145, ENST00000873146, ENST00000873147, ENST00000873148, ENST00000873149, ENST00000873150, ENST00000873151, ENST00000873152, ENST00000873153, ENST00000873154, ENST00000873155, ENST00000927853, ENST00000927854, ENST00000927855, ENST00000927856, ENST00000927857, ENST00000927858, ENST00000927859, ENST00000927860, ENST00000927861, ENST00000927862, ENST00000927863, ENST00000957158, ENST00000957159, ENST00000957160, ENST00000957161, ENST00000957162, ENST00000957163, ENST00000957164, ENST00000957165, ENST00000957166, ENST00000957167, ENST00000957168, ENST00000957169, ENST00000957170, ENST00000957171, ENST00000957172

RefSeq mRNA: 9 — MANE Select: NM_001301073 NM_001301073, NM_001301074, NM_001301075, NM_001301077, NM_001301080, NM_001301082, NM_001301083, NM_001301086, NM_004779

CCDS: CCDS4329, CCDS75361, CCDS78074, CCDS78075

Canonical transcript exons

ENST00000285896 — 7 exons

Exon	Start	End
ENSE00001021164	154875290	154876792
ENSE00002109928	154858627	154858768
ENSE00003505608	154865192	154865385
ENSE00003537719	154872541	154872651
ENSE00003603360	154871730	154871874
ENSE00003616901	154863207	154863395
ENSE00003685454	154870661	154870822

Expression profiles

Bgee: expression breadth ubiquitous, 295 present calls, max score 97.90.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 28.2794 / max 155.1247, expressed in 1817 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
59756	19.8043	1811
59753	3.1199	1492
59754	2.9337	1258
59755	2.4214	1198

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	97.90	gold quality
oocyte	CL:0000023	97.57	gold quality
monocyte	CL:0000576	97.21	gold quality
mononuclear cell	CL:0000842	97.11	gold quality
leukocyte	CL:0000738	97.07	gold quality
sperm	CL:0000019	96.82	gold quality
right lung	UBERON:0002167	96.58	gold quality
ganglionic eminence	UBERON:0004023	96.54	gold quality
calcaneal tendon	UBERON:0003701	96.51	gold quality
cortical plate	UBERON:0005343	96.50	gold quality
granulocyte	CL:0000094	95.83	gold quality
male germ cell	CL:0000015	95.75	gold quality
rectum	UBERON:0001052	95.65	gold quality
upper lobe of left lung	UBERON:0008952	95.50	gold quality
ventricular zone	UBERON:0003053	95.49	gold quality
synovial joint	UBERON:0002217	95.37	gold quality
upper lobe of lung	UBERON:0008948	95.23	gold quality
lymph node	UBERON:0000029	95.15	gold quality
blood	UBERON:0000178	95.14	gold quality
mucosa of paranasal sinus	UBERON:0005030	94.90	gold quality
adrenal tissue	UBERON:0018303	94.77	gold quality
tendon	UBERON:0000043	94.74	gold quality
popliteal artery	UBERON:0002250	94.68	gold quality
tibial artery	UBERON:0007610	94.68	gold quality
bone marrow	UBERON:0002371	94.61	gold quality
right adrenal gland cortex	UBERON:0035827	94.58	gold quality
subcutaneous adipose tissue	UBERON:0002190	94.57	gold quality
saphenous vein	UBERON:0007318	94.41	gold quality
endometrium	UBERON:0001295	94.40	gold quality
descending thoracic aorta	UBERON:0002345	94.38	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-MTAB-6379	no	2182.77
E-ANND-3	no	0.00

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

2 targets.

