AGFG1

Summary

AGFG1 (ArfGAP with FG repeats 1, HGNC:5175) is a protein-coding gene on chromosome 2q36.3, encoding Arf-GAP domain and FG repeat-containing protein 1 (P52594). Required for vesicle docking or fusion during acrosome biogenesis.

The protein encoded by this gene is related to nucleoporins, a class of proteins that mediate nucleocytoplasmic transport. The encoded protein binds the activation domain of the human immunodeficiency virus Rev protein when Rev is assembled onto its RNA target, and is required for the nuclear export of Rev-directed RNAs. Multiple transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 3267 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 87 total — 1 pathogenic
• MANE Select transcript: NM_004504

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:5175
Approved symbol	AGFG1
Name	ArfGAP with FG repeats 1
Location	2q36.3
Locus type	gene with protein product
Status	Approved
Aliases	RIP, RAB
Ensembl gene	ENSG00000173744
Ensembl biotype	protein_coding
OMIM	600862
Entrez	3267

Gene structure

Transcript identifiers

Ensembl transcripts: 23 — 22 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000310078, ENST00000373671, ENST00000409171, ENST00000409315, ENST00000409979, ENST00000456594, ENST00000458212, ENST00000486932, ENST00000900794, ENST00000928136, ENST00000928137, ENST00000928138, ENST00000966411, ENST00000966412, ENST00000966413, ENST00000966414, ENST00000966415, ENST00000966416, ENST00000966417, ENST00000966418, ENST00000966419, ENST00000966420, ENST00000966421

RefSeq mRNA: 4 — MANE Select: NM_004504 NM_001135187, NM_001135188, NM_001135189, NM_004504

CCDS: CCDS2467, CCDS46533, CCDS46534, CCDS46535

Canonical transcript exons

ENST00000310078 — 13 exons

Exon	Start	End
ENSE00001183943	227553704	227553795
ENSE00001183947	227551959	227552117
ENSE00001183950	227536901	227536993
ENSE00001183952	227536625	227536704
ENSE00001183955	227534845	227535025
ENSE00001183961	227533549	227533758
ENSE00001183964	227531091	227531210
ENSE00001183965	227524762	227524915
ENSE00001183976	227491547	227491640
ENSE00001855491	227472156	227472588
ENSE00001882126	227554436	227561217
ENSE00003493160	227523763	227523925
ENSE00003537674	227519948	227520063

Expression profiles

Bgee: expression breadth ubiquitous, 293 present calls, max score 99.88.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 50.1889 / max 669.3664, expressed in 1821 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
25743	48.8532	1820
25748	1.0761	662
25747	0.1691	57
25746	0.0537	7
25745	0.0369	9

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sperm	CL:0000019	99.88	gold quality
male germ cell	CL:0000015	98.40	gold quality
islet of Langerhans	UBERON:0000006	95.32	gold quality
right testis	UBERON:0004534	95.20	gold quality
left testis	UBERON:0004533	95.11	gold quality
right lung	UBERON:0002167	94.83	gold quality
omental fat pad	UBERON:0010414	94.62	gold quality
peritoneum	UBERON:0002358	94.58	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	94.53	gold quality
monocyte	CL:0000576	94.51	gold quality
upper lobe of left lung	UBERON:0008952	94.41	gold quality
bone marrow	UBERON:0002371	94.39	gold quality
leukocyte	CL:0000738	94.32	gold quality
mononuclear cell	CL:0000842	94.27	gold quality
adipose tissue of abdominal region	UBERON:0007808	94.26	gold quality
gall bladder	UBERON:0002110	94.23	gold quality
pericardium	UBERON:0002407	94.11	gold quality
blood	UBERON:0000178	94.10	gold quality
colonic epithelium	UBERON:0000397	94.08	gold quality
upper lobe of lung	UBERON:0008948	94.08	gold quality
testis	UBERON:0000473	93.94	gold quality
cortical plate	UBERON:0005343	93.74	gold quality
subcutaneous adipose tissue	UBERON:0002190	93.61	gold quality
adrenal tissue	UBERON:0018303	93.53	gold quality
spinal cord	UBERON:0002240	93.51	gold quality
bone marrow cell	CL:0002092	93.36	gold quality
adipose tissue	UBERON:0001013	93.25	gold quality
left coronary artery	UBERON:0001626	93.07	gold quality
connective tissue	UBERON:0002384	92.95	gold quality
right adrenal gland	UBERON:0001233	92.94	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	15.30

