ARHGEF26

Summary

ARHGEF26 (Rho guanine nucleotide exchange factor 26, HGNC:24490) is a protein-coding gene on chromosome 3q25.2, encoding Rho guanine nucleotide exchange factor 26 (Q96DR7). Activates RhoG GTPase by promoting the exchange of GDP by GTP.

This gene encodes a member of the Rho-guanine nucleotide exchange factor (Rho-GEF) family. These proteins regulate Rho GTPases by catalyzing the exchange of GDP for GTP. The encoded protein specifically activates RhoG and plays a role in the promotion of macropinocytosis. Underexpression of the encoded protein may be a predictive marker of chemoresistant disease. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene.

Source: NCBI Gene 26084 — RefSeq curated summary.

At a glance

• GWAS associations: 9
• Clinical variants (ClinVar): 164 total — 1 likely-pathogenic
• MANE Select transcript: NM_015595

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:24490
Approved symbol	ARHGEF26
Name	Rho guanine nucleotide exchange factor 26
Location	3q25.2
Locus type	gene with protein product
Status	Approved
Aliases	DKFZP434D146, SGEF
Ensembl gene	ENSG00000114790
Ensembl biotype	protein_coding
OMIM	617552
Entrez	26084

Gene structure

Transcript identifiers

Ensembl transcripts: 16 — 15 protein_coding, 1 retained_intron

ENST00000356448, ENST00000465093, ENST00000465817, ENST00000483068, ENST00000496710, ENST00000889515, ENST00000889516, ENST00000889517, ENST00000889518, ENST00000889519, ENST00000889520, ENST00000889521, ENST00000889522, ENST00000889523, ENST00000924187, ENST00000946651

RefSeq mRNA: 3 — MANE Select: NM_015595 NM_001251962, NM_001251963, NM_015595

CCDS: CCDS46938, CCDS58858

Canonical transcript exons

ENST00000465093 — 15 exons

Exon	Start	End
ENSE00000805473	154225856	154226010
ENSE00000934025	154152772	154152932
ENSE00000934026	154187685	154187837
ENSE00000934028	154194644	154194718
ENSE00000934029	154217869	154217958
ENSE00000967924	154191289	154191418
ENSE00001006119	154124410	154124449
ENSE00001006126	154129574	154129719
ENSE00001006132	154149389	154149445
ENSE00001530601	154121390	154121519
ENSE00001828036	154255331	154257825
ENSE00002079120	154121942	154123075
ENSE00003469376	154240370	154240579
ENSE00003627969	154254720	154254824
ENSE00003659097	154253116	154253183

Expression profiles

Bgee: expression breadth ubiquitous, 131 present calls, max score 93.23.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 5.6862 / max 88.6418, expressed in 1123 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
39346	5.5408	1104
39347	0.1129	34
202988	0.0325	5

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
lower esophagus muscularis layer	UBERON:0035833	93.23	gold quality
lower esophagus	UBERON:0013473	93.18	gold quality
tibial nerve	UBERON:0001323	92.27	gold quality
muscle layer of sigmoid colon	UBERON:0035805	91.79	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	91.28	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	91.12	gold quality
sural nerve	UBERON:0015488	90.86	gold quality
right lung	UBERON:0002167	90.60	gold quality
descending thoracic aorta	UBERON:0002345	89.04	gold quality
right lobe of liver	UBERON:0001114	88.80	gold quality
upper lobe of left lung	UBERON:0008952	88.38	gold quality
liver	UBERON:0002107	88.16	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	87.92	gold quality
lung	UBERON:0002048	87.28	gold quality
thoracic aorta	UBERON:0001515	87.23	gold quality
ascending aorta	UBERON:0001496	87.10	gold quality
left coronary artery	UBERON:0001626	86.81	gold quality
esophagus	UBERON:0001043	85.85	gold quality
nucleus accumbens	UBERON:0001882	85.42	gold quality
caudate nucleus	UBERON:0001873	85.20	gold quality
amygdala	UBERON:0001876	85.14	gold quality
temporal lobe	UBERON:0001871	85.00	gold quality
mucosa of stomach	UBERON:0001199	84.77	gold quality
colon	UBERON:0001155	84.48	gold quality
fundus of stomach	UBERON:0001160	83.91	gold quality
putamen	UBERON:0001874	83.83	gold quality
smooth muscle tissue	UBERON:0001135	83.69	gold quality
lower esophagus mucosa	UBERON:0035834	83.43	gold quality
ventricular zone	UBERON:0003053	83.35	gold quality
skin of abdomen	UBERON:0001416	83.19	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-GEOD-130148	yes	6.83
E-MTAB-10137	no	39.54
E-MTAB-7303	no	8.35
E-ANND-3	no	2.31

