ARHGEF5

Summary

ARHGEF5 (Rho guanine nucleotide exchange factor 5, HGNC:13209) is a protein-coding gene on chromosome 7q35, encoding Rho guanine nucleotide exchange factor 5 (Q12774). Guanine nucleotide exchange factor which activates Rho GTPases. It is a selective cancer dependency (DepMap: 23.1% of cell lines).

Rho GTPases play a fundamental role in numerous cellular processes initiated by extracellular stimuli that work through G protein coupled receptors. The encoded protein may form a complex with G proteins and stimulate Rho-dependent signals. This protein may be involved in the control of cytoskeletal organization.

Source: NCBI Gene 7984 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 145 total
• Cancer dependency (DepMap): dependent in 23.1% of screened cell lines
• MANE Select transcript: NM_005435

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:13209
Approved symbol	ARHGEF5
Name	Rho guanine nucleotide exchange factor 5
Location	7q35
Locus type	gene with protein product
Status	Approved
Aliases	TIM, TIM1, GEF5, P60
Ensembl gene	ENSG00000050327
Ensembl biotype	protein_coding
OMIM	600888
Entrez	7984

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 5 protein_coding

ENST00000056217, ENST00000471847, ENST00000474817, ENST00000498580, ENST00000940327

RefSeq mRNA: 1 — MANE Select: NM_005435 NM_005435

CCDS: CCDS34771

Canonical transcript exons

ENST00000056217 — 15 exons

Exon	Start	End
ENSE00000729267	144378762	144378866
ENSE00001513539	144355402	144355501
ENSE00001894090	144379899	144380632
ENSE00002441301	144367102	144367355
ENSE00002443613	144362658	144365823
ENSE00002445481	144372683	144372757
ENSE00002454696	144375514	144375675
ENSE00002462644	144371877	144372029
ENSE00002471873	144373195	144373284
ENSE00002479484	144374732	144374889
ENSE00002481353	144372299	144372428
ENSE00002502329	144371161	144371321
ENSE00002505698	144377120	144377190
ENSE00003341391	144366355	144366412
ENSE00003473239	144366846	144366910

Expression profiles

Bgee: expression breadth ubiquitous, 136 present calls, max score 93.77.

FANTOM5 (CAGE): breadth broad, TPM avg 0.3655 / max 8.5784, expressed in 225 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
81805	0.3655	225

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
lower esophagus mucosa	UBERON:0035834	93.77	gold quality
skin of leg	UBERON:0001511	92.20	gold quality
zone of skin	UBERON:0000014	92.04	gold quality
skin of abdomen	UBERON:0001416	91.88	gold quality
mucosa of transverse colon	UBERON:0004991	91.61	gold quality
esophagus mucosa	UBERON:0002469	90.75	gold quality
left lobe of thyroid gland	UBERON:0001120	90.18	gold quality
thyroid gland	UBERON:0002046	89.37	gold quality
right lobe of thyroid gland	UBERON:0001119	89.25	gold quality
duodenum	UBERON:0002114	86.97	gold quality
metanephros cortex	UBERON:0010533	86.25	gold quality
minor salivary gland	UBERON:0001830	85.34	gold quality
adult mammalian kidney	UBERON:0000082	85.33	gold quality
transverse colon	UBERON:0001157	85.26	gold quality
saliva-secreting gland	UBERON:0001044	85.25	gold quality
body of pancreas	UBERON:0001150	84.37	gold quality
prostate gland	UBERON:0002367	84.37	gold quality
pancreas	UBERON:0001264	83.91	gold quality
vagina	UBERON:0000996	83.67	gold quality
esophagus	UBERON:0001043	83.32	gold quality
cortex of kidney	UBERON:0001225	83.13	gold quality
islet of Langerhans	UBERON:0000006	83.06	gold quality
kidney	UBERON:0002113	83.01	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	82.73	gold quality
body of stomach	UBERON:0001161	82.54	gold quality
adenohypophysis	UBERON:0002196	82.27	gold quality
small intestine	UBERON:0002108	82.08	gold quality
tonsil	UBERON:0002372	81.75	gold quality
small intestine Peyer’s patch	UBERON:0003454	81.72	gold quality
stomach	UBERON:0000945	81.57	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	10.51

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): TGFB2

miRNA regulators (miRDB)

19 targeting ARHGEF5, 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-4715-3P	99.98	66.03	670
HSA-MIR-767-5P	99.95	70.85	993
HSA-MIR-4493	99.90	66.48	977
HSA-MIR-4503	99.85	71.45	1869
HSA-MIR-34B-5P	99.78	67.56	1175
HSA-MIR-449C-5P	99.78	67.63	1168
HSA-MIR-2682-5P	99.73	67.38	1055
HSA-MIR-1825	99.72	68.11	1089
HSA-MIR-3714	99.71	70.74	2671
HSA-MIR-6832-3P	99.52	70.44	1726
HSA-MIR-199A-5P	99.51	69.71	1107
HSA-MIR-199B-5P	99.51	69.74	1098
HSA-MIR-4480	99.42	66.02	735
HSA-MIR-4469	97.93	65.81	1319
HSA-MIR-665	97.60	65.64	1781
HSA-MIR-6865-3P	97.54	64.67	684
HSA-MIR-1287-5P	96.80	65.30	743
HSA-MIR-5586-3P	95.51	67.00	805
HSA-MIR-25-5P	87.02	64.95	84

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 23.1% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 13)

• association in humans of TIM-1 and hypersensitivity and the relationship between TIM1, hygiene, and the environment. (PMID:15681748)
• The expression level of TIM was decreased in hepatocellular carcinoma. (PMID:18444243)
• RhoA guanine nucleotide exchange factor Arhgef5 regulates immature dendritic cell migration (PMID:19713215)
• Overexpression of Arhgef5 promoted actin stress fiber remodeling through activating RhoA, and the activation of RhoA or Cdc42 was required for Src-induced podosome formation. (PMID:21525037)
• Tim-Tipin complex might play a role in coupling DNA unwinding and DNA synthesis by directly affecting the catalytic activities of replication fork proteins. (PMID:23359676)
• This study performed whole exome sequencing demonistrated that the true de novo variants represent mutations in genes (KCNH5, CLCN4, and ARHGEF15) not previously associated with epilepsies in humans. (PMID:23647072)
• In conclusion, ARHGEF5/Src can be considered as a prognostic biomarker and a therapeutic target for patients with resected NSCLC. (PMID:24126923)
• A receiver operating characteristic curve constructed with HSP105 and TIM gave a sensitivity of 54.3% and 95% (38/40) specificity in discriminating esophageal squamous cell carcinoma from matched controls. (PMID:24157810)
• The auto-inhibitory state of Rho guanine nucleotide exchange factor ARHGEF5/TIM can be relieved by targeting its SH3 domain with rationally designed peptide aptamers. (PMID:25645980)
• Targeting rho guanine nucleotide exchange factor ARHGEF5/TIM with auto-inhibitory peptides in human breast cancer. (PMID:25743165)
• Data indicate that Rho guanine nucleotide exchange factor 5 (ARHGEF5) is expressed in most human lung adenocarcinoma tissues and cell lines. (PMID:25777963)
• Tim protein and DDX11 physically and functionally interact and act in concert to preserve replication fork progression in perturbed conditions. (PMID:26503245)
• Interaction between hTIM-1 and Envelope Protein Is Important for JEV Infection. (PMID:37515282)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
mus_musculus	Arhgef5	ENSMUSG00000033542
rattus_norvegicus	Arhgef5	ENSRNOG00000005506
caenorhabditis_elegans		WBGENE00019487

Paralogs (6): NGEF (ENSG00000066248), ARHGEF26 (ENSG00000114790), ARHGEF16 (ENSG00000130762), ARHGEF19 (ENSG00000142632), ARHGEF15 (ENSG00000198844), ARHGEF35 (ENSG00000213214)

Protein

Protein identifiers

Rho guanine nucleotide exchange factor 5 — Q12774 (reviewed: Q12774)

Alternative names: Ephexin-3, Guanine nucleotide regulatory protein TIM, Oncogene TIM, Transforming immortalized mammary oncogene, p60 TIM

All UniProt accessions (4): A0A090N7S2, C9J591, Q12774, H0Y895

UniProt curated annotations — full annotation on UniProt →

Function. Guanine nucleotide exchange factor which activates Rho GTPases. Strongly activates RHOA. Also strongly activates RHOB, weakly activates RHOC and RHOG and shows no effect on RHOD, RHOV, RHOQ or RAC1. Involved in regulation of cell shape and actin cytoskeletal organization. Plays a role in actin organization by generating a loss of actin stress fibers and the formation of membrane ruffles and filopodia. Required for SRC-induced podosome formation. Involved in positive regulation of immature dendritic cell migration.

