SYDE2

protein-coding

synapse defective Rho GTPase homolog 2, the group of C2 domain containing

Gene summary

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. [provided by Alliance of Genome Resources, Jul 2025]

MANE transcript

NM_032184.2

Inheritance

ClinVar variants

U:153B:14

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.74

Max pathogenic AF

—

Genomic locus

chr1:85,156,889-85,201,724

External References & Databases

Ensembl (ENSG00000097096)

Transcript & Mutation Effects

hg38 • Region Span ~44.8 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

multiple congenital anomalies/dysmorphic syndromeLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0019042

Submitter: Ambry Genetics

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to SYDE2 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 152

not providedTotal: 9

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_032184.2. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			1 clinvar		1 clinvar	2
missense			150 clinvar	10 clinvar	3 clinvar	163
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	153	10	4	167

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 21 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_032184.2	RefSeq	NP_115560.1	7	MANE Select
ENST00000341460.6	Ensembl	ENSP00000340594.5	7	MANE Select
ENST00000696556.1	Ensembl	ENSP00000512715.1	7	Standard
ENST00000696556.2	Ensembl	ENSP00000512715.1	7	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Signal Transduction
Rho GTPase cycle
Signaling by Rho GTPases

Biological Process

signal transduction
regulation of small GTPase mediated signal transduction
activation of GTPase activity

Molecular Function

GTPase activator activity

Cellular Component

cytosol

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000341460
Coding exons: 7
Length: 44174
Individuals with no LoFs: 124006
Homozygous LoFs: 2
Heterozygous LoFs: 633
Defined: 124641
p: 0.00255

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.787	531	585	0.908	0.0000278	7763
Missense (PolyPhen)		184	193.43	0.95123		2745
Synonymous	1.22	193	216	0.894	0.0000103	2340
Loss of Function	1.57	32	43.1	0.742	0.00000263	555

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00032	0.00032	rare
Latino/Admixed American	0.00099	0.00099	rare
Ashkenazi Jewish	0.0036	0.0036	notable
East Asian	0.0011	0.0011	notable
Finnish	0.012	0.012	notable
European (Non-Finnish)	0.0019	0.0019	notable
South Asian	0.0021	0.0020	notable
Other	0.0018	0.0018	notable

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: GTPase activator for the Rho-type GTPases by converting them to an inactive GDP-bound state. {ECO:0000250}.;

Recessive Scores

pRec: 0.125

Intolerance Scores

LoFtool: 0.975
RVIS EVS: 0.72
RVIS percentile EVS: 85.83

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.581

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium