WIPI1

Summary

WIPI1 (WD repeat domain, phosphoinositide interacting 1, HGNC:25471) is a protein-coding gene on chromosome 17q24.2, encoding WD repeat domain phosphoinositide-interacting protein 1 (Q5MNZ9). Component of the autophagy machinery that controls the major intracellular degradation process by which cytoplasmic materials are packaged into autophagosomes and delivered to lysosomes for degradation.

This gene encodes a WD40 repeat protein. Members of the WD40 repeat family are key components of many essential biologic functions. They regulate the assembly of multiprotein complexes by presenting a beta-propeller platform for simultaneous and reversible protein-protein interactions. Members of the WIPI subfamily of WD40 repeat proteins have a 7-bladed propeller structure and contain a conserved motif for interaction with phospholipids. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 55062 — RefSeq curated summary.

At a glance

• GWAS associations: 9
• MANE Select transcript: NM_017983

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25471
Approved symbol	WIPI1
Name	WD repeat domain, phosphoinositide interacting 1
Location	17q24.2
Locus type	gene with protein product
Status	Approved
Aliases	FLJ10055, WIPI49, ATG18, ATG18A
Ensembl gene	ENSG00000070540
Ensembl biotype	protein_coding
OMIM	609224
Entrez	55062

Gene structure

Transcript identifiers

Ensembl transcripts: 16 — 9 protein_coding, 3 protein_coding_CDS_not_defined, 2 retained_intron, 2 nonsense_mediated_decay

ENST00000262139, ENST00000546360, ENST00000585393, ENST00000586815, ENST00000587731, ENST00000589316, ENST00000589459, ENST00000590402, ENST00000591494, ENST00000591744, ENST00000592645, ENST00000891619, ENST00000891620, ENST00000891621, ENST00000891622, ENST00000959788

RefSeq mRNA: 2 — MANE Select: NM_017983 NM_001320772, NM_017983

CCDS: CCDS11677, CCDS82193

Canonical transcript exons

ENST00000262139 — 13 exons

Exon	Start	End
ENSE00001260858	68421281	68421820
ENSE00002751572	68457342	68457496
ENSE00003467887	68426075	68426175
ENSE00003472970	68434556	68434626
ENSE00003476575	68433468	68433575
ENSE00003495671	68452910	68452992
ENSE00003510797	68428829	68428936
ENSE00003551788	68444493	68444589
ENSE00003566705	68435620	68435712
ENSE00003573404	68427135	68427253
ENSE00003664339	68429996	68430160
ENSE00003675054	68450728	68450897
ENSE00003690505	68436382	68436479

Expression profiles

Bgee: expression breadth ubiquitous, 289 present calls, max score 98.56.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 27.9579 / max 197.0390, expressed in 1794 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
167741	27.9579	1794

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
stromal cell of endometrium	CL:0002255	98.56	gold quality
sperm	CL:0000019	98.04	gold quality
gastrocnemius	UBERON:0001388	95.98	gold quality
minor salivary gland	UBERON:0001830	95.98	gold quality
hindlimb stylopod muscle	UBERON:0004252	95.94	gold quality
muscle of leg	UBERON:0001383	95.87	gold quality
biceps brachii	UBERON:0001507	95.73	gold quality
heart left ventricle	UBERON:0002084	95.62	gold quality
saliva-secreting gland	UBERON:0001044	95.52	gold quality
cardiac ventricle	UBERON:0002082	95.49	gold quality
muscle organ	UBERON:0001630	95.47	gold quality
skeletal muscle organ	UBERON:0014892	95.47	gold quality
skeletal muscle tissue	UBERON:0001134	95.28	gold quality
sural nerve	UBERON:0015488	95.20	gold quality
male germ cell	CL:0000015	95.18	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	95.18	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	95.09	gold quality
placenta	UBERON:0001987	95.07	gold quality
rectum	UBERON:0001052	94.95	gold quality
right atrium auricular region	UBERON:0006631	94.89	gold quality
mouth mucosa	UBERON:0003729	94.83	gold quality
decidua	UBERON:0002450	94.81	gold quality
parotid gland	UBERON:0001831	94.75	gold quality
apex of heart	UBERON:0002098	94.72	gold quality
triceps brachii	UBERON:0001509	94.69	gold quality
heart	UBERON:0000948	94.48	gold quality
tibial nerve	UBERON:0001323	94.28	gold quality
cardiac atrium	UBERON:0002081	94.27	gold quality
muscle tissue	UBERON:0002385	94.18	gold quality
palpebral conjunctiva	UBERON:0001812	94.14	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-GEOD-135922	yes	19.15
E-ANND-3	yes	14.09

