GULP1

Summary

GULP1 (GULP PTB domain containing engulfment adaptor 1, HGNC:18649) is a protein-coding gene on chromosome 2q32.1-q32.2, encoding PTB domain-containing engulfment adapter protein 1 (Q9UBP9). May function as an adapter protein.

The protein encoded by this gene is an adapter protein necessary for the engulfment of apoptotic cells by phagocytes. Several transcript variants, some protein coding and some thought not to be protein coding, have been found for this gene.

Source: NCBI Gene 51454 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 42 total
• MANE Select transcript: NM_016315

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18649
Approved symbol	GULP1
Name	GULP PTB domain containing engulfment adaptor 1
Location	2q32.1-q32.2
Locus type	gene with protein product
Status	Approved
Aliases	CED6, CED-6, GULP
Ensembl gene	ENSG00000144366
Ensembl biotype	protein_coding
OMIM	608165
Entrez	51454

Gene structure

Transcript identifiers

Ensembl transcripts: 104 — 97 protein_coding, 5 protein_coding_CDS_not_defined, 2 retained_intron

ENST00000359135, ENST00000409580, ENST00000409609, ENST00000409637, ENST00000409805, ENST00000409830, ENST00000409843, ENST00000409927, ENST00000410051, ENST00000433052, ENST00000451191, ENST00000467422, ENST00000476422, ENST00000478306, ENST00000479019, ENST00000486445, ENST00000495745, ENST00000496976, ENST00000699997, ENST00000699998, ENST00000908903, ENST00000908904, ENST00000908905, ENST00000908906, ENST00000908907, ENST00000908908, ENST00000908909, ENST00000908910, ENST00000908911, ENST00000908912, ENST00000908913, ENST00000908914, ENST00000908915, ENST00000908916, ENST00000908917, ENST00000908918, ENST00000908919, ENST00000908920, ENST00000908921, ENST00000908922, ENST00000908923, ENST00000919984, ENST00000919985, ENST00000919986, ENST00000919987, ENST00000919988, ENST00000919989, ENST00000919990, ENST00000919991, ENST00000919992, ENST00000919993, ENST00000919994, ENST00000919995, ENST00000919996, ENST00000919997, ENST00000919998, ENST00000919999, ENST00000920000, ENST00000920001, ENST00000920002, ENST00000920003, ENST00000920004, ENST00000920005, ENST00000920006, ENST00000920007, ENST00000920008, ENST00000920009, ENST00000920010, ENST00000920011, ENST00000920012, ENST00000920013, ENST00000920014, ENST00000920015, ENST00000920016, ENST00000920017, ENST00000920018, ENST00000920019, ENST00000920020, ENST00000963744, ENST00000963745, ENST00000963746, ENST00000963747, ENST00000963748, ENST00000963749, ENST00000963750, ENST00000963751, ENST00000963752, ENST00000963753, ENST00000963754, ENST00000963755, ENST00000963756, ENST00000963757, ENST00000963758, ENST00000963759, ENST00000963760, ENST00000963761, ENST00000963762, ENST00000963763, ENST00000963764, ENST00000963765, ENST00000963766, ENST00000963767, ENST00000963768, ENST00000963769

RefSeq mRNA: 32 — MANE Select: NM_016315 NM_001252668, NM_001252669, NM_001375925, NM_001375926, NM_001375927, NM_001375928, NM_001375929, NM_001375930, NM_001375931, NM_001375932, NM_001375933, NM_001375934, NM_001375935, NM_001375936, NM_001375937, NM_001375938, NM_001375939, NM_001375940, NM_001375941, NM_001375942, NM_001375943, NM_001375944, NM_001375945, NM_001375946, NM_001375947, NM_001375948, NM_001375949, NM_001375950, NM_001375951, NM_001375952, NM_001375953, NM_016315

CCDS: CCDS2295, CCDS58742, CCDS58743, CCDS92915, CCDS92916

Canonical transcript exons

ENST00000409830 — 12 exons

Exon	Start	End
ENSE00001238990	188383763	188383889
ENSE00001581541	188291874	188292166
ENSE00001586850	188593940	188595926
ENSE00003488649	188587855	188587949
ENSE00003507033	188483431	188483492
ENSE00003533636	188529097	188529195
ENSE00003547501	188541181	188541318
ENSE00003593100	188477659	188477730
ENSE00003637690	188522756	188522827
ENSE00003645508	188584265	188584403
ENSE00003649873	188569239	188569355
ENSE00003688788	188570028	188570120

Expression profiles

Bgee: expression breadth ubiquitous, 285 present calls, max score 99.15.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 17.4757 / max 549.7980, expressed in 1402 samples.