Target	Regulation
MSMB	Unknown
PMP22	Unknown

Upstream regulators (CollecTRI, top): FOXO1

miRNA regulators (miRDB)

73 targeting CNOT8, 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-3613-3P	100.00	76.36	7965
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-6793-5P	99.97	65.95	758
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-2110	99.96	66.68	1930
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-LET-7C-3P	99.95	73.42	2862
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-3912-5P	99.95	66.11	925
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-3671	99.90	73.04	3897
HSA-MIR-374A-5P	99.90	71.34	2923
HSA-MIR-374B-5P	99.90	69.98	2734
HSA-MIR-8087	99.90	69.55	1351
HSA-MIR-4271	99.88	68.32	2244

Literature-anchored findings (GeneRIF, showing 16)

• Cellular POP2 protein binds to central adaptor protein ASC and pathogen recognition receptor PAN1, blocking formation of cryopyrin and PAN1-containing inflammasomes, activation of caspase-1, and subsequent processing of bioactive interleukin-1 beta. (PMID:17178784)
• Data show that Ccr4-Not function in RNA splicing and nuclear export, and that CNOT8 binds CNOT6 in yeast two-hybrid assays. (PMID:19558367)
• Data show that efficient cell proliferation requires both CNOT7 and CNOT8, although combined knockdown of both subunits further reduces cell proliferation indicating partial redundancy between these proteins. (PMID:19605561)
• CCR4-NOT is the deadenylase that removes poly(A) from messages destabilized by miRNAs in human cells. (PMID:20065043)
• MK2 phosphorylation reduces the ability of TTP to promote deadenylation by inhibiting the recruitment of CAF1 deadenylase in a mechanism that does not involve sequestration of TTP by 14-3-3. (PMID:20595389)
• Tob interactions with Caf1 and a C-terminal domain of PABPC1 (PMID:20595394)
• Together, these results indicate that Tob mediates the recruitment of Caf1 to the target of CPEB3 and elicits deadenylation and decay of the mRNA. (PMID:21336257)
• N-terminus played a role in modulating hCaf1 activity, stability and aggregation (PMID:22683897)
• The NOT1 MIF4G domain binds CAF1 through a pre-formed interface and leaves the CAF1 catalytic site fully accessible to RNA substrates. (PMID:22977175)
• The anti-proliferative activity of BTG/TOB proteins is mediated via the Caf1a (CNOT7) and Caf1b (CNOT8) deadenylase subunits of the Ccr4-not complex. (PMID:23236473)
• The loss of CAF-1 p48 subunit causes a strong defect in packaging DNA into nucleosomes. (PMID:24036545)
• show that SMG7 binds directly to POP2, a catalytic subunit of the CCR4-NOT deadenylase complex, and elicits deadenylation-dependent decapping and 5’-to-3’ decay of NMD targets (PMID:24115769)
• CNOT7/hCAF1 is involved in ICAM-1 and IL-8 regulation by TTP in HPMEC. (PMID:25038453)
• These results indicate that Caf1 and Ccr4 cooperate in mRNA deadenylation and suggest that the enzyme activities of Caf1 and Ccr4 are regulated via allosteric interactions within the nuclease module. (PMID:25944446)
• A network-based variable selection approach for identification of modules and biomarker genes associated with end-stage kidney disease. (PMID:31464346)
• Frequent loss of BTG1 activity and impaired interactions with the Caf1 subunit of the Ccr4-Not deadenylase in non-Hodgkin lymphoma. (PMID:33021411)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	cnot8	ENSDARG00000020043
mus_musculus	Cnot8	ENSMUSG00000020515
rattus_norvegicus	Cnot8	ENSRNOG00000002630
drosophila_melanogaster	Pop2	FBGN0036239
caenorhabditis_elegans		WBGENE00000369

Paralogs (1): CNOT7 (ENSG00000198791)

Protein

Protein identifiers

CCR4-NOT transcription complex subunit 8 — Q9UFF9 (reviewed: Q9UFF9)

Alternative names: CAF1-like protein, CAF2, CCR4-associated factor 8, Caf1b

All UniProt accessions (11): Q9UFF9, B7Z9U0, E5RFJ4, E5RGE4, E5RHD6, E5RHG0, E5RHL9, E5RHP3, E5RIL2, E5RIU0, E5RJC5

UniProt curated annotations — full annotation on UniProt →

Function. Has 3’-5’ poly(A) exoribonuclease activity for synthetic poly(A) RNA substrate. Its function seems to be partially redundant with that of CNOT7. Catalytic component of the CCR4-NOT complex which is linked to various cellular processes including bulk mRNA degradation, miRNA-mediated repression, translational repression during translational initiation and general transcription regulation. During miRNA-mediated repression the complex also seems to act as translational repressor during translational initiation. Additional complex functions may be a consequence of its influence on mRNA expression. Associates with members of the BTG family such as TOB1 and BTG2 and is required for their anti-proliferative activity.

