SGSM3

protein-coding

small G protein signaling modulator 3, the group of Small G protein signaling modulators

Gene summary

Enables GTPase activator activity and small GTPase binding activity. Involved in several processes, including Rap protein signal transduction; positive regulation of GTPase activity; and regulation of Rab protein signal transduction. Located in Golgi apparatus and cytosol. [provided by Alliance of Genome Resources, Jun 2026]

Previous symbols:

RUTBC3

MANE transcript

NM_015705.6

Inheritance

ClinVar variants

P:4U:158B:26

Top phenotype

neurodevelopmental disorder

gnomAD constraint

pLI —, LoF o/e 0.66

Max pathogenic AF

—

Genomic locus

chr22:40,370,591-40,410,289

External References & Databases

Ensembl (ENSG00000100359)

Transcript & Mutation Effects

hg38 • Region Span ~39.7 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

neurodevelopmental disorderLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0700092

Submitter: Ambry Genetics

intellectual disabilityLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0001071

Submitter: G2P

neurodevelopmental disorderSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0700092

Submitter: PanelApp Australia

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to SGSM3 variants in ClinVar

6 Conditions Cataloged

not specifiedTotal: 138

not providedTotal: 32

Intellectual developmental disorder, autosomal recessive 84Total: 5

EBV-positive nodal T- and NK-cell lymphomaTotal: 1

AutismTotal: 1

SGSM3-related intellectual disabilityTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_015705.6. 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			3 clinvar	16 clinvar	3 clinvar	22
missense			142 clinvar	6 clinvar	1 clinvar	149
nonsense	1 clinvar	1 clinvar	2 clinvar			4
start loss						0
frameshift		2 clinvar	1 clinvar			3
splice donor/acceptor (+/-2bp)			10 clinvar			10
Total	1	3	158	22	4	188

Highest pathogenic variant AF is 0.00019862222

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 126 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_015705.6	RefSeq	NP_056520.2	21	MANE Select
ENST00000248929.14	Ensembl	ENSP00000248929.8	21	MANE Select
NM_001301849.2	RefSeq	NP_001288778.1	19	Standard
NM_001350039.2	RefSeq	NP_001336968.1	21	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Ectoderm Differentiation

Biological Process

intracellular protein transport
cell cycle arrest
regulation of Rab protein signal transduction
Rap protein signal transduction
positive regulation of GTPase activity

Molecular Function

GTPase activator activity
protein binding
Rab GTPase binding

Cellular Component

cytosol
gap junction

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000248929
Coding exons: 21
Length: 39699
Individuals with no LoFs: 125587
Homozygous LoFs: 0
Heterozygous LoFs: 161
Defined: 125748
p: 0.000640

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.162	475	485	0.979	0.0000328	4833
Missense (PolyPhen)		140	169.05	0.82814		1754
Synonymous	-1.72	244	212	1.15	0.0000151	1504
Loss of Function	2.09	30	45.1	0.665	0.00000228	475

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00043	0.00043	rare
Latino/Admixed American	0.00021	0.00020	rare
Ashkenazi Jewish	0.0096	0.0083	notable
East Asian	0.00038	0.00038	rare
Finnish	0.000047	0.000046	rare
European (Non-Finnish)	0.00038	0.00037	rare
South Asian	0.00027	0.00026	rare
Other	0.0010	0.00098	notable

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: May play a cooperative role in NF2-mediated growth suppression of cells. {ECO:0000269|PubMed:15541357}.;

Recessive Scores

pRec: 0.105

Intolerance Scores

LoFtool: 0.792
RVIS EVS: -2.45
RVIS percentile EVS: 1.01

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.834

Gene Damage Prediction

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