Subunit / interactions. Interacts with SRC. Forms a ternary complex with SRC and the PI3K 85 kDa subunit. Interacts with and is activated by the heterodimer formed by GNB1 and GNG2. Interacts with ODAM (via C-terminus). Interacts with RHOA.

Subcellular location. Cytoplasm. Nucleus. Cell projection. Podosome.

Tissue specificity. Ubiquitously expressed with highest levels in placenta. High levels are also found in colon, kidney, trachea, prostate, liver, pancreas, pituitary gland, thyroid gland and mammary gland. In fetal tissues, expressed at high levels in kidney, lung and liver. Expressed at low levels in lung and heart.

Post-translational modifications. Activation of SRC induces tyrosine phosphorylation of ARHGEF5.

Domain organisation. The PH domain binds to phosphoinositides and is essential for podosome formation.

Isoforms (2)

UniProt ID	Names	Canonical?
Q12774-1	1	yes
Q12774-2	2

RefSeq proteins (1): NP_005426* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000219	DH_dom	Domain
IPR001331	GDS_CDC24_CS	Conserved_site
IPR001452	SH3_domain	Domain
IPR001849	PH_domain	Domain
IPR011993	PH-like_dom_sf	Homologous_superfamily
IPR029212	ARHGEF5/35_N	Domain
IPR035899	DBL_dom_sf	Homologous_superfamily
IPR036028	SH3-like_dom_sf	Homologous_superfamily
IPR047270	PH_ephexin	Domain
IPR047271	Ephexin-like	Family

Pfam: PF00018, PF00169, PF00621, PF15441

UniProt features (37 total): compositionally biased region 19, modified residue 8, domain 3, region of interest 3, sequence conflict 2, chain 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q12774-F1	48.84	0.18

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 (8): 184, 445, 450, 866, 983, 1011, 1044, 1126

Function

Pathways and Gene Ontology

Reactome pathways

17 pathways

ID	Pathway
R-HSA-193648	NRAGE signals death through JNK
R-HSA-416482	G alpha (12/13) signalling events
R-HSA-8980692	RHOA GTPase cycle
R-HSA-9013026	RHOB GTPase cycle
R-HSA-9013106	RHOC GTPase cycle
R-HSA-9013148	CDC42 GTPase cycle
R-HSA-9013149	RAC1 GTPase cycle
R-HSA-9013408	RHOG GTPase cycle
R-HSA-162582	Signal Transduction
R-HSA-193704	p75 NTR receptor-mediated signalling
R-HSA-194315	Signaling by Rho GTPases
R-HSA-204998	Cell death signalling via NRAGE, NRIF and NADE
R-HSA-372790	Signaling by GPCR
R-HSA-388396	GPCR downstream signalling
R-HSA-73887	Death Receptor Signaling
R-HSA-9012999	RHO GTPase cycle
R-HSA-9716542	Signaling by Rho GTPases, Miro GTPases and RHOBTB3

MSigDB gene sets: 195 (showing top): GSE45365_HEALTHY_VS_MCMV_INFECTION_CD8_TCELL_IFNAR_KO_DN, BIOCARTA_RHO_PATHWAY, GCACCTT_MIR18A_MIR18B, GOBP_ACTIN_FILAMENT_BUNDLE_ORGANIZATION, GOBP_DENDRITIC_CELL_MIGRATION, GOBP_MYELOID_LEUKOCYTE_MIGRATION, GOBP_CELL_CHEMOTAXIS, GOBP_REGULATION_OF_PHOSPHORYLATION, GOBP_REGULATION_OF_PODOSOME_ASSEMBLY, TGCTGCT_MIR15A_MIR16_MIR15B_MIR195_MIR424_MIR497, GTCTACC_MIR379, GOBP_POSITIVE_REGULATION_OF_PROTEIN_LOCALIZATION, GOBP_REGULATION_OF_GTPASE_ACTIVITY, GOBP_REGULATION_OF_SMALL_GTPASE_MEDIATED_SIGNAL_TRANSDUCTION, GOBP_POSITIVE_REGULATION_OF_MAPK_CASCADE

GO Biological Process (13): myeloid dendritic cell chemotaxis (GO:0002408), actin cytoskeleton organization (GO:0030036), regulation of actin cytoskeleton organization (GO:0032956), intracellular signal transduction (GO:0035556), regulation of GTPase activity (GO:0043087), positive regulation of JUN kinase activity (GO:0043507), regulation of small GTPase mediated signal transduction (GO:0051056), obsolete positive regulation of DNA-binding transcription factor activity (GO:0051091), regulation of cytoskeleton organization (GO:0051493), positive regulation of stress fiber assembly (GO:0051496), hematopoietic stem cell homeostasis (GO:0061484), positive regulation of podosome assembly (GO:0071803), positive regulation of protein import (GO:1904591)

