DENND10

Summary

DENND10 (DENN domain containing 10, HGNC:31793) is a protein-coding gene on chromosome 10q26.11, encoding DENN domain-containing protein 10 (Q8TCE6). Guanine nucleotide exchange factor (GEF) regulating homeostasis of late endocytic pathway, including endosomal positioning, maturation and secretion, possibly through activating Rab proteins such as RAB27A and RAB27B.

Enables guanyl-nucleotide exchange factor activity and small GTPase binding activity. Involved in endosome transport via multivesicular body sorting pathway; protein transport; and regulation of early endosome to late endosome transport. Located in late endosome.

Source: NCBI Gene 404636 — RefSeq curated summary.

At a glance

• GWAS associations: 6
• Clinical variants (ClinVar): 45 total
• MANE Select transcript: NM_207009

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:31793
Approved symbol	DENND10
Name	DENN domain containing 10
Location	10q26.11
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000119979
Ensembl biotype	protein_coding
Entrez	404636

Gene structure

Transcript identifiers

Ensembl transcripts: 17 — 9 protein_coding, 8 protein_coding_CDS_not_defined

ENST00000361432, ENST00000448258, ENST00000462327, ENST00000472379, ENST00000487888, ENST00000489936, ENST00000489988, ENST00000493766, ENST00000497903, ENST00000498549, ENST00000648560, ENST00000857542, ENST00000857543, ENST00000857544, ENST00000931616, ENST00000931617, ENST00000963812

RefSeq mRNA: 4 — MANE Select: NM_207009 NM_001303111, NM_001303112, NM_001303113, NM_207009

CCDS: CCDS7609

Canonical transcript exons

ENST00000361432 — 9 exons

Exon	Start	End
ENSE00001890185	119136471	119137984
ENSE00003491751	119120341	119120452
ENSE00003512030	119111849	119111928
ENSE00003515910	119107968	119108164
ENSE00003526169	119123469	119123569
ENSE00003637260	119129515	119129622
ENSE00003640521	119132515	119132609
ENSE00003653936	119117519	119117667
ENSE00003682624	119104113	119104197

Expression profiles

Bgee: expression breadth ubiquitous, 161 present calls, max score 96.86.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 11.6741 / max 61.8116, expressed in 1797 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
107306	11.6741	1797

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
monocyte	CL:0000576	96.86	gold quality
leukocyte	CL:0000738	96.56	gold quality
stromal cell of endometrium	CL:0002255	95.17	gold quality
calcaneal tendon	UBERON:0003701	92.71	gold quality
granulocyte	CL:0000094	92.03	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	91.13	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	90.93	gold quality
islet of Langerhans	UBERON:0000006	90.65	gold quality
ventricular zone	UBERON:0003053	90.59	gold quality
Brodmann (1909) area 9	UBERON:0013540	90.53	gold quality
anterior cingulate cortex	UBERON:0009835	90.42	gold quality
cortical plate	UBERON:0005343	90.23	gold quality
ganglionic eminence	UBERON:0004023	90.04	gold quality
lower esophagus mucosa	UBERON:0035834	90.01	gold quality
right frontal lobe	UBERON:0002810	89.69	gold quality
gall bladder	UBERON:0002110	89.60	gold quality
prefrontal cortex	UBERON:0000451	89.48	gold quality
smooth muscle tissue	UBERON:0001135	89.20	gold quality
ectocervix	UBERON:0012249	89.19	gold quality
right lobe of liver	UBERON:0001114	88.79	gold quality
adrenal tissue	UBERON:0018303	88.73	gold quality
rectum	UBERON:0001052	88.63	gold quality
left adrenal gland	UBERON:0001234	88.53	gold quality
vermiform appendix	UBERON:0001154	88.52	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	88.50	gold quality
right ovary	UBERON:0002118	88.45	gold quality
muscle of leg	UBERON:0001383	88.41	gold quality
left ovary	UBERON:0002119	88.39	gold quality
right adrenal gland cortex	UBERON:0035827	88.27	gold quality
gastrocnemius	UBERON:0001388	88.24	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-HCAD-6	yes	42.78
E-MTAB-10042	yes	14.30
E-ANND-3	yes	7.49