Subunit / interactions. Component of the CCR4-NOT complex; distinct complexes seem to exist that differ in the participation of probably mutually exclusive catalytic subunits; the complex contains two deadenylase subunits, CNOT6 or CNOT6L, and CNOT7 or CNOT8. In the complex interacts directly with CNOT1. Interacts with BTG1, BTG2 and TOB1. Interacts with BTG4.

Subcellular location. Cytoplasm. Nucleus.

Similarity. Belongs to the CAF1 family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q9UFF9-1	1	yes
Q9UFF9-2	2
Q9UFF9-3	3

RefSeq proteins (9): NP_001288002, NP_001288003, NP_001288004, NP_001288006, NP_001288009, NP_001288011, NP_001288012, NP_001288015, NP_004770 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR006941	RNase_CAF1	Family
IPR012337	RNaseH-like_sf	Homologous_superfamily
IPR036397	RNaseH_sf	Homologous_superfamily
IPR039637	CNOT7/CNOT8/Pop2	Family

Pfam: PF04857

UniProt features (15 total): binding site 5, sequence conflict 4, mutagenesis site 2, splice variant 2, chain 1, sequence variant 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
9E7U	ELECTRON MICROSCOPY	3.5

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UFF9-F1	90.51	0.83

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (5): 40; 40; 42; 161; 230

Mutagenesis-validated functional residues (2):

Position	Phenotype
42	impairs deadenylation and decay of mrnai-targeted mrna; when associated with a-40.
40	impairs deadenylation and decay of mrnai-targeted mrna; when associated with a-42.

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-429947	Deadenylation of mRNA
R-HSA-6804115	TP53 regulates transcription of additional cell cycle genes whose exact role in the p53 pathway remain uncertain
R-HSA-9820841	M-decay: degradation of maternal mRNAs by maternally stored factors

MSigDB gene sets: 187 (showing top): GSE45365_NK_CELL_VS_BCELL_DN, BORCZUK_MALIGNANT_MESOTHELIOMA_UP, GOMF_RNA_NUCLEASE_ACTIVITY, GOBP_REGULATION_OF_MRNA_CATABOLIC_PROCESS, GOMF_NUCLEASE_ACTIVITY, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, CACCAGC_MIR138, GOBP_TRANSLATION, GOBP_POST_TRANSCRIPTIONAL_REGULATION_OF_GENE_EXPRESSION, GOBP_REGULATION_OF_CATABOLIC_PROCESS, GOBP_POSITIVE_REGULATION_OF_CATABOLIC_PROCESS, GAZDA_DIAMOND_BLACKFAN_ANEMIA_PROGENITOR_DN, REACTOME_DEADENYLATION_OF_MRNA, GNF2_PAK2, ZHOU_INFLAMMATORY_RESPONSE_LIVE_DN

GO Biological Process (7): nuclear-transcribed mRNA catabolic process, deadenylation-dependent decay (GO:0000288), nuclear-transcribed mRNA poly(A) tail shortening (GO:0000289), regulation of translation (GO:0006417), positive regulation of cell population proliferation (GO:0008284), miRNA-mediated gene silencing by mRNA destabilization (GO:0035279), positive regulation of mRNA catabolic process (GO:0061014), regulatory ncRNA-mediated gene silencing (GO:0031047)

GO Molecular Function (9): 3’-5’-RNA exonuclease activity (GO:0000175), RNA binding (GO:0003723), poly(A)-specific ribonuclease activity (GO:0004535), metal ion binding (GO:0046872), nucleic acid binding (GO:0003676), nuclease activity (GO:0004518), exonuclease activity (GO:0004527), protein binding (GO:0005515), hydrolase activity (GO:0016787)

