SGSM1

Summary

SGSM1 (small G protein signaling modulator 1, HGNC:29410) is a protein-coding gene on chromosome 22q11.23, encoding Small G protein signaling modulator 1 (Q2NKQ1). Interacts with numerous Rab family members, functioning as Rab effector for some, and as GTPase activator for others.

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.

Source: NCBI Gene 129049 — RefSeq curated summary.

At a glance

• GWAS associations: 7
• Clinical variants (ClinVar): 180 total
• MANE Select transcript: NM_001098497

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29410
Approved symbol	SGSM1
Name	small G protein signaling modulator 1
Location	22q11.23
Locus type	gene with protein product
Status	Approved
Aliases	KIAA1941
Ensembl gene	ENSG00000167037
Ensembl biotype	protein_coding
OMIM	611417
Entrez	129049

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 6 protein_coding, 2 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000400358, ENST00000400359, ENST00000470591, ENST00000473458, ENST00000480523, ENST00000610372, ENST00000872030, ENST00000930603, ENST00000945264

RefSeq mRNA: 4 — MANE Select: NM_001098497 NM_001039948, NM_001098497, NM_001098498, NM_133454

CCDS: CCDS46674, CCDS46675, CCDS74834

Canonical transcript exons

ENST00000400358 — 25 exons

Exon	Start	End
ENSE00001563186	24806211	24806344
ENSE00001564168	24924186	24927578
ENSE00001691958	24844897	24844972
ENSE00003467853	24867093	24867160
ENSE00003479251	24868376	24868539
ENSE00003480530	24855285	24855430
ENSE00003488189	24912643	24912752
ENSE00003489374	24901833	24901957
ENSE00003492521	24886600	24886728
ENSE00003517128	24847634	24847796
ENSE00003527545	24897972	24898559
ENSE00003535233	24884053	24884198
ENSE00003536158	24859716	24859840
ENSE00003555394	24868723	24868855
ENSE00003561747	24855549	24855680
ENSE00003581952	24876577	24876715
ENSE00003605150	24806441	24806484
ENSE00003605788	24854996	24855063
ENSE00003616985	24850280	24850432
ENSE00003647504	24879462	24879526
ENSE00003657550	24919826	24919993
ENSE00003672696	24895223	24895291
ENSE00003687103	24905105	24905187
ENSE00003691067	24917658	24917754
ENSE00003691966	24893431	24893613

Expression profiles

Bgee: expression breadth ubiquitous, 197 present calls, max score 93.04.

FANTOM5 (CAGE): breadth broad, TPM avg 1.2645 / max 57.6478, expressed in 396 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
191435	0.9163	324
191434	0.3482	166

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cardiac muscle of right atrium	UBERON:0003379	93.04	gold quality
Brodmann (1909) area 23	UBERON:0013554	92.54	gold quality
middle temporal gyrus	UBERON:0002771	88.05	gold quality
superior frontal gyrus	UBERON:0002661	87.22	gold quality
postcentral gyrus	UBERON:0002581	86.53	gold quality
entorhinal cortex	UBERON:0002728	86.22	gold quality
hypothalamus	UBERON:0001898	85.75	gold quality
cerebellar hemisphere	UBERON:0002245	85.48	gold quality
cerebellar cortex	UBERON:0002129	85.46	gold quality
cardiac atrium	UBERON:0002081	85.19	gold quality
cerebellum	UBERON:0002037	85.14	gold quality
primary visual cortex	UBERON:0002436	84.99	gold quality
right hemisphere of cerebellum	UBERON:0014890	84.98	gold quality
right atrium auricular region	UBERON:0006631	84.95	gold quality
pancreatic ductal cell	CL:0002079	84.44	silver quality
parietal lobe	UBERON:0001872	84.06	gold quality
substantia nigra pars compacta	UBERON:0001965	83.65	gold quality
nucleus accumbens	UBERON:0001882	83.26	gold quality
frontal cortex	UBERON:0001870	82.94	gold quality
prefrontal cortex	UBERON:0000451	82.65	gold quality
anterior cingulate cortex	UBERON:0009835	82.57	gold quality
pituitary gland	UBERON:0000007	82.55	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	82.47	gold quality
Brodmann (1909) area 9	UBERON:0013540	82.40	gold quality
neocortex	UBERON:0001950	82.38	gold quality
right frontal lobe	UBERON:0002810	82.15	gold quality
cerebral cortex	UBERON:0000956	81.75	gold quality
adenohypophysis	UBERON:0002196	81.20	gold quality
occipital lobe	UBERON:0002021	81.05	gold quality
brain	UBERON:0000955	80.98	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.83
E-MTAB-6142	no	0.89