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

126 targeting ARHGEF26, 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-5692A	100.00	74.40	6850
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-3667-3P	99.99	67.17	1636
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-12136	99.98	72.81	5713
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-3148	99.97	75.06	6478
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-2110	99.96	66.68	1930
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-548J-3P	99.94	72.61	4881

Literature-anchored findings (GeneRIF, showing 13)

• SGEF gene on chromosome 3q25.2. CSGEF expression controlled by androgen-responsive promoter of SGEF gene. SGEF may be regulator of Rho guanosine triphosphatases. CSGEF may function as regulator of Rho guanosine triphosphatase in prostate (PMID:12697679)
• The invasive capacity of HPV transformed cells requires the hDlg-dependent enhancement of SGEF/RhoG activity. (PMID:22383878)
• SGEF is a novel promoter of human prostate cancer progression and development. (PMID:22824926)
• We report for the first time an SGEF function for RhoG that excludes GEF and the ability of SGEF to enhance EGFR stability and signaling by delaying its lysosomal sorting and degradation (PMID:23661635)
• Data indicate that the Src homology 3 domain-containing GEF (SGEF) promotes fibroblast growth factor-inducible 14 (Fn14) proinvasive signaling in glioblastoma via TNF receptor-associated factor 2 (TRAF2). (PMID:23775076)
• A novel function of SGEF that excludes GEF. (PMID:24399467)
• Data support evidence for SGEF role in both the promotion of cell invasion and cell survival signaling within glioblastoma tumors and promoting chemotherapeutic resistance. (PMID:26764186)
• yrosine phosphorylation of SGEF suppresses its interaction with RhoG, the elevation of RhoG activity, and SGEF-mediated promotion of cell migration. We identified tyrosine 530 (Y530), which is located within the Dbl homology domain, as a major phosphorylation site of SGEF by Src, and Y530F mutation blocked the inhibitory effect of Src on SGEF (PMID:27437949)
• SGEF plays a role in activating RhoG during invadopodia disassembly (PMID:28202690)
• Phenome-wide association scanning showed that CCDC92 likely affects coronary artery disease through insulin resistance pathways, whereas experimental analysis suggests that ARHGEF26 influences the transendothelial migration of leukocytes. (PMID:28714974)
• High SGEF expression is associated with lung adenocarcinoma. (PMID:29454349)
• ARHGEF26 enhances Salmonella invasion and inflammation in cells and mice. (PMID:34242364)
• Endothelial ARHGEF26 is an angiogenic factor promoting VEGF signalling. (PMID:34849650)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
mus_musculus	Arhgef26	ENSMUSG00000036885
rattus_norvegicus	Arhgef26	ENSRNOG00000014549
caenorhabditis_elegans		WBGENE00019487

Paralogs (6): ARHGEF5 (ENSG00000050327), NGEF (ENSG00000066248), ARHGEF16 (ENSG00000130762), ARHGEF19 (ENSG00000142632), ARHGEF15 (ENSG00000198844), ARHGEF35 (ENSG00000213214)

Protein

Protein identifiers

Rho guanine nucleotide exchange factor 26 — Q96DR7 (reviewed: Q96DR7)

Alternative names: SH3 domain-containing guanine exchange factor

All UniProt accessions (2): Q96DR7, A0A140VJU4

UniProt curated annotations — full annotation on UniProt →

Function. Activates RhoG GTPase by promoting the exchange of GDP by GTP. Required for the formation of membrane ruffles during macropinocytosis. Required for the formation of cup-like structures during trans-endothelial migration of leukocytes. In case of Salmonella enterica infection, activated by SopB, which induces cytoskeleton rearrangements and promotes bacterial entry.

