SGSM2

protein-coding

small G protein signaling modulator 2, the group of Small G protein signaling modulators

Gene summary

The protein encoded by this gene is a GTPase activator with activity towards RAB32 and RAB33B, which are regulators of membrane trafficking. The encoded protein inactivates RAB32 and can bind RAB9A-GTP, a protein required for RAB32 activation. [provided by RefSeq, Oct 2016]

Previous symbols:

RUTBC1

MANE transcript

NM_014853.3

Inheritance

—

ClinVar variants

U:203B:7

Top phenotype

Prostate cancer

gnomAD constraint

pLI —, LoF o/e 0.43

Max pathogenic AF

—

Genomic locus

chr17:2,337,498-2,381,058

External References & Databases

Ensembl (ENSG00000141258)

Transcript & Mutation Effects

hg38 • Region Span ~43.6 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 SGSM2 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 192

not providedTotal: 7

Prostate cancerTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_014853.3. 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			4 clinvar	1 clinvar	3 clinvar	8
missense			197 clinvar	1 clinvar	2 clinvar	200
nonsense						0
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	203	2	5	210

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 52 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_014853.3	RefSeq	NP_055668.2	24	MANE Select
ENST00000268989.8	Ensembl	ENSP00000268989.3	24	MANE Select
NM_001098509.2	RefSeq	NP_001091979.1	23	Standard
NM_001346700.2	RefSeq	NP_001333629.1	23	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

intracellular protein transport
late endosome to Golgi transport
positive regulation of GTPase activity
activation of GTPase activity

Molecular Function

GTPase activator activity
Rab GTPase binding

Cellular Component

cytoplasm
melanosome

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000268989
Coding exons: 24
Length: 43561
Individuals with no LoFs: 125665
Homozygous LoFs: 0
Heterozygous LoFs: 83
Defined: 125748
p: 0.000330

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.299	649	671	0.967	0.0000441	6840
Missense (PolyPhen)		149	195.88	0.76066		1973
Synonymous	-1.49	316	284	1.11	0.0000202	2039
Loss of Function	3.95	24	55.9	0.430	0.00000265	633

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00012	0.00012	rare
Latino/Admixed American	0.00047	0.00046	rare
Ashkenazi Jewish	0.00010	0.000099	rare
East Asian	0.00050	0.00049	rare
Finnish	0.00029	0.00028	rare
European (Non-Finnish)	0.00032	0.00031	rare
South Asian	0.00043	0.00042	rare
Other	0.00019	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Possesses GTPase activator activity towards RAB32, RAB33B and RAB38 (PubMed:26620560, PubMed:21808068). Regulates the trafficking of melanogenic enzymes TYR, TYRP1 and DCT/TYRP2 to melanosomes in melanocytes by inactivating RAB32 and RAB38. Inhibits RAB32 and RAB38 activation both directly by promoting their GTPase activity and indirectly by disrupting the RAB9A-HPS4 interaction which is required for RAB32/38 activation (PubMed:26620560). {ECO:0000269|PubMed:21808068, ECO:0000269|PubMed:26620560}.;

Recessive Scores

pRec: 0.0990

Intolerance Scores

LoFtool: 0.760
RVIS EVS: -0.74
RVIS percentile EVS: 13.8

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.792

Gene Damage Prediction

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