GO Molecular Function (4): guanyl-nucleotide exchange factor activity (GO:0005085), GTP binding (GO:0005525), lipid binding (GO:0008289), protein binding (GO:0005515)

GO Cellular Component (9): podosome (GO:0002102), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), cytosol (GO:0005829), plasma membrane (GO:0005886), cell periphery (GO:0071944), cell projection (GO:0042995), anchoring junction (GO:0070161)

Reactome top-level categories

Rollup of top-9 pathways:

Category	Pathways
RHO GTPase cycle	6
Signal Transduction	3
Cell death signalling via NRAGE, NRIF and NADE	1
GPCR downstream signalling	1
Death Receptor Signaling	1
Signaling by Rho GTPases, Miro GTPases and RHOBTB3	1
p75 NTR receptor-mediated signalling	1
Signaling by GPCR	1
Signaling by Rho GTPases	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
cytoskeleton organization	2
intracellular anatomical structure	2
binding	2
dendritic cell chemotaxis	1
myeloid leukocyte migration	1
actin filament-based process	1
actin cytoskeleton organization	1
regulation of actin filament-based process	1
regulation of cytoskeleton organization	1
signal transduction	1
GTPase activity	1
regulation of hydrolase activity	1
JUN kinase activity	1
positive regulation of MAP kinase activity	1
regulation of JUN kinase activity	1
small GTPase-mediated signal transduction	1
regulation of intracellular signal transduction	1
regulation of organelle organization	1
positive regulation of actin filament bundle assembly	1
stress fiber assembly	1
regulation of stress fiber assembly	1
homeostasis of number of cells	1
positive regulation of protein-containing complex assembly	1
podosome assembly	1
regulation of podosome assembly	1
positive regulation of plasma membrane bounded cell projection assembly	1
protein import	1
positive regulation of protein transport	1
regulation of protein import	1
GTP binding	1
GDP binding	1
GTPase regulator activity	1
guanyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
actin-based cell projection	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
cytoplasm	1
membrane	1

Protein interactions and networks

STRING

870 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ARHGEF5	GAREM1	Q9H706	689
ARHGEF5	RHOG	P35238	678
ARHGEF5	MCF2	P10911	608
ARHGEF5	DTNA	Q9Y4J8	580
ARHGEF5	CDC42	P21181	549
ARHGEF5	GRB2	P29354	527
ARHGEF5	SRGAP2	O75044	522
ARHGEF5	PTPN20	Q4JDL3	494
ARHGEF5	NQO2	P16083	491
ARHGEF5	CORO6	Q6QEF8	483
ARHGEF5	SHC1	P29353	481
ARHGEF5	TCAF1	Q9Y4C2	476
ARHGEF5	A0A1B0GVM2	A0A1B0GVM2	472
ARHGEF5	OPHN1	O60890	469
ARHGEF5	ARHGEF6	Q15052	462

IntAct

143 interactions, top by confidence:

A	B	Type	Score
GRB2	EGFR	psi-mi:“MI:0914”(association)	0.980
GRB2	ARHGEF5	psi-mi:“MI:0915”(physical association)	0.820
SHC1	AP2A1	psi-mi:“MI:0914”(association)	0.730
TRIM27	ARHGEF5	psi-mi:“MI:0915”(physical association)	0.720
ARHGEF5	EFHC2	psi-mi:“MI:0915”(physical association)	0.720
HSPBAP1	ARHGEF5	psi-mi:“MI:0915”(physical association)	0.720
ARHGEF5	TRIM54	psi-mi:“MI:0915”(physical association)	0.720
ARHGEF5	TRIM27	psi-mi:“MI:0915”(physical association)	0.720
EFHC2	ARHGEF5	psi-mi:“MI:0915”(physical association)	0.720
ARHGEF5	HSPBAP1	psi-mi:“MI:0915”(physical association)	0.720
TRIM54	ARHGEF5	psi-mi:“MI:0915”(physical association)	0.720
ARHGEF5	COG6	psi-mi:“MI:0915”(physical association)	0.700
COG6	ARHGEF5	psi-mi:“MI:0915”(physical association)	0.700
YWHAG	BLTP3B	psi-mi:“MI:2364”(proximity)	0.640
SHC1	AP2A2	psi-mi:“MI:0914”(association)	0.640
YWHAB	BLTP3B	psi-mi:“MI:2364”(proximity)	0.610
ARHGEF5	SHC1	psi-mi:“MI:0914”(association)	0.600
YWHAH	BLTP3B	psi-mi:“MI:2364”(proximity)	0.570
CALCOCO2	ARHGEF5	psi-mi:“MI:0915”(physical association)	0.560
ARHGEF5	CALCOCO2	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (97): ARHGEF5 (Two-hybrid), CALCOCO2 (Two-hybrid), TRIM54 (Two-hybrid), HSPBAP1 (Two-hybrid), EFHC2 (Two-hybrid), ARHGEF5 (Affinity Capture-MS), EFHC2 (Two-hybrid), ARHGEF5 (Affinity Capture-MS), ARHGEF5 (Affinity Capture-MS), SHC1 (Affinity Capture-Western), GRB2 (Affinity Capture-Western), ARHGEF5 (Affinity Capture-MS), ARHGEF5 (Affinity Capture-MS), COG6 (Two-hybrid), ARHGEF5 (Affinity Capture-MS)

