MCF2L2

Summary

MCF2L2 (MCF.2 cell line derived transforming sequence-like 2, HGNC:30319) is a protein-coding gene on chromosome 3q27.1, encoding Probable guanine nucleotide exchange factor MCF2L2 (Q86YR7). Probably functions as a guanine nucleotide exchange factor.

Predicted to enable guanyl-nucleotide exchange factor activity. Predicted to be located in cytosol. Predicted to be active in cytoplasm.

Source: NCBI Gene 23101 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 165 total — 2 pathogenic
• MANE Select transcript: NM_015078

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:30319
Approved symbol	MCF2L2
Name	MCF.2 cell line derived transforming sequence-like 2
Location	3q27.1
Locus type	gene with protein product
Status	Approved
Aliases	KIAA0861, ARHGEF22
Ensembl gene	ENSG00000053524
Ensembl biotype	protein_coding
OMIM	619946
Entrez	23101

Gene structure

Transcript identifiers

Ensembl transcripts: 14 — 7 retained_intron, 6 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000328913, ENST00000414362, ENST00000447025, ENST00000459750, ENST00000461074, ENST00000464626, ENST00000468976, ENST00000473233, ENST00000475664, ENST00000478652, ENST00000482017, ENST00000488149, ENST00000492331, ENST00000640043

RefSeq mRNA: 1 — MANE Select: NM_015078 NM_015078

CCDS: CCDS3243

Canonical transcript exons

ENST00000328913 — 30 exons

Exon	Start	End
ENSE00001228284	183178041	183179503
ENSE00001957042	183427902	183428619
ENSE00002219361	183180071	183180159
ENSE00002294725	183224098	183224190
ENSE00002305944	183228297	183228366
ENSE00003468576	183379297	183379411
ENSE00003470260	183215969	183216094
ENSE00003479830	183295300	183295477
ENSE00003483726	183338800	183338919
ENSE00003490737	183300005	183300196
ENSE00003497451	183341540	183341630
ENSE00003510927	183323235	183323351
ENSE00003512296	183223346	183223438
ENSE00003514924	183229666	183229781
ENSE00003522390	183310915	183311029
ENSE00003523862	183192999	183193096
ENSE00003529764	183276872	183276957
ENSE00003536277	183311648	183311772
ENSE00003544927	183230951	183231017
ENSE00003555147	183195222	183195255
ENSE00003582022	183207608	183207823
ENSE00003582845	183219856	183219924
ENSE00003591303	183318068	183318217
ENSE00003661537	183309716	183309835
ENSE00003681616	183296976	183297167
ENSE00003682757	183179577	183179692
ENSE00003684386	183389696	183389779
ENSE00003685968	183205876	183205954
ENSE00003688695	183206122	183206214
ENSE00003690652	183289120	183289220

Expression profiles

Bgee: expression breadth ubiquitous, 167 present calls, max score 90.32.

FANTOM5 (CAGE): breadth broad, TPM avg 2.6724 / max 114.8289, expressed in 528 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
45824	1.4486	474
45822	0.8033	153
45823	0.1597	74
45825	0.1558	67
45820	0.0760	9
45802	0.0178	7
45819	0.0061	4
45821	0.0051	2

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right frontal lobe	UBERON:0002810	90.32	gold quality
cingulate cortex	UBERON:0003027	88.67	gold quality
anterior cingulate cortex	UBERON:0009835	88.55	gold quality
adrenal tissue	UBERON:0018303	86.96	gold quality
prefrontal cortex	UBERON:0000451	85.99	gold quality
Brodmann (1909) area 9	UBERON:0013540	84.61	gold quality
nucleus accumbens	UBERON:0001882	83.68	gold quality
amygdala	UBERON:0001876	83.65	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	81.80	gold quality
right adrenal gland cortex	UBERON:0035827	81.68	gold quality
left adrenal gland	UBERON:0001234	81.10	gold quality
left adrenal gland cortex	UBERON:0035825	81.08	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	81.07	gold quality
right adrenal gland	UBERON:0001233	80.23	gold quality
caudate nucleus	UBERON:0001873	80.08	gold quality
adrenal gland	UBERON:0002369	80.06	gold quality
cerebellar hemisphere	UBERON:0002245	80.05	gold quality
right hemisphere of cerebellum	UBERON:0014890	80.00	gold quality
cerebellar cortex	UBERON:0002129	79.92	gold quality
adenohypophysis	UBERON:0002196	79.82	gold quality
islet of Langerhans	UBERON:0000006	79.62	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	79.33	gold quality
neocortex	UBERON:0001950	79.09	gold quality
putamen	UBERON:0001874	78.53	gold quality
adrenal cortex	UBERON:0001235	78.37	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	78.25	gold quality
frontal cortex	UBERON:0001870	77.87	gold quality
sural nerve	UBERON:0015488	77.34	gold quality
pituitary gland	UBERON:0000007	76.70	gold quality
cerebellum	UBERON:0002037	76.31	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-HCAD-25	yes	4859.35
E-MTAB-6678	yes	4.72
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): RUNX1