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): BHLHA15

miRNA regulators (miRDB)

362 targeting AGFG1, 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-513A-5P	100.00	69.77	2465
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-4776-3P	100.00	68.73	1340
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-4455	100.00	65.48	1587
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-1184	99.99	68.19	1458
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-103A-3P	99.98	69.14	1595
HSA-MIR-107	99.98	69.14	1595
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-520D-5P	99.98	73.34	4883

Literature-anchored findings (GeneRIF, showing 16)

• hRIP is an essential cellular Rev cofactor, which acts at a previously unanticipated step in HIV-1 RNA export. (PMID:14701878)
• Study demonstrates that the clathrin-mediated endocytosis of the SNARE VAMP7 is directly mediated by Hrb, a clathrin adaptor and ArfGAP. (PMID:18775314)
• HRB is involved in clathrin-dependent endocytosis and recruits TI-VAMP in this process (PMID:18819912)
• Association ofalpha-synuclein with Rab attachment receptor protein and soluble sensitive factor attachment receptors (SNAREs) highlights a key role for membrane transport defects in alpha-synuclein-mediated pathology. (PMID:21439320)
• The authors show that cells lacking functional HRB have significantly reduced production of influenza virus progeny and that this defect results from impaired viral ribonucleoprotein (vRNP) delivery to the plasma membrane. (PMID:21752912)
• The top primary GWAS association of Airway hyperresponsiveness was in rs6731443 (P-value 2.5E-06) located within the AGFG1 genes. (PMID:23984888)
• Selenite caused CYLD upregulation via LEF1 and cIAP downregulation, both of which contribute to the degradation of ubiquitin chains on RIP1 and subsequent caspase-8 activation and colorectal tumor cell apoptosis. (PMID:24577083)
• HRB knock-down affected CD4 downregulation induced by Nef but not by HIV-1 Vpu. (PMID:26701340)
• Necroptotic RIP1 phosphorylation and ubiquitination seem to be tightly coordinated: inhibition or absence of RIP1 kinase activity blocks necroptotic RIP1 ubiquitination, whereas mutation of RIP1 necroptosis-associated ubiquitination site (K115R) dampens RIP1 kinase activity during necroptotic signaling. (PMID:27518435)
• human miR-186, 210 and 222 directly regulate the human genes Dicer1, HRB and HIV-EP2, thus may be filling key roles during HIV-1 replication and miRNA biogenesis. (PMID:30682089)
• Analyses indicated that circAGFG1 acts as a sponge for miR-203 to repress the effect of miR-203 on its target, ZNF281. In conclusion, study suggests that circAGFG1 promotes NSCLC growth and metastasis though a circAGFG1/miR-203/ZNF281 axis. (PMID:31243884)
• CircAGFG1 promoted RAF1 expression by sponging miR-370-3p and further activated RAF/MEK/ERK pathway to regulate cervical cancer progression. (PMID:31703640)
• CircAGFG1 aggravates the progression of cervical cancer by downregulating p53. (PMID:32141537)
• Circular RNA circ-AGFG1 contributes to esophageal squamous cell carcinoma progression and glutamine catabolism by targeting microRNA-497-5p/solute carrier family 1 member 5 axis. (PMID:36206112)
• CircAGFG1 absence decreases PKM2 expression to enhance oxaliplatin sensitivity in colorectal cancer in a miR-7-5p-dependent manner. (PMID:37691430)
• CircAGFG1 Promotes Ovarian Cancer Progression Through the miR-409-3 p/ZEB1 Axis. (PMID:38752261)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	agfg1b	ENSDARG00000019526
danio_rerio	agfg1a	ENSDARG00000030020
mus_musculus	Agfg1	ENSMUSG00000026159
rattus_norvegicus	Agfg1	ENSRNOG00000015619