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): KDM4A

miRNA regulators (miRDB)

30 targeting WIPI1, 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-7110-3P	100.00	73.18	2486
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-381-3P	99.93	71.87	2854
HSA-MIR-300	99.92	71.76	2856
HSA-MIR-380-3P	99.89	70.18	1978
HSA-MIR-7162-3P	99.89	68.16	1682
HSA-MIR-12119	99.87	68.35	1653
HSA-MIR-4503	99.85	71.45	1869
HSA-MIR-6817-3P	99.79	68.35	2126
HSA-MIR-6512-3P	99.65	66.07	1468
HSA-MIR-6720-5P	99.65	66.22	1459
HSA-MIR-6832-3P	99.52	70.44	1726
HSA-MIR-519D-5P	99.41	69.30	2057
HSA-MIR-2054	99.20	68.89	1699
HSA-MIR-5583-3P	99.06	65.68	1018
HSA-MIR-4710	98.61	65.96	1048
HSA-MIR-6776-3P	98.38	66.34	655
HSA-MIR-4659B-5P	98.03	66.84	979
HSA-MIR-4659A-5P	98.03	66.42	819
HSA-MIR-7703	97.64	67.00	965
HSA-MIR-6828-3P	96.06	67.61	1155
HSA-MIR-584-5P	95.82	68.05	848

Literature-anchored findings (GeneRIF, showing 14)

• share an evolutionary conserved function in autophagy and that autophagic capacity may be compromised in human cancers (PMID:15602573)
• Quantification of WIPI-1 puncta should be suitable to assay mammalian autophagy (PMID:17618624)
• Studies define a distinct role for WIPI1 and TORC1 signaling in controlling the transcription of melanogenic enzymes and melanosome maturation, a process that is distinct from starvation-induced autophagy. (PMID:21317285)
• Freeze-fracture replica immunolabelling reveals WD-repeat protein interacting with phosphoinositides 1 and 2 (WIPI-1 and WIPI-2) as membrane components of autophagosomes and the plasma membrane (PM). (PMID:21564513)
• the detection of WIPI1 mRNA is likely to be a convenient method of monitoring autophagosome formation in a wide range of cell types (PMID:24384561)
• WIPI-1 and WIPI-2 are functionally required in mediating the PI3P signal at the onset of autophagy in NB4 cells. (PMID:24991767)
• Data suggest WIPI1/WIPI2 co-localize with microtubule-associated light chain 3 and autophagy related proteins 2/14L, participate in biogenesis of phagosomes, autophagy, and mobilization of lipids to/from intracellular droplets. [review-like article] (PMID:25233424)
• The specific autophagosomal localization of both WIPI1 and WIPI2 (refered to as WIPI puncta) has been employed to assess autophagy using fluorescence microscopy methods, such as confocal and live-cell video microscopy (PMID:25462558)
• BAG1, CHMP2B, PEX3, and WIPI1 confirmed a strong differential gene expression, in 355 melanoma samples. (PMID:30622661)
• WIPI1 is a conserved mediator of right ventricular failure. (PMID:31021818)
• WIPI1 promotes osteosarcoma cell proliferation by inhibiting CDKN1A. (PMID:33636294)
• WIPI1 promotes fission of endosomal transport carriers and formation of autophagosomes through distinct mechanisms. (PMID:33685363)
• WIPI-1 inhibits metastasis and tumour growth via the WIPI-1-TRIM21 axis and MYC regulation in nasopharyngeal carcinoma. (PMID:34689010)
• The ABL-MYC axis controls WIPI1-enhanced autophagy in lifespan extension. (PMID:37620393)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	wipi1	ENSDARG00000040657
mus_musculus	Wipi1	ENSMUSG00000041895
rattus_norvegicus	Wipi1	ENSRNOG00000003827
drosophila_melanogaster	Atg18a	FBGN0035850
caenorhabditis_elegans		WBGENE00018294

