RASGEF1C

Summary

RASGEF1C (RasGEF domain family member 1C, HGNC:27400) is a protein-coding gene on chromosome 5q35.3, encoding Ras-GEF domain-containing family member 1C (Q8N431). Guanine nucleotide exchange factor (GEF).

Predicted to enable guanyl-nucleotide exchange factor activity. Predicted to be involved in Ras protein signal transduction. Predicted to be active in plasma membrane.

Source: NCBI Gene 255426 — RefSeq curated summary.

At a glance

• GWAS associations: 6
• Clinical variants (ClinVar): 77 total
• MANE Select transcript: NM_175062

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:27400
Approved symbol	RASGEF1C
Name	RasGEF domain family member 1C
Location	5q35.3
Locus type	gene with protein product
Status	Approved
Aliases	FLJ35841
Ensembl gene	ENSG00000146090
Ensembl biotype	protein_coding
Entrez	255426

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 7 protein_coding, 2 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000361132, ENST00000393371, ENST00000519456, ENST00000519883, ENST00000520209, ENST00000522500, ENST00000615330, ENST00000923269, ENST00000967585, ENST00000967586

RefSeq mRNA: 1 — MANE Select: NM_175062 NM_175062

CCDS: CCDS4452

Canonical transcript exons

ENST00000361132 — 14 exons

Exon	Start	End
ENSE00000973877	180119346	180119448
ENSE00000973880	180118609	180118704
ENSE00001434617	180209028	180209211
ENSE00001724966	180137590	180137712
ENSE00001745008	180100795	180101525
ENSE00001780567	180136378	180136515
ENSE00001801825	180137876	180138058
ENSE00002447919	180118787	180118866
ENSE00003521852	180111457	180111580
ENSE00003527217	180114446	180114541
ENSE00003565248	180121060	180121149
ENSE00003587120	180128410	180128610
ENSE00003664233	180102071	180102143
ENSE00003690129	180127609	180127683

Expression profiles

Bgee: expression breadth ubiquitous, 155 present calls, max score 91.19.

FANTOM5 (CAGE): breadth broad, TPM avg 0.9682 / max 81.9881, expressed in 339 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
65282	0.9270	332
65281	0.0341	11
65280	0.0071	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right hemisphere of cerebellum	UBERON:0014890	91.19	gold quality
cerebellar hemisphere	UBERON:0002245	91.03	gold quality
cerebellar cortex	UBERON:0002129	91.01	gold quality
cerebellum	UBERON:0002037	89.64	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	89.32	gold quality
sural nerve	UBERON:0015488	86.69	gold quality
cortical plate	UBERON:0005343	85.02	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	82.94	gold quality
tibial nerve	UBERON:0001323	82.39	gold quality
spinal cord	UBERON:0002240	80.53	gold quality
prefrontal cortex	UBERON:0000451	80.46	gold quality
anterior cingulate cortex	UBERON:0009835	79.99	gold quality
right frontal lobe	UBERON:0002810	79.15	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	78.18	gold quality
Brodmann (1909) area 9	UBERON:0013540	78.14	gold quality
neocortex	UBERON:0001950	77.20	gold quality
frontal cortex	UBERON:0001870	76.84	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	76.30	gold quality
amygdala	UBERON:0001876	75.10	gold quality
ganglionic eminence	UBERON:0004023	74.68	gold quality
cerebral cortex	UBERON:0000956	74.61	gold quality
left testis	UBERON:0004533	73.54	gold quality
cerebellar vermis	UBERON:0004720	72.81	gold quality
substantia nigra	UBERON:0002038	72.79	gold quality
right testis	UBERON:0004534	72.66	gold quality
ventricular zone	UBERON:0003053	72.56	gold quality
testis	UBERON:0000473	71.94	gold quality
midbrain	UBERON:0001891	71.04	gold quality
brain	UBERON:0000955	70.89	gold quality
temporal lobe	UBERON:0001871	70.60	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.79