GO Cellular Component (6): P-body (GO:0000932), nucleus (GO:0005634), cytosol (GO:0005829), CCR4-NOT complex (GO:0030014), CCR4-NOT core complex (GO:0030015), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Deadenylation-dependent mRNA decay	1
TP53 Regulates Transcription of Cell Cycle Genes	1
Maternal to zygotic transition (MZT)	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
nuclear-transcribed mRNA catabolic process	2
mRNA destabilization	2
binding	2
cellular anatomical structure	2
intracellular protein-containing complex	2
nuclear-transcribed mRNA catabolic process, deadenylation-dependent decay	1
translation	1
post-transcriptional regulation of gene expression	1
regulation of protein metabolic process	1
cell population proliferation	1
regulation of cell population proliferation	1
positive regulation of cellular process	1
miRNA-mediated post-transcriptional gene silencing	1
mRNA catabolic process	1
positive regulation of catabolic process	1
regulation of mRNA catabolic process	1
positive regulation of mRNA metabolic process	1
negative regulation of gene expression	1
3’-5’ exonuclease activity	1
RNA exonuclease activity, producing 5’-phosphomonoesters	1
nucleic acid binding	1
3’-5’-RNA exonuclease activity	1
cation binding	1
catalytic activity, acting on a nucleic acid	1
nuclease activity	1
hydrolase activity, acting on ester bonds	1
catalytic activity	1
cytoplasmic ribonucleoprotein granule	1
intracellular membrane-bounded organelle	1
cytoplasm	1
CCR4-NOT complex	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

1202 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CNOT8	CNOT1	A5YKK6	999
CNOT8	CNOT3	O75175	997
CNOT8	CNOT6L	Q96LI5	997
CNOT8	CNOT6	Q9ULM6	997
CNOT8	CNOT2	Q9NZN8	995
CNOT8	CNOT9	Q92600	988
CNOT8	CNOT4	O95628	972
CNOT8	CNOT7	Q9UIV1	936
CNOT8	CNOT10	Q9H9A5	915
CNOT8	BTG4	Q9NY30	895
CNOT8	CNOT11	Q9UKZ1	802
CNOT8	TOB1	P50616	676
CNOT8	TOB2	Q14106	675
CNOT8	SMG5	Q9UPR3	646
CNOT8	DCP2	Q8IU60	644

IntAct

130 interactions, top by confidence:

A	B	Type	Score
TNRC6C	PABPC1	psi-mi:“MI:0914”(association)	0.910
CNOT8	CNOT1	psi-mi:“MI:0915”(physical association)	0.850
CNOT1	CNOT8	psi-mi:“MI:0915”(physical association)	0.850
CNOT8	BTG1	psi-mi:“MI:0915”(physical association)	0.830
BTG1	CNOT8	psi-mi:“MI:0915”(physical association)	0.830
CNOT6L	CNOT1	psi-mi:“MI:0914”(association)	0.810
PATL1	LSM1	psi-mi:“MI:0914”(association)	0.770
CNOT11	CNOT1	psi-mi:“MI:0914”(association)	0.770
CNOT8	CNOT6L	psi-mi:“MI:0915”(physical association)	0.750
CNOT6L	CNOT8	psi-mi:“MI:0915”(physical association)	0.750
CNOT2	CNOT1	psi-mi:“MI:0914”(association)	0.740
CNOT3	CNOT1	psi-mi:“MI:0914”(association)	0.740
CNOT3	CNOT8	psi-mi:“MI:0915”(physical association)	0.730
CNOT8	CNOT3	psi-mi:“MI:0915”(physical association)	0.730
TOB1	CNOT1	psi-mi:“MI:0914”(association)	0.710
BTG2	CNOT8	psi-mi:“MI:0915”(physical association)	0.700
CNOT8	BTG2	psi-mi:“MI:0915”(physical association)	0.700