Paralogs (28): ARAP2 (ENSG00000047365), ACAP1 (ENSG00000072818), SMAP2 (ENSG00000084070), ASAP3 (ENSG00000088280), ARFGAP1 (ENSG00000101199), ADAP1 (ENSG00000105963), AGFG2 (ENSG00000106351), GIT1 (ENSG00000108262), SMAP1 (ENSG00000112305), ACAP2 (ENSG00000114331), ARAP3 (ENSG00000120318), ACAP3 (ENSG00000131584), AGAP3 (ENSG00000133612), AGAP2 (ENSG00000135439), APPL2 (ENSG00000136044), GIT2 (ENSG00000139436), ARFGAP2 (ENSG00000149182), ASAP2 (ENSG00000151693), ASAP1 (ENSG00000153317), APPL1 (ENSG00000157500), AGAP1 (ENSG00000157985), AGAP5 (ENSG00000172650), ADAP2 (ENSG00000184060), ARAP1 (ENSG00000186635), AGAP4 (ENSG00000188234), AGAP6 (ENSG00000204149), AGAP9 (ENSG00000204172), ARFGAP3 (ENSG00000242247)

Protein

Protein identifiers

Arf-GAP domain and FG repeat-containing protein 1 — P52594 (reviewed: P52594)

Alternative names: HIV-1 Rev-binding protein, Nucleoporin-like protein RIP, Rev-interacting protein, Rev/Rex activation domain-binding protein

All UniProt accessions (6): P52594, A0A0S2Z3Z1, A0A0S2Z444, B8ZZY2, C9J2I0, H7C0S7

UniProt curated annotations — full annotation on UniProt →

Function. Required for vesicle docking or fusion during acrosome biogenesis. May play a role in RNA trafficking or localization. In case of infection by HIV-1, acts as a cofactor for viral Rev and promotes movement of Rev-responsive element-containing RNAs from the nuclear periphery to the cytoplasm. This step is essential for HIV-1 replication.

Subunit / interactions. Interacts with EPS15R and EPS15. Interacts with FCHO1.

Subcellular location. Nucleus. Cytoplasmic vesicle.

Tissue specificity. Ubiquitously expressed.

Post-translational modifications. O-glycosylated.

Domain organisation. Contains FG repeats. The FG repeat region is required for acting as a cofactor of HIV-1 Rev.

Isoforms (4)

UniProt ID	Names	Canonical?
P52594-1	1	yes
P52594-2	2
P52594-3	3
P52594-4	4

RefSeq proteins (4): NP_001128659, NP_001128660, NP_001128661, NP_004495* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001164	ArfGAP_dom	Domain
IPR037278	ARFGAP/RecO	Homologous_superfamily
IPR038508	ArfGAP_dom_sf	Homologous_superfamily
IPR052248	Arf-GAP_FG-repeat_protein	Family

Pfam: PF01412

UniProt features (34 total): helix 8, turn 5, strand 5, modified residue 4, splice variant 3, sequence conflict 3, chain 1, domain 1, zinc finger region 1, region of interest 1, compositionally biased region 1, glycosylation site 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
2OLM	X-RAY DIFFRACTION	1.48
2VX8	X-RAY DIFFRACTION	2.2
2D9L	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P52594-F1	57.58	0.22

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 (4): 167, 177, 181, 362

Glycosylation sites (1): 367

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-8856825	Cargo recognition for clathrin-mediated endocytosis
R-HSA-8856828	Clathrin-mediated endocytosis
R-HSA-199991	Membrane Trafficking
R-HSA-5653656	Vesicle-mediated transport

MSigDB gene sets: 396 (showing top): GSE45365_NK_CELL_VS_BCELL_UP, SHEPARD_BMYB_MORPHOLINO_UP, GOBP_INTERMEDIATE_FILAMENT_BASED_PROCESS, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, DACOSTA_UV_RESPONSE_VIA_ERCC3_XPCS_DN, GOBP_INTERMEDIATE_FILAMENT_ORGANIZATION, GOBP_VESICLE_ORGANIZATION, IVANOVA_HEMATOPOIESIS_MATURE_CELL, LINDGREN_BLADDER_CANCER_CLUSTER_3_DN, GOBP_MALE_GAMETE_GENERATION, REACTOME_MEMBRANE_TRAFFICKING, GOBP_NUCLEAR_TRANSPORT, GOBP_SECRETORY_GRANULE_ORGANIZATION, GOBP_CELLULAR_COMPONENT_ASSEMBLY_INVOLVED_IN_MORPHOGENESIS, MILI_PSEUDOPODIA_HAPTOTAXIS_UP

