SYDE2

Summary

SYDE2 (synapse defective Rho GTPase homolog 2, HGNC:25841) is a protein-coding gene on chromosome 1p22.3, encoding Rho GTPase-activating protein SYDE2 (Q5VT97). GTPase activator for the Rho-type GTPases by converting them to an inactive GDP-bound state.

Predicted to enable GTPase activator activity. Acts upstream of or within cell migration. Predicted to be located in cytosol. Predicted to be active in synaptic membrane.

Source: NCBI Gene 84144 — RefSeq curated summary.

At a glance

• Gene–disease (curated): multiple congenital anomalies/dysmorphic syndrome (Limited, GenCC)
• GWAS associations: 3
• Clinical variants (ClinVar): 158 total
• MANE Select transcript: NM_032184

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25841
Approved symbol	SYDE2
Name	synapse defective Rho GTPase homolog 2
Location	1p22.3
Locus type	gene with protein product
Status	Approved
Aliases	FLJ13815
Ensembl gene	ENSG00000097096
Ensembl biotype	protein_coding
OMIM	620834
Entrez	84144

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 3 protein_coding, 1 retained_intron

ENST00000234668, ENST00000341460, ENST00000696556, ENST00000914228

RefSeq mRNA: 1 — MANE Select: NM_032184 NM_032184

CCDS: CCDS44169

Canonical transcript exons

ENST00000341460 — 7 exons

Exon	Start	End
ENSE00001365429	85169044	85169225
ENSE00001375384	85164526	85164757
ENSE00001385789	85178146	85178272
ENSE00001453080	85156889	85159249
ENSE00001453081	85182098	85183200
ENSE00001453082	85200252	85201016
ENSE00003668857	85190057	85190752

Expression profiles

Bgee: expression breadth ubiquitous, 166 present calls, max score 81.27.

FANTOM5 (CAGE): breadth broad, TPM avg 2.3524 / max 29.0184, expressed in 846 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
13019	1.4610	602
13020	0.5315	244
13018	0.3599	206

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	81.27	gold quality
calcaneal tendon	UBERON:0003701	79.97	gold quality
muscle layer of sigmoid colon	UBERON:0035805	75.20	gold quality
smooth muscle tissue	UBERON:0001135	74.75	gold quality
lower esophagus muscularis layer	UBERON:0035833	74.60	gold quality
lower esophagus	UBERON:0013473	74.56	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	74.07	gold quality
islet of Langerhans	UBERON:0000006	73.62	gold quality
colonic epithelium	UBERON:0000397	73.12	gold quality
stromal cell of endometrium	CL:0002255	72.36	gold quality
pigmented layer of retina	UBERON:0001782	71.16	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	70.52	gold quality
gall bladder	UBERON:0002110	70.08	gold quality
pancreas	UBERON:0001264	68.77	gold quality
adrenal tissue	UBERON:0018303	68.62	gold quality
heart left ventricle	UBERON:0002084	68.54	gold quality
rectum	UBERON:0001052	68.53	gold quality
cardiac ventricle	UBERON:0002082	67.97	gold quality
right lung	UBERON:0002167	67.58	gold quality
heart	UBERON:0000948	67.44	gold quality
right atrium auricular region	UBERON:0006631	67.44	gold quality
transverse colon	UBERON:0001157	67.34	gold quality
colon	UBERON:0001155	67.08	gold quality
body of pancreas	UBERON:0001150	67.05	gold quality
cardiac atrium	UBERON:0002081	66.75	gold quality
lung	UBERON:0002048	66.31	gold quality
large intestine	UBERON:0000059	66.28	gold quality
urinary bladder	UBERON:0001255	66.26	gold quality
vermiform appendix	UBERON:0001154	66.14	gold quality
stomach	UBERON:0000945	65.57	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