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

104 targeting SGSM1, 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-9-5P	100.00	72.28	2361
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-507	99.97	70.11	1915
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-6755-5P	99.95	65.59	464
HSA-MIR-5010-5P	99.94	64.11	705
HSA-MIR-218-5P	99.93	72.22	2103
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-627-3P	99.90	71.42	3316
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-5003-3P	99.85	69.29	2517
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-6515-3P	99.82	68.19	1933
HSA-MIR-6739-5P	99.80	67.87	2806

Literature-anchored findings (GeneRIF, showing 4)

• Identification of novel protein SGSM1 which modulate small G protein (RAP and RAB)-mediated signaling pathway. (PMID:17509819)
• These data show that RUTBC2 can act as a Rab36 GAP in cells and suggest that RUTBC2 links Rab9A function to Rab36 function in the endosomal system. (PMID:22637480)
• Reduced SGSM1 Stability is associated with Nasopharyngeal Carcinoma Metastasis. (PMID:30573520)
• Prognostic biomarker SGSM1 and its correlation with immune infiltration in gliomas. (PMID:35484511)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	sgsm1a	ENSDARG00000028857
danio_rerio	sgsm1b	ENSDARG00000075376
mus_musculus	Sgsm1	ENSMUSG00000042216
rattus_norvegicus	Sgsm1	ENSRNOG00000000708

Paralogs (45): RABGAP1 (ENSG00000011454), TBC1D22A (ENSG00000054611), TBC1D22B (ENSG00000065491), TBC1D1 (ENSG00000065882), EVI5 (ENSG00000067208), TBC1D25 (ENSG00000068354), TBC1D2 (ENSG00000095383), TBC1D10A (ENSG00000099992), SGSM3 (ENSG00000100359), TBC1D17 (ENSG00000104946), TBC1D13 (ENSG00000107021), TBC1D12 (ENSG00000108239), TBC1D9 (ENSG00000109436), TBC1D30 (ENSG00000111490), TBC1D15 (ENSG00000121749), TBC1D5 (ENSG00000131374), TBC1D14 (ENSG00000132405), TBC1D8B (ENSG00000133138), TBC1D4 (ENSG00000136111), GRTP1 (ENSG00000139835), SGSM2 (ENSG00000141258), EVI5L (ENSG00000142459), TBCK (ENSG00000145348), USP6NL (ENSG00000148429), RABGAP1L (ENSG00000152061), TBC1D21 (ENSG00000167139), TBC1D2B (ENSG00000167202), TBC1D16 (ENSG00000167291), TBC1D10B (ENSG00000169221), TBC1D10C (ENSG00000175463), TBC1D28 (ENSG00000189375), TBC1D9B (ENSG00000197226), TBC1D8 (ENSG00000204634), TBC1D26 (ENSG00000214946), TBC1D3G (ENSG00000260287), TBC1D3K (ENSG00000273513), TBC1D3H (ENSG00000274226), TBC1D3D (ENSG00000274419), TBC1D3L (ENSG00000274512), TBC1D3 (ENSG00000274611)

Protein

Protein identifiers

Small G protein signaling modulator 1 — Q2NKQ1 (reviewed: Q2NKQ1)

Alternative names: RUN and TBC1 domain-containing protein 2

All UniProt accessions (2): Q2NKQ1, A0A087X241

UniProt curated annotations — full annotation on UniProt →

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 a GTPase effector with RAB9A and RAB9B; does not stimulate GTP hydrolysis with RAB9A and RAB9B.