Paralogs (3): WDR45B (ENSG00000141580), WIPI2 (ENSG00000157954), WDR45 (ENSG00000196998)

Protein

Protein identifiers

WD repeat domain phosphoinositide-interacting protein 1 — Q5MNZ9 (reviewed: Q5MNZ9)

Alternative names: Atg18 protein homolog, WD40 repeat protein interacting with phosphoinositides of 49 kDa

All UniProt accessions (6): Q5MNZ9, G5EA37, K7EK57, K7EKC5, K7EKN0, K7ELY0

UniProt curated annotations — full annotation on UniProt →

Function. Component of the autophagy machinery that controls the major intracellular degradation process by which cytoplasmic materials are packaged into autophagosomes and delivered to lysosomes for degradation. Plays an important role in starvation- and calcium-mediated autophagy, as well as in mitophagy. Functions downstream of the ULK1 and PI3-kinases that produce phosphatidylinositol 3-phosphate (PtdIns3P) on membranes of the endoplasmic reticulum once activated. Binds phosphatidylinositol 3-phosphate (PtdIns3P), and maybe other phosphoinositides including PtdIns3,5P2 and PtdIns5P, and is recruited to phagophore assembly sites at the endoplasmic reticulum membranes. There, it assists WIPI2 in the recruitment of ATG12-ATG5-ATG16L1, a complex that directly controls the elongation of the nascent autophagosomal membrane. Together with WDR45/WIPI4, promotes ATG2 (ATG2A or ATG2B)-mediated lipid transfer by enhancing ATG2-association with phosphatidylinositol 3-monophosphate (PI3P)-containing membranes. Involved in xenophagy of Staphylococcus aureus. Invading S.aureus cells become entrapped in autophagosome-like WIPI1 positive vesicles targeted for lysosomal degradation. Also plays a distinct role in controlling the transcription of melanogenic enzymes and melanosome maturation, a process that is distinct from starvation-induced autophagy. May also regulate the trafficking of proteins involved in the mannose-6-phosphate receptor (MPR) recycling pathway.

Subunit / interactions. Interacts with androgen receptor (AR) and the estrogen receptors ESR1 and ESR2. Interacts with WIPI2. Interacts with WDR45. Interacts with ATG16L1. May interact with NUDC.

Subcellular location. Golgi apparatus. trans-Golgi network. Endosome. Cytoplasmic vesicle. Clathrin-coated vesicle. Preautophagosomal structure membrane. Cytoplasm. Cytoskeleton.

Tissue specificity. Ubiquitously expressed. Highly expressed in skeletal muscle, heart, testis, pancreas and placenta. Highly expressed in G361, Sk-mel-28, Sk-mel-13, WM852 and WM451 cells. Up-regulated in a variety of tumor tissues.

Domain organisation. The N-terminus might form a beta-propeller domain involved in specific binding to phosphatidylinositol 3,5-bisphosphate (PIP2), leading to the association of the protein to the membrane. Association to the membrane can also occur through binding to phosphatidylinositol 3-monophosphate (PI3P). The L/FRRG motif is required for recruitment to PtdIns3P.

