GADD45GIP1

Summary

GADD45GIP1 (GADD45G interacting protein 1, HGNC:29996) is a protein-coding gene on chromosome 19p13.13, encoding Large ribosomal subunit protein mL64 (Q8TAE8). Acts as a negative regulator of G1 to S cell cycle phase progression by inhibiting cyclin-dependent kinases. It is a selective cancer dependency (DepMap: 17.3% of cell lines).

This gene encodes a nuclear-localized protein that may be induced by p53 and regulates the cell cycle by inhibiting G1 to S phase progression. The encoded protein may interact with other cell cycle regulators.

Source: NCBI Gene 90480 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 52 total
• Cancer dependency (DepMap): dependent in 17.3% of screened cell lines
• MANE Select transcript: NM_052850

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29996
Approved symbol	GADD45GIP1
Name	GADD45G interacting protein 1
Location	19p13.13
Locus type	gene with protein product
Status	Approved
Aliases	PLINP-1, MGC4667, MGC4758, CKBBP2, PRG6, Plinp1, CRIF1, CKbetaBP2, mL64
Ensembl gene	ENSG00000179271
Ensembl biotype	protein_coding
OMIM	605162
Entrez	90480

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000316939, ENST00000907460

RefSeq mRNA: 1 — MANE Select: NM_052850 NM_052850

CCDS: CCDS12290

Canonical transcript exons

ENST00000316939 — 2 exons

Exon	Start	End
ENSE00001256350	12953119	12954526
ENSE00001256359	12956863	12957223

Expression profiles

Bgee: expression breadth ubiquitous, 252 present calls, max score 96.06.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 118.6167 / max 538.1246, expressed in 1823 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
179438	118.6167	1823

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
apex of heart	UBERON:0002098	96.06	gold quality
hindlimb stylopod muscle	UBERON:0004252	95.74	gold quality
mucosa of transverse colon	UBERON:0004991	93.86	gold quality
heart left ventricle	UBERON:0002084	93.70	gold quality
gastrocnemius	UBERON:0001388	93.66	gold quality
right atrium auricular region	UBERON:0006631	93.52	gold quality
cardiac ventricle	UBERON:0002082	93.40	gold quality
triceps brachii	UBERON:0001509	93.21	gold quality
muscle of leg	UBERON:0001383	93.12	gold quality
anterior cingulate cortex	UBERON:0009835	92.99	gold quality
cingulate cortex	UBERON:0003027	92.90	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	92.82	gold quality
cardiac atrium	UBERON:0002081	92.66	gold quality
right adrenal gland	UBERON:0001233	92.38	gold quality
muscle organ	UBERON:0001630	92.18	gold quality
prefrontal cortex	UBERON:0000451	92.12	gold quality
amygdala	UBERON:0001876	92.12	gold quality
left adrenal gland	UBERON:0001234	92.07	gold quality
lower esophagus mucosa	UBERON:0035834	91.99	gold quality
heart	UBERON:0000948	91.95	gold quality
left adrenal gland cortex	UBERON:0035825	91.95	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	91.83	gold quality
right adrenal gland cortex	UBERON:0035827	91.54	gold quality
putamen	UBERON:0001874	91.52	gold quality
ascending aorta	UBERON:0001496	91.51	gold quality
nucleus accumbens	UBERON:0001882	91.49	gold quality
thoracic aorta	UBERON:0001515	91.47	gold quality
caudate nucleus	UBERON:0001873	91.45	gold quality
Brodmann (1909) area 9	UBERON:0013540	91.45	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	91.31	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-CURD-112	yes	51.09
E-ANND-3	yes	10.80

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AR, ELF3, NFE2L2, NR4A1

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 17.3% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 26)