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

82 targeting DENND10, 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-3613-3P	100.00	76.36	7965
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-4481	100.00	66.42	1669
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-4745-5P	99.98	65.95	1028
HSA-MIR-507	99.97	70.11	1915
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-557	99.96	70.01	1640
HSA-MIR-23C	99.95	73.92	3192
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-450B-5P	99.92	71.48	3175
HSA-MIR-145-5P	99.92	71.13	1836
HSA-MIR-5195-3P	99.92	70.92	1877
HSA-MIR-1297	99.91	73.41	3162
HSA-MIR-106A-5P	99.90	73.94	2683
HSA-MIR-17-5P	99.89	73.83	2665
HSA-MIR-380-3P	99.89	70.18	1978
HSA-MIR-106B-5P	99.88	74.72	2795
HSA-MIR-20A-5P	99.88	74.76	2769
HSA-MIR-20B-5P	99.88	74.01	2621
HSA-MIR-519D-3P	99.88	73.97	2607
HSA-MIR-93-5P	99.88	73.98	2606
HSA-MIR-526B-3P	99.88	74.06	2587

Literature-anchored findings (GeneRIF, showing 1)

• FAM45A defines a novel regulatory step in the homeostasis of late endocytic pathway, including endosomal positioning, maturation and secretion, possibly through activating Rab proteins such as Rab27a/b. (PMID:30771381)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Dennd10	ENSMUSG00000024993
rattus_norvegicus	Dennd10	ENSRNOG00000010230

Protein

Protein identifiers

DENN domain-containing protein 10 — Q8TCE6 (reviewed: Q8TCE6)

Alternative names: Protein FAM45A

All UniProt accessions (3): Q8TCE6, A0A3B3IRE4, A0A3B3IUD3

UniProt curated annotations — full annotation on UniProt →

Function. Guanine nucleotide exchange factor (GEF) regulating homeostasis of late endocytic pathway, including endosomal positioning, maturation and secretion, possibly through activating Rab proteins such as RAB27A and RAB27B. Promotes the exchange of GDP to GTP, converting inactive GDP-bound RAB27A and RAB27B into their active GTP-bound form.

Subunit / interactions. Interacts with the coiled-coil heterodimer of CCDC22 and CCDC93; the interaction is direct. Interacts with RAB27A and RAB27B (GDP-bound forms preferentially).

Subcellular location. Late endosome.

Similarity. Belongs to the DENND10 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q8TCE6-1	1	yes
Q8TCE6-2	2

RefSeq proteins (4): NP_001290040, NP_001290041, NP_001290042, NP_996892* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR037516	Tripartite_DENN	Domain
IPR042431	FAM45	Family

Pfam: PF08616

UniProt features (9 total): domain 3, mutagenesis site 3, chain 1, splice variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
8P0V	ELECTRON MICROSCOPY	6.5

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8TCE6-F1	90.99	0.78

Functional residue map

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

Mutagenesis-validated functional residues (3):

Position	Phenotype
27	impairs interaction with ccdc93.
123	impairs interaction with ccdc93.
127	impairs interaction with ccdc93.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 125 (showing top): TGCACTT_MIR519C_MIR519B_MIR519A, GOBP_VESICLE_MEDIATED_TRANSPORT, GOMF_GTPASE_BINDING, GOBP_REGULATION_OF_VESICLE_MEDIATED_TRANSPORT, GOBP_REGULATION_OF_CELLULAR_LOCALIZATION, GOBP_REGULATION_OF_EARLY_ENDOSOME_TO_LATE_ENDOSOME_TRANSPORT, GOBP_MULTIVESICULAR_BODY_SORTING_PATHWAY, GOBP_VESICLE_MEDIATED_TRANSPORT_BETWEEN_ENDOSOMAL_COMPARTMENTS, GOBP_ENDOCYTIC_RECYCLING, GOBP_LOCALIZATION_WITHIN_MEMBRANE, GOBP_REGULATION_OF_TRANSPORT, GOBP_REGULATION_OF_INTRACELLULAR_TRANSPORT, GOMF_GUANYL_NUCLEOTIDE_EXCHANGE_FACTOR_ACTIVITY, GOCC_MEMBRANE_PROTEIN_COMPLEX, GOMF_NUCLEOSIDE_TRIPHOSPHATASE_REGULATOR_ACTIVITY

GO Biological Process (3): protein transport (GO:0015031), endosome transport via multivesicular body sorting pathway (GO:0032509), regulation of early endosome to late endosome transport (GO:2000641)

GO Molecular Function (3): guanyl-nucleotide exchange factor activity (GO:0005085), small GTPase binding (GO:0031267), protein binding (GO:0005515)

GO Cellular Component (2): late endosome (GO:0005770), endosome (GO:0005768)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
transport	1
intracellular protein localization	1
establishment of protein localization	1
endosomal transport	1
multivesicular body sorting pathway	1
regulation of intracellular transport	1
early endosome to late endosome transport	1
regulation of vesicle-mediated transport	1
GTP binding	1
GDP binding	1
GTPase regulator activity	1
GTPase binding	1
binding	1
endosome	1
endomembrane system	1
cytoplasmic vesicle	1