Subunit / interactions. Interacts with RAB9A (GTP-bound form) and RAB9B (GTP-bound form); has much lower affinity for GDP-bound RAB9A and RAB9B. Interacts with RAB3A, RAB4A, RAB5A, RAB8A, RAB11A, RAP1A, RAP1B, RAP2A and RAP2B. No interaction with RAB27A.

Subcellular location. Golgi apparatus. trans-Golgi network. Cytoplasmic vesicle membrane. Cytoplasm.

Tissue specificity. Mainly expressed in brain, heart and testis.

Similarity. Belongs to the RUTBC family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q2NKQ1-1	1	yes
Q2NKQ1-3	2
Q2NKQ1-4	3

RefSeq proteins (4): NP_001035037, NP_001091967, NP_001091968, NP_597711 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000195	Rab-GAP-TBC_dom	Domain
IPR004012	Run_dom	Domain
IPR021935	SGSM1/2_RBD	Domain
IPR035969	Rab-GAP_TBC_sf	Homologous_superfamily
IPR037213	Run_dom_sf	Homologous_superfamily
IPR037745	SGSM1/2	Domain
IPR047344	RUN_SGSM1	Domain

Pfam: PF00566, PF02759, PF12068

UniProt features (21 total): compositionally biased region 7, region of interest 5, splice variant 4, domain 2, sequence variant 2, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q2NKQ1-F1	66.94	0.34

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 62 (showing top): GOMF_GTPASE_BINDING, CREIGHTON_ENDOCRINE_THERAPY_RESISTANCE_5, GOMF_ENZYME_ACTIVATOR_ACTIVITY, GOMF_NUCLEOSIDE_TRIPHOSPHATASE_REGULATOR_ACTIVITY, GOMF_ENZYME_REGULATOR_ACTIVITY, MIKKELSEN_MEF_HCP_WITH_H3K27ME3, BRUINS_UVC_RESPONSE_VIA_TP53_GROUP_C, GLI1_TARGET_GENES, HAND1_TARGET_GENES, MIER1_TARGET_GENES, RLF_TARGET_GENES, SFMBT1_TARGET_GENES, ZNF213_TARGET_GENES, ZNF322_TARGET_GENES, ZNF37A_TARGET_GENES

GO Biological Process (0):

GO Molecular Function (3): GTPase activator activity (GO:0005096), small GTPase binding (GO:0031267), protein binding (GO:0005515)

GO Cellular Component (6): cytoplasm (GO:0005737), Golgi apparatus (GO:0005794), cytosol (GO:0005829), cytoplasmic vesicle membrane (GO:0030659), membrane (GO:0016020), cytoplasmic vesicle (GO:0031410)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
cytoplasm	3
GTPase activity	1
enzyme activator activity	1
GTPase regulator activity	1
GTPase binding	1
binding	1
intracellular anatomical structure	1
endomembrane system	1
intracellular membrane-bounded organelle	1
vesicle membrane	1
cytoplasmic vesicle	1
intracellular vesicle	1

Protein interactions and networks

STRING

810 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SGSM1	SGSM3	Q96HU1	911
SGSM1	RAB4A	P20338	782
SGSM1	RAP1B	P09526	762
SGSM1	RAP2A	P10114	752
SGSM1	RAB11A	P24410	697
SGSM1	RAB3A	P20336	688
SGSM1	RAB8A	P24407	686
SGSM1	RAP1A	P10113	663
SGSM1	RAP2B	P17964	652
SGSM1	RAB5A	P20339	629
SGSM1	RAB36	O95755	541
SGSM1	DPYSL4	O14531	502
SGSM1	TBC1D21	Q8IYX1	444
SGSM1	TBC1D19	Q8N5T2	436
SGSM1	C22orf15	Q8WYQ4	434
SGSM1	WSCD2	Q2TBF2	434