• results suggest that CRIF1 is a novel nuclear protein that interacts with Gadd45 and may play a role in negative regulation of cell cycle progression and cell growth (PMID:12716909)
• Phosphorylation of serine-221 in CKBBP2/CRIF1 promotes proliferation of green monkey COS7 cells. (PMID:17069992)
• NAC-1 contributes to tumor growth and survival by at least inhibiting Gadd45GIP1 expression, which has a tumor suppressor effect in cancer cells. (PMID:17804717)
• Results suggest that CRIF1 acts as an AR corepressor and may play an important role in the regulation of AR-positive growth of prostate cancer. (PMID:17885209)
• CRIF1, unlike KEAP1 (which only interacts with N-terminal region of NRF2), physically interacts with both N- and C-terminal regions of NRF2 and promotes NRF2 ubiquitination and subsequent proteasome-mediated NRF2 protein degradation (PMID:20427290)
• results indicated cell cycle arrest of Jurkat cells in the G0/G1 phase to be induced by primary cultured leukemic BMSCs associated with increased expression of CRIF1 by leukemic cells (PMID:21911160)
• CKbetaBP2/CRIF1 is expressed with STAT3 in prostate cancer where STAT3 may help to offset the AR repressor effect of CKbetaBP2/CRIF1. (PMID:24103312)
• CRIF1 may play a regulatory role in the BM microenvironment-induced leukemia cell cycle arrest possibly through interacting with CDK2 and acting as a cyclin-dependent kinase inhibitor. (PMID:24520316)
• CRIF1 knockdown partially induces endothelial activation via increased ROS production and phosphorylation of p66shc (PMID:24906005)
• The results identify the ROS-Sp1-Crif1 pathway to be a new mechanism underlying Abeta-induced mitochondrial dysfunction and suggest that ROS-mediated downregulation of Crif1 is a crucial event in AD pathology. (PMID:25361083)
• Crif1 is an indispensable regulator of PKAalpha cat that modulates the PKA/CREB signaling pathway to promote adipogenic differentiation of bone marrow mesenchymal stem cells after irradiation (PMID:25847389)
• our results support a novel function of nuclear Lck in promoting human leukemic T cell survival through interaction with a tumor suppressor, CRIF1 (PMID:25997448)
• Study shows that Lck interacts with CRIF1 in the mitochondria and negatively regulates CRIF1-mediated translation of mitochondrion-encoded proteins. (PMID:26210498)
• Results demonstrate that knockdown of CRIF1 in HUVECs induces mitochondrial dysfunction and reduces SIRT1 expression along with decreased eNOS phosphorylation and increased eNOS acetylation, thereby promoting endothelial dysfunction. These findings indicate that CRIF1 plays an important role in maintaining mitochondrial and endothelial function through its effects on the SIRT1-eNOS pathway. (PMID:28117598)
• SNF5 is indispensable for CRIF1-enhanced p53 activity and its function in the suppression of cell cycle arrest in human cancer cells. (PMID:28235567)
• NRF2 Ser40 phosphorylation was inhibited in Crif1-deficient bone marrow multipotent mesenchymal stromal cells even in the presence of three kinds of PKC agonists, suggesting that CRIF1 might co-activate PKC-delta to phosphorylate NRF2 Ser40. (PMID:28819452)
• strongly suggest that CRIF1 deficiency promotes endothelial cell inflammation by increasing VCAM-1 expression, elevating inflammatory cytokines levels, and activating the transcription factor NF-kappaB, all of which were inhibited by SIRT1 overexpression (PMID:29474366)
• High CRIF1 expression is associated with radioresistant osteosarcoma. (PMID:31548420)
• CRIF1 deficiency induced mitophagy via p66shc-regulated ROS in endothelial cells. (PMID:31806365)
• CR6-interacting factor 1 deficiency reduces endothelial nitric oxide synthase activity by inhibiting biosynthesis of tetrahydrobiopterin. (PMID:31964986)
• CRIF1 overexpression facilitates tumor growth and metastasis through inducing ROS/NFkappaB pathway in hepatocellular carcinoma. (PMID:32382077)
• Downregulation of CR6-interacting factor 1 suppresses keloid fibroblast growth via the TGF-beta/Smad signaling pathway. (PMID:33436666)
• CRIF1 deficiency suppresses endothelial cell migration via upregulation of RhoGDI2. (PMID:34437633)
• CRIF1 promotes the progression of non-small-cell lung cancer by SIRT3- mediated deacetylation of PYCR1. (PMID:35716330)
• Crif1 deficiency in dopamine neurons triggers early-onset parkinsonism. (PMID:37648779)
• CRIF1 deficiency induces FOXP3[LOW] inflammatory non-suppressive regulatory T cells, thereby promoting antitumor immunity. (PMID:38536932)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	gadd45gip1	ENSDARG00000039338
mus_musculus	Gadd45gip1	ENSMUSG00000033751
rattus_norvegicus	Gadd45gip1	ENSRNOG00000003011
drosophila_melanogaster	CRIF	FBGN0037102
caenorhabditis_elegans	K07A1.10	WBGENE00010616

Protein

Protein identifiers

Large ribosomal subunit protein mL64 — Q8TAE8 (reviewed: Q8TAE8)