106 targeting SYDE2, 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-340-5P	100.00	72.50	4437
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-518D-5P	100.00	67.51	979
HSA-MIR-518E-5P	100.00	67.66	954
HSA-MIR-518F-5P	100.00	67.51	979
HSA-MIR-519A-5P	100.00	67.66	954
HSA-MIR-519B-5P	100.00	67.66	954
HSA-MIR-519C-5P	100.00	67.66	954
HSA-MIR-520C-5P	100.00	67.51	979
HSA-MIR-522-5P	100.00	67.66	954
HSA-MIR-523-5P	100.00	67.66	954
HSA-MIR-526A-5P	100.00	67.51	979
HSA-MIR-6748-5P	100.00	65.81	1057
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-520G-5P	99.99	66.76	658
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-103A-3P	99.98	69.14	1595
HSA-MIR-107	99.98	69.14	1595
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-568	99.98	69.86	2084
HSA-MIR-373-5P	99.98	75.36	4753

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	SYDE2	ENSDARG00000099479
mus_musculus	Syde2	ENSMUSG00000036863
rattus_norvegicus	Syde2	ENSRNOG00000026186
drosophila_melanogaster	RhoGAP100F	FBGN0039883
caenorhabditis_elegans		WBGENE00006363

Paralogs (4): SYDE1 (ENSG00000105137), CHN2 (ENSG00000106069), CHN1 (ENSG00000128656), ARHGAP35 (ENSG00000160007)

Protein

Protein identifiers

Rho GTPase-activating protein SYDE2 — Q5VT97 (reviewed: Q5VT97)

Alternative names: Synapse defective protein 1 homolog 2

All UniProt accessions (2): Q5VT97, A0A8Q3WMH8

UniProt curated annotations — full annotation on UniProt →

Function. GTPase activator for the Rho-type GTPases by converting them to an inactive GDP-bound state.

Isoforms (2)

UniProt ID	Names	Canonical?
Q5VT97-1	1	yes
Q5VT97-2	2

RefSeq proteins (1): NP_115560* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000008	C2_dom	Domain
IPR000198	RhoGAP_dom	Domain
IPR008936	Rho_GTPase_activation_prot	Homologous_superfamily
IPR035892	C2_domain_sf	Homologous_superfamily
IPR052118	Rho-GAP_regulator	Family
IPR057459	SYDE1/2_C2	Domain

Pfam: PF00620, PF25336

UniProt features (18 total): sequence variant 3, sequence conflict 3, region of interest 3, modified residue 3, domain 2, splice variant 2, chain 1, site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q5VT97-F1	51.94	0.17

Functional residue map

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

Catalytic / active sites (1): 854 (arginine finger; crucial for gtp hydrolysis by stabilizing the transition state)

Post-translational modifications (3): 315, 317, 622

Function

Pathways and Gene Ontology

Reactome pathways

5 pathways

ID	Pathway
R-HSA-9013149	RAC1 GTPase cycle
R-HSA-162582	Signal Transduction
R-HSA-194315	Signaling by Rho GTPases
R-HSA-9012999	RHO GTPase cycle
R-HSA-9716542	Signaling by Rho GTPases, Miro GTPases and RHOBTB3

MSigDB gene sets: 131 (showing top): GOBP_ACTIVATION_OF_GTPASE_ACTIVITY, GOBP_REGULATION_OF_GTPASE_ACTIVITY, GOBP_REGULATION_OF_SMALL_GTPASE_MEDIATED_SIGNAL_TRANSDUCTION, GOBP_POSITIVE_REGULATION_OF_CATALYTIC_ACTIVITY, GOBP_REGULATION_OF_HYDROLASE_ACTIVITY, GOBP_POSITIVE_REGULATION_OF_MOLECULAR_FUNCTION, GOBP_RAS_PROTEIN_SIGNAL_TRANSDUCTION, ZHANG_BREAST_CANCER_PROGENITORS_UP, GOBP_SMALL_GTPASE_MEDIATED_SIGNAL_TRANSDUCTION, chr1p22, GOCC_SYNAPSE, GOCC_PLASMA_MEMBRANE_REGION, GOCC_SYNAPTIC_MEMBRANE, GOMF_ENZYME_ACTIVATOR_ACTIVITY, GOMF_NUCLEOSIDE_TRIPHOSPHATASE_REGULATOR_ACTIVITY