Subunit / interactions. Interacts with ICAM1 and RHOG.

Subcellular location. Cell projection. Ruffle.

Tissue specificity. Isoform 1 is broadly expressed, with highest levels in liver (at protein level). Certain mRNA species appear to be specifically expressed in prostate and liver.

Induction. Certain mRNA species appear to be up-regulated by androgens in prostate cancer cells.

Isoforms (3)

UniProt ID	Names	Canonical?
Q96DR7-1	1	yes
Q96DR7-3	2
Q96DR7-4	3

RefSeq proteins (3): NP_001238891, NP_001238892, NP_056410* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000219	DH_dom	Domain
IPR001452	SH3_domain	Domain
IPR001849	PH_domain	Domain
IPR011993	PH-like_dom_sf	Homologous_superfamily
IPR035797	ARHGEF16/ARHGEF26_SH3	Domain
IPR035899	DBL_dom_sf	Homologous_superfamily
IPR036028	SH3-like_dom_sf	Homologous_superfamily
IPR047270	PH_ephexin	Domain
IPR047271	Ephexin-like	Family
IPR055251	SOS1_NGEF_PH	Domain

Pfam: PF00018, PF00621, PF22697

UniProt features (24 total): sequence conflict 4, domain 3, splice variant 3, sequence variant 3, region of interest 3, modified residue 2, compositionally biased region 2, chain 1, mutagenesis site 1, strand 1, helix 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
6MYE	X-RAY DIFFRACTION	1.1
7YKG	X-RAY DIFFRACTION	2.16

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96DR7-F1	63.60	0.32

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): 392, 22

Mutagenesis-validated functional residues (1):

Position	Phenotype
826	fails to localize at sites of membrane ruffling.

Function

Pathways and Gene Ontology

Reactome pathways

13 pathways

ID	Pathway
R-HSA-193648	NRAGE signals death through JNK
R-HSA-416482	G alpha (12/13) signalling events
R-HSA-9013148	CDC42 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: 131 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_BRAIN_TUMORAL_MACROPHAGE_DN, GOBP_ENDOTHELIAL_CELL_DEVELOPMENT, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_EPITHELIAL_CELL_DEVELOPMENT, REACTOME_NRAGE_SIGNALS_DEATH_THROUGH_JNK, GOCC_RUFFLE, IWANAGA_E2F1_TARGETS_NOT_INDUCED_BY_SERUM, GOBP_REGULATION_OF_ACTIN_FILAMENT_BASED_PROCESS, DAWSON_METHYLATED_IN_LYMPHOMA_TCL1, GOBP_ENDOTHELIUM_DEVELOPMENT, CAIRO_HEPATOBLASTOMA_DN, SCHAEFFER_PROSTATE_DEVELOPMENT_12HR_UP, SCHAEFFER_PROSTATE_DEVELOPMENT_48HR_UP, GOBP_EPITHELIAL_CELL_MORPHOGENESIS, GOBP_CELL_PROJECTION_ORGANIZATION

GO Biological Process (3): endothelial cell morphogenesis (GO:0001886), regulation of actin cytoskeleton organization (GO:0032956), ruffle assembly (GO:0097178)

GO Molecular Function (2): guanyl-nucleotide exchange factor activity (GO:0005085), protein binding (GO:0005515)

GO Cellular Component (3): ruffle (GO:0001726), cytosol (GO:0005829), cell projection (GO:0042995)

Reactome top-level categories

Rollup of top-9 pathways:

Category	Pathways
Signal Transduction	3
RHO GTPase cycle	2
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	2
endothelial cell development	1
epithelial cell morphogenesis	1
actin cytoskeleton organization	1
regulation of actin filament-based process	1
regulation of cytoskeleton organization	1
ruffle organization	1
plasma membrane bounded cell projection assembly	1
GTP binding	1
GDP binding	1
GTPase regulator activity	1
binding	1
cell leading edge	1
plasma membrane bounded cell projection	1
cytoplasm	1