BioGRID (129): CNOT8 (Two-hybrid), CNOT8 (Two-hybrid), TOB2 (Two-hybrid), CNOT8 (Affinity Capture-MS), CNOT8 (Affinity Capture-Western), CNOT8 (Affinity Capture-Western), CNOT8 (Affinity Capture-Western), CNOT8 (Affinity Capture-Western), CNOT1 (Affinity Capture-Western), CNOT3 (Affinity Capture-Western), CNOT2 (Affinity Capture-Western), CNOT8 (Affinity Capture-MS), CNOT8 (Affinity Capture-MS), CNOT8 (Affinity Capture-MS), CNOT8 (Affinity Capture-MS)

ESM2 similar proteins: A4II96, A7SLW1, A7YW45, A9RBS1, O14744, O23617, O48538, O64773, O74856, O80738, O80765, O81209, O81210, P07805, P46513, Q06429, Q08BM8, Q0WUI9, Q17345, Q17819, Q2HXK9, Q3KQ85, Q3ZC01, Q4R5M3, Q556Y2, Q5R698, Q5ZJV9, Q60809, Q6NUA1, Q8BLR2, Q8CIG8, Q8GWT4, Q90ZA1, Q948U0, Q96A23, Q9D8X5, Q9FMS6, Q9LEU4, Q9LMI0, Q9LRA7

Diamond homologs: A4II96, O64773, O74856, P39008, Q08BM8, Q17345, Q3KQ85, Q3ZC01, Q5ZJV9, Q60809, Q9C6M9, Q9D8X5, Q9FMS6, Q9LEU4, Q9LXM2, Q9LXM4, Q9S9P2, Q9SAI2, Q9SFX6, Q9SHJ0, Q9SKZ2, Q9UFF9, Q9UIV1

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
CNOT8	“form complex”	“CCR4-NOT complex”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 74 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
TP53 regulates transcription of additional cell cycle genes whose exact role in the p53 pathway remain uncertain	9	114.0×	2e-15
Deadenylation of mRNA	9	96.4×	9e-15
M-decay: degradation of maternal mRNAs by maternally stored factors	11	87.5×	3e-17
Regulation of MECP2 expression and activity	5	44.9×	1e-06
Estrogen-dependent gene expression	6	11.1×	2e-04

GO biological processes:

GO term	Partners	Fold	FDR
positive regulation of nuclear-transcribed mRNA catabolic process, deadenylation-dependent decay	6	108.7×	1e-09
nuclear-transcribed mRNA poly(A) tail shortening	8	103.5×	9e-13
regulatory ncRNA-mediated gene silencing	8	87.0×	3e-12
regulation of translation	7	24.7×	9e-07
negative regulation of translation	6	19.0×	3e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	16
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1671 predictions. Top by Δscore:

Variant	Effect	Δscore
5:154865332:A:T	donor_gain	1.0000
5:154870658:TAGAG:T	acceptor_gain	1.0000
5:154870659:A:AG	acceptor_gain	1.0000
5:154870659:AGAGA:A	acceptor_gain	1.0000
5:154870660:G:GG	acceptor_gain	1.0000
5:154870660:GA:G	acceptor_gain	1.0000
5:154870660:GAGA:G	acceptor_gain	1.0000
5:154870660:GAGAG:G	acceptor_gain	1.0000
5:154870734:G:GT	donor_gain	1.0000
5:154870780:G:GT	donor_gain	1.0000
5:154871728:A:AG	acceptor_gain	1.0000
5:154871728:AGT:A	acceptor_gain	1.0000
5:154871729:G:GG	acceptor_gain	1.0000
5:154871729:GT:G	acceptor_gain	1.0000
5:154871729:GTG:G	acceptor_gain	1.0000
5:154872532:C:G	acceptor_gain	1.0000
5:154872534:T:G	acceptor_gain	1.0000
5:154872540:GGGA:G	acceptor_gain	1.0000
5:154872649:GAG:G	donor_gain	1.0000
5:154872649:GAGGT:G	donor_loss	1.0000
5:154872652:G:C	donor_loss	1.0000
5:154872653:T:A	donor_loss	1.0000
5:154875288:A:AG	acceptor_gain	1.0000
5:154875288:AGTT:A	acceptor_gain	1.0000
5:154875289:G:GA	acceptor_gain	1.0000
5:154875289:GT:G	acceptor_gain	1.0000
5:154875289:GTT:G	acceptor_gain	1.0000
5:154875289:GTTG:G	acceptor_gain	1.0000
5:154875289:GTTGT:G	acceptor_gain	1.0000
5:154858446:G:GT	donor_gain	0.9900

