DENND11

Summary

DENND11 (DENN domain containing 11, HGNC:29472) is a protein-coding gene on chromosome 7q34, encoding DENN domain-containing protein 11 (A4D1U4). Probable guanine nucleotide exchange factor (GEF).

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

Source: NCBI Gene 57189 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 91 total
• MANE Select transcript: NM_001080392

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29472
Approved symbol	DENND11
Name	DENN domain containing 11
Location	7q34
Locus type	gene with protein product
Status	Approved
Aliases	LCHN
Ensembl gene	ENSG00000257093
Ensembl biotype	protein_coding
OMIM	620122
Entrez	57189

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000482493, ENST00000536163

RefSeq mRNA: 1 — MANE Select: NM_001080392 NM_001080392

CCDS: CCDS47726

Canonical transcript exons

ENST00000536163 — 9 exons

Exon	Start	End
ENSE00002213932	141656728	141662851
ENSE00002228279	141664172	141664240
ENSE00002231131	141666287	141666425
ENSE00002254944	141664904	141665054
ENSE00002273371	141665187	141665318
ENSE00002431900	141674067	141674220
ENSE00002482437	141701886	141702166
ENSE00002515268	141685478	141685636
ENSE00003529586	141686559	141686658

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 92.30.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 19.5509 / max 641.6926, expressed in 1743 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
86582	18.7836	1740
86581	0.7673	400

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
corpus callosum	UBERON:0002336	92.30	gold quality
ventricular zone	UBERON:0003053	91.18	gold quality
putamen	UBERON:0001874	89.20	gold quality
ganglionic eminence	UBERON:0004023	87.90	gold quality
amygdala	UBERON:0001876	87.74	gold quality
temporal lobe	UBERON:0001871	87.68	gold quality
rectum	UBERON:0001052	87.65	gold quality
substantia nigra	UBERON:0002038	87.63	gold quality
Ammon’s horn	UBERON:0001954	87.51	gold quality
caudate nucleus	UBERON:0001873	87.34	gold quality
islet of Langerhans	UBERON:0000006	86.98	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	86.73	gold quality
pancreas	UBERON:0001264	86.36	gold quality
nucleus accumbens	UBERON:0001882	86.34	gold quality
body of pancreas	UBERON:0001150	86.31	gold quality
body of stomach	UBERON:0001161	86.25	gold quality
primary visual cortex	UBERON:0002436	86.08	gold quality
minor salivary gland	UBERON:0001830	85.97	gold quality
prefrontal cortex	UBERON:0000451	85.87	gold quality
lymph node	UBERON:0000029	85.85	gold quality
stomach	UBERON:0000945	85.78	gold quality
saliva-secreting gland	UBERON:0001044	85.61	gold quality
brain	UBERON:0000955	85.60	gold quality
vermiform appendix	UBERON:0001154	85.27	gold quality
cerebral cortex	UBERON:0000956	85.24	gold quality
superior frontal gyrus	UBERON:0002661	85.16	gold quality
frontal cortex	UBERON:0001870	85.15	gold quality
cerebellum	UBERON:0002037	85.15	gold quality
cerebellar cortex	UBERON:0002129	85.14	gold quality
cerebellar hemisphere	UBERON:0002245	85.07	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-GEOD-99795	no	17.00
E-ANND-3	no	0.82

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

190 targeting DENND11, 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-3134	100.00	66.43	777
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-4673	100.00	66.64	1490
HSA-MIR-3162-3P	100.00	65.37	363
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-4645-5P	99.98	65.81	1284
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-7152-3P	99.97	67.47	849
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-4760-3P	99.93	70.50	2385

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	dennd11	ENSDARG00000062381
mus_musculus	Dennd11	ENSMUSG00000037172
rattus_norvegicus	Dennd11	ENSRNOG00000011854

Protein

Protein identifiers

DENN domain-containing protein 11 — A4D1U4 (reviewed: A4D1U4)

Alternative names: Protein LCHN

All UniProt accessions (2): A4D1U4, C9J7X6

UniProt curated annotations — full annotation on UniProt →

Function. Probable guanine nucleotide exchange factor (GEF). May promote the exchange of GDP to GTP, converting inactive GDP-bound small GTPases into their active GTP-bound form. May play a role in neuritogenesis, as well as in neuronal recovery and/or restructuring in the hippocampus following transient cerebral ischemia.