Similarity. Belongs to the WD repeat PROPPIN family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q5MNZ9-1	1, WIPI-1 alpha	yes
Q5MNZ9-2	2, WIPI-1 beta

RefSeq proteins (2): NP_001307701, NP_060453* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001680	WD40_rpt	Repeat
IPR015943	WD40/YVTN_repeat-like_dom_sf	Homologous_superfamily
IPR036322	WD40_repeat_dom_sf	Homologous_superfamily
IPR048720	PROPPIN	Family

Pfam: PF21032

UniProt features (29 total): mutagenesis site 12, repeat 7, sequence conflict 3, short sequence motif 2, sequence variant 2, chain 1, splice variant 1, region of interest 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q5MNZ9-F1	78.37	0.66

Functional residue map

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

Mutagenesis-validated functional residues (12):

Position	Phenotype
203	loss of binding to phosphoinositides and abolishes puncta formation.
205	loss of binding to phosphoinositides and abolishes puncta formation.
208	loss of binding to phosphoinositides and abolishes puncta formation.
209	loss of binding to phosphoinositides and abolishes puncta formation.
212	loss of binding to phosphoinositides and abolishes puncta formation.
226–227	loss of binding to phosphoinositides, does not disrupt the mpr pathway.
226	loss of binding to phosphoinositides and abolishes puncta formation.
227	loss of binding to phosphoinositides and abolishes puncta formation.
228	loss of binding to phosphoinositides and abolishes puncta formation.
251	loss of binding to phosphoinositides and abolishes puncta formation.
255	loss of binding to phosphoinositides and abolishes puncta formation.
257	loss of binding to phosphoinositides and abolishes puncta formation.

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-1632852	Macroautophagy
R-HSA-381038	XBP1(S) activates chaperone genes

MSigDB gene sets: 308 (showing top): GOBP_REGULATION_OF_AUTOPHAGY, REACTOME_UNFOLDED_PROTEIN_RESPONSE_UPR, WWTAAGGC_UNKNOWN, GOBP_VACUOLE_ORGANIZATION, GOBP_VESICLE_LOCALIZATION, GOCC_VACUOLAR_MEMBRANE, NKX25_02, GOBP_POSITIVE_REGULATION_OF_VACUOLE_ORGANIZATION, GCANCTGNY_MYOD_Q6, GOZGIT_ESR1_TARGETS_DN, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_UP, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_VESICLE_TARGETING, IVANOVA_HEMATOPOIESIS_MATURE_CELL

GO Biological Process (11): autophagosome assembly (GO:0000045), autophagy of mitochondrion (GO:0000422), pexophagy (GO:0000425), autophagy (GO:0006914), cellular response to starvation (GO:0009267), protein localization to phagophore assembly site (GO:0034497), nucleophagy (GO:0044804), obsolete vesicle targeting, trans-Golgi to endosome (GO:0048203), glycophagy (GO:0061723), positive regulation of autophagosome assembly (GO:2000786), response to stress (GO:0006950)

GO Molecular Function (8): signaling receptor binding (GO:0005102), nuclear estrogen receptor binding (GO:0030331), protein-macromolecule adaptor activity (GO:0030674), phosphatidylinositol-3-phosphate binding (GO:0032266), nuclear androgen receptor binding (GO:0050681), phosphatidylinositol-3,5-bisphosphate binding (GO:0080025), protein binding (GO:0005515), lipid binding (GO:0008289)