GO Biological Process (7): acrosome assembly (GO:0001675), mRNA export from nucleus (GO:0006406), spermatid nucleus differentiation (GO:0007289), intermediate filament organization (GO:0045109), spermatogenesis (GO:0007283), cell differentiation (GO:0030154), mRNA transport (GO:0051028)

GO Molecular Function (6): DNA binding (GO:0003677), RNA binding (GO:0003723), GTPase activator activity (GO:0005096), zinc ion binding (GO:0008270), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (7): nuclear pore (GO:0005643), cytoplasm (GO:0005737), cytosol (GO:0005829), cytoplasmic vesicle (GO:0031410), cell projection (GO:0042995), neuronal cell body (GO:0043025), nucleus (GO:0005634)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Clathrin-mediated endocytosis	1
Membrane Trafficking	1
Vesicle-mediated transport	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
developmental process involved in reproduction	2
spermatid development	2
nucleic acid binding	2
cytoplasm	2
cellular component assembly involved in morphogenesis	1
cellular process involved in reproduction in multicellular organism	1
secretory granule organization	1
organelle assembly	1
RNA export from nucleus	1
gene expression	1
mRNA transport	1
nucleus organization	1
intermediate filament cytoskeleton organization	1
supramolecular fiber organization	1
male gamete generation	1
cellular developmental process	1
RNA transport	1
GTPase activity	1
enzyme activator activity	1
GTPase regulator activity	1
transition metal ion binding	1
binding	1
cation binding	1
nuclear envelope	1
nuclear protein-containing complex	1
intracellular anatomical structure	1
intracellular vesicle	1
somatodendritic compartment	1
cell body	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

1374 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
AGFG1	GDI2	P50395	899
AGFG1	VAMP7	P51809	871
AGFG1	GDI1	P31150	858
AGFG1	RAB3A	P20336	768
AGFG1	VTI1B	Q9UEU0	753
AGFG1	RAB1A	P11476	712
AGFG1	EPS15	P42566	625
AGFG1	FCHO1	O14526	601
AGFG1	GOPC	Q9HD26	589
AGFG1	DPY19L2	Q6NUT2	588
AGFG1	ATP6AP1	Q15904	588
AGFG1	STON2	Q8WXE9	580
AGFG1	HCFC1	P51610	550
AGFG1	ITSN2	Q9NZM3	545
AGFG1	SPATA16	Q9BXB7	544
AGFG1	RAB4A	P20338	544

IntAct

71 interactions, top by confidence:

A	B	Type	Score
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
AGFG1	EPS15	psi-mi:“MI:0915”(physical association)	0.660
CEP170	KIF2A	psi-mi:“MI:2364”(proximity)	0.650
VAMP7	AGFG1	psi-mi:“MI:0915”(physical association)	0.640
AGFG1	VAMP7	psi-mi:“MI:0915”(physical association)	0.640
AGFG1	VAMP7	psi-mi:“MI:0407”(direct interaction)	0.640
VAMP7	AGFG1	psi-mi:“MI:0407”(direct interaction)	0.640
YWHAG	BLTP3B	psi-mi:“MI:0914”(association)	0.640
KLHL22	METTL15	psi-mi:“MI:0914”(association)	0.640
CD27	TCAF2	psi-mi:“MI:0914”(association)	0.640
YWHAH	BLTP3B	psi-mi:“MI:0914”(association)	0.570
AGFG1	POLE2	psi-mi:“MI:0915”(physical association)	0.560
AGFG1	NYAP2	psi-mi:“MI:0915”(physical association)	0.560
POLE2	AGFG1	psi-mi:“MI:0915”(physical association)	0.560
PIP	TBKBP1	psi-mi:“MI:0914”(association)	0.530
VCAM1	PSMD11	psi-mi:“MI:0914”(association)	0.530
AGFG1	MFHAS1	psi-mi:“MI:0407”(direct interaction)	0.440
AP2B1	AGFG1	psi-mi:“MI:0407”(direct interaction)	0.440
Vamp7	AGFG1	psi-mi:“MI:0407”(direct interaction)	0.410
Xpo1	IFT56	psi-mi:“MI:0914”(association)	0.350