Similarity. Belongs to the DENND11 family.

RefSeq proteins (1): NP_001073861* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR018626	LCHN/Anr2	Family
IPR037516	Tripartite_DENN	Domain
IPR051731	DENND11/AVL9_GEFs	Family

Pfam: PF09804

UniProt features (9 total): domain 3, modified residue 2, initiator methionine 1, chain 1, region of interest 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-A4D1U4-F1	78.87	0.62

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (2): 2, 41

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 133 (showing top): GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, PATIL_LIVER_CANCER, CUI_TCF21_TARGETS_2_DN, CHANDRAN_METASTASIS_UP, SANA_TNF_SIGNALING_UP, GOMF_GUANYL_NUCLEOTIDE_EXCHANGE_FACTOR_ACTIVITY, GARY_CD5_TARGETS_UP, GEORGES_TARGETS_OF_MIR192_AND_MIR215, GOMF_NUCLEOSIDE_TRIPHOSPHATASE_REGULATOR_ACTIVITY, GOMF_ENZYME_REGULATOR_ACTIVITY, CHANDRAN_METASTASIS_TOP50_UP, GINESTIER_BREAST_CANCER_20Q13_AMPLIFICATION_DN, WHITFIELD_CELL_CYCLE_G1_S, WANG_RESPONSE_TO_GSK3_INHIBITOR_SB216763_DN, TORCHIA_TARGETS_OF_EWSR1_FLI1_FUSION_DN

GO Biological Process (0):

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

GO Cellular Component (1): cytoplasm (GO:0005737)

GO top-level categories

Rollup of top GO terms by namespace:

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

Protein interactions and networks

STRING

262 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DENND11	AVL9	Q8NBF6	938
DENND11	DENND10	Q8TCE6	937
DENND11	DENND6A	Q8IWF6	933
DENND11	VAMP1	P23763	509
DENND11	RIC1	Q4ADV7	503
DENND11	SCAND1	P57086	478
DENND11	YKT6	O15498	476
DENND11	RAB33B	Q9H082	469
DENND11	VAMP4	O75379	463
DENND11	RAB30	Q15771	457
DENND11	ALLC	Q8N6M5	454
DENND11	NUDT22	Q9BRQ3	450
DENND11	VAMP5	O95183	444
DENND11	DNM1L	O00429	444
DENND11	RNF103	O00237	423

IntAct

30 interactions, top by confidence:

A	B	Type	Score
EFNB3	DENND11	psi-mi:“MI:0914”(association)	0.640
KLK5	DENND11	psi-mi:“MI:0914”(association)	0.640
DKKL1	DENND11	psi-mi:“MI:0914”(association)	0.640
TGOLN2	DENND11	psi-mi:“MI:0914”(association)	0.530
FAM174A	BLTP3B	psi-mi:“MI:0914”(association)	0.530
DKKL1	VWA8	psi-mi:“MI:0914”(association)	0.350
TGOLN2	DENND11	psi-mi:“MI:0914”(association)	0.350
KLK11	DENND11	psi-mi:“MI:0914”(association)	0.350
	DENND11	psi-mi:“MI:0914”(association)	0.350
M	DENND11	psi-mi:“MI:0914”(association)	0.350
HCST	TMEM120B	psi-mi:“MI:0914”(association)	0.350
CSTL1	DENND11	psi-mi:“MI:0914”(association)	0.350
KLK15	DENND11	psi-mi:“MI:0914”(association)	0.350
DNAJA2	DENND11	psi-mi:“MI:0914”(association)	0.350
LAGE3	PPIAL4C	psi-mi:“MI:0914”(association)	0.350
GZMH	DENND11	psi-mi:“MI:0914”(association)	0.350
HS2ST1	DENND11	psi-mi:“MI:0914”(association)	0.350
CD226	TMED7-TICAM2	psi-mi:“MI:0914”(association)	0.350
UPK2	IFT56	psi-mi:“MI:0914”(association)	0.350
VASN	DENND11	psi-mi:“MI:0914”(association)	0.350
SLC31A1	DENND11	psi-mi:“MI:0914”(association)	0.350