IntAct

11 interactions, top by confidence:

A	B	Type	Score
CETN2	SFI1	psi-mi:“MI:0914”(association)	0.740
SGSM1	CETN1	psi-mi:“MI:0915”(physical association)	0.660
CETN1	SFI1	psi-mi:“MI:0914”(association)	0.640
SGSM1	CETN2	psi-mi:“MI:0914”(association)	0.530
SGSM1	CETN3	psi-mi:“MI:0914”(association)	0.350
SLC4A5	ESYT2	psi-mi:“MI:0914”(association)	0.350

BioGRID (21): SGSM1 (Two-hybrid), SGSM1 (Two-hybrid), SGSM1 (Two-hybrid), SGSM1 (Affinity Capture-MS), SGSM1 (Affinity Capture-RNA), SGSM1 (Affinity Capture-MS), SGSM1 (Two-hybrid), SGSM1 (Two-hybrid), CETN1 (Two-hybrid), OCIAD1 (Affinity Capture-MS), RANBP3 (Affinity Capture-MS), CETN2 (Affinity Capture-MS), ABCB10 (Affinity Capture-MS), PDGFRL (Affinity Capture-MS), ACADVL (Affinity Capture-MS)

ESM2 similar proteins: A0A1L8F1M4, A0A8M9QN10, A0JMQ9, A6NIR3, A8DZE6, A8WH69, B2KF05, F1QCY8, O43147, O43900, O54880, P0C6P5, P59729, P97433, Q13009, Q18PD9, Q2NKQ1, Q32L09, Q3U5C7, Q58D79, Q5EB20, Q5PQS0, Q5U464, Q60592, Q6IVY4, Q6P0Q8, Q6ZQF7, Q6ZUJ8, Q71QF9, Q768S4, Q7T2V3, Q7TNN8, Q7TSI1, Q7ZVP1, Q803A0, Q80U12, Q80VL3, Q80Y24, Q8BPQ7, Q8BRB7

Diamond homologs: A1A5B6, O43147, P09379, P48365, Q2NKQ1, Q3MII6, Q6FWI1, Q80U12, Q8BPQ7, Q8BYH7, Q8TBP0, Q8TC07, Q94BY9, Q9CXF4, Q9HA65, Q9UUH7, I2HAA0, Q09830, Q6BU76, Q28CB1, Q8R3D1, Q9NVG8, P48566, Q12344

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	153
Likely benign	9
Benign	3

Top pathogenic / likely-pathogenic (0)

SpliceAI

4454 predictions. Top by Δscore:

Variant	Effect	Δscore
22:24806481:GGAG:G	donor_gain	1.0000
22:24806482:GAGG:G	donor_gain	1.0000
22:24806484:GGTG:G	donor_loss	1.0000
22:24844970:GTG:G	donor_gain	1.0000
22:24844973:G:GG	donor_gain	1.0000
22:24844973:G:T	donor_loss	1.0000
22:24844974:T:A	donor_loss	1.0000
22:24847793:GCGC:G	donor_gain	1.0000
22:24847795:GC:G	donor_gain	1.0000
22:24850269:T:A	acceptor_gain	1.0000
22:24850428:AGCAG:A	donor_loss	1.0000
22:24850429:GCAG:G	donor_gain	1.0000
22:24850430:CAGG:C	donor_loss	1.0000
22:24850431:AGGTG:A	donor_loss	1.0000
22:24850432:GG:G	donor_loss	1.0000
22:24850433:GTGAG:G	donor_loss	1.0000
22:24850434:T:A	donor_loss	1.0000
22:24855301:A:AG	acceptor_gain	1.0000
22:24855302:G:GG	acceptor_gain	1.0000
22:24855302:GA:G	acceptor_gain	1.0000
22:24855429:GT:G	donor_gain	1.0000
22:24855430:TG:T	donor_loss	1.0000
22:24855431:G:GA	donor_loss	1.0000
22:24855431:G:GG	donor_gain	1.0000
22:24855537:A:AG	acceptor_gain	1.0000
22:24855547:A:AG	acceptor_gain	1.0000
22:24855548:G:GG	acceptor_gain	1.0000
22:24855677:GCCG:G	donor_gain	1.0000
22:24859713:CAG:C	acceptor_gain	1.0000
22:24859714:AGA:A	acceptor_gain	1.0000