FANTOM5 promoters (17 alternative TSS)

Promoter ID	TPM avg	Samples expressed
24173	5.3215	1035
24170	3.5901	647
24168	2.2866	1077
24169	2.2101	902
24167	1.7170	764
24172	0.5862	338
24166	0.4971	261
24171	0.3875	177
24175	0.2505	122
24176	0.1811	103

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
corpus epididymis	UBERON:0004359	99.15	gold quality
pigmented layer of retina	UBERON:0001782	98.27	gold quality
choroid plexus epithelium	UBERON:0003911	98.09	gold quality
cauda epididymis	UBERON:0004360	97.04	gold quality
seminal vesicle	UBERON:0000998	96.83	gold quality
blood vessel layer	UBERON:0004797	96.62	gold quality
calcaneal tendon	UBERON:0003701	96.58	gold quality
ventricular zone	UBERON:0003053	96.31	gold quality
caput epididymis	UBERON:0004358	96.11	gold quality
renal glomerulus	UBERON:0000074	95.90	gold quality
mucosa of paranasal sinus	UBERON:0005030	95.62	gold quality
adrenal tissue	UBERON:0018303	95.62	gold quality
placenta	UBERON:0001987	95.47	gold quality
metanephric glomerulus	UBERON:0004736	95.34	gold quality
jejunal mucosa	UBERON:0000399	95.14	gold quality
bronchial epithelial cell	CL:0002328	94.79	gold quality
cartilage tissue	UBERON:0002418	93.96	gold quality
hair follicle	UBERON:0002073	93.95	gold quality
descending thoracic aorta	UBERON:0002345	93.62	gold quality
sperm	CL:0000019	93.50	gold quality
tendon	UBERON:0000043	93.45	gold quality
endometrium	UBERON:0001295	93.45	gold quality
epithelium of bronchus	UBERON:0002031	93.40	gold quality
synovial joint	UBERON:0002217	93.23	gold quality
bronchus	UBERON:0002185	93.15	gold quality
nephron tubule	UBERON:0001231	93.11	gold quality
thoracic aorta	UBERON:0001515	93.07	gold quality
mammalian vulva	UBERON:0000997	93.01	gold quality
ascending aorta	UBERON:0001496	92.95	gold quality
stromal cell of endometrium	CL:0002255	92.85	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	8.51
E-CURD-11	no	286.83

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): GATA2

miRNA regulators (miRDB)

116 targeting GULP1, 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-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-450A-1-3P	100.00	69.33	1837
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-568	99.98	69.86	2084
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-548A-5P	99.94	71.27	3482
HSA-MIR-548AD-5P	99.94	71.23	3502
HSA-MIR-548AE-5P	99.94	71.23	3502
HSA-MIR-548AK	99.94	71.24	3488
HSA-MIR-548AM-5P	99.94	71.24	3488
HSA-MIR-548AP-5P	99.94	71.14	3489
HSA-MIR-548AQ-5P	99.94	71.34	3426

Literature-anchored findings (GeneRIF, showing 17)

