DENND6B

Summary

DENND6B (DENN domain containing 6B, HGNC:32690) is a protein-coding gene on chromosome 22q13.33, encoding Protein DENND6B (Q8NEG7). Guanine nucleotide exchange factor (GEF) for RAB14.

Enables guanyl-nucleotide exchange factor activity. Predicted to be located in cytosol. Predicted to be active in recycling endosome.

Source: NCBI Gene 414918 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 128 total
• MANE Select transcript: NM_001001794

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:32690
Approved symbol	DENND6B
Name	DENN domain containing 6B
Location	22q13.33
Locus type	gene with protein product
Status	Approved
Aliases	MGC33692, AFI1B
Ensembl gene	ENSG00000205593
Ensembl biotype	protein_coding
OMIM	620562
Entrez	414918

Gene structure

Transcript identifiers

Ensembl transcripts: 14 — 11 protein_coding, 3 retained_intron

ENST00000413817, ENST00000433760, ENST00000460087, ENST00000471942, ENST00000495607, ENST00000872969, ENST00000872970, ENST00000872971, ENST00000872972, ENST00000872973, ENST00000942388, ENST00000942389, ENST00000942390, ENST00000942391

RefSeq mRNA: 1 — MANE Select: NM_001001794 NM_001001794

CCDS: CCDS46732

Canonical transcript exons

ENST00000413817 — 20 exons

Exon	Start	End
ENSE00001629926	50314207	50314272
ENSE00001707559	50326812	50327012
ENSE00001773502	50313814	50313878
ENSE00001812929	50309030	50312261
ENSE00003490260	50312523	50312625
ENSE00003507721	50314400	50314494
ENSE00003516431	50314605	50314700
ENSE00003523094	50318847	50318889
ENSE00003588833	50315714	50315769
ENSE00003591266	50316370	50316475
ENSE00003601187	50312343	50312417
ENSE00003619480	50316174	50316253
ENSE00003638478	50316025	50316087
ENSE00003644602	50317908	50318020
ENSE00003653292	50314799	50314921
ENSE00003676594	50317293	50317373
ENSE00003681433	50318965	50319003
ENSE00003682494	50312999	50313108
ENSE00003683113	50313446	50313499
ENSE00003693950	50313635	50313724

Expression profiles

Bgee: expression breadth ubiquitous, 179 present calls, max score 97.12.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 4.4664 / max 77.4706, expressed in 1258 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
194738	4.2707	1244
194737	0.1957	92

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right uterine tube	UBERON:0001302	97.12	gold quality
right hemisphere of cerebellum	UBERON:0014890	91.40	gold quality
cerebellar hemisphere	UBERON:0002245	90.46	gold quality
cortical plate	UBERON:0005343	90.39	gold quality
adenohypophysis	UBERON:0002196	90.38	gold quality
cerebellar cortex	UBERON:0002129	90.29	gold quality
right frontal lobe	UBERON:0002810	90.04	gold quality
pituitary gland	UBERON:0000007	89.16	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	89.08	gold quality
ventricular zone	UBERON:0003053	89.05	gold quality
cerebellum	UBERON:0002037	88.50	gold quality
anterior cingulate cortex	UBERON:0009835	88.22	gold quality
Brodmann (1909) area 9	UBERON:0013540	87.70	gold quality
prefrontal cortex	UBERON:0000451	86.52	gold quality
nucleus accumbens	UBERON:0001882	85.87	gold quality
hypothalamus	UBERON:0001898	85.38	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	85.18	gold quality
bronchial epithelial cell	CL:0002328	85.09	gold quality
neocortex	UBERON:0001950	85.04	gold quality
caudate nucleus	UBERON:0001873	84.88	gold quality
ganglionic eminence	UBERON:0004023	84.79	gold quality
metanephros cortex	UBERON:0010533	84.65	gold quality
frontal cortex	UBERON:0001870	84.61	gold quality
amygdala	UBERON:0001876	84.31	gold quality
bronchus	UBERON:0002185	84.07	gold quality
right lobe of thyroid gland	UBERON:0001119	83.79	gold quality
left testis	UBERON:0004533	83.74	gold quality
right testis	UBERON:0004534	83.67	gold quality
left lobe of thyroid gland	UBERON:0001120	83.17	gold quality
putamen	UBERON:0001874	83.06	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	8.19