BioGRID (145): POLE2 (Two-hybrid), NYAP2 (Two-hybrid), EPS15 (Co-fractionation), AGFG1 (Affinity Capture-MS), AGFG1 (Affinity Capture-MS), AGFG1 (Affinity Capture-MS), AGFG1 (Proximity Label-MS), AGFG1 (Affinity Capture-MS), AGFG1 (Affinity Capture-MS), AGFG1 (Affinity Capture-MS), AGFG1 (Proximity Label-MS), AGFG1 (Affinity Capture-MS), AGFG1 (Affinity Capture-RNA), AGFG1 (Reconstituted Complex), AGFG1 (Co-localization)

ESM2 similar proteins: A0JME2, A5H447, A6NF01, A8CG34, E9Q3G8, F4ID16, G0SDP9, G5E8Z2, O08587, O15504, O88797, O95081, P20676, P49790, P49791, P52591, P52594, P98082, Q03173, Q0VA45, Q2TA45, Q4KLH5, Q5FVW4, Q5PRE5, Q5RB98, Q5SV85, Q5XGN1, Q5ZI22, Q5ZIE8, Q5ZM88, Q64028, Q640Z6, Q6P0U9, Q80WC7, Q86XN7, Q8CIC2, Q8K2K6, Q8K3Z9, Q8L7F7, Q8R080

Diamond homologs: A1L520, A1Z7A6, A5PK26, A6NIR3, O43150, O74345, O75689, O80925, O82171, O94601, O97902, P35197, P38682, P40529, P52594, Q04412, Q09531, Q0WQQ1, Q10165, Q10367, Q14161, Q15027, Q15057, Q17R07, Q1AAU6, Q1ZXH8, Q28CM8, Q2TA45, Q3MID3, Q3UHD9, Q4KLH5, Q4KLN7, Q4LDD4, Q4R4C9, Q5F413, Q5FVC7, Q5R787, Q5RAT7, Q5U464, Q5VTM2

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 73 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
Apoptosis	5	17.5×	2e-03
Programmed Cell Death	5	15.2×	2e-03
Constitutive Signaling by Aberrant PI3K in Cancer	5	13.2×	2e-03
Cargo recognition for clathrin-mediated endocytosis	6	13.1×	2e-03
Clathrin-mediated endocytosis	6	10.7×	2e-03
PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling	5	10.1×	4e-03
Membrane Trafficking	8	6.2×	2e-03
Vesicle-mediated transport	8	5.8×	2e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	51
Likely benign	7
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
58848	GRCh38/hg38 2q36.3-37.2(chr2:227343278-235339168)x1	Pathogenic

SpliceAI

3047 predictions. Top by Δscore:

Variant	Effect	Δscore
2:227472585:GCCT:G	donor_gain	1.0000
2:227472588:TG:T	donor_loss	1.0000
2:227472589:G:GG	donor_gain	1.0000
2:227472590:T:G	donor_loss	1.0000
2:227472591:GAGT:G	donor_loss	1.0000
2:227491541:TTTTA:T	acceptor_loss	1.0000
2:227491543:TTAG:T	acceptor_loss	1.0000
2:227491545:A:AG	acceptor_gain	1.0000
2:227491546:G:A	acceptor_loss	1.0000
2:227491546:G:GG	acceptor_gain	1.0000
2:227491546:GGCGA:G	acceptor_gain	1.0000
2:227491636:ATGAA:A	donor_gain	1.0000
2:227491637:TGAA:T	donor_gain	1.0000
2:227491638:G:GT	donor_gain	1.0000
2:227491638:GAA:G	donor_gain	1.0000
2:227491639:AA:A	donor_gain	1.0000
2:227491640:AG:A	donor_loss	1.0000
2:227491641:G:GG	donor_gain	1.0000
2:227491641:G:T	donor_loss	1.0000
2:227491642:T:G	donor_loss	1.0000
2:227520060:GATG:G	donor_gain	1.0000
2:227520064:G:GG	donor_gain	1.0000
2:227523758:TTTA:T	acceptor_loss	1.0000
2:227523761:AGG:A	acceptor_loss	1.0000
2:227523762:GGT:G	acceptor_gain	1.0000
2:227523762:GGTA:G	acceptor_gain	1.0000
2:227523762:GGTAT:G	acceptor_gain	1.0000
2:227523923:CAGG:C	donor_loss	1.0000
2:227523926:G:GA	donor_loss	1.0000
2:227523927:T:A	donor_loss	1.0000