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

25 targeting RASGEF1C, 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-548AW	99.99	72.57	3559
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-34C-5P	99.97	70.45	1577
HSA-MIR-449B-5P	99.97	70.26	1580
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-185-3P	99.95	67.01	1743
HSA-MIR-450B-5P	99.92	71.48	3175
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-548AJ-5P	99.78	71.12	3085
HSA-MIR-548F-5P	99.78	71.02	3093
HSA-MIR-548G-5P	99.78	71.12	3085
HSA-MIR-548X-5P	99.78	71.12	3085
HSA-MIR-6745	99.74	65.33	1321
HSA-MIR-6132	99.60	65.83	1554
HSA-MIR-6836-5P	99.60	65.62	1538
HSA-MIR-363-5P	99.46	64.51	1015
HSA-MIR-4318	99.38	66.94	1505
HSA-MIR-4483	98.09	64.12	1642
HSA-MIR-3126-5P	96.87	65.83	912
HSA-MIR-6875-5P	96.87	65.49	958
HSA-MIR-2355-3P	96.84	68.54	909
HSA-MIR-1915-5P	95.25	65.78	571
HSA-MIR-5588-3P	94.96	65.59	500

Literature-anchored findings (GeneRIF, showing 1)

• Natural selection at the RASGEF1C (GGC) repeat in human and divergent genotypes in late-onset neurocognitive disorder. (PMID:34584172)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Rasgef1c	ENSMUSG00000020374
rattus_norvegicus	Rasgef1c	ENSRNOG00000003005

Paralogs (24): RASGRF1 (ENSG00000058335), RASGRP2 (ENSG00000068831), RAPGEF3 (ENSG00000079337), RAPGEF4 (ENSG00000091428), SOS2 (ENSG00000100485), RAPGEF1 (ENSG00000107263), RAPGEFL1 (ENSG00000108352), RAPGEF2 (ENSG00000109756), RASGRF2 (ENSG00000113319), SOS1 (ENSG00000115904), RALGPS2 (ENSG00000116191), RAPGEF5 (ENSG00000136237), RALGPS1 (ENSG00000136828), RASGEF1B (ENSG00000138670), RGL1 (ENSG00000143344), RASGRP3 (ENSG00000152689), RAPGEF6 (ENSG00000158987), RGL4 (ENSG00000159496), RALGDS (ENSG00000160271), RASGRP4 (ENSG00000171777), RASGRP1 (ENSG00000172575), RASGEF1A (ENSG00000198915), RGL3 (ENSG00000205517), RGL2 (ENSG00000237441)

Protein

Protein identifiers

Ras-GEF domain-containing family member 1C — Q8N431 (reviewed: Q8N431)

All UniProt accessions (2): Q8N431, I6L9E5

UniProt curated annotations — full annotation on UniProt →

Function. Guanine nucleotide exchange factor (GEF).

Isoforms (2)

UniProt ID	Names	Canonical?
Q8N431-1	1	yes
Q8N431-2	2

RefSeq proteins (1): NP_778232* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000651	Ras-like_Gua-exchang_fac_N	Domain
IPR001895	RASGEF_cat_dom	Domain
IPR008937	Ras-like_GEF	Family
IPR019804	Ras_G-nucl-exch_fac_CS	Conserved_site
IPR023578	Ras_GEF_dom_sf	Homologous_superfamily
IPR036964	RASGEF_cat_dom_sf	Homologous_superfamily

Pfam: PF00617, PF00618

UniProt features (5 total): domain 2, chain 1, region of interest 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8N431-F1	86.44	0.76

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 33 (showing top): BENPORATH_ES_WITH_H3K27ME3, GOBP_RAS_PROTEIN_SIGNAL_TRANSDUCTION, GOBP_SMALL_GTPASE_MEDIATED_SIGNAL_TRANSDUCTION, ACEVEDO_METHYLATED_IN_LIVER_CANCER_DN, GOMF_GUANYL_NUCLEOTIDE_EXCHANGE_FACTOR_ACTIVITY, GOMF_NUCLEOSIDE_TRIPHOSPHATASE_REGULATOR_ACTIVITY, GOMF_ENZYME_REGULATOR_ACTIVITY, MEISSNER_NPC_HCP_WITH_H3K4ME2_AND_H3K27ME3, MIKKELSEN_MCV6_HCP_WITH_H3K27ME3, MIKKELSEN_NPC_HCP_WITH_H3K27ME3, MIKKELSEN_MEF_HCP_WITH_H3K27ME3, BRUINS_UVC_RESPONSE_VIA_TP53_GROUP_B, LIM_MAMMARY_LUMINAL_PROGENITOR_UP, EBNA1BP2_TARGET_GENES, NCOA2_TARGET_GENES

GO Biological Process (2): Ras protein signal transduction (GO:0007265), small GTPase-mediated signal transduction (GO:0007264)