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

9 targeting DENND6B, 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-4692	100.00	67.32	2066
HSA-MIR-4524A-3P	99.72	66.85	2406
HSA-MIR-3202	99.66	67.70	2737
HSA-MIR-218-1-3P	98.63	67.97	832
HSA-MIR-3179	98.22	65.90	1445
HSA-MIR-93-3P	98.15	66.65	1309
HSA-MIR-4329	97.68	66.26	1003
HSA-MIR-939-5P	97.10	65.80	1579
HSA-MIR-1343-5P	96.48	66.06	1506

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	dennd6b	ENSDARG00000011605
mus_musculus	Dennd6b	ENSMUSG00000015377
rattus_norvegicus	Dennd6b	ENSRNOG00000029866
drosophila_melanogaster	CG3309	FBGN0029756
caenorhabditis_elegans		WBGENE00018777

Paralogs (1): DENND6A (ENSG00000174839)

Protein

Protein identifiers

Protein DENND6B — Q8NEG7 (reviewed: Q8NEG7)

Alternative names: DENN domain-containing protein 6B

All UniProt accessions (2): Q8NEG7, H0Y7N0

UniProt curated annotations — full annotation on UniProt →

Function. Guanine nucleotide exchange factor (GEF) for RAB14. Also has some, lesser GEF activity towards RAB35.

Subcellular location. Recycling endosome. Cytoplasm.

Similarity. Belongs to the DENND6 family.

RefSeq proteins (1): NP_001001794* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001194	cDENN_dom	Domain
IPR024224	DENND6	Family
IPR037516	Tripartite_DENN	Domain

Pfam: PF02141

UniProt features (4 total): domain 3, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8NEG7-F1	86.35	0.64

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-8876198	RAB GEFs exchange GTP for GDP on RABs

MSigDB gene sets: 79 (showing top): REACTOME_MEMBRANE_TRAFFICKING, FOSTER_TOLERANT_MACROPHAGE_UP, TAKEDA_TARGETS_OF_NUP98_HOXA9_FUSION_8D_UP, chr22q13, GOMF_GUANYL_NUCLEOTIDE_EXCHANGE_FACTOR_ACTIVITY, SANSOM_APC_MYC_TARGETS, SANSOM_APC_TARGETS_REQUIRE_MYC, GOCC_RECYCLING_ENDOSOME, GOMF_NUCLEOSIDE_TRIPHOSPHATASE_REGULATOR_ACTIVITY, GOMF_ENZYME_REGULATOR_ACTIVITY, DODD_NASOPHARYNGEAL_CARCINOMA_DN, MARTENS_TRETINOIN_RESPONSE_UP, GOBERT_OLIGODENDROCYTE_DIFFERENTIATION_DN, REACTOME_VESICLE_MEDIATED_TRANSPORT, REACTOME_RAB_GEFS_EXCHANGE_GTP_FOR_GDP_ON_RABS

GO Biological Process (0):

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

GO Cellular Component (4): cytosol (GO:0005829), recycling endosome (GO:0055037), cytoplasm (GO:0005737), endosome (GO:0005768)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Rab regulation of trafficking	1

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
cytoplasm	1
endosome	1
intracellular anatomical structure	1
endomembrane system	1
cytoplasmic vesicle	1