Protein interactions and networks

STRING

2021 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DENND10	AVL9	Q8NBF6	940
DENND10	DENND11	A4D1U4	937
DENND10	DENND6A	Q8IWF6	935
DENND10	VPS29	Q9UBQ0	681
DENND10	VPS26C	O14972	673
DENND10	FUOM	A2VDF0	643
DENND10	CCDC22	O60826	637
DENND10	VPS35L	Q7Z3J2	626
DENND10	COMMD1	Q8N668	537
DENND10	RAB27B	O00194	528
DENND10	RIC1	Q4ADV7	509
DENND10	DNM1L	O00429	488
DENND10	RAB30	Q15771	459
DENND10	CCDC102A	Q96A19	457
DENND10	RAB33B	Q9H082	457

IntAct

63 interactions, top by confidence:

A	B	Type	Score
CCDC22	CCDC93	psi-mi:“MI:0915”(physical association)	0.960
CCDC22	CCDC93	psi-mi:“MI:0914”(association)	0.960
COMMD2	CCDC22	psi-mi:“MI:0914”(association)	0.930
ODAD1	HGS	psi-mi:“MI:0914”(association)	0.850
CCDC22	VPS26C	psi-mi:“MI:0914”(association)	0.790
VPS26C	CCDC22	psi-mi:“MI:0914”(association)	0.790
DENND10	CCDC93	psi-mi:“MI:0915”(physical association)	0.770
DENND10	CCDC93	psi-mi:“MI:0914”(association)	0.770
VPS29	VPS26C	psi-mi:“MI:0914”(association)	0.760
COMMD1	VPS26C	psi-mi:“MI:0914”(association)	0.730
VPS35L	VPS26C	psi-mi:“MI:0914”(association)	0.730
COMMD4	VPS26C	psi-mi:“MI:0914”(association)	0.730
VPS29	VPS26B	psi-mi:“MI:0914”(association)	0.730
COMMD3	VPS26C	psi-mi:“MI:0914”(association)	0.640
COMMD6	VPS26C	psi-mi:“MI:0914”(association)	0.640
DENND10	VPS26C	psi-mi:“MI:0914”(association)	0.640
CCDC93	VPS26C	psi-mi:“MI:0914”(association)	0.640

BioGRID (65): FAM45A (Affinity Capture-MS), FAM45A (Affinity Capture-MS), FAM45A (Affinity Capture-MS), FAM45A (Affinity Capture-MS), FAM45A (Affinity Capture-MS), FAM45A (Affinity Capture-MS), FAM45A (Affinity Capture-MS), FAM45A (Affinity Capture-MS), FAM45A (Affinity Capture-MS), FAM45A (Affinity Capture-MS), FAM45A (Affinity Capture-MS), FAM45B (Affinity Capture-MS), FAM45A (Affinity Capture-MS), FAM45A (Affinity Capture-MS), FAM45A (Affinity Capture-MS)

ESM2 similar proteins: A6H8H2, A8E7G4, A8XSV3, B2RY04, B4IB36, B4QL99, E9PXF8, P29742, P34574, P50748, P53675, Q08BC6, Q0II26, Q14185, Q19317, Q29NZ8, Q55FE3, Q5EA76, Q5F3R2, Q5U4T8, Q5VZ89, Q5XH29, Q66HC3, Q66KD9, Q6DF78, Q6DFW0, Q6IQX0, Q6NRQ2, Q6NSW5, Q6NTN5, Q6PA97, Q7YTB0, Q7Z401, Q80Y84, Q811U4, Q86WG5, Q8BUR4, Q8C3Y4, Q8IWA4, Q8LPU4

Diamond homologs: A8E7G4, Q55FE3, Q6NSW5, Q8TCE6, Q9D8N2

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 38 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Neddylation	11	18.6×	7e-10

GO biological processes:

GO term	Partners	Fold	FDR
endocytic recycling	6	47.2×	5e-07

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	43
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1786 predictions. Top by Δscore:

Variant	Effect	Δscore
10:119104203:G:GT	donor_gain	1.0000
10:119104878:G:GT	donor_gain	1.0000
10:119111896:G:GT	donor_gain	1.0000
10:119111923:GT:G	donor_gain	1.0000
10:119117513:TTACA:T	acceptor_loss	1.0000
10:119117514:TACA:T	acceptor_loss	1.0000
10:119117515:ACAG:A	acceptor_loss	1.0000
10:119117516:CAGAA:C	acceptor_loss	1.0000
10:119117517:A:AG	acceptor_gain	1.0000
10:119117517:A:C	acceptor_loss	1.0000
10:119117517:AGAAT:A	acceptor_gain	1.0000
10:119117518:G:GA	acceptor_gain	1.0000
10:119117518:G:T	acceptor_loss	1.0000
10:119117518:GA:G	acceptor_gain	1.0000
10:119117518:GAAT:G	acceptor_gain	1.0000
10:119117518:GAATG:G	acceptor_gain	1.0000
10:119117665:AAGGT:A	donor_loss	1.0000
10:119117668:GTA:G	donor_loss	1.0000
10:119120339:A:AG	acceptor_gain	1.0000
10:119120340:G:GG	acceptor_gain	1.0000
10:119120340:GAC:G	acceptor_gain	1.0000
10:119104202:GGAC:G	donor_gain	0.9900
10:119104222:G:GT	donor_gain	0.9900
10:119104307:G:GT	donor_gain	0.9900
10:119105018:GGAAT:G	donor_gain	0.9900
10:119105019:GAATG:G	donor_gain	0.9900
10:119105020:A:T	donor_gain	0.9900
10:119111843:GAACA:G	acceptor_loss	0.9900
10:119111844:AACAG:A	acceptor_loss	0.9900
10:119111846:CAGGT:C	acceptor_loss	0.9900

AlphaMissense

2350 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:119104192:T:C	L17P	0.996
10:119108000:T:A	W30R	0.996
10:119108000:T:C	W30R	0.996
10:119108114:T:A	W68R	0.994
10:119108114:T:C	W68R	0.994
10:119120386:C:A	A176E	0.993
10:119129524:C:A	A235D	0.992
10:119107994:T:A	W28R	0.991
10:119107994:T:C	W28R	0.991
10:119129578:T:A	V253E	0.990
10:119136616:T:C	L348P	0.990
10:119129572:T:A	V251E	0.988
10:119107969:A:C	E19D	0.985
10:119107969:A:T	E19D	0.985
10:119117572:T:A	V129D	0.985
10:119104188:G:A	G16R	0.984
10:119104188:G:C	G16R	0.984
10:119120385:G:C	A176P	0.984
10:119123503:T:A	W210R	0.984
10:119123503:T:C	W210R	0.984
10:119108006:T:G	Y32D	0.983
10:119108120:T:G	Y70D	0.983
10:119117523:T:G	Y113D	0.983
10:119117614:T:C	F143S	0.983
10:119120395:T:C	L179P	0.983
10:119129523:G:C	A235P	0.983
10:119120389:T:C	L177P	0.982
10:119123474:T:C	L200P	0.980
10:119123474:T:G	L200R	0.980
10:119129527:G:A	G236E	0.980

dbSNP variants (sampled 300 via entrez): RS1000008696 (10:119134212 C>A,T), RS1000123878 (10:119124978 G>A,C,T), RS1000201772 (10:119128871 T>C), RS1000262331 (10:119128654 G>GT), RS1000354896 (10:119103132 G>A), RS1000445118 (10:119109171 G>A,T), RS1000481764 (10:119121804 A>G), RS1000548083 (10:119114928 C>G,T), RS1000559176 (10:119134940 G>A), RS1000722753 (10:119123327 T>C,G), RS1000778177 (10:119107861 T>C,G), RS1000843138 (10:119117524 A>T), RS1000918770 (10:119134561 C>T), RS1001005926 (10:119110884 G>A), RS1001025816 (10:119121511 G>C)

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
GCST004860_11	Alcoholic chronic pancreatitis	6.000000e-06
GCST004860_130	Alcoholic chronic pancreatitis	7.000000e-06
GCST004860_135	Alcoholic chronic pancreatitis	5.000000e-06
GCST004860_156	Alcoholic chronic pancreatitis	2.000000e-07
GCST004860_17	Alcoholic chronic pancreatitis	6.000000e-06
GCST004860_41	Alcoholic chronic pancreatitis	7.000000e-06

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

24 total (human), top 24 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	increases expression, affects cotreatment	2
trichostatin A	affects expression	1
K 7174	increases expression	1
abrine	decreases expression	1
bisphenol S	affects cotreatment, increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Sunitinib	increases expression	1
Air Pollutants, Occupational	decreases expression	1
Benzo(a)pyrene	decreases expression	1
Dexamethasone	affects cotreatment, increases expression	1
Doxorubicin	decreases expression	1
Indomethacin	affects cotreatment, increases expression	1
Ivermectin	decreases expression	1
Nickel	decreases expression	1
Oxygen	decreases expression	1
Plant Extracts	increases expression, affects cotreatment	1
Smoke	decreases expression	1
Thiram	decreases expression	1
Valproic Acid	decreases expression	1
1-Methyl-3-isobutylxanthine	increases expression, affects cotreatment	1
Aflatoxin B1	decreases expression	1
Antirheumatic Agents	increases expression	1
Okadaic Acid	decreases expression	1
Copper Sulfate	decreases expression	1

Clinical trials (associated diseases)

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