AlphaMissense

1958 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:154865192:G:C	D40H	1.000
5:154865193:A:C	D40A	1.000
5:154865193:A:T	D40V	1.000
5:154865194:C:A	D40E	1.000
5:154865194:C:G	D40E	1.000
5:154865201:T:C	F43L	1.000
5:154865201:T:G	F43V	1.000
5:154865202:T:C	F43S	1.000
5:154865202:T:G	F43C	1.000
5:154865203:T:A	F43L	1.000
5:154865203:T:G	F43L	1.000
5:154865205:C:A	P44Q	1.000
5:154865207:G:C	G45R	1.000
5:154865207:G:T	G45C	1.000
5:154865208:G:A	G45D	1.000
5:154865271:G:C	R66P	1.000
5:154865306:G:C	G78R	1.000
5:154865307:G:A	G78D	1.000
5:154865357:T:A	W95R	1.000
5:154865357:T:C	W95R	1.000
5:154865364:T:C	F97S	1.000
5:154865375:T:C	F101L	1.000
5:154865376:T:C	F101S	1.000
5:154865377:T:A	F101L	1.000
5:154865377:T:G	F101L	1.000
5:154870693:T:C	L115P	1.000
5:154870696:T:C	L116P	1.000
5:154870737:G:A	G130R	1.000
5:154870737:G:C	G130R	1.000
5:154870737:G:T	G130W	1.000

dbSNP variants (sampled 300 via entrez): RS1000054909 (5:154857924 T>A,C,G), RS1000085772 (5:154858416 C>G), RS1000114927 (5:154858164 C>T), RS1000191266 (5:154859495 A>T), RS1000334940 (5:154864345 A>G), RS1000484269 (5:154864197 A>C), RS1000622536 (5:154869965 G>A,T), RS1000728517 (5:154869584 C>T), RS1000932917 (5:154870467 A>G), RS1001265252 (5:154872518 C>G,T), RS1001606302 (5:154862827 G>A,T), RS1001758288 (5:154865831 C>T), RS1001933002 (5:154860913 T>C), RS1001973602 (5:154863149 G>A,T), RS1002042923 (5:154867746 TAGG>T)

Disease associations

OMIM: gene MIM:603731 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST009391_712	Metabolite levels	5.000000e-06
GCST90002385_349	High light scatter reticulocyte count	1.000000e-09

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0010531	S-adenosylhomocysteine measurement
EFO:0007986	reticulocyte count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects expression, affects cotreatment, increases expression	2
aristolochic acid I	decreases expression	1
dicrotophos	decreases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
sodium arsenite	decreases expression, increases abundance	1
cobaltous chloride	increases expression	1
zinc chromate	increases abundance, increases expression	1
methacrylaldehyde	increases abundance, affects cotreatment, increases oxidation	1
chromium hexavalent ion	increases expression, increases abundance	1
ICG 001	increases expression	1
Acrolein	affects cotreatment, increases oxidation, increases abundance	1
Air Pollutants	increases oxidation, affects cotreatment, increases abundance	1
Arsenic	decreases expression, increases abundance	1
Vehicle Emissions	decreases expression	1
Dexamethasone	affects cotreatment, increases expression	1
Doxorubicin	decreases expression	1
Indomethacin	increases expression, affects cotreatment	1
Ozone	affects cotreatment, increases oxidation, increases abundance	1
Quercetin	decreases expression	1
Selenium	decreases expression	1
Thiram	decreases expression	1
Valproic Acid	affects expression	1
1-Methyl-3-isobutylxanthine	affects cotreatment, increases expression	1
Cyclosporine	decreases expression	1
Aflatoxin B1	decreases methylation	1
Cadmium Chloride	decreases expression	1
Copper Sulfate	decreases expression	1
Lactic Acid	decreases expression	1
tert-Butylhydroperoxide	decreases expression	1

Clinical trials (associated diseases)

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