AlphaMissense

7263 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
22:24844902:G:C	K23N	1.000
22:24844902:G:T	K23N	1.000
22:24844918:G:C	A29P	1.000
22:24844937:T:A	V35D	1.000
22:24850378:C:A	A134D	1.000
22:24855287:G:A	G176R	1.000
22:24855287:G:C	G176R	1.000
22:24855335:T:A	W192R	1.000
22:24855335:T:C	W192R	1.000
22:24855655:G:A	G259D	1.000
22:24859740:G:T	G276W	1.000
22:24859741:G:A	G276E	1.000
22:24859747:T:C	L278P	1.000
22:24859753:T:C	L280P	1.000
22:24859785:T:A	W291R	1.000
22:24859785:T:C	W291R	1.000
22:24867143:T:C	L326P	1.000
22:24867148:T:C	C328R	1.000
22:24868403:T:A	V341D	1.000
22:24868439:T:C	F353S	1.000
22:24868469:T:C	L363P	1.000
22:24868478:T:C	L366P	1.000
22:24868508:T:C	L376S	1.000
22:24868522:T:A	W381R	1.000
22:24868522:T:C	W381R	1.000
22:24868820:T:C	F419S	1.000
22:24879503:T:C	I546T	1.000
22:24879512:G:T	R549I	1.000
22:24879517:T:C	F551L	1.000
22:24879519:C:A	F551L	1.000

dbSNP variants (sampled 300 via entrez): RS1000030597 (22:24875331 G>T), RS1000038528 (22:24900800 C>G), RS1000110273 (22:24917145 G>A), RS1000126232 (22:24806086 G>A), RS1000127392 (22:24890780 G>A,T), RS1000148278 (22:24881530 C>T), RS1000150185 (22:24820669 G>A), RS1000155615 (22:24842124 C>T), RS1000196154 (22:24893698 C>CT), RS1000211332 (22:24923630 A>C,T), RS1000231973 (22:24831764 G>A,C), RS1000289122 (22:24906475 C>T), RS1000307858 (22:24923341 G>A), RS1000317173 (22:24911573 G>A), RS1000371763 (22:24812808 C>T)

Disease associations

OMIM: gene MIM:611417 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

7 associations (top):

Study	Trait	p-value
GCST002481_6	Acne (severe)	6.000000e-07
GCST003542_202	Night sleep phenotypes	3.000000e-06
GCST004030_19	Primary sclerosing cholangitis	3.000000e-08
GCST006138_18	Resting-state electroencephalogram vigilance	3.000000e-06
GCST006631_52	Nicotine dependence and major depression (severity of comorbidity)	9.000000e-06
GCST007160_34	Refractive astigmatism	4.000000e-07
GCST009863_27	Insulin-related traits (multivariate analysis)	5.000000e-09

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0004357	electroencephalogram measurement
EFO:0007006	depressive symptom measurement
EFO:0009262	nicotine dependence symptom count
EFO:0004467	insulin measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

15 total (human), top 15 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Nickel	decreases expression	2
triphenyl phosphate	affects expression	1
sodium arsenite	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
abrine	decreases expression	1
Decitabine	affects expression	1
Sunitinib	increases expression	1
Cisplatin	affects expression	1
Estradiol	decreases expression	1
Potassium Dichromate	increases expression	1
Smoke	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Valproic Acid	increases methylation	1
Okadaic Acid	increases expression	1

Clinical trials (associated diseases)

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