miRNA regulators (miRDB)

66 targeting MCF2L2, 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-5692A	100.00	74.40	6850
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-548A-5P	99.94	71.27	3482
HSA-MIR-548AD-5P	99.94	71.23	3502
HSA-MIR-548AE-5P	99.94	71.23	3502
HSA-MIR-548AK	99.94	71.24	3488
HSA-MIR-548AM-5P	99.94	71.24	3488
HSA-MIR-548AP-5P	99.94	71.14	3489
HSA-MIR-548AR-5P	99.94	71.28	3515
HSA-MIR-548AS-5P	99.94	71.22	3482
HSA-MIR-548AU-5P	99.94	71.24	3488
HSA-MIR-548AY-5P	99.94	71.23	3502
HSA-MIR-548B-5P	99.94	71.23	3502
HSA-MIR-548BB-5P	99.94	71.27	3509
HSA-MIR-548C-5P	99.94	71.24	3488
HSA-MIR-548D-5P	99.94	71.23	3502
HSA-MIR-548H-5P	99.94	71.24	3488
HSA-MIR-548I	99.94	71.25	3481
HSA-MIR-548J-5P	99.94	71.14	3489
HSA-MIR-548O-5P	99.94	71.24	3488
HSA-MIR-548W	99.94	71.24	3488
HSA-MIR-548Y	99.94	71.28	3514
HSA-MIR-548AQ-5P	99.94	71.34	3426
HSA-MIR-548J-3P	99.94	72.61	4881

Literature-anchored findings (GeneRIF, showing 2)

• Results suggest that the genetic polymorphisms within MCF2L2 may confer an increased susceptibility to PCOS in the Chinese population. Data may provide a basis for further studies of the role of the MCF2L2 gene in the etiology of PCOS. (PMID:19648752)
• MCF2L2 Leu359Ile polymorphism is associated with decreased risk of diabetic nephropathy in female type 1 diabetes mellitus. (PMID:20667095)

Cross-species orthologs

1 orthologs

Organism	Symbol	Gene ID
danio_rerio	mcf2l2	ENSDARG00000079742

Paralogs (22): TRIO (ENSG00000038382), PLEKHG2 (ENSG00000090924), MCF2 (ENSG00000101977), ARHGEF7 (ENSG00000102606), PLEKHG1 (ENSG00000120278), MCF2L (ENSG00000126217), ARHGEF6 (ENSG00000129675), ARHGEF9 (ENSG00000131089), VAV3 (ENSG00000134215), VAV1 (ENSG00000141968), TIAM2 (ENSG00000146426), KIAA1755 (ENSG00000149633), PLEKHG4B (ENSG00000153404), TIAM1 (ENSG00000156299), KALRN (ENSG00000160145), VAV2 (ENSG00000160293), ARHGEF40 (ENSG00000165801), SPATA13 (ENSG00000182957), SESTD1 (ENSG00000187231), PLEKHN1 (ENSG00000187583), PLEKHG4 (ENSG00000196155), ARHGEF25 (ENSG00000240771)

Protein

Protein identifiers

Probable guanine nucleotide exchange factor MCF2L2 — Q86YR7 (reviewed: Q86YR7)

Alternative names: Dbs-related Rho family guanine nucleotide exchange factor, MCF2-transforming sequence-like protein 2

All UniProt accessions (3): A0A1W2PP43, C9J326, Q86YR7

UniProt curated annotations — full annotation on UniProt →

Function. Probably functions as a guanine nucleotide exchange factor.