BioGRID (32): KIAA1147 (Two-hybrid), KIAA1147 (Affinity Capture-MS), KIAA1147 (Affinity Capture-MS), KIAA1147 (Affinity Capture-MS), KIAA1147 (Affinity Capture-MS), KIAA1147 (Affinity Capture-MS), KIAA1147 (Affinity Capture-MS), KIAA1147 (Affinity Capture-MS), KIAA1147 (Affinity Capture-MS), KIAA1147 (Affinity Capture-RNA), KIAA1147 (Affinity Capture-MS), KIAA1147 (Affinity Capture-MS), KIAA1147 (Affinity Capture-MS), KIAA1147 (Affinity Capture-MS), KIAA1147 (Affinity Capture-MS)

ESM2 similar proteins: A1L3F5, A2RT67, A2RUS2, A4D1U4, B1H2P5, D3ZXK7, D4ACE5, E7F240, F1MDL2, F1QEB7, F1R7R1, H2LP95, O75161, O94967, P48553, P59240, Q059U7, Q0PGW2, Q28DH9, Q3TLI0, Q3U0J8, Q3UHG7, Q4R5A4, Q5FVM6, Q5JPI3, Q5M7Q1, Q5M9F0, Q5R989, Q5RC14, Q5XPI3, Q5XPI4, Q5ZJK1, Q6DDX8, Q6NXD8, Q6VNB8, Q7TSG1, Q80TA6, Q8CGF6, Q8IY22, Q8IZQ1

Diamond homologs: A4D1U4, Q0PGW2, Q1LX49, Q3UHG7, Q4FZX0

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	79
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1708 predictions. Top by Δscore:

Variant	Effect	Δscore
7:141664120:AGTG:A	donor_gain	1.0000
7:141664170:A:AC	donor_gain	1.0000
7:141664171:C:CA	donor_gain	1.0000
7:141664171:CAG:C	donor_gain	1.0000
7:141664171:CAGCA:C	donor_gain	1.0000
7:141664887:C:A	donor_gain	1.0000
7:141664893:G:C	donor_gain	1.0000
7:141664898:CACTA:C	donor_loss	1.0000
7:141664899:ACTAC:A	donor_loss	1.0000
7:141664900:CTA:C	donor_loss	1.0000
7:141664901:TA:T	donor_loss	1.0000
7:141664902:ACC:A	donor_loss	1.0000
7:141664903:CC:C	donor_loss	1.0000
7:141664903:CCT:C	donor_gain	1.0000
7:141664929:T:TA	donor_gain	1.0000
7:141664932:C:CA	donor_gain	1.0000
7:141665050:GGTGC:G	acceptor_gain	1.0000
7:141665052:TGC:T	acceptor_gain	1.0000
7:141665053:GC:G	acceptor_gain	1.0000
7:141665054:CC:C	acceptor_gain	1.0000
7:141665055:C:CC	acceptor_gain	1.0000
7:141665181:A:AC	donor_gain	1.0000
7:141665182:C:CC	donor_gain	1.0000
7:141665183:TCA:T	donor_loss	1.0000
7:141665184:CA:C	donor_loss	1.0000
7:141665185:A:AC	donor_gain	1.0000
7:141665185:ACAGG:A	donor_gain	1.0000
7:141665186:C:CC	donor_gain	1.0000
7:141665186:CAGG:C	donor_gain	1.0000
7:141665186:CAGGC:C	donor_gain	1.0000