GO Biological Process (5): signal transduction (GO:0007165), cell migration (GO:0016477), regulation of Ras protein signal transduction (GO:0046578), regulation of small GTPase mediated signal transduction (GO:0051056), activation of GTPase activity (GO:0090630)

GO Molecular Function (1): GTPase activator activity (GO:0005096)

GO Cellular Component (2): cytosol (GO:0005829), synaptic membrane (GO:0097060)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
RHO GTPase cycle	1
Signaling by Rho GTPases, Miro GTPases and RHOBTB3	1
Signaling by Rho GTPases	1
Signal Transduction	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
cell motility	1
Ras protein signal transduction	1
regulation of small GTPase mediated signal transduction	1
small GTPase-mediated signal transduction	1
regulation of intracellular signal transduction	1
positive regulation of GTPase activity	1
GTPase activity	1
enzyme activator activity	1
GTPase regulator activity	1
cytoplasm	1
cellular anatomical structure	1
synapse	1
plasma membrane region	1

Protein interactions and networks

STRING

854 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SYDE2	ARRDC2	Q8TBH0	481
SYDE2	C1orf52	Q8N6N3	477
SYDE2	GCM1	Q9NP62	472
SYDE2	RASL11B	Q9BPW5	470
SYDE2	CNTROB	Q8N137	461
SYDE2	CNKSR1	Q969H4	460
SYDE2	ELP4	Q96EB1	459
SYDE2	PPP4R3A	Q6IN85	458
SYDE2	RAB3A	P20336	452
SYDE2	RHOF	Q9HBH0	445
SYDE2	CHRM5	P08912	445
SYDE2	SUPT7L	O94864	441
SYDE2	RBM18	Q96H35	440
SYDE2	CBR3	O75828	430
SYDE2	GEN1	Q17RS7	428

IntAct

28 interactions, top by confidence:

A	B	Type	Score
S100B	S100A4	psi-mi:“MI:0914”(association)	0.870
YWHAH	PLEKHG3	psi-mi:“MI:0914”(association)	0.610
YWHAH	BLTP3B	psi-mi:“MI:2364”(proximity)	0.570
YWHAQ	IGLC7	psi-mi:“MI:0914”(association)	0.530
SYDE2	RCN1	psi-mi:“MI:0915”(physical association)	0.400
SYDE2	H4C16	psi-mi:“MI:0915”(physical association)	0.400
YWHAB	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
YWHAG	C1orf226	psi-mi:“MI:0914”(association)	0.350
YWHAZ	SPEG	psi-mi:“MI:0914”(association)	0.350
ACTR2		psi-mi:“MI:0914”(association)	0.350
YWHAB	BRAF	psi-mi:“MI:0914”(association)	0.350
YWHAE	DEPDC5	psi-mi:“MI:0914”(association)	0.350
YWHAB	FOXO6	psi-mi:“MI:0914”(association)	0.350
YWHAG	FOXO6	psi-mi:“MI:0914”(association)	0.350
YWHAQ	FOXO6	psi-mi:“MI:0914”(association)	0.350
YWHAH	FOXO6	psi-mi:“MI:0914”(association)	0.350
S100B	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
YWHAZ	HECTD4	psi-mi:“MI:0914”(association)	0.350
APBB2	APBB1	psi-mi:“MI:0914”(association)	0.350
CREB3L2	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
P4HA3	ARHGAP10	psi-mi:“MI:0914”(association)	0.350
YWHAB	E2F8	psi-mi:“MI:2364”(proximity)	0.270
YWHAE	E2F8	psi-mi:“MI:2364”(proximity)	0.270
YWHAH	E2F8	psi-mi:“MI:2364”(proximity)	0.270
YWHAQ	E2F8	psi-mi:“MI:2364”(proximity)	0.270
YWHAZ	E2F8	psi-mi:“MI:2364”(proximity)	0.270
YWHAG	E2F8	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (57): SYDE2 (Affinity Capture-MS), SYDE2 (Affinity Capture-MS), SYDE2 (Affinity Capture-MS), SYDE2 (Affinity Capture-RNA), SYDE2 (Proximity Label-MS), SYDE2 (Proximity Label-MS), SYDE2 (FRET), APBB1 (Affinity Capture-MS), GOPC (Affinity Capture-MS), KIAA1671 (Affinity Capture-MS), KPNA2 (Affinity Capture-MS), LRPAP1 (Affinity Capture-MS), MPRIP (Affinity Capture-MS), NUDT21 (Affinity Capture-MS), PALM2-AKAP2 (Affinity Capture-MS)