Protein interactions and networks

STRING

662 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ARHGEF26	RHOG	P35238	726
ARHGEF26	SCRIB	Q14160	549
ARHGEF26	RABIF	P47224	447
ARHGEF26	DOCK1	Q14185	403
ARHGEF26	DOCK4	Q8N1I0	395
ARHGEF26	CDC42	P21181	393
ARHGEF26	OR51T1	Q8NGJ9	385
ARHGEF26	ARHGEF33	A8MVX0	371
ARHGEF26	MCF2	P10911	363
ARHGEF26	EVI5	O60447	345
ARHGEF26	DOCK9	Q9BZ29	343
ARHGEF26	CANT1	Q8WVQ1	341
ARHGEF26	ARHGEF37	A1IGU5	341
ARHGEF26	ARHGEF7	Q14155	341
ARHGEF26	RHOBTB3	O94955	340

IntAct

151 interactions, top by confidence:

A	B	Type	Score
KBTBD7	METTL15	psi-mi:“MI:0914”(association)	0.730
ARHGEF26	CASK	psi-mi:“MI:0914”(association)	0.690
ARHGEF26	CASK	psi-mi:“MI:0407”(direct interaction)	0.690
ARHGEF26	LIN7B	psi-mi:“MI:0407”(direct interaction)	0.690
KCNJ2	KCNJ18	psi-mi:“MI:2364”(proximity)	0.660
APBA1	LIN7A	psi-mi:“MI:0914”(association)	0.590
ARHGEF26	DLG1	psi-mi:“MI:0407”(direct interaction)	0.590
ARHGEF26	DLG3	psi-mi:“MI:0407”(direct interaction)	0.590
ARHGEF26	SCRIB	psi-mi:“MI:0407”(direct interaction)	0.590
SCRIB	ARHGEF26	psi-mi:“MI:0407”(direct interaction)	0.590
ARHGEF26	APBA1	psi-mi:“MI:0407”(direct interaction)	0.590
APBA1	ARHGEF26	psi-mi:“MI:0407”(direct interaction)	0.590
DCAF8	DCAF8L1	psi-mi:“MI:0914”(association)	0.530
LIN7C	ABLIM1	psi-mi:“MI:0914”(association)	0.530
LIN7B	CASK	psi-mi:“MI:0914”(association)	0.530
DCAF8	TCP1	psi-mi:“MI:0914”(association)	0.530
ARHGEF26	CPS1	psi-mi:“MI:0914”(association)	0.530
MAST2	ARHGEF26	psi-mi:“MI:0407”(direct interaction)	0.440
ARHGEF26	SNTG1	psi-mi:“MI:0407”(direct interaction)	0.440
ARHGEF26	DLG2	psi-mi:“MI:0407”(direct interaction)	0.440
ARHGEF26	SYNJ2BP	psi-mi:“MI:0407”(direct interaction)	0.440
ARHGEF26	DLG4	psi-mi:“MI:0407”(direct interaction)	0.440
ARHGEF26	SNTB1	psi-mi:“MI:0407”(direct interaction)	0.440

BioGRID (69): ARHGEF26 (Affinity Capture-MS), MUT (Affinity Capture-MS), MTIF2 (Affinity Capture-MS), AARS2 (Affinity Capture-MS), CPS1 (Affinity Capture-MS), CPT2 (Affinity Capture-MS), PDPR (Affinity Capture-MS), DARS2 (Affinity Capture-MS), SIRT3 (Affinity Capture-MS), ARHGEF26 (Affinity Capture-MS), ARHGEF26 (Affinity Capture-MS), MTIF2 (Affinity Capture-MS), ARHGEF26 (Affinity Capture-MS), CPS1 (Affinity Capture-MS), CPT2 (Affinity Capture-MS)

ESM2 similar proteins: A0A8I3NFE2, A0FI79, B1AVH7, B5DFA1, D2H0G5, D7PF45, O00750, O15357, O70143, P29353, P97573, P98083, Q00IB7, Q0IIE2, Q15678, Q16825, Q17R13, Q2I6J0, Q2I6J1, Q2V2M9, Q5JV73, Q5M824, Q5R7W7, Q5U2X5, Q61120, Q62130, Q62136, Q62728, Q62925, Q69Z98, Q6P4S2, Q6P549, Q80TI1, Q8AY68, Q8BMC3, Q8BYW1, Q8IWQ3, Q8K245, Q92529, Q92835

Diamond homologs: A5YM69, E9Q7D5, O94989, Q12774, 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

1 interactions.

