SGSM1

protein-coding

small G protein signaling modulator 1, the group of Small G protein signaling modulators

Gene summary

Enables GTPase activator activity and small GTPase binding activity. Predicted to act upstream of or within positive regulation of transcription by RNA polymerase II. Located in cytoplasmic vesicle membrane and cytosol. [provided by Alliance of Genome Resources, Jul 2025]

Previous symbols:

RUTBC2

MANE transcript

NM_001098497.3

Inheritance

—

ClinVar variants

U:150B:9

Top phenotype

EBV-positive nodal T- and NK-cell lymphoma

gnomAD constraint

pLI —, LoF o/e 0.33

Max pathogenic AF

—

Genomic locus

chr22:24,806,169-24,927,578

External References & Databases

Ensembl (ENSG00000167037)

Transcript & Mutation Effects

hg38 • Region Span ~121.4 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to SGSM1 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 160

not providedTotal: 4

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

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001098497.3. 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				2 clinvar	3 clinvar	5
missense			147 clinvar	4 clinvar		151
nonsense						0
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	150	6	3	159

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 23 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001098497.3	RefSeq	NP_001091967.1	25	MANE Select
ENST00000400358.9	Ensembl	ENSP00000383211.4	25	MANE Select
NM_001039948.4	RefSeq	NP_001035037.1	26	Standard
NM_001098498.3	RefSeq	NP_001091968.1	24	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

intracellular protein transport
activation of GTPase activity

Molecular Function

GTPase activator activity
Rab GTPase binding

Cellular Component

cytoplasm
Golgi apparatus
cytosol
cytoplasmic vesicle membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000400359
Coding exons: 26
Length: 121310
Individuals with no LoFs: 125649
Homozygous LoFs: 0
Heterozygous LoFs: 43
Defined: 125692
p: 0.000171

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.97	556	703	0.791	0.0000438	7563
Missense (PolyPhen)		137	208.44	0.65727		2196
Synonymous	0.0423	293	294	0.997	0.0000201	2183
Loss of Function	4.80	20	60.2	0.332	0.00000292	670

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00013	0.00012	rare
Latino/Admixed American	0.00018	0.00017	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00022	0.00022	rare
Finnish	0.00014	0.00014	rare
European (Non-Finnish)	0.00019	0.00018	rare
South Asian	0.00021	0.00020	rare
Other	0.00017	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Interacts with numerous Rab family members, functioning as Rab effector for some, and as GTPase activator for others. Promotes GTP hydrolysis by RAB34 and RAB36. Probably functions as GTPase effector with RAB9A and RAB9B; does not stimulate GTP hydrolysis with RAB9A and RAB9B. {ECO:0000269|PubMed:22637480}.;

Recessive Scores

pRec: 0.103

Intolerance Scores

LoFtool: 0.661
RVIS EVS: -0.7
RVIS percentile EVS: 14.83

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.285

Gene Damage Prediction

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