ESM2 similar proteins: A0JNG6, A2AKB4, A7YWL5, B0BN13, O35181, O43734, O70142, O70240, O88286, O88566, P0DPB3, P0DPB4, P56975, P70298, P86174, P97303, Q00IB7, Q1LY51, Q2M3C6, Q2T9L4, Q3TY60, Q498S6, Q4V7B1, Q568Z1, Q5HZN9, Q5JTD0, Q5SYB0, Q5U5E5, Q5VT97, Q69ZB8, Q6PG95, Q6UXB0, Q6ZU67, Q76N89, Q80YE4, Q86XD5, Q8BWU3, Q8BZB3, Q8CD60, Q8N365

Diamond homologs: A0A0G2JTR4, A1A4S6, A2AB59, A2RUV4, A4IF90, A4II46, A6QNS3, A6X8Z5, A7KAX9, A7YY57, A8WRJ2, D3ZFJ3, E7EZG2, E7F3F0, F1LXF1, O14559, O94466, P11274, P15882, P30337, P34288, P38339, P46941, P52757, P55194, P81128, P97393, Q03070, Q08DP6, Q10164, Q12979, Q13017, Q15311, Q17QN0, Q20498, Q2M1Z3, Q3TBD2, Q3UIA2, Q52LW3, Q53QZ3

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
SYDE2	“down-regulates activity”	RAC1	“gtpase-activating protein”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 26 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	6	228.4×	8e-12
Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex	6	201.5×	1e-11
SARS-CoV-1 targets host intracellular signalling and regulatory pathways	6	201.5×	1e-11
Activation of BH3-only proteins	6	149.0×	6e-11
RHO GTPases activate PKNs	6	95.2×	9e-10
Intrinsic Pathway for Apoptosis	6	87.8×	1e-09
SARS-CoV-1-host interactions	6	52.7×	3e-08
Apoptosis	6	50.4×	3e-08

GO biological processes:

GO term	Partners	Fold	FDR
protein targeting	5	76.3×	9e-07
intracellular protein localization	6	26.2×	8e-06

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	133
Likely benign	10
Benign	4

Top pathogenic / likely-pathogenic (0)

SpliceAI

1413 predictions. Top by Δscore:

Variant	Effect	Δscore
1:85159245:CTGCA:C	acceptor_gain	1.0000
1:85159250:C:CC	acceptor_gain	1.0000
1:85164521:TTTA:T	donor_loss	1.0000
1:85164522:TTACC:T	donor_loss	1.0000
1:85164523:TA:T	donor_loss	1.0000
1:85164524:AC:A	donor_loss	1.0000
1:85164755:TGC:T	acceptor_gain	1.0000
1:85164758:C:CC	acceptor_gain	1.0000
1:85165306:A:AC	donor_gain	1.0000
1:85165307:T:C	donor_gain	1.0000
1:85169038:GCTTA:G	donor_loss	1.0000
1:85169039:CTTAC:C	donor_loss	1.0000
1:85169040:TTA:T	donor_loss	1.0000
1:85169041:TACC:T	donor_loss	1.0000
1:85169042:ACCT:A	donor_loss	1.0000
1:85169043:C:G	donor_loss	1.0000
1:85183198:AACC:A	acceptor_loss	1.0000
1:85183199:ACC:A	acceptor_loss	1.0000
1:85183200:CC:C	acceptor_loss	1.0000
1:85183201:C:CA	acceptor_loss	1.0000
1:85183202:T:C	acceptor_gain	1.0000
1:85190051:TTTTA:T	donor_loss	1.0000
1:85190053:TTA:T	donor_loss	1.0000
1:85190054:TAC:T	donor_loss	1.0000
1:85190055:A:AT	donor_loss	1.0000
1:85190756:T:TC	acceptor_gain	1.0000
1:85159246:TGCA:T	acceptor_gain	0.9900
1:85159248:CA:C	acceptor_gain	0.9900
1:85162347:CTAGT:C	donor_gain	0.9900
1:85164753:GTTGC:G	acceptor_gain	0.9900