A	Effect	B	Mechanism
ARHGEF26	“up-regulates activity”	CDC42	“guanine nucleotide exchange factor”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 107 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
Ras activation upon Ca2+ influx through NMDA receptor	5	40.8×	8e-06
Unblocking of NMDA receptors, glutamate binding and activation	5	38.8×	8e-06
Negative regulation of NMDA receptor-mediated neuronal transmission	5	38.8×	8e-06
Assembly and cell surface presentation of NMDA receptors	10	36.2×	2e-11
Dopamine Neurotransmitter Release Cycle	5	35.5×	1e-05
Long-term potentiation	5	34.0×	1e-05
Neurexins and neuroligins	11	30.9×	1e-11
Protein-protein interactions at synapses	7	26.6×	7e-07

GO biological processes:

GO term	Partners	Fold	FDR
establishment or maintenance of epithelial cell apical/basal polarity	11	63.3×	5e-15
protein localization to synapse	6	45.5×	5e-07
receptor clustering	7	43.3×	7e-08
regulation of postsynaptic membrane neurotransmitter receptor levels	7	34.4×	3e-07
protein-containing complex assembly	9	10.2×	2e-05
cell-cell adhesion	10	10.1×	7e-06
chemical synaptic transmission	7	5.4×	9e-03
nervous system development	9	4.1×	9e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	139
Likely benign	4
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
4278484	NM_015595.4(ARHGEF26):c.1083+1G>T	Likely pathogenic

SpliceAI

2942 predictions. Top by Δscore:

Variant	Effect	Δscore
3:154129569:TGCA:T	acceptor_loss	1.0000
3:154129570:GCA:G	acceptor_loss	1.0000
3:154129571:CA:C	acceptor_loss	1.0000
3:154129572:A:AC	acceptor_loss	1.0000
3:154129572:A:AG	acceptor_gain	1.0000
3:154129573:G:GG	acceptor_gain	1.0000
3:154129573:GA:G	acceptor_gain	1.0000
3:154129573:GAA:G	acceptor_gain	1.0000
3:154129573:GAAA:G	acceptor_gain	1.0000
3:154129573:GAAAA:G	acceptor_gain	1.0000
3:154129715:CTGCG:C	donor_gain	1.0000
3:154129716:TGCG:T	donor_gain	1.0000
3:154129717:GCG:G	donor_gain	1.0000
3:154129717:GCGG:G	donor_gain	1.0000
3:154129718:CG:C	donor_gain	1.0000
3:154129718:CGG:C	donor_loss	1.0000
3:154129719:GG:G	donor_gain	1.0000
3:154129719:GGTG:G	donor_loss	1.0000
3:154129720:G:GG	donor_gain	1.0000
3:154129720:GTGA:G	donor_loss	1.0000
3:154129721:T:G	donor_loss	1.0000
3:154149443:GAG:G	donor_gain	1.0000
3:154149443:GAGG:G	donor_loss	1.0000
3:154149444:AGG:A	donor_loss	1.0000
3:154149447:T:G	donor_loss	1.0000
3:154152767:ACCAG:A	acceptor_gain	1.0000
3:154152768:C:G	acceptor_gain	1.0000
3:154152768:CCA:C	acceptor_loss	1.0000
3:154152769:CAG:C	acceptor_loss	1.0000
3:154152770:A:AG	acceptor_gain	1.0000

AlphaMissense

5707 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:154152893:T:C	L483P	1.000
3:154187819:G:C	R541P	1.000
3:154217942:T:C	L640P	1.000
3:154217947:T:C	F642L	1.000
3:154217949:T:A	F642L	1.000
3:154217949:T:G	F642L	1.000
3:154225989:T:C	L690P	1.000
3:154240387:T:A	V703D	1.000
3:154253132:T:A	W773R	1.000
3:154253132:T:C	W773R	1.000
3:154152814:A:C	S457R	0.999
3:154152816:C:A	S457R	0.999
3:154152816:C:G	S457R	0.999
3:154152893:T:A	L483H	0.999
3:154152914:T:A	V490D	0.999
3:154187791:T:C	Y532H	0.999
3:154187791:T:G	Y532D	0.999
3:154187792:A:G	Y532C	0.999
3:154187795:G:A	C533Y	0.999
3:154187796:C:G	C533W	0.999
3:154187809:T:G	Y538D	0.999
3:154187814:A:C	Q539H	0.999
3:154187814:A:T	Q539H	0.999
3:154187825:T:C	L543P	0.999
3:154191368:T:C	F574L	0.999
3:154191370:T:A	F574L	0.999
3:154191370:T:G	F574L	0.999
3:154191372:T:C	L575P	0.999
3:154191378:T:C	L577P	0.999
3:154191381:C:A	P578H	0.999

dbSNP variants (sampled 300 via entrez): RS1000024094 (3:154230741 G>A,T), RS1000025926 (3:154164325 A>G), RS1000053449 (3:154230340 C>A), RS1000054707 (3:154236317 A>G), RS1000110302 (3:154182175 A>G), RS1000126565 (3:154230536 T>C), RS1000128224 (3:154156534 T>C), RS1000133967 (3:154184489 G>A), RS1000199425 (3:154129057 A>G), RS1000202742 (3:154137665 C>A), RS1000276346 (3:154208149 C>A,T), RS1000287006 (3:154242446 T>C), RS1000300580 (3:154140917 C>T), RS1000306982 (3:154174198 G>A), RS1000348998 (3:154159295 C>T)

Disease associations

OMIM: gene MIM:617552 | disease phenotypes: MIM:615351

GenCC curated gene-disease

Mondo (1): muscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type B14 (MONDO:0014141)

Orphanet (0):

HPO phenotypes

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

GWAS associations

9 associations (top):

Study	Trait	p-value
GCST004787_6	Coronary artery disease (myocardial infarction, percutaneous transluminal coronary angioplasty, coronary artery bypass grafting, angina or chromic ischemic heart disease)	3.000000e-08
GCST005196_112	Coronary artery disease	1.000000e-14
GCST006627_97	Diastolic blood pressure	2.000000e-14
GCST007267_11	Systolic blood pressure	1.000000e-12
GCST007990_2	Coronary artery disease	1.000000e-09
GCST010866_47	Coronary artery disease	2.000000e-08
GCST010988_119	Adult body size	4.000000e-15
GCST010989_234	Body size at age 10	7.000000e-12
GCST011365_95	Myocardial infarction	2.000000e-08

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0006336	diastolic blood pressure
EFO:0006335	systolic blood pressure
EFO:0009819	comparative body size at age 10, self-reported

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression, decreases methylation, increases expression	5
sodium arsenite	decreases expression, increases abundance, increases expression	4
potassium chromate(VI)	increases expression, affects cotreatment, decreases expression	2
Arsenic	decreases expression, increases abundance, increases expression	2
Cisplatin	affects cotreatment, increases expression	2
Estradiol	affects cotreatment, increases expression, decreases expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
aristolochic acid I	decreases expression	1
FR900359	decreases phosphorylation	1
methylmercuric chloride	decreases expression	1
tris(2-butoxyethyl) phosphate	affects expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
butyraldehyde	decreases expression	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, increases expression	1
hydroquinone	decreases expression	1
S-(1,2-dichlorovinyl)cysteine	increases expression, affects response to substance	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
chromium hexavalent ion	affects expression	1
CGP 52608	affects binding, increases reaction	1
entinostat	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	decreases expression, affects cotreatment	1
2,2’,4,4’,5-brominated diphenyl ether	decreases expression	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
jinfukang	increases expression, affects cotreatment	1
NSC 689534	affects binding, decreases expression	1
Sunitinib	decreases expression	1
Fulvestrant	increases methylation	1
Amphotericin B	increases expression	1
Benzo(a)pyrene	affects methylation, increases methylation	1

Clinical trials (associated diseases)

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