Tissue specificity. Significantly expressed in brain and modestly in pancreas, brain and testis.

Disease relevance. Type 2 diabetes mellitus (T2D) [MIM:125853] A multifactorial disorder of glucose homeostasis caused by a lack of sensitivity to insulin. Affected individuals usually have an obese body habitus and manifestations of a metabolic syndrome characterized by diabetes, insulin resistance, hypertension and hypertriglyceridemia. The disease results in long-term complications that affect the eyes, kidneys, nerves, and blood vessels. Disease susceptibility may be associated with variants affecting the gene represented in this entry.

Similarity. Belongs to the MCF2 family.

Isoforms (4)

UniProt ID	Names	Canonical?
Q86YR7-1	1	yes
Q86YR7-2	2
Q86YR7-3	3
Q86YR7-4	4

RefSeq proteins (1): NP_055893* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000219	DH_dom	Domain
IPR001251	CRAL-TRIO_dom	Domain
IPR001849	PH_domain	Domain
IPR011993	PH-like_dom_sf	Homologous_superfamily
IPR018159	Spectrin/alpha-actinin	Repeat
IPR035899	DBL_dom_sf	Homologous_superfamily
IPR036865	CRAL-TRIO_dom_sf	Homologous_superfamily
IPR051336	RhoGEF_Guanine_NuclExch_SF	Family
IPR055251	SOS1_NGEF_PH	Domain
IPR056466	Spectrin_DBS	Domain

Pfam: PF00621, PF13716, PF22697, PF23289

UniProt features (31 total): sequence variant 11, compositionally biased region 7, splice variant 5, domain 3, region of interest 2, chain 1, repeat 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q86YR7-F1	73.88	0.39

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 58 (showing top): GSE45365_HEALTHY_VS_MCMV_INFECTION_CD8_TCELL_IFNAR_KO_DN, YAGI_AML_WITH_11Q23_REARRANGED, GOMF_GUANYL_NUCLEOTIDE_EXCHANGE_FACTOR_ACTIVITY, WANG_SMARCE1_TARGETS_UP, GOMF_NUCLEOSIDE_TRIPHOSPHATASE_REGULATOR_ACTIVITY, GOMF_ENZYME_REGULATOR_ACTIVITY, MODULE_49, TAYLOR_METHYLATED_IN_ACUTE_LYMPHOBLASTIC_LEUKEMIA, PEDRIOLI_MIR31_TARGETS_UP, DIDO1_TARGET_GENES, FOXN3_TARGET_GENES, GLI4_TARGET_GENES, GREB1_TARGET_GENES, HES2_TARGET_GENES, KMT2D_TARGET_GENES

GO Biological Process (0):

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

GO Cellular Component (2): cytoplasm (GO:0005737), cytosol (GO:0005829)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
GTP binding	1
GDP binding	1
GTPase regulator activity	1
intracellular anatomical structure	1
cytoplasm	1

Protein interactions and networks

STRING

518 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MCF2L2	B3GNT5	Q9BYG0	527
MCF2L2	KLHL6	Q8WZ60	510
MCF2L2	PLPPR4	Q7Z2D5	502
MCF2L2	MDN1	Q9NU22	499
MCF2L2	ZDHHC14	Q8IZN3	456
MCF2L2	NAALADL2	Q58DX5	455
MCF2L2	RAB31	Q13636	452
MCF2L2	PPM1L	Q5SGD2	439
MCF2L2	ATP11B	Q9Y2G3	435
MCF2L2	YEATS2	Q9ULM3	418
MCF2L2	MYH9	P35579	410
MCF2L2	SLC66A1LP	A1A4F0	398
MCF2L2	MAP6D1	Q9H9H5	394
MCF2L2	ABCC5	O15440	373
MCF2L2	UCKL1	Q9NWZ5	371

IntAct

9 interactions, top by confidence:

A	B	Type	Score
MCF2L2	CANX	psi-mi:“MI:0915”(physical association)	0.400
SIRT1	KPNA3	psi-mi:“MI:0915”(physical association)	0.400
MEGF10	MCF2L2	psi-mi:“MI:0915”(physical association)	0.370
SPG11	MCF2L2	psi-mi:“MI:0915”(physical association)	0.370
MYC		psi-mi:“MI:0914”(association)	0.350
MCF2L2	CDK6	psi-mi:“MI:0914”(association)	0.350
DISC1	MCF2L2	psi-mi:“MI:0915”(physical association)	0.000
OLIG2	MCF2L2	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (40): HIC2 (Affinity Capture-MS), CDK6 (Affinity Capture-MS), CHRAC1 (Affinity Capture-MS), MCF2L2 (Proximity Label-MS), MCF2L2 (Affinity Capture-MS), ANKFY1 (Affinity Capture-MS), DPY30 (Affinity Capture-MS), EXOSC6 (Affinity Capture-MS), MAX (Affinity Capture-MS), MGA (Affinity Capture-MS), MRPS14 (Affinity Capture-MS), MRPS26 (Affinity Capture-MS), MRPS31 (Affinity Capture-MS), NUP205 (Affinity Capture-MS), PSMD12 (Affinity Capture-MS)

ESM2 similar proteins: A0A0G2JEB6, A0JM56, B0DOB4, B0FXQ5, B1ANS9, B4F7L9, B4GQJ7, B5DHW4, B7FF06, B7FF07, B7FF08, B7FF09, B7FF12, C5IAW9, F1LW30, F1P4W9, O08747, O95185, P0DM40, Q008S8, Q18264, Q32NR9, Q3V0B4, Q402B2, Q4G0P3, Q5R4M2, Q5T0N1, Q5XI14, Q6AXU1, Q6DCF6, Q6NRS1, Q6P2C0, Q6P5D8, Q6UXZ4, Q6ZTR5, Q6ZU64, Q761X5, Q7T2Z5, Q80W93, Q86YR7

Diamond homologs: A1IGU3, A1IGU4, A2CG49, A8MVU1, E7F1U2, F1M0Z1, F1M707, O15068, O43307, O60229, O75962, O77774, P10911, P91620, P91621, P97924, Q09014, Q0KL02, Q13009, Q1LUA6, Q3UTH8, Q58DL7, Q58EX7, Q5RDK0, Q60610, Q63406, Q64096, Q6KAU7, Q6P720, Q86VW2, Q86YR7, Q96PX9, Q9CWR0, Q9H7P9, Q9QX73, A8DYP0, Q14155, Q5M7P4, Q6GNM9, Q6GPX2

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	0
Uncertain significance	136
Likely benign	15
Benign	0

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
986757	GRCh37/hg19 3q27.1(chr3:182902731-182945128)x1	Pathogenic
986758	GRCh37/hg19 3q27.1(chr3:182871341-182987855)x1	Pathogenic

SpliceAI

5544 predictions. Top by Δscore:

Variant	Effect	Δscore
3:183180069:A:AC	donor_gain	1.0000
3:183180070:C:CC	donor_gain	1.0000
3:183180070:CA:C	donor_gain	1.0000
3:183180070:CACT:C	donor_gain	1.0000
3:183180087:T:A	donor_gain	1.0000
3:183193092:CTTTG:C	acceptor_gain	1.0000
3:183193097:C:CC	acceptor_gain	1.0000
3:183228295:A:AC	donor_gain	1.0000
3:183228296:C:CC	donor_gain	1.0000
3:183228296:CT:C	donor_gain	1.0000
3:183228296:CTCT:C	donor_gain	1.0000
3:183231043:G:C	acceptor_gain	1.0000
3:183231043:G:GC	acceptor_gain	1.0000
3:183276866:TCTTA:T	donor_loss	1.0000
3:183276867:CTTA:C	donor_loss	1.0000
3:183276868:TTACC:T	donor_loss	1.0000
3:183276869:TACCT:T	donor_loss	1.0000
3:183276870:ACCT:A	donor_loss	1.0000
3:183296970:CATTA:C	donor_loss	1.0000
3:183296971:ATTAC:A	donor_loss	1.0000
3:183296972:TTACC:T	donor_loss	1.0000
3:183296973:TAC:T	donor_loss	1.0000
3:183296974:A:AT	donor_loss	1.0000
3:183296975:C:CA	donor_loss	1.0000
3:183309726:T:TA	donor_gain	1.0000
3:183309831:TTAGC:T	acceptor_gain	1.0000
3:183309832:TAGC:T	acceptor_gain	1.0000
3:183309833:AGCC:A	acceptor_loss	1.0000
3:183309834:GCC:G	acceptor_loss	1.0000
3:183309836:C:CC	acceptor_gain	1.0000