• Interaction of CED-6/GULP, an adapter protein involved in engulfment of apoptotic cells with CED-1 and CD91/low density lipoprotein receptor-related protein (LRP). (PMID:11729193)
• GULP is a likely downstream molecule in the stabilin-2-mediated signaling pathway and plays an important role in stabilin-2-mediated phagocytosis (PMID:18230608)
• Phosphatidylserine-recognizing SR-BI activates associated GULP; activated GULP induces MAPK phosphorylation; activated MAPK increases GTP-bound Rac1; and activated Rac1 induces a rearrangement of the actin cytoskeleton. (PMID:19122200)
• the GULP1 gene and the apoptotic engulfment pathway are involved in schizophrenia in subjects of European ancestry (PMID:19721717)
• these results indicate that GULP functions as an adaptor protein for stabilin-1-mediated phagocytosis. (PMID:20599701)
• This study identify GULP1 as a novel neuronal amyloid-beta precursor protein interacting protein that alters trafficking and processing of amyloid-beta precursor protein. (PMID:20674096)
• overexpression of GULP1 enhanced the generation of APP CTFs (C-terminal fragments) and Abeta, whereas knockdown of GULP1 suppressed APP CTFs and Abeta production. (PMID:21486224)
• The apoptotic engulfment protein Ced-6 participates in clathrin-mediated yolk uptake in Drosophila egg chambers. (PMID:22398720)
• GULP expression positively regulates TGF-beta signaling leading to growth inhibition, this may represent an attractive target to achieve TGF-beta responsiveness in ovarian cells. (PMID:22451657)
• GULP1 only mediates LRP1 transactivation (PMID:23167255)
• This study highlights and provides new implications for the role of GULP1 associated molecular mechanism(s) in COPD-emphysema development or progression. (PMID:28284325)
• GULP1 methylation was associated with clinicopathological parameters such as stage III/IV, poorly differentiated grade, residual disease, worse overall and disease specific survival in ovarian cancer. (PMID:29964205)
• Results indicate that GULP, engulfment adaptor PTB domain containing 1 (GULP1) threonine 35 (T35) phosphorylation is a mechanism for the regulation of GULP1-amyloid beta precursor protein (APP) interaction and thereby APP processing. (PMID:31373844)
• the phagocytic adaptor protein Gulp1 regulates EphB/ephrinB trogocytosis to achieve efficient cell rearrangements of cultured cells and during embryonic development (PMID:31409653)
• The knockdown of GULP1 and ABR using siRNAs decreased phagocytosis by 40%. (PMID:31516309)
• GULP1 regulates the NRF2-KEAP1 signaling axis in urothelial carcinoma. (PMID:32817372)
• GULP1 as a Downstream Effector of the Estrogen Receptor-beta Modulates Cisplatin Sensitivity in Bladder Cancer. (PMID:39467629)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	gulp1a	ENSDARG00000001733
danio_rerio	gulp1b	ENSDARG00000057833
mus_musculus	Gulp1	ENSMUSG00000056870
rattus_norvegicus	Gulp1	ENSRNOG00000003242
drosophila_melanogaster	ced-6	FBGN0029092
caenorhabditis_elegans		WBGENE00000420

Paralogs (11): MAPK8IP2 (ENSG00000008735), NUMBL (ENSG00000105245), MAPK8IP1 (ENSG00000121653), NUMB (ENSG00000133961), DAB2 (ENSG00000153071), LDLRAP1 (ENSG00000157978), DAB1 (ENSG00000173406), FAM43B (ENSG00000183114), FAM43A (ENSG00000185112), NOS1AP (ENSG00000198929), C1orf226 (ENSG00000239887)

Protein

Protein identifiers

PTB domain-containing engulfment adapter protein 1 — Q9UBP9 (reviewed: Q9UBP9)

Alternative names: Cell death protein 6 homolog, PTB domain adapter protein CED-6, Protein GULP

All UniProt accessions (6): Q9UBP9, A0A8V8TP70, A0A8V8TQW5, B8ZZL1, H0Y6R1, H7BZV7

UniProt curated annotations — full annotation on UniProt →

Function. May function as an adapter protein. Required for efficient phagocytosis of apoptotic cells. Modulates cellular glycosphingolipid and cholesterol transport. May play a role in the internalization and endosomal trafficking of various LRP1 ligands, such as PSAP. Increases cellular levels of GTP-bound ARF6.

Subunit / interactions. Homodimer. Interacts with clathrin. Interacts with GDP-bound ARF6, but not with GTP-bound ARF6. Part of a complex composed of GULP1, ACAP1 and ARF6. Interacts with ACAP1, LRP1, MEGF10 and STAB2.

Subcellular location. Cytoplasm.

Tissue specificity. Widely expressed. Detected in macrophages, pancreas, kidney, skeletal muscle, heart, colon, intestine, lung, placenta and ovary.