GO Cellular Component (14): Golgi membrane (GO:0000139), phagophore assembly site (GO:0000407), autophagosome membrane (GO:0000421), cytoplasm (GO:0005737), trans-Golgi network (GO:0005802), cytosol (GO:0005829), cytoskeleton (GO:0005856), endosome membrane (GO:0010008), clathrin-coated vesicle (GO:0030136), phagophore assembly site membrane (GO:0034045), endosome (GO:0005768), Golgi apparatus (GO:0005794), membrane (GO:0016020), cytoplasmic vesicle (GO:0031410)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Autophagy	1
IRE1alpha activates chaperones	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cytoplasm	4
cellular anatomical structure	4
macroautophagy	3
autophagosome assembly	2
protein binding	2
nuclear receptor binding	2
phosphatidylinositol phosphate binding	2
binding	2
bounding membrane of organelle	2
endomembrane system	2
Atg12 activating enzyme activity	1
protein-phosphatidylethanolamide deconjugating activity	1
Atg12 conjugating enzyme activity	1
Atg12 ligase activity	1
organelle assembly	1
Atg1/ULK1 kinase complex assembly	1
autophagosome organization	1
autophagy	1
autophagy of peroxisome	1
catabolic process	1
transmembrane transport	1
process utilizing autophagic mechanism	1
cellular response to nutrient levels	1
cellular response to stress	1
response to starvation	1
intracellular protein localization	1
glycogen catabolic process	1
positive regulation of macroautophagy	1
positive regulation of vacuole organization	1
positive regulation of organelle assembly	1
regulation of autophagosome assembly	1
response to stimulus	1
molecular adaptor activity	1
phosphatidylinositol bisphosphate binding	1
Golgi apparatus	1
vacuolar membrane	1
autophagosome	1
intracellular anatomical structure	1
Golgi apparatus subcompartment	1
intracellular membraneless organelle	1

Protein interactions and networks

STRING

1248 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
WIPI1	ATG2A	Q2TAZ0	978
WIPI1	OTUD7B	Q6GQQ9	962
WIPI1	VAC14	Q08AM6	945
WIPI1	ATG12	O94817	936
WIPI1	ATG2B	Q96BY7	929
WIPI1	BECN1	Q14457	912
WIPI1	PIK3C3	Q8NEB9	901
WIPI1	ULK1	O75385	900
WIPI1	ATG5	Q9H1Y0	897
WIPI1	ATG13	O75143	876
WIPI1	ATG101	Q9BSB4	875
WIPI1	ATG14	Q6ZNE5	868
WIPI1	RB1CC1	Q8TDY2	864
WIPI1	ZFYVE1	Q9HBF4	853
WIPI1	F5GZY7	F5GZY7	840

IntAct

13 interactions, top by confidence:

A	B	Type	Score
DNASE2B	ARSA	psi-mi:“MI:0914”(association)	0.530
WIPI1	RACK1	psi-mi:“MI:0914”(association)	0.480
	WIPI1	psi-mi:“MI:0915”(physical association)	0.400
WIPI1	GEMIN8	psi-mi:“MI:0915”(physical association)	0.370
WIPI1	LGALS7	psi-mi:“MI:0914”(association)	0.350
BECN1		psi-mi:“MI:0914”(association)	0.350
SWSAP1	NACA	psi-mi:“MI:2364”(proximity)	0.270
WIPI1	GET1	psi-mi:“MI:2364”(proximity)	0.270
ATG12	WIPI1	psi-mi:“MI:0403”(colocalization)	0.270
KCTD15	WIPI1	psi-mi:“MI:0915”(physical association)	0.000
PPA1	WIPI1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (63): WIPI1 (Affinity Capture-MS), GNB2L1 (Affinity Capture-MS), CEP76 (Affinity Capture-MS), S100A7 (Affinity Capture-MS), UHRF1 (Affinity Capture-MS), UHRF1 (Affinity Capture-MS), GNB2L1 (Affinity Capture-MS), WIPI1 (Affinity Capture-MS), CEP76 (Affinity Capture-MS), WIPI1 (Positive Genetic), WIPI1 (Affinity Capture-Western), WIPI1 (Two-hybrid), WIPI1 (Proximity Label-MS), WIPI1 (Proximity Label-MS), WIPI1 (Proximity Label-MS)

ESM2 similar proteins: A1CBB8, A1CTE6, A1DE24, A2QCU8, A2RAG5, A6QTX7, A6SJ85, A7EW77, A7KAM8, B6Q4Z5, B8M7Q5, B8N4F5, I1RKA1, P0CS28, P0CS29, Q00659, Q0CKB1, Q0CW30, Q0CY32, Q0U2J8, Q1DKJ3, Q2GSJ9, Q2GV40, Q2U6D5, Q2UFN8, Q2UM42, Q2URJ0, Q4IBR4, Q4IQC1, Q4P4N1, Q4WKB2, Q4WVD0, Q524W4, Q5B464, Q5BH53, Q5MNZ9, Q5QA94, Q5U2Y0, Q6C044, Q6DCN1