Alternative names: 39S ribosomal protein L59, mitochondrial, CKII beta-associating protein, CR6-interacting factor 1, Growth arrest and DNA damage-inducible proteins-interacting protein 1, Papillomavirus L2-interacting nuclear protein 1, p53-responsive gene 6 protein

All UniProt accessions (1): Q8TAE8

UniProt curated annotations — full annotation on UniProt →

Function. Acts as a negative regulator of G1 to S cell cycle phase progression by inhibiting cyclin-dependent kinases. Inhibitory effects are additive with GADD45 proteins but also occur in the absence of GADD45 proteins. Acts as a repressor of the orphan nuclear receptor NR4A1 by inhibiting AB domain-mediated transcriptional activity. May be involved in the hormone-mediated regulation of NR4A1 transcriptional activity. May play a role in mitochondrial protein synthesis.

Subunit / interactions. Component of the mitochondrial large ribosomal subunit (mt-LSU). Mature mammalian 55S mitochondrial ribosomes consist of a small (28S) and a large (39S) subunit. The 28S small subunit contains a 12S ribosomal RNA (12S mt-rRNA) and 30 different proteins. The 39S large subunit contains a 16S rRNA (16S mt-rRNA), a copy of mitochondrial valine transfer RNA (mt-tRNA(Val)), which plays an integral structural role, and 52 different proteins. Interacts with GADD45A, GADD45B and GADD45G. Interacts with NR4A1 via the NR4A1 AB domain. Interacts with ATAD3A and ATAD3B. (Microbial infection) Interacts with the human papilloma virus type 16 (HPV 16) minor capsid protein L2.

Subcellular location. Mitochondrion. Nucleus.

Tissue specificity. Widely expressed. Highly expressed in the thyroid gland, heart, lymph nodes, trachea and adrenal tissues. Expressed at lower level in liver skeletal muscle, kidney, pancreas, testis, ovary and stomach. Barely detectable in adrenal adenoma and papillary thyroid cancer.

Induction. Down-regulated by p53/TP53 in apoptotic cells.

Miscellaneous. Cells overexpressing GADD45GIP1 were more likely to be in G1 and less likely to be in S phase and grow more slowly than control cells. Inhibiting the expression of GADD45GIP1 promotes cell cycle progression.

Similarity. Belongs to the mitochondrion-specific ribosomal protein mL64 family.

RefSeq proteins (1): NP_443082* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR018472	Ribosomal_mL64	Family
IPR043035	Ribosomal_mL64_sf	Homologous_superfamily

Pfam: PF10147

UniProt features (18 total): helix 7, region of interest 2, compositionally biased region 2, strand 2, chain 1, turn 1, coiled-coil region 1, short sequence motif 1, sequence conflict 1

Structure

Experimental structures (PDB)

85 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
7OF0	ELECTRON MICROSCOPY	2.2
7QI4	ELECTRON MICROSCOPY	2.21
8RRI	ELECTRON MICROSCOPY	2.4
8QU5	ELECTRON MICROSCOPY	2.42
9OLF	ELECTRON MICROSCOPY	2.46
7OF7	ELECTRON MICROSCOPY	2.5
7PO4	ELECTRON MICROSCOPY	2.56
6ZM6	ELECTRON MICROSCOPY	2.59
7O9M	ELECTRON MICROSCOPY	2.6
7OF6	ELECTRON MICROSCOPY	2.6
9CN3	ELECTRON MICROSCOPY	2.62
7QI5	ELECTRON MICROSCOPY	2.63
7OF2	ELECTRON MICROSCOPY	2.7
7OF3	ELECTRON MICROSCOPY	2.7
7OF4	ELECTRON MICROSCOPY	2.7
9PR4	ELECTRON MICROSCOPY	2.77
9PRA	ELECTRON MICROSCOPY	2.83
8ANY	ELECTRON MICROSCOPY	2.85
6ZM5	ELECTRON MICROSCOPY	2.89
7QH7	ELECTRON MICROSCOPY	2.89
7ODR	ELECTRON MICROSCOPY	2.9
7OF5	ELECTRON MICROSCOPY	2.9
8K2A	ELECTRON MICROSCOPY	2.9
8OIT	ELECTRON MICROSCOPY	2.9
9PGL	ELECTRON MICROSCOPY	2.9
9PGF	ELECTRON MICROSCOPY	2.93
6VMI	ELECTRON MICROSCOPY	2.96
6VLZ	ELECTRON MICROSCOPY	2.97
7QI6	ELECTRON MICROSCOPY	2.98
9PSM	ELECTRON MICROSCOPY	2.98