AlphaMissense

2975 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:141662714:A:G	L437P	1.000
7:141662750:A:G	L425P	1.000
7:141665009:A:T	V333D	1.000
7:141665053:G:C	C318W	1.000
7:141665187:A:G	C318R	1.000
7:141665189:G:T	A317D	1.000
7:141666294:G:C	C271W	1.000
7:141666295:C:T	C271Y	1.000
7:141666296:A:G	C271R	1.000
7:141666359:A:G	W250R	1.000
7:141666359:A:T	W250R	1.000
7:141685493:A:G	L171S	1.000
7:141685535:A:G	L157P	1.000
7:141685541:C:T	G155D	1.000
7:141685542:C:G	G155R	1.000
7:141685548:A:G	S153P	1.000
7:141685556:C:G	R150P	1.000
7:141685566:G:T	R147S	1.000
7:141685604:G:T	A134D	1.000
7:141685605:C:G	A134P	1.000
7:141685607:A:G	L133P	1.000
7:141685610:C:T	G132D	1.000
7:141685611:C:G	G132R	1.000
7:141686565:T:A	D121V	1.000
7:141686566:C:G	D121H	1.000
7:141686586:C:T	G114E	1.000
7:141686588:A:C	S113R	1.000
7:141686588:A:T	S113R	1.000
7:141686590:T:G	S113R	1.000
7:141686603:G:C	F108L	1.000

dbSNP variants (sampled 300 via entrez): RS1000002656 (7:141666728 A>G), RS1000007889 (7:141671326 A>G), RS1000038207 (7:141679091 G>A), RS1000231891 (7:141672244 C>G), RS1000409725 (7:141691537 A>C), RS1000491190 (7:141692895 A>T), RS1000546696 (7:141662604 T>C), RS1000571008 (7:141673758 C>G), RS1000616689 (7:141661185 G>A), RS1000748198 (7:141699633 ATAAG>A), RS1000789057 (7:141699032 T>C), RS1000982752 (7:141674107 C>T), RS1001201860 (7:141687236 T>G), RS1001256344 (7:141679685 C>G), RS1001288325 (7:141667411 A>G)

Disease associations

OMIM: gene MIM:620122 | 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
GCST008019_6	Bitter taste perception (phenylthiocarbamide) in obesity with metabolic syndrome	2.000000e-06
GCST012353_1	Serum metabolite concentrations in chronic kidney disease	9.000000e-12

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

31 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases expression, affects expression, affects cotreatment	8
trichostatin A	affects cotreatment, decreases expression	3
Acetaminophen	decreases expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Tobacco Smoke Pollution	affects expression, increases expression	2
Cyclosporine	decreases expression	2
aristolochic acid I	decreases expression	1
triphenyl phosphate	affects expression	1
2-methyl-4-isothiazolin-3-one	decreases expression	1
butyraldehyde	decreases expression	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, decreases expression	1
di-n-butylphosphoric acid	affects expression	1
2-palmitoylglycerol	increases expression	1
entinostat	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
Resveratrol	affects cotreatment, increases expression	1
Temozolomide	decreases expression	1
Vorinostat	decreases expression	1
Air Pollutants	decreases expression	1
Coumestrol	decreases expression, affects cotreatment	1
Diuron	decreases expression	1
Doxorubicin	decreases expression	1
Hydrogen Peroxide	increases expression	1
Plant Extracts	increases expression, affects cotreatment	1
Tretinoin	decreases expression	1
Aflatoxin B1	decreases methylation	1
Cadmium Chloride	decreases expression	1
Okadaic Acid	decreases expression	1

Clinical trials (associated diseases)

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