Diamond homologs: A1CBB8, A1DE24, A2RAG5, A3GFE3, A5DHI9, A5DVU7, A6QTX7, A6SJ85, A7A258, A7EW77, A7KAM8, A7TPY4, I1RKA1, O16466, P0CS28, P0CS29, P43601, P50079, Q0CW30, Q0U2J8, Q0WPK3, Q1DKJ3, Q2GV40, Q2U6D5, Q4P4N1, Q4WVD0, Q524W4, Q54NA2, Q59P11, Q5ABA6, Q5BH53, Q5MNZ6, Q5MNZ9, Q5QA94, Q5QJC0, Q5R7W0, Q5ZHN3, Q5ZL16, Q640T2, Q68F45

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
PIP3	up-regulates	WIPI1	“chemical activation”
WIPI1	“up-regulates quantity”	ATG16L1	binding
TFE3	“up-regulates quantity by expression”	WIPI1	“transcriptional regulation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

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

Top pathogenic / likely-pathogenic (0)

SpliceAI

2299 predictions. Top by Δscore:

Variant	Effect	Δscore
17:68426073:A:AC	donor_gain	1.0000
17:68426074:C:CC	donor_gain	1.0000
17:68426087:ATTCT:A	donor_gain	1.0000
17:68427277:G:C	acceptor_gain	1.0000
17:68427277:G:GC	acceptor_gain	1.0000
17:68433571:CATAC:C	acceptor_gain	1.0000
17:68433573:TAC:T	acceptor_gain	1.0000
17:68433573:TACC:T	acceptor_loss	1.0000
17:68433574:ACCTA:A	acceptor_loss	1.0000
17:68433575:CCTA:C	acceptor_loss	1.0000
17:68433576:CT:C	acceptor_loss	1.0000
17:68433577:T:C	acceptor_loss	1.0000
17:68434625:CC:C	acceptor_gain	1.0000
17:68434626:CC:C	acceptor_gain	1.0000
17:68435309:A:AC	donor_gain	1.0000
17:68435310:C:CC	donor_gain	1.0000
17:68435613:GACTC:G	donor_loss	1.0000
17:68435614:ACTC:A	donor_loss	1.0000
17:68435615:CT:C	donor_loss	1.0000
17:68435616:TCACT:T	donor_loss	1.0000
17:68435617:CACT:C	donor_loss	1.0000
17:68435618:A:AC	donor_gain	1.0000
17:68435618:ACTTT:A	donor_loss	1.0000
17:68435619:C:CC	donor_gain	1.0000
17:68435719:G:C	acceptor_gain	1.0000
17:68436375:AACTT:A	donor_loss	1.0000
17:68436376:ACTTA:A	donor_loss	1.0000
17:68436377:CTTAC:C	donor_loss	1.0000
17:68436378:TTAC:T	donor_loss	1.0000
17:68436379:TAC:T	donor_loss	1.0000

AlphaMissense

2904 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:68433515:A:C	S251R	1.000
17:68433515:A:T	S251R	1.000
17:68433517:T:G	S251R	1.000
17:68433528:A:G	L247P	1.000
17:68434567:T:A	R227S	1.000
17:68434567:T:G	R227S	1.000
17:68434568:C:G	R227T	1.000
17:68434613:C:G	R212P	1.000
17:68434626:C:G	G208R	1.000
17:68435632:A:C	S203R	1.000
17:68435632:A:T	S203R	1.000
17:68435634:T:G	S203R	1.000
17:68444585:A:G	L113P	1.000
17:68450780:A:C	I94S	1.000
17:68450780:A:G	I94T	1.000
17:68450849:A:G	L71P	1.000
17:68450849:A:T	L71Q	1.000
17:68450862:A:T	F67I	1.000
17:68428916:A:G	L329P	0.999
17:68430047:G:T	A305D	0.999
17:68430048:C:G	A305P	0.999
17:68433491:G:C	F259L	0.999
17:68433491:G:T	F259L	0.999
17:68433492:A:G	F259S	0.999
17:68433493:A:G	F259L	0.999
17:68433516:C:A	S251I	0.999
17:68433528:A:T	L247H	0.999
17:68434565:C:T	G228E	0.999
17:68434568:C:A	R227I	0.999
17:68434625:C:A	G208V	0.999