AlphaMissense

3681 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:227472462:T:C	L14P	1.000
2:227472471:T:C	L17P	1.000
2:227472474:G:C	R18P	1.000
2:227472506:T:A	C29S	1.000
2:227472506:T:C	C29R	1.000
2:227472507:G:A	C29Y	1.000
2:227472507:G:C	C29S	1.000
2:227472507:G:T	C29F	1.000
2:227472508:C:G	C29W	1.000
2:227472515:T:A	C32S	1.000
2:227472515:T:C	C32R	1.000
2:227472516:G:A	C32Y	1.000
2:227472516:G:C	C32S	1.000
2:227472516:G:T	C32F	1.000
2:227472517:C:G	C32W	1.000
2:227472527:G:C	G36R	1.000
2:227472528:G:A	G36D	1.000
2:227472531:C:A	P37H	1.000
2:227472531:C:G	P37R	1.000
2:227472536:T:C	Y39H	1.000
2:227472536:T:G	Y39D	1.000
2:227472554:G:C	G45R	1.000
2:227472555:G:A	G45D	1.000
2:227472555:G:T	G45V	1.000
2:227472557:T:C	S46P	1.000
2:227472561:T:C	F47S	1.000
2:227472566:T:A	C49S	1.000
2:227472566:T:C	C49R	1.000
2:227472567:G:A	C49Y	1.000
2:227472567:G:C	C49S	1.000

dbSNP variants (sampled 300 via entrez): RS1000005669 (2:227478793 G>A), RS1000017734 (2:227534010 A>G), RS1000112242 (2:227485233 C>T), RS1000163107 (2:227544598 G>A,T), RS1000199318 (2:227490812 G>A), RS1000257008 (2:227501505 G>A,C), RS1000268058 (2:227556084 C>T), RS1000270226 (2:227536350 T>A,G), RS1000289204 (2:227471491 G>A), RS1000299640 (2:227536058 T>C), RS1000329977 (2:227508094 T>C), RS1000341564 (2:227506443 C>G), RS1000348980 (2:227487970 A>G), RS1000392210 (2:227471867 C>A,T), RS1000401476 (2:227487614 T>A)

Disease associations

OMIM: gene MIM:600862 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST002152_1	Airway hyperresponsiveness	2.000000e-06
GCST003124_15	Mild influenza (H1N1) infection	3.000000e-08
GCST009798_81	Asthma	1.000000e-09

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0005414	airway hyperresponsiveness
EFO:1001488	influenza A (H1N1)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases expression, affects expression, decreases methylation	3
trichostatin A	decreases expression	2
Acetaminophen	decreases expression, increases expression	2
Estradiol	affects expression, increases expression	2
Aflatoxin B1	increases methylation	2
aristolochic acid I	decreases expression	1
FR900359	affects phosphorylation	1
bisphenol F	increases expression	1
geldanamycin	increases expression	1
methylmercuric chloride	increases expression	1
deoxynivalenol	increases expression	1
sodium arsenate	decreases expression	1
sodium arsenite	increases expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
K 7174	increases expression	1
jinfukang	decreases expression	1
bisphenol AF	increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Vorinostat	decreases expression	1
Atrazine	increases expression	1
Caffeine	decreases phosphorylation	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Ethyl Methanesulfonate	decreases expression	1
Ivermectin	decreases expression	1
Methyl Methanesulfonate	decreases expression	1
Piroxicam	decreases expression	1
Plant Extracts	affects cotreatment, increases expression	1
Theophylline	increases expression	1
Thimerosal	decreases expression	1

Clinical trials (associated diseases)

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