Similarity. Belongs to the ced-6 family.

Isoforms (4)

UniProt ID	Names	Canonical?
Q9UBP9-1	1	yes
Q9UBP9-2	2
Q9UBP9-3	3
Q9UBP9-4	4

RefSeq proteins (32): NP_001239597, NP_001239598, NP_001362854, NP_001362855, NP_001362856, NP_001362857, NP_001362858, NP_001362859, NP_001362860, NP_001362861, NP_001362862, NP_001362863, NP_001362864, NP_001362865, NP_001362866, NP_001362867, NP_001362868, NP_001362869, NP_001362870, NP_001362871, NP_001362872, NP_001362873, NP_001362874, NP_001362875, NP_001362876, NP_001362877, NP_001362878, NP_001362879, NP_001362880, NP_001362881, NP_001362882, NP_057399* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR006020	PTB/PI_dom	Domain
IPR011993	PH-like_dom_sf	Homologous_superfamily
IPR051133	Adapter_Engulfment-Domain	Family

Pfam: PF00640

UniProt features (29 total): strand 7, splice variant 4, helix 4, turn 4, mutagenesis site 2, modified residue 2, chain 1, domain 1, sequence conflict 1, region of interest 1, coiled-coil region 1, compositionally biased region 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
6ITU	X-RAY DIFFRACTION	2.17

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UBP9-F1	75.09	0.49

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 (2): 16, 223

Mutagenesis-validated functional residues (2):

Position	Phenotype
176	loss of dimerization; when associated with p-183.
183	loss of dimerization; when associated with p-176.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 194 (showing top): ELVIDGE_HYPOXIA_DN, MODULE_52, SCHWAB_TARGETS_OF_BMYB_POLYMORPHIC_VARIANTS_DN, GOZGIT_ESR1_TARGETS_DN, GOBP_VESICLE_MEDIATED_TRANSPORT, MODULE_118, WANG_LMO4_TARGETS_DN, MILI_PSEUDOPODIA_HAPTOTAXIS_UP, CHARAFE_BREAST_CANCER_BASAL_VS_MESENCHYMAL_DN, KINSEY_TARGETS_OF_EWSR1_FLII_FUSION_DN, RIGGI_EWING_SARCOMA_PROGENITOR_DN, MODULE_99, ONDER_CDH1_TARGETS_2_UP, DEBIASI_APOPTOSIS_BY_REOVIRUS_INFECTION_UP, FLECHNER_BIOPSY_KIDNEY_TRANSPLANT_REJECTED_VS_OK_DN

GO Biological Process (4): lipid transport (GO:0006869), phagocytosis, engulfment (GO:0006911), apoptotic process (GO:0006915), phagocytosis (GO:0006909)

GO Molecular Function (0):

GO Cellular Component (1): cytoplasm (GO:0005737)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
transport	1
lipid localization	1
phagocytosis	1
plasma membrane invagination	1
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
endocytosis	1
intracellular anatomical structure	1
cellular anatomical structure	1

Protein interactions and networks

STRING

762 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GULP1	IFT122	Q9HBG6	990
GULP1	ELMO2	Q96JJ3	938
GULP1	DOCK1	Q14185	925
GULP1	ELMO3	Q96BJ8	908
GULP1	ELMO1	Q92556	893
GULP1	STAB2	Q8WWQ8	856
GULP1	LRP1	Q07954	851
GULP1	CRK	P46108	839
GULP1	ABCA1	O95477	829
GULP1	MEGF10	Q96KG7	793
GULP1	WDR35	Q9P2L0	766
GULP1	ADGRB1	O14514	717
GULP1	DIRC1	Q969H9	692
GULP1	ACAP1	Q15027	678
GULP1	ABI1	Q8IZP0	616

IntAct

36 interactions, top by confidence:

A	B	Type	Score
PICK1	ILVBL	psi-mi:“MI:0914”(association)	0.530
MLLT6	RGPD8	psi-mi:“MI:0914”(association)	0.530
SYNGAP1	YWHAE	psi-mi:“MI:0914”(association)	0.530
GNG5	GNAS	psi-mi:“MI:0914”(association)	0.530
ITGB3	GULP1	psi-mi:“MI:0407”(direct interaction)	0.440
ITGB7	GULP1	psi-mi:“MI:0407”(direct interaction)	0.440
CNTF	GULP1	psi-mi:“MI:0915”(physical association)	0.400
SYNGR4	GULP1	psi-mi:“MI:0915”(physical association)	0.400
GULP1	ced-1	psi-mi:“MI:0915”(physical association)	0.370
GULP1	SMC2	psi-mi:“MI:0915”(physical association)	0.370
CREB3L2	GULP1	psi-mi:“MI:0915”(physical association)	0.370
GULP1	EPS8	psi-mi:“MI:0915”(physical association)	0.370
PLEKHA7	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
AP2M1	C1orf226	psi-mi:“MI:0914”(association)	0.350
ANKRD36B	CCDC66	psi-mi:“MI:0914”(association)	0.350
PSD4	TYMS	psi-mi:“MI:0914”(association)	0.350
ANGPTL3	CCDC91	psi-mi:“MI:0914”(association)	0.350
ANLN	UBA6	psi-mi:“MI:0914”(association)	0.350
SERBP1	UBA6	psi-mi:“MI:0914”(association)	0.350
FTL	SH3PXD2B	psi-mi:“MI:0914”(association)	0.350
PAAT	HIP1	psi-mi:“MI:0914”(association)	0.350
DNAJC6	PIK3C2A	psi-mi:“MI:0914”(association)	0.350
RLN1	MANBA	psi-mi:“MI:0914”(association)	0.350
POLG2	VSIG8	psi-mi:“MI:0914”(association)	0.350
PSD4	BCR	psi-mi:“MI:0914”(association)	0.350
GKN1	TMOD1	psi-mi:“MI:0914”(association)	0.350
SERP2	PSEN1	psi-mi:“MI:0914”(association)	0.350
AP2M1	PER1	psi-mi:“MI:0914”(association)	0.350
SNW1		psi-mi:“MI:0914”(association)	0.350

BioGRID (53): GULP1 (Affinity Capture-MS), GULP1 (Affinity Capture-MS), GULP1 (Affinity Capture-MS), GULP1 (Affinity Capture-MS), GULP1 (Affinity Capture-MS), GULP1 (Affinity Capture-MS), GULP1 (Affinity Capture-MS), GULP1 (Affinity Capture-RNA), GULP1 (Proximity Label-MS), GULP1 (Proximity Label-MS), GULP1 (Proximity Label-MS), GULP1 (Proximity Label-MS), GULP1 (Proximity Label-MS), GULP1 (Proximity Label-MS), GULP1 (Reconstituted Complex)

ESM2 similar proteins: A6QQV9, D3ZAR1, D4AB98, F1LYQ8, F7EL49, F8VPU2, O54960, O60343, O70143, O75052, O97790, P29353, P42331, P98083, Q0IIE2, Q15678, Q2I6J1, Q32PV0, Q4V8Y7, Q5M824, Q5PQS4, Q5R7W7, Q5RAB8, Q5SW96, Q60949, Q61120, Q62130, Q62136, Q67FQ3, Q69Z98, Q801G1, Q80T23, Q812E4, Q86TI0, Q8AY68, Q8BN58, Q8BYJ6, Q8BYW1, Q8BZI0, Q8C0V9

Diamond homologs: A1L1I3, O08919, O88797, P16554, P49757, P98078, P98081, P98082, Q2LC84, Q5PQS4, Q5SW96, Q801G1, Q8C142, Q8K2A1, Q9QZS3, Q9UBP9, Q9XTY6, Q9Y6R0, A0A8I3NFE2, A5PMU4, D3ZAR1, O09127, O15357, O70143, P0C6S7, P29321, P29353, P54753, P54754, P54755, P54756, P54758, P59672, P98083, Q03145, Q07498, Q09YL6, Q0IIE2, Q2I6J1, Q32PV0

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	28
Likely benign	2
Benign	3

Top pathogenic / likely-pathogenic (0)

SpliceAI

4029 predictions. Top by Δscore:

Variant	Effect	Δscore
2:188383761:A:AG	acceptor_gain	1.0000
2:188383762:G:GG	acceptor_gain	1.0000
2:188383762:GTT:G	acceptor_gain	1.0000
2:188477728:AAGGT:A	donor_loss	1.0000
2:188477729:AGG:A	donor_loss	1.0000
2:188477731:G:GA	donor_loss	1.0000
2:188477732:T:A	donor_loss	1.0000
2:188483429:A:AG	acceptor_gain	1.0000
2:188483430:G:GG	acceptor_gain	1.0000
2:188541315:GTGT:G	donor_gain	1.0000
2:188541317:GT:G	donor_gain	1.0000
2:188541319:G:GG	donor_gain	1.0000
2:188569225:T:TA	acceptor_gain	1.0000
2:188569233:A:AG	acceptor_gain	1.0000
2:188569234:C:G	acceptor_gain	1.0000
2:188569235:A:AG	acceptor_gain	1.0000
2:188569235:ACAG:A	acceptor_gain	1.0000
2:188569236:C:G	acceptor_gain	1.0000
2:188569237:A:AG	acceptor_gain	1.0000
2:188569237:AG:A	acceptor_gain	1.0000
2:188569237:AGGC:A	acceptor_loss	1.0000
2:188569238:G:GT	acceptor_gain	1.0000
2:188569238:GG:G	acceptor_gain	1.0000
2:188569238:GGC:G	acceptor_gain	1.0000
2:188569238:GGCT:G	acceptor_gain	1.0000
2:188569351:AAAGA:A	donor_gain	1.0000
2:188569352:AAGA:A	donor_gain	1.0000
2:188569353:AGA:A	donor_gain	1.0000
2:188569353:AGAG:A	donor_loss	1.0000
2:188569354:GA:G	donor_gain	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000000768 (2:188577987 G>A,C), RS1000008296 (2:188454255 G>T), RS1000016147 (2:188353765 A>C), RS1000019391 (2:188503340 A>G), RS1000026766 (2:188319029 C>A,T), RS1000041404 (2:188491034 G>A,C), RS1000052286 (2:188314409 G>C,T), RS1000068122 (2:188528379 C>T), RS1000069045 (2:188497751 G>A), RS1000076234 (2:188497256 G>A), RS1000089207 (2:188541680 C>T), RS1000092345 (2:188357138 T>C), RS1000094098 (2:188325301 A>G), RS1000095123 (2:188584194 G>A), RS1000099694 (2:188424065 A>G)

Disease associations

OMIM: gene MIM:608165 | 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
GCST003264_203	Post bronchodilator FEV1/FVC ratio	4.000000e-06
GCST003264_229	Post bronchodilator FEV1/FVC ratio	4.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004713	FEV/FVC ratio

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases abundance, increases expression, affects expression, affects cotreatment	4
Estradiol	decreases expression, decreases reaction, increases expression	4
Benzo(a)pyrene	affects methylation, decreases expression, affects expression	3
Valproic Acid	affects expression, increases expression	3
Cyclosporine	increases expression	3
Aflatoxin B1	decreases expression, decreases methylation, affects expression	3
graphene oxide	increases expression	2
mercuric bromide	increases expression, affects cotreatment	2
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	increases expression, affects cotreatment, decreases expression	2
Air Pollutants	increases abundance, increases expression, decreases expression	2
Cisplatin	decreases expression, affects cotreatment, increases expression	2
Doxorubicin	decreases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Particulate Matter	increases abundance, increases expression, decreases expression	2
aristolochic acid I	decreases expression	1
methylmercuric chloride	decreases expression, increases expression	1
methyleugenol	decreases expression	1
pirinixic acid	affects binding, decreases expression, increases activity	1
bisphenol A	increases methylation	1
trichostatin A	increases expression, decreases expression	1
beta-lapachone	increases expression	1
arsenite	affects binding, decreases reaction	1
fenvalerate	decreases expression	1
butyraldehyde	decreases expression	1
manganese chloride	affects cotreatment, decreases expression, increases abundance	1
potassium chromate(VI)	increases expression	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, decreases expression	1
nickel sulfate	increases expression	1
diallyl trisulfide	decreases expression	1
epigallocatechin gallate	decreases expression	1

Clinical trials (associated diseases)

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