ESM2 similar proteins: A4FU49, A6QQS3, A6X8Z5, D3ZUE1, E9Q0C6, E9Q7D5, F6XZJ7, I3L273, O54963, P0C671, Q05860, Q12774, Q13127, Q32MG2, Q3V3Q4, Q4R729, Q4V8E9, Q5DTZ0, Q5R7U0, Q5SWP3, Q5U2M8, Q5VV67, Q66HG9, Q68A65, Q68DA7, Q6AXV6, Q6NZN1, Q70KF4, Q7TSG5, Q8BHW6, Q8C4A5, Q8CC96, Q8K4E0, Q8N1P7, Q8N3K9, Q8N5Q1, Q8NA61, Q8VIG1, Q921B4, Q923B3

Diamond homologs: A5YM69, E9Q7D5, Q12774, O94989, Q3U5C8, Q5BKC9, Q5FWH6, Q5RDX5, Q5VV41, Q8BWA8, Q8C120, Q8CHT1, Q8IW93, Q8N5V2, Q96DR7, Q8TEJ3, O42287, Q15811, Q9Z0R6, A1IGU3, A1IGU4, A1IGU5, Q62417, Q9NZM3, O60229, Q498M5, Q8BZT2, Q8IVI9

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
ARHGEF5	“up-regulates activity”	RHOA	“guanine nucleotide exchange factor”
SRC	“up-regulates activity”	ARHGEF5	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 92 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
Activation of BAD and translocation to mitochondria	7	88.8×	9e-11
Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex	7	78.4×	2e-10
SARS-CoV-1 targets host intracellular signalling and regulatory pathways	7	78.4×	2e-10
Activation of BH3-only proteins	7	57.9×	2e-09
RHO GTPases activate PKNs	10	52.9×	9e-13
Intrinsic Pathway for Apoptosis	7	34.2×	8e-08
FOXO-mediated transcription	5	28.0×	2e-05
SARS-CoV-1-host interactions	7	20.5×	2e-06

GO biological processes:

GO term	Partners	Fold	FDR
protein targeting	5	21.6×	1e-03
substantia nigra development	5	21.6×	1e-03
cerebral cortex development	5	12.1×	5e-03
positive regulation of cell growth	5	10.8×	7e-03
intracellular protein localization	7	8.6×	3e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	125
Likely benign	14
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2229 predictions. Top by Δscore:

Variant	Effect	Δscore
7:144355498:CCAGG:C	donor_loss	1.0000
7:144355499:CAGG:C	donor_loss	1.0000
7:144355502:GTGG:G	donor_loss	1.0000
7:144355503:T:G	donor_loss	1.0000
7:144366911:G:GG	donor_gain	1.0000
7:144367083:A:AG	acceptor_gain	1.0000
7:144367083:AT:A	acceptor_gain	1.0000
7:144367084:T:G	acceptor_gain	1.0000
7:144367084:T:TA	acceptor_gain	1.0000
7:144367092:T:A	acceptor_gain	1.0000
7:144367100:A:AG	acceptor_gain	1.0000
7:144367101:G:GA	acceptor_gain	1.0000
7:144367101:GC:G	acceptor_gain	1.0000
7:144367101:GCCC:G	acceptor_gain	1.0000
7:144367101:GCCCA:G	acceptor_gain	1.0000
7:144367351:AAGAG:A	donor_loss	1.0000
7:144367352:AGAGG:A	donor_loss	1.0000
7:144367353:G:GT	donor_gain	1.0000
7:144367353:GAG:G	donor_gain	1.0000
7:144367354:AGGT:A	donor_loss	1.0000
7:144367357:T:G	donor_loss	1.0000
7:144371299:G:GT	donor_gain	1.0000
7:144371872:TACA:T	acceptor_loss	1.0000
7:144372007:G:GT	donor_gain	1.0000
7:144372008:A:T	donor_gain	1.0000
7:144372027:G:GT	donor_gain	1.0000
7:144372027:GAT:G	donor_gain	1.0000
7:144372030:G:GG	donor_gain	1.0000
7:144372669:T:A	acceptor_gain	1.0000
7:144372678:A:AG	acceptor_gain	1.0000