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8TAE8-F1	87.95	0.63

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-5368286	Mitochondrial translation initiation
R-HSA-5389840	Mitochondrial translation elongation
R-HSA-5419276	Mitochondrial translation termination
R-HSA-9937383	Mitochondrial ribosome-associated quality control

MSigDB gene sets: 100 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_COLON_TUMORAL_MACROPHAGE_UP, GOBP_MITOCHONDRIAL_TRANSLATION, DARWICHE_SKIN_TUMOR_PROMOTER_DN, DARWICHE_PAPILLOMA_RISK_LOW_DN, DARWICHE_PAPILLOMA_RISK_HIGH_DN, DARWICHE_SQUAMOUS_CELL_CARCINOMA_DN, GOBP_TRANSLATION, GOMF_STRUCTURAL_CONSTITUENT_OF_RIBOSOME, GOCC_MITOCHONDRIAL_ENVELOPE, ACEVEDO_LIVER_CANCER_UP, GOCC_LARGE_RIBOSOMAL_SUBUNIT, GOCC_RIBOSOME, GOCC_ORGANELLAR_RIBOSOME, GOCC_MITOCHONDRIAL_MATRIX, GOCC_ORGANELLE_INNER_MEMBRANE

GO Biological Process (1): mitochondrial translation (GO:0032543)

GO Molecular Function (2): structural constituent of ribosome (GO:0003735), protein binding (GO:0005515)

GO Cellular Component (8): nucleoplasm (GO:0005654), mitochondrion (GO:0005739), mitochondrial inner membrane (GO:0005743), mitochondrial matrix (GO:0005759), mitochondrial large ribosomal subunit (GO:0005762), nucleus (GO:0005634), ribosome (GO:0005840), ribonucleoprotein complex (GO:1990904)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Mitochondrial translation	4

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
mitochondrion	2
intracellular membrane-bounded organelle	2
translation	1
mitochondrial gene expression	1
structural molecule activity	1
ribosome	1
binding	1
nuclear lumen	1
cellular anatomical structure	1
cytoplasm	1
organelle inner membrane	1
mitochondrial membrane	1
intracellular organelle lumen	1
organellar large ribosomal subunit	1
mitochondrial ribosome	1
mitochondrial protein-containing complex	1
intracellular membraneless organelle	1
protein-containing complex	1

Protein interactions and networks

STRING

1202 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GADD45GIP1	GADD45A	P24522	980
GADD45GIP1	GADD45G	O95257	960
GADD45GIP1	NACC1	Q96RE7	903
GADD45GIP1	AIFM2	Q9BRQ8	766
GADD45GIP1	GADD45B	O75293	735
GADD45GIP1	EPX	P11678	717
GADD45GIP1	WFDC5	Q8TCV5	715
GADD45GIP1	TCHP	Q9BT92	680
GADD45GIP1	TP53	P04637	619
GADD45GIP1	MRPL11	Q9Y3B7	592
GADD45GIP1	MRPL58	Q14197	591
GADD45GIP1	ERAL1	O75616	574
GADD45GIP1	CDKN1A	P38936	570
GADD45GIP1	MRPS21	P82921	549
GADD45GIP1	MRPL37	Q9BZE1	537

IntAct

317 interactions, top by confidence:

A	B	Type	Score
GADD45GIP1	MRPL38	psi-mi:“MI:0915”(physical association)	0.740
MRPS30	GTPBP10	psi-mi:“MI:0914”(association)	0.640
GADD45GIP1	STAT3	psi-mi:“MI:0915”(physical association)	0.630
GADD45GIP1	GADD45G	psi-mi:“MI:0915”(physical association)	0.590
GADD45GIP1	GADD45G	psi-mi:“MI:0407”(direct interaction)	0.590
GADD45A	GADD45GIP1	psi-mi:“MI:0407”(direct interaction)	0.590
GADD45GIP1	Gadd45b	psi-mi:“MI:0407”(direct interaction)	0.590
GADD45GIP1	GADD45A	psi-mi:“MI:0915”(physical association)	0.590
GADD45GIP1	Gadd45b	psi-mi:“MI:0915”(physical association)	0.590
GADD45G	GADD45GIP1	psi-mi:“MI:0915”(physical association)	0.590
Gadd45b	GADD45GIP1	psi-mi:“MI:0915”(physical association)	0.590
MYO15B	GADD45GIP1	psi-mi:“MI:0915”(physical association)	0.560
EAF1	GADD45GIP1	psi-mi:“MI:0915”(physical association)	0.560
MBD3	GADD45GIP1	psi-mi:“MI:0915”(physical association)	0.560
KRT27	GADD45GIP1	psi-mi:“MI:0915”(physical association)	0.560
CADPS	GADD45GIP1	psi-mi:“MI:0915”(physical association)	0.560
GADD45GIP1	PRDM6	psi-mi:“MI:0915”(physical association)	0.560
KRT31	GADD45GIP1	psi-mi:“MI:0915”(physical association)	0.560
CBY2	GADD45GIP1	psi-mi:“MI:0915”(physical association)	0.560
KANK2	GADD45GIP1	psi-mi:“MI:0915”(physical association)	0.560
MTUS2	GADD45GIP1	psi-mi:“MI:0915”(physical association)	0.560
MIPOL1	GADD45GIP1	psi-mi:“MI:0915”(physical association)	0.560
MKRN3	GADD45GIP1	psi-mi:“MI:0915”(physical association)	0.560
CEP70	GADD45GIP1	psi-mi:“MI:0915”(physical association)	0.560
TRAF1	GADD45GIP1	psi-mi:“MI:0915”(physical association)	0.560
GOLGA6L9	GADD45GIP1	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (355): GADD45GIP1 (Affinity Capture-MS), GADD45GIP1 (Affinity Capture-MS), GADD45GIP1 (Affinity Capture-MS), GADD45GIP1 (Affinity Capture-MS), GADD45GIP1 (Affinity Capture-MS), GADD45GIP1 (Affinity Capture-MS), GADD45GIP1 (Affinity Capture-MS), GADD45GIP1 (Affinity Capture-MS), GADD45GIP1 (Affinity Capture-MS), GADD45GIP1 (Affinity Capture-MS), GADD45GIP1 (Affinity Capture-MS), GADD45GIP1 (Affinity Capture-MS), GADD45GIP1 (Affinity Capture-MS), ELF3 (Affinity Capture-Western), ELF3 (Co-localization)

ESM2 similar proteins: A1A4P4, A1CH36, A2ALW5, A5AAL8, B0BN56, O42911, O70279, P0C2B7, P58468, P83565, Q0CLE8, Q1ECT8, Q290P4, Q2GVC2, Q3SZ86, Q4G0I0, Q4V7Q1, Q5B4U6, Q5BJW9, Q5RFR4, Q5XJW2, Q61733, Q6RUT7, Q753F1, Q7SDU5, Q7SHR9, Q80ZS3, Q86TS9, Q8BGX2, Q8BK72, Q8CHP5, Q8SPE7, Q8TAE8, Q8VD26, Q8WUQ7, Q96AN5, Q96DF8, Q9BRP8, Q9BSF4, Q9BYN8

Diamond homologs: A1A4P4, Q5XJW2, Q8SPE7, Q8TAE8, Q9CR59

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
GADD45GIP1	“form complex”	“39S mitochondrial large ribosomal subunit”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 123 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
Mitochondrial translation	18	34.4×	6e-21
Mitochondrial translation initiation	18	31.7×	1e-20
Mitochondrial translation elongation	18	31.7×	1e-20
Mitochondrial ribosome-associated quality control	18	30.7×	1e-20
Mitochondrial translation termination	18	27.4×	9e-20
Translation	19	16.4×	1e-16

GO biological processes:

GO term	Partners	Fold	FDR
mitochondrial translation	19	32.4×	3e-21
translation	12	12.1×	7e-08

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	45
Likely benign	3
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

266 predictions. Top by Δscore:

Variant	Effect	Δscore
19:12954523:CTCC:C	acceptor_gain	1.0000
19:12954524:TCC:T	acceptor_gain	1.0000
19:12954525:CC:C	acceptor_gain	1.0000
19:12954525:CCC:C	acceptor_gain	1.0000
19:12954526:CC:C	acceptor_gain	1.0000
19:12954527:C:CC	acceptor_gain	1.0000
19:12954527:C:CG	acceptor_loss	1.0000
19:12956859:GCAC:G	donor_loss	1.0000
19:12956860:CA:C	donor_loss	1.0000
19:12956862:CC:C	donor_loss	1.0000
19:12956862:CCT:C	donor_gain	1.0000
19:12956862:CCTCT:C	donor_gain	1.0000
19:12954522:GCTCC:G	acceptor_gain	0.9900
19:12954523:CTCCC:C	acceptor_gain	0.9900
19:12954524:TCCCT:T	acceptor_gain	0.9900
19:12954527:C:T	acceptor_gain	0.9900
19:12954530:C:CT	acceptor_gain	0.9900
19:12954531:A:T	acceptor_gain	0.9900
19:12956858:CGCA:C	donor_gain	0.9900
19:12956861:A:AC	donor_gain	0.9900
19:12956862:C:CC	donor_gain	0.9900
19:12956897:TC:T	donor_gain	0.9900
19:12956858:CG:C	donor_gain	0.9800
19:12954525:CCCT:C	acceptor_gain	0.9600
19:12954526:CCT:C	acceptor_gain	0.9600
19:12954527:CTGCA:C	acceptor_gain	0.9600
19:12954524:TCCC:T	acceptor_gain	0.9500
19:12954528:T:A	acceptor_gain	0.9400
19:12956930:TCGGG:T	donor_gain	0.9100
19:12955176:A:AC	donor_gain	0.9000