AlphaMissense

7848 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:85182303:A:T	V780D	1.000
1:85164540:A:G	L1024P	0.999
1:85164663:C:T	G983E	0.999
1:85164675:G:T	A979D	0.999
1:85164693:A:G	M973T	0.999
1:85169215:C:A	K894N	0.999
1:85169215:C:G	K894N	0.999
1:85169219:A:G	L893P	0.999
1:85178223:A:G	L865P	0.999
1:85178247:C:T	G857D	0.999
1:85178256:C:G	R854P	0.999
1:85182286:C:G	G786R	0.999
1:85182297:A:G	L782P	0.999
1:85182351:A:T	V764D	0.999
1:85182357:C:T	G762E	0.999
1:85182358:C:G	G762R	0.999
1:85182358:C:T	G762R	0.999
1:85182411:A:G	L744P	0.999
1:85182446:G:C	F732L	0.999
1:85182446:G:T	F732L	0.999
1:85182447:A:G	F732S	0.999
1:85182448:A:G	F732L	0.999
1:85182517:C:G	D709H	0.999
1:85182525:A:T	I706N	0.999
1:85182532:A:G	C704R	0.999
1:85182576:G:T	A689D	0.999
1:85158793:A:G	L1181P	0.998
1:85164552:A:G	L1020P	0.998
1:85164664:C:G	G983R	0.998
1:85164664:C:T	G983R	0.998

dbSNP variants (sampled 300 via entrez): RS1000046583 (1:85202788 G>C), RS1000073049 (1:85199443 G>A), RS1000116338 (1:85165421 T>C), RS1000150510 (1:85183696 G>A), RS1000334531 (1:85166164 A>C), RS1000359635 (1:85196701 A>G), RS1000427319 (1:85184086 A>T), RS1000477460 (1:85185531 G>A,C), RS1000509291 (1:85178904 C>T), RS1000539439 (1:85157746 G>GA), RS1000540612 (1:85178568 C>G), RS1000618614 (1:85186277 C>G,T), RS1000667626 (1:85178581 C>T), RS1000706261 (1:85192726 A>G), RS1000733850 (1:85176908 A>C,G)

Disease associations

OMIM: gene MIM:620834 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
multiple congenital anomalies/dysmorphic syndrome	Limited	Autosomal recessive

Mondo (1): multiple congenital anomalies/dysmorphic syndrome (MONDO:0019042)

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST006658_8	Longevity	9.000000e-06
GCST008158_144	Body mass index	7.000000e-06
GCST009597_242	Multiple sclerosis	2.000000e-09

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression	2
FR900359	affects phosphorylation	1
triphenyl phosphate	affects expression	1
2-methyl-4-isothiazolin-3-one	increases expression	1
manganese chloride	increases abundance, increases expression	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	decreases expression, affects cotreatment	1
muconaldehyde	increases expression	1
di-n-butylphosphoric acid	affects expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
abrine	increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
jinfukang	affects cotreatment, decreases expression	1
Irinotecan	increases expression	1
Leflunomide	increases expression	1
Acetaminophen	increases expression	1
Air Pollutants	increases abundance, increases expression	1
Arsenic	affects methylation	1
Cisplatin	affects cotreatment, decreases expression	1
Coumestrol	affects cotreatment, decreases expression	1
Doxorubicin	decreases expression	1
Estradiol	decreases expression	1
Manganese	increases abundance, increases expression	1
Smoke	decreases expression	1
Tetrachlorodibenzodioxin	decreases expression	1
Thiram	increases expression	1
Tobacco Smoke Pollution	decreases expression	1
Vanadates	decreases expression	1
Aflatoxin B1	decreases methylation	1
Asbestos, Crocidolite	increases expression	1
Cadmium Chloride	decreases expression	1

Clinical trials (associated diseases)

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