AlphaMissense

10391 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:144373273:T:C	F1377L	1.000
7:144373275:T:A	F1377L	1.000
7:144373275:T:G	F1377L	1.000
7:144377136:T:A	W1493R	1.000
7:144377136:T:C	W1493R	1.000
7:144367281:T:A	W1153R	0.999
7:144367281:T:C	W1153R	0.999
7:144367283:G:C	W1153C	0.999
7:144367283:G:T	W1153C	0.999
7:144371174:T:C	L1182P	0.999
7:144371198:T:C	L1190P	0.999
7:144371203:A:C	S1192R	0.999
7:144371205:T:A	S1192R	0.999
7:144371205:T:G	S1192R	0.999
7:144371207:T:C	L1193P	0.999
7:144371228:T:C	F1200S	0.999
7:144371314:A:C	S1229R	0.999
7:144371316:C:A	S1229R	0.999
7:144371316:C:G	S1229R	0.999
7:144371891:T:C	L1236P	0.999
7:144372382:T:C	L1310P	0.999
7:144372388:T:C	L1312P	0.999
7:144372391:C:A	P1313H	0.999
7:144372391:C:G	P1313R	0.999
7:144372399:C:A	R1316S	0.999
7:144372400:G:C	R1316P	0.999
7:144372412:T:C	L1320P	0.999
7:144373247:T:C	L1368P	0.999
7:144374847:T:C	L1419P	0.999
7:144374853:T:C	L1421P	0.999

dbSNP variants (sampled 300 via entrez): RS1001388042 (7:144373672 C>G), RS1001431258 (7:144377777 T>C), RS1002896850 (7:144376311 T>C), RS1003096877 (7:144379261 C>T), RS1004498817 (7:144377623 C>G,T), RS1004721183 (7:144365184 C>G), RS1004837191 (7:144369758 T>C), RS1005033395 (7:144377874 C>G,T), RS1005346588 (7:144378225 T>C), RS1006013932 (7:144381060 A>G), RS1007632448 (7:144377686 T>C), RS1008003036 (7:144381133 A>G), RS1009185955 (7:144378415 C>G,T), RS1009409836 (7:144378062 T>C), RS1010125915 (7:144377315 G>A,C,T)

Disease associations

OMIM: gene MIM:600888 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST001937_6	Breast cancer	7.000000e-11
GCST003264_1057	Post bronchodilator FEV1/FVC ratio	4.000000e-06
GCST010797_7	Breast cancer, ovarian cancer or prostate cancer (pleiotropy)	7.000000e-12
GCST90006989_2	Gut microbiota relative abundance (Parabacteroides)	5.000000e-06

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004713	FEV/FVC ratio
EFO:0007874	gut microbiome measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

23 total (human), top 23 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Cyclosporine	increases expression	2
FR900359	increases phosphorylation	1
triphenyl phosphate	affects expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
sodium arsenite	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
(+)-JQ1 compound	decreases expression	1
Benzo(a)pyrene	increases expression	1
Caffeine	affects phosphorylation	1
Dichlorodiphenyl Dichloroethylene	decreases expression	1
Diethylhexyl Phthalate	increases expression	1
Gasoline	affects cotreatment, increases abundance, increases expression	1
Phenobarbital	affects expression	1
Polycyclic Aromatic Hydrocarbons	affects cotreatment, increases abundance, increases expression	1
Quercetin	decreases phosphorylation	1
Silicon Dioxide	decreases expression	1
Smoke	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Cadmium Chloride	decreases expression	1
Okadaic Acid	increases expression	1
1-Butanol	affects cotreatment, increases abundance, increases expression	1
Particulate Matter	affects cotreatment, increases abundance, increases expression	1

Clinical trials (associated diseases)

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