AlphaMissense

1406 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:12954352:G:C	F175L	0.989
19:12954352:G:T	F175L	0.989
19:12954354:A:G	F175L	0.989
19:12954494:A:G	M128T	0.984
19:12954304:C:A	K191N	0.981
19:12954304:C:G	K191N	0.981
19:12957030:G:C	F61L	0.978
19:12957030:G:T	F61L	0.978
19:12957032:A:G	F61L	0.978
19:12954353:A:G	F175S	0.976
19:12954398:G:T	A160D	0.976
19:12954405:C:G	A158P	0.971
19:12954317:C:G	R187P	0.966
19:12954399:C:G	A160P	0.966
19:12954493:C:A	M128I	0.965
19:12954493:C:G	M128I	0.965
19:12954493:C:T	M128I	0.965
19:12956987:A:G	W76R	0.963
19:12956987:A:T	W76R	0.963
19:12954344:A:G	L178P	0.962
19:12954361:A:C	S172R	0.961
19:12954361:A:T	S172R	0.961
19:12954363:T:G	S172R	0.961
19:12954494:A:C	M128R	0.959
19:12954353:A:C	F175C	0.955
19:12957036:C:A	K59N	0.950
19:12957036:C:G	K59N	0.950
19:12956985:C:A	W76C	0.947
19:12956985:C:G	W76C	0.947
19:12954318:G:T	R187S	0.946

dbSNP variants (sampled 300 via entrez): RS1000443090 (19:12957455 A>T), RS1000837711 (19:12955859 A>G), RS1002853026 (19:12954581 A>G), RS1003686526 (19:12958622 A>G), RS1004186283 (19:12958287 T>C), RS1004411921 (19:12953997 T>C), RS1005124372 (19:12955660 G>A,C), RS1005430416 (19:12953130 T>A), RS1005660306 (19:12952754 C>T), RS1005693621 (19:12957906 C>CAT), RS1005744509 (19:12957907 A>G), RS1006296394 (19:12956674 CAAACA>C), RS1006799462 (19:12957250 TC>T), RS1007643749 (19:12953670 C>A,T), RS1007756970 (19:12954105 T>A,C)

Disease associations

OMIM: gene MIM:605162 | 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
GCST002595_9	Clozapine-induced agranulocytosis	1.000000e-06

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

24 total (human), top 24 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Cadmium Chloride	decreases expression, increases methylation, increases expression	2
arsenite	affects binding, increases reaction	1
sodium arsenite	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
2,3,5-(triglutathion-S-yl)hydroquinone	increases ADP-ribosylation	1
K 7174	decreases expression	1
ICG 001	decreases expression	1
bisphenol B	increases expression	1
2-methyl-2H-pyrazole-3-carboxylic acid (2-methyl-4-o-tolylazophenyl)amide	decreases expression	1
2-(1H-indazol-4-yl)-6-(4-methanesulfonylpiperazin-1-ylmethyl)-4-morpholin-4-ylthieno(3,2-d)pyrimidine	decreases expression, increases response to substance	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	decreases expression	1
Temozolomide	decreases expression	1
Benzo(a)pyrene	affects methylation	1
Coumestrol	increases expression	1
Doxorubicin	increases expression	1
Lipopolysaccharides	affects expression, affects response to substance	1
Ribonucleotides	affects binding	1
Rotenone	decreases expression	1
Smoke	decreases expression	1
T-2 Toxin	increases expression	1
Tetrachlorodibenzodioxin	decreases expression	1
Thiram	decreases expression	1
Antirheumatic Agents	increases expression	1
Copper Sulfate	decreases expression	1

Clinical trials (associated diseases)

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