dbSNP variants (sampled 300 via entrez): RS1000047717 (17:68442560 G>T), RS1000074772 (17:68449412 C>T), RS1000145471 (17:68448061 C>T), RS1000167453 (17:68425684 A>G), RS1000420079 (17:68442814 G>A), RS1000439235 (17:68435562 G>A,C,T), RS1000487652 (17:68423623 C>A), RS1000601104 (17:68440661 A>G), RS1000650232 (17:68426422 A>C), RS1000797538 (17:68453565 G>A), RS1001126417 (17:68420934 T>G), RS1001195531 (17:68450372 C>T), RS1001477570 (17:68438007 G>A), RS1001510059 (17:68437520 C>T), RS1001515373 (17:68421160 G>A)

Disease associations

OMIM: gene MIM:609224 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

9 associations (top):

Study	Trait	p-value
GCST004621_195	Red cell distribution width	5.000000e-10
GCST006804_139	Red cell distribution width	2.000000e-10
GCST010242_225	HDL cholesterol levels	9.000000e-09
GCST90002387_198	Immature fraction of reticulocytes	1.000000e-11
GCST90002389_240	Lymphocyte percentage of white cells	2.000000e-09
GCST90002391_97	Mean corpuscular hemoglobin concentration	2.000000e-14
GCST90002399_250	Neutrophil percentage of white cells	3.000000e-09
GCST90002404_173	Red cell distribution width	2.000000e-26
GCST90013406_167	Liver enzyme levels (alkaline phosphatase)	4.000000e-29

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:0009188	Red cell distribution width
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0007993	lymphocyte percentage of leukocytes
EFO:0004528	mean corpuscular hemoglobin concentration
EFO:0007990	neutrophil percentage of leukocytes
EFO:0004533	alkaline phosphatase measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, increases expression	7
sodium arsenite	affects cotreatment, increases abundance, increases expression, decreases expression	4
Estradiol	affects cotreatment, increases expression, affects binding, increases reaction, affects expression	4
Tunicamycin	increases expression	4
Cyclosporine	increases expression	4
Aflatoxin B1	increases methylation, decreases expression	4
methylmercuric chloride	decreases expression, increases expression	3
bisphenol A	affects expression, decreases expression, increases expression	3
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression, increases expression	3
Fluoxetine	increases expression	3
Acetaminophen	affects response to substance, increases expression	2
Amiodarone	increases expression	2
Amitriptyline	increases expression	2
trans-1,4-Bis(2-chlorobenzaminomethyl)cyclohexane Dihydrochloride	increases expression	2
Calcitriol	affects cotreatment, increases expression	2
Chlorpromazine	increases expression	2
Clomipramine	increases expression	2
Clozapine	increases expression	2
Flecainide	increases expression	2
Imipramine	increases expression	2
Ketoconazole	increases expression	2
Perhexiline	increases expression	2
Tamoxifen	increases expression	2
Thioridazine	increases expression	2
Tretinoin	increases expression	2
Zimeldine	increases expression	2
Sertraline	increases expression	2
afuresertib	increases expression	1
2,4,6-tribromophenol	increases expression	1
lasiocarpine	decreases expression	1

Cellosaurus cell lines

1 cell lines: 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_5F67	HEK293A/GFP-WIPI1	Transformed cell line	Female

Clinical trials (associated diseases)

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