AlphaMissense

7398 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:183341606:G:C	F100L	0.997
3:183341606:G:T	F100L	0.997
3:183341608:A:G	F100L	0.997
3:183389707:G:T	A50D	0.993
3:183323239:C:G	R200P	0.991
3:183379312:A:G	L87P	0.991
3:183341586:C:G	R107P	0.990
3:183341598:A:T	V103D	0.990
3:183341607:A:G	F100S	0.990
3:183323252:A:G	W196R	0.989
3:183323252:A:T	W196R	0.989
3:183379316:A:C	Y86D	0.989
3:183379381:A:T	I64N	0.989
3:183341575:A:G	W111R	0.988
3:183341575:A:T	W111R	0.988
3:183341589:C:A	R106I	0.988
3:183323323:A:G	L172P	0.987
3:183341588:T:A	R106S	0.987
3:183341588:T:G	R106S	0.987
3:183338911:A:C	F125L	0.986
3:183338911:A:T	F125L	0.986
3:183338913:A:G	F125L	0.986
3:183323296:A:G	L181P	0.985
3:183341589:C:G	R106T	0.985
3:183341601:A:T	V102D	0.984
3:183229674:A:C	F679L	0.983
3:183229674:A:T	F679L	0.983
3:183229676:A:G	F679L	0.983
3:183323250:C:A	W196C	0.983
3:183323250:C:G	W196C	0.983

dbSNP variants (sampled 300 via entrez): RS1000006011 (3:183347386 A>T), RS1000008253 (3:183287178 A>C), RS1000010194 (3:183329023 G>A,C,T), RS1000015716 (3:183298117 C>T), RS1000039760 (3:183382268 A>T), RS1000077240 (3:183334324 T>C), RS1000081085 (3:183193189 G>A,C), RS1000082372 (3:183242643 G>T), RS1000087714 (3:183370772 T>C), RS1000093114 (3:183296307 C>T), RS1000117631 (3:183426462 C>A), RS1000127211 (3:183265117 T>G), RS1000135796 (3:183199917 G>C,T), RS1000138457 (3:183375259 G>A,T), RS1000167968 (3:183250092 T>A,G)

Disease associations

OMIM: gene MIM:619946 | disease phenotypes: MIM:206900

GenCC curated gene-disease

Mondo (1): anophthalmia/microphthalmia-esophageal atresia syndrome (MONDO:0008799)

Orphanet (1): Anophthalmia/microphthalmia-esophageal atresia syndrome (Orphanet:77298)

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST003158_3	Subjective response to lithium treatment	9.000000e-07
GCST005171_36	QT interval	2.000000e-06
GCST009441_12	Age-related cognitive decline (memory) (slope of z-scores)	5.000000e-06

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004682	QT interval
EFO:0007710	cognitive decline measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

25 total (human), top 25 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases methylation	2
sodium arsenite	increases expression	1
aflatoxin B2	decreases methylation	1
nickel sulfate	increases expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	increases expression	1
perfluorohexanesulfonic acid	increases expression	1
abrine	increases expression	1
Grape Seed Proanthocyanidins	affects cotreatment, increases expression	1
bisphenol S	decreases methylation	1
Sunitinib	increases expression	1
Fulvestrant	increases methylation	1
Acetaminophen	decreases expression	1
Catechin	affects cotreatment, increases expression	1
Doxorubicin	decreases expression	1
Estradiol	increases expression, affects binding	1
Lipopolysaccharides	increases expression, affects response to substance	1
Methotrexate	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Valproic Acid	increases methylation	1
Vanadates	decreases expression	1
Aflatoxin B1	increases methylation	1
Okadaic Acid	increases expression	1
S-Nitrosoglutathione	decreases expression	1

Clinical trials (associated diseases)

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