Protein interactions and networks

STRING

334 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DENND6B	RUSC2	Q8N2Y8	497
DENND6B	ACAP2	Q15057	462
DENND6B	PPP6R2	O75170	462
DENND6B	TMCO6	Q96DC7	449
DENND6B	OR9I1	Q8NGQ6	448
DENND6B	DENND10	Q8TCE6	446
DENND6B	GGNBP2	Q9H3C7	438
DENND6B	TBC1D22A	Q8WUA7	428
DENND6B	DENND1A	Q8TEH3	411
DENND6B	ATP6V1F	Q16864	408
DENND6B	SYCE3	A1L190	404
DENND6B	DENND1B	Q6P3S1	401
DENND6B	AVL9	Q8NBF6	385
DENND6B	TMEM116	Q8NCL8	381
DENND6B	SCFD1	Q8WVM8	376

IntAct

7 interactions, top by confidence:

A	B	Type	Score
DENND6B	MTA2	psi-mi:“MI:0915”(physical association)	0.400
MYC		psi-mi:“MI:0914”(association)	0.350
DENND6A	EML3	psi-mi:“MI:0914”(association)	0.350
	EBAG9	psi-mi:“MI:0914”(association)	0.350
LCOR	DENND6B	psi-mi:“MI:0915”(physical association)	0.000
DENND6B	UBA1	psi-mi:“MI:0220”(ubiquitination reaction)	0.000

BioGRID (13): DENND6B (Biochemical Activity), DENND6B (Proximity Label-MS), DENND6B (Affinity Capture-RNA), DENND6B (Affinity Capture-RNA), DENND6B (Affinity Capture-MS), DENND6B (Affinity Capture-MS), DENND6B (Proximity Label-MS), DENND6B (Proximity Label-MS), DENND6B (Two-hybrid), DENND6B (Affinity Capture-RNA), PTCD1 (Cross-Linking-MS (XL-MS)), MTA1 (Cross-Linking-MS (XL-MS)), APP (Reconstituted Complex)

ESM2 similar proteins: A4K436, A6NMX2, A6QLH6, A7Z026, B2RYF1, D4ABL6, E9PV86, F1QH17, O00459, O08908, O75864, O94759, O95260, P07903, P07992, P23726, P56223, P97679, Q0VGM9, Q1JQD7, Q1LZ75, Q29RM4, Q2PFX0, Q3KRC5, Q3U2P1, Q5R5M3, Q5RD33, Q5RE34, Q5RJZ1, Q5RKZ7, Q63788, Q6DC64, Q6H1L8, Q6ZN54, Q8BKR5, Q8CIW5, Q8NEG7, Q91XI1, Q96CN4, Q96FI4

Diamond homologs: Q54VA9, Q5F3L4, Q8BH65, Q8IWF6, Q8NEG7, Q9D9V7

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	102
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2722 predictions. Top by Δscore:

Variant	Effect	Δscore
22:50312342:CCAG:C	donor_gain	1.0000
22:50312413:ATGTT:A	acceptor_gain	1.0000
22:50312414:TGTT:T	acceptor_gain	1.0000
22:50312415:GTT:G	acceptor_gain	1.0000
22:50312416:TT:T	acceptor_gain	1.0000
22:50312416:TTCTG:T	acceptor_loss	1.0000
22:50312417:TCT:T	acceptor_loss	1.0000
22:50312418:C:CC	acceptor_gain	1.0000
22:50312421:C:CT	acceptor_gain	1.0000
22:50312426:C:CT	acceptor_gain	1.0000
22:50312427:A:T	acceptor_gain	1.0000
22:50312521:A:AC	donor_gain	1.0000
22:50312522:C:CC	donor_gain	1.0000
22:50312522:CCG:C	donor_gain	1.0000
22:50312529:A:AC	donor_gain	1.0000
22:50312530:C:CC	donor_gain	1.0000
22:50312533:ATAG:A	donor_gain	1.0000
22:50312535:AG:A	donor_gain	1.0000
22:50312539:T:TA	donor_gain	1.0000
22:50312594:A:T	acceptor_gain	1.0000
22:50312622:CCGC:C	acceptor_gain	1.0000
22:50312623:CGCC:C	acceptor_gain	1.0000
22:50313104:GGAGT:G	acceptor_gain	1.0000
22:50313107:GT:G	acceptor_gain	1.0000
22:50313448:T:TA	donor_gain	1.0000
22:50313630:CTCA:C	donor_loss	1.0000
22:50313631:TCACC:T	donor_loss	1.0000
22:50313632:CACC:C	donor_loss	1.0000
22:50313633:A:AC	donor_gain	1.0000
22:50313633:AC:A	donor_gain	1.0000