GO Molecular Function (1): guanyl-nucleotide exchange factor activity (GO:0005085)

GO Cellular Component (1): plasma membrane (GO:0005886)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
small GTPase-mediated signal transduction	1
intracellular signaling cassette	1
GTP binding	1
GDP binding	1
GTPase regulator activity	1
membrane	1
cell periphery	1

Protein interactions and networks

STRING

876 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RASGEF1C	TMEM244	Q5VVB8	526
RASGEF1C	ISOC1	Q96CN7	500
RASGEF1C	RADIL	Q96JH8	493
RASGEF1C	MAP10	Q9P2G4	491
RASGEF1C	C1orf115	Q9H7X2	488
RASGEF1C	LYZL4	Q96KX0	477
RASGEF1C	OR8H1	Q8NGG4	474
RASGEF1C	FAM13B	Q9NYF5	465
RASGEF1C	LIX1	Q8N485	457
RASGEF1C	ZNF23	P17027	424
RASGEF1C	ZNF507	Q8TCN5	415
RASGEF1C	PLCH1	Q4KWH8	409
RASGEF1C	ZNF25	P17030	400
RASGEF1C	KIF16B	Q96L93	388
RASGEF1C	CCDC148	Q8NFR7	377

IntAct

3 interactions, top by confidence:

A	B	Type	Score
RASGEF1C	S100A7A	psi-mi:“MI:0915”(physical association)	0.400
TNK2	RASGEF1C	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (9): S100A7A (Affinity Capture-MS), RASGEF1C (Affinity Capture-RNA), RASGEF1C (Affinity Capture-RNA), RASGEF1C (Affinity Capture-MS), RASGEF1C (Affinity Capture-RNA), S100A7A (Affinity Capture-MS), RASGEF1C (Affinity Capture-MS), RASGEF1C (Affinity Capture-MS), RASGEF1C (Affinity Capture-MS)

ESM2 similar proteins: A0A0G2JTR4, A0A2R8QFQ6, A0JM95, A4IFE4, A6QNS3, C1C3R6, D3Z649, D4ABL6, E9PV86, F1QH17, G3MWR8, O46404, Q0VAM2, Q12800, Q12979, Q13507, Q28EC1, Q3ULA2, Q3UNW5, Q4V860, Q5R6F2, Q5RB16, Q5RC04, Q5SSL4, Q5VWJ9, Q5ZLX4, Q63789, Q64143, Q6DHR3, Q6NZH6, Q6UVM3, Q6UVM4, Q6ZPR4, Q7RTP6, Q7T2U9, Q7Z6J6, Q8CE50, Q8CJ19, Q8JZL7, Q8N431

Diamond homologs: A0JM95, A4IFE4, F1M386, F1MSG6, F1PBJ0, Q0VAM2, Q28EC1, Q5RC04, Q6DBW1, Q6DHR3, Q8CHG7, Q8IS18, Q8IS19, Q8JZL7, Q8MVR1, Q8N431, Q8N9B8, Q95KH6, Q9D300, Q9Y4G8, O95398, P28818, P83900, Q02342, Q8C0Q9, Q8VCC8, Q8WZA2, Q92565, Q9EQZ6, Q9UHV5, Q9Z1C7, Q9Z1C8, A2AR50, A4IJ06, A6N9I4, A8XQD5, A8XWC4, G5EDB9, O14795, O45818

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
RASGEF1C	up-regulates	HRAS	binding
RASGEF1C	up-regulates	KRAS	binding
RASGEF1C	up-regulates	NRAS	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	69
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

3205 predictions. Top by Δscore:

Variant	Effect	Δscore
5:180102069:A:AG	donor_loss	1.0000
5:180102142:ACC:A	acceptor_loss	1.0000
5:180102143:CCTAG:C	acceptor_loss	1.0000
5:180102144:C:CA	acceptor_loss	1.0000
5:180102145:T:C	acceptor_loss	1.0000
5:180114538:CAAT:C	acceptor_gain	1.0000
5:180118604:CCTA:C	donor_loss	1.0000
5:180118605:CTA:C	donor_loss	1.0000
5:180118606:TA:T	donor_loss	1.0000
5:180118607:A:AC	donor_gain	1.0000
5:180118608:C:CC	donor_gain	1.0000
5:180118608:CCTT:C	donor_gain	1.0000
5:180118700:TGGTG:T	acceptor_gain	1.0000
5:180118705:C:CC	acceptor_gain	1.0000
5:180118705:C:T	acceptor_loss	1.0000
5:180118706:T:A	acceptor_loss	1.0000
5:180118782:TTTA:T	donor_loss	1.0000
5:180118783:TTA:T	donor_loss	1.0000
5:180118784:TA:T	donor_loss	1.0000
5:180118785:A:C	donor_loss	1.0000
5:180118786:C:A	donor_loss	1.0000
5:180118863:CCGG:C	acceptor_gain	1.0000
5:180118864:CGG:C	acceptor_gain	1.0000
5:180118864:CGGC:C	acceptor_gain	1.0000
5:180118867:C:CC	acceptor_gain	1.0000
5:180119342:TCA:T	donor_loss	1.0000
5:180119343:CA:C	donor_loss	1.0000
5:180119344:A:AC	donor_gain	1.0000
5:180119344:ACAG:A	donor_loss	1.0000
5:180119345:C:CA	donor_gain	1.0000

AlphaMissense

3070 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:180114507:T:G	D373A	1.000
5:180114510:T:A	K372I	1.000
5:180118667:C:A	R342M	1.000
5:180118667:C:G	R342T	1.000
5:180118836:A:G	L313P	1.000
5:180118839:C:A	R312M	1.000
5:180118839:C:G	R312T	1.000
5:180118845:A:T	V310D	1.000
5:180118863:C:T	G304D	1.000
5:180119365:G:C	N296K	1.000
5:180119365:G:T	N296K	1.000
5:180119371:G:C	N294K	1.000
5:180119371:G:T	N294K	1.000
5:180119386:G:C	C289W	1.000
5:180128426:A:G	L208P	1.000
5:180102128:G:A	S440F	0.999
5:180102128:G:T	S440Y	0.999
5:180102129:A:G	S440P	0.999
5:180102140:A:G	L436P	0.999
5:180114507:T:A	D373V	0.999
5:180114507:T:C	D373G	0.999
5:180114508:C:G	D373H	0.999
5:180114519:A:G	L369P	0.999
5:180114531:G:C	P365R	0.999
5:180114531:G:T	P365H	0.999
5:180114537:A:T	V363D	0.999
5:180118666:C:A	R342S	0.999
5:180118666:C:G	R342S	0.999
5:180118678:G:C	F338L	0.999
5:180118678:G:T	F338L	0.999

dbSNP variants (sampled 300 via entrez): RS1000115785 (5:180173639 G>A), RS1000133140 (5:180133026 C>T), RS1000137194 (5:180198219 A>G), RS1000157561 (5:180153823 A>C), RS1000178296 (5:180114349 G>A,T), RS1000183854 (5:180184995 G>A), RS1000209646 (5:180114610 G>C), RS1000235480 (5:180127480 C>A,T), RS1000245586 (5:180193566 C>T), RS1000302261 (5:180211151 C>T), RS1000304760 (5:180142623 G>A), RS1000309532 (5:180156711 G>A), RS1000315386 (5:180170783 C>A,T), RS1000320045 (5:180119261 T>C), RS1000325766 (5:180142832 C>A,T)

Disease associations

OMIM: gene `` | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST005023_25	Initial pursuit acceleration	6.000000e-06
GCST007430_35	Peak expiratory flow	1.000000e-12
GCST007431_49	Lung function (FEV1/FVC)	2.000000e-33
GCST007432_69	FEV1	3.000000e-08
GCST010396_3	Gut microbiota (bacterial taxa, hurdle binary method)	9.000000e-06
GCST010397_54	Gut microbiota (bacterial taxa, rank normal transformation method)	3.000000e-06

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0008434	initial pursuit acceleration
EFO:0009718	peak expiratory flow
EFO:0004713	FEV/FVC ratio
EFO:0004314	forced expiratory volume
EFO:0007874	gut microbiome 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
Benzo(a)pyrene	affects methylation	2
Phenylmercuric Acetate	decreases expression, affects cotreatment	2
sodium arsenite	increases expression	1
aflatoxin B2	decreases methylation	1
S-(1,2-dichlorovinyl)cysteine	affects cotreatment, decreases expression	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
Arsenic	affects methylation	1
Lead	affects expression	1
Lipopolysaccharides	affects cotreatment, decreases expression	1
Thiram	increases expression	1
Valproic Acid	increases methylation	1
Cadmium Chloride	increases expression	1
Acrylamide	decreases expression	1

Clinical trials (associated diseases)

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