AlphaMissense

3793 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
22:50326839:G:C	F50L	1.000
22:50326839:G:T	F50L	1.000
22:50326841:A:G	F50L	1.000
22:50314467:G:C	N335K	0.999
22:50314467:G:T	N335K	0.999
22:50316233:A:G	W194R	0.999
22:50316233:A:T	W194R	0.999
22:50316475:A:G	S152P	0.999
22:50317998:G:C	F94L	0.999
22:50317998:G:T	F94L	0.999
22:50318000:A:G	F94L	0.999
22:50326840:A:C	F50C	0.999
22:50314477:C:T	G332E	0.998
22:50314478:C:G	G332R	0.998
22:50314478:C:T	G332R	0.998
22:50316474:G:A	S152F	0.998
22:50317296:C:A	Q150H	0.998
22:50317296:C:G	Q150H	0.998
22:50317338:G:C	F136L	0.998
22:50317338:G:T	F136L	0.998
22:50317340:A:G	F136L	0.998
22:50317351:C:T	G132D	0.998
22:50326825:C:T	G55D	0.998
22:50326840:A:G	F50S	0.998
22:50326841:A:C	F50V	0.998
22:50326841:A:T	F50I	0.998
22:50326868:A:G	W41R	0.998
22:50326868:A:T	W41R	0.998
22:50314471:G:A	T334I	0.997
22:50314660:A:C	Y308D	0.997

dbSNP variants (sampled 300 via entrez): RS1000154582 (22:50311810 C>T), RS1000228583 (22:50310782 C>A), RS1000255006 (22:50311668 T>C), RS1000666891 (22:50311125 C>T), RS1000839053 (22:50320739 A>C), RS1000885248 (22:50316648 T>C), RS1000889111 (22:50309675 T>C), RS1000923418 (22:50326579 G>A), RS1000935765 (22:50320730 T>C), RS1000983662 (22:50315724 C>A,G,T), RS1001070773 (22:50321220 C>T), RS1001124369 (22:50321756 T>C), RS1001136519 (22:50326667 G>C), RS1001211399 (22:50328745 C>T), RS1001404042 (22:50326798 TCGCGCC>T,TCGCGCCCGCGCC)

Disease associations

OMIM: gene MIM:620562 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST002481_12	Acne (severe)	4.000000e-06
GCST008595_234	Cognitive ability, years of educational attainment or schizophrenia (pleiotropy)	4.000000e-08

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004337	intelligence
EFO:0004784	self reported educational attainment

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

20 total (human), top 20 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Smoke	decreases expression, increases abundance, increases expression	2
aristolochic acid I	increases expression	1
aflatoxin B2	increases methylation	1
beta-methylcholine	affects expression	1
ICG 001	increases expression	1
palbociclib	increases expression	1
jinfukang	increases expression, affects cotreatment	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	increases expression	1
Erlotinib Hydrochloride	decreases expression	1
Temozolomide	decreases expression	1
Sunitinib	decreases expression	1
Air Pollutants	increases abundance, increases expression	1
Calcitriol	increases expression	1
Cisplatin	affects cotreatment, increases expression	1
Diethylhexyl Phthalate	decreases expression	1
Doxorubicin	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Valproic Acid	increases methylation	1
Okadaic Acid	decreases expression	1
Acrylamide	decreases expression	1

Clinical trials (associated diseases)

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