DENND1B

Summary

DENND1B (DENN domain containing 1B, HGNC:28404) is a protein-coding gene on chromosome 1q31.3, encoding DENN domain-containing protein 1B (Q6P3S1). Guanine nucleotide exchange factor (GEF) for RAB35 that acts as a regulator of T-cell receptor (TCR) internalization in TH2 cells.

Clathrin (see MIM 118955)-mediated endocytosis is a major mechanism for internalization of proteins and lipids. Members of the connecdenn family, such as DENND1B, function as guanine nucleotide exchange factors (GEFs) for the early endosomal small GTPase RAB35 (MIM 604199) and bind to clathrin and clathrin adaptor protein-2 (AP2; see MIM 601024). Thus, connecdenns link RAB35 activation with the clathrin machinery (Marat and McPherson, 2010 [PubMed 20154091]).

Source: NCBI Gene 163486 — RefSeq curated summary.

At a glance

• GWAS associations: 27
• Clinical variants (ClinVar): 73 total
• Phenotypes (HPO): 1
• MANE Select transcript: NM_001195215

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28404
Approved symbol	DENND1B
Name	DENN domain containing 1B
Location	1q31.3
Locus type	gene with protein product
Status	Approved
Aliases	MGC27044, FLJ20054
Ensembl gene	ENSG00000213047
Ensembl biotype	protein_coding
OMIM	613292
Entrez	163486

Gene structure

Transcript identifiers

Ensembl transcripts: 18 — 11 protein_coding, 4 retained_intron, 2 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000235453, ENST00000294737, ENST00000294738, ENST00000367396, ENST00000422998, ENST00000463124, ENST00000468589, ENST00000477581, ENST00000495550, ENST00000496935, ENST00000620048, ENST00000887105, ENST00000887106, ENST00000887107, ENST00000887108, ENST00000887109, ENST00000887110, ENST00000887111

RefSeq mRNA: 4 — MANE Select: NM_001195215 NM_001195215, NM_001195216, NM_001300858, NM_144977

CCDS: CCDS41452, CCDS72996, CCDS72997

Canonical transcript exons

ENST00000620048 — 23 exons

Exon	Start	End
ENSE00000999425	197553022	197553112
ENSE00001300703	197583152	197583253
ENSE00001444420	197647055	197647114
ENSE00001601342	197607073	197607174
ENSE00001665696	197595208	197595333
ENSE00001691273	197504748	197510972
ENSE00003463695	197540959	197541015
ENSE00003483417	197674120	197674169
ENSE00003542033	197546733	197546773
ENSE00003547066	197511728	197511944
ENSE00003559665	197645690	197645743
ENSE00003566447	197617659	197617759
ENSE00003567558	197611931	197611976
ENSE00003570802	197642711	197642821
ENSE00003583644	197545922	197545990
ENSE00003586442	197652235	197652315
ENSE00003604571	197772868	197772932
ENSE00003612228	197715031	197715074
ENSE00003643884	197512871	197512953
ENSE00003652817	197539964	197540071
ENSE00003657772	197672037	197672156
ENSE00003669174	197658300	197658369
ENSE00003733641	197775139	197775480

Expression profiles

Bgee: expression breadth ubiquitous, 281 present calls, max score 95.23.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 10.2697 / max 279.5946, expressed in 1634 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
16509	4.3697	1287
16507	3.8856	1130
16503	0.8063	444
16508	0.3241	178
16506	0.3006	124
16504	0.2989	137
16510	0.2086	96
16505	0.0759	15

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
jejunal mucosa	UBERON:0000399	95.23	gold quality
heart right ventricle	UBERON:0002080	91.10	gold quality
jejunum	UBERON:0002115	90.03	gold quality
colonic mucosa	UBERON:0000317	89.79	gold quality
mucosa of paranasal sinus	UBERON:0005030	89.74	gold quality
bone marrow cell	CL:0002092	89.66	gold quality
mucosa of sigmoid colon	UBERON:0004993	89.64	gold quality
renal medulla	UBERON:0000362	89.58	gold quality
buccal mucosa cell	CL:0002336	89.23	gold quality
oral cavity	UBERON:0000167	89.00	gold quality
trabecular bone tissue	UBERON:0002483	88.94	gold quality
ileal mucosa	UBERON:0000331	88.37	gold quality
biceps brachii	UBERON:0001507	87.82	gold quality
bone marrow	UBERON:0002371	87.43	gold quality
bronchial epithelial cell	CL:0002328	86.95	gold quality
oviduct epithelium	UBERON:0004804	86.86	gold quality
calcaneal tendon	UBERON:0003701	86.84	gold quality
palpebral conjunctiva	UBERON:0001812	86.64	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	86.56	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	86.37	gold quality
cervix squamous epithelium	UBERON:0006922	85.88	gold quality
corpus epididymis	UBERON:0004359	85.85	gold quality
penis	UBERON:0000989	85.79	gold quality
dorsal root ganglion	UBERON:0000044	85.73	gold quality
tonsil	UBERON:0002372	85.65	gold quality
parotid gland	UBERON:0001831	85.60	gold quality
epithelium of bronchus	UBERON:0002031	85.37	gold quality
amniotic fluid	UBERON:0000173	85.29	gold quality
cervix epithelium	UBERON:0004801	85.15	gold quality
lower lobe of lung	UBERON:0008949	85.15	gold quality

Single-cell (SCXA)

Detected in 6 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-MTAB-6075	yes	920.78
E-MTAB-9067	yes	12.08
E-CURD-112	yes	10.82
E-ANND-3	yes	5.87
E-GEOD-99795	no	355.64
E-MTAB-7381	no	333.03

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

89 targeting DENND1B, 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-340-5P	100.00	72.50	4437
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-568	99.98	69.86	2084
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-4760-3P	99.93	70.50	2385
HSA-MIR-1-3P	99.93	72.35	1914
HSA-MIR-206	99.93	72.50	1893
HSA-MIR-613	99.91	71.50	1710
HSA-MIR-374A-5P	99.90	71.34	2923
HSA-MIR-374B-5P	99.90	69.98	2734
HSA-MIR-369-3P	99.85	70.52	2264
HSA-MIR-944	99.82	70.85	3042
HSA-MIR-3133	99.81	70.92	3506
HSA-MIR-374C-5P	99.80	72.06	2910
HSA-MIR-655-3P	99.80	72.19	2909
HSA-MIR-323A-3P	99.79	70.30	1739
HSA-MIR-577	99.78	69.13	2479
HSA-MIR-548AG	99.77	69.25	1492
HSA-MIR-3617-5P	99.75	69.41	1968

Literature-anchored findings (GeneRIF, showing 8)

• We have identified a locus containing DENND1B on chromosome 1q31.3 that is associated with susceptibility to asthma. (PMID:20032318)
• analysis of DENND1B-S complexed with its substrate Rab35 (PMID:22065758)
• Data indicate that folliculin-CT is structurally similar to the DENN domain of DENND1B. (PMID:22977732)
• Increased fraction of exhaled nitric oxide in healthy newborns seems strongly influenced by genetics including father’s atopy and child’s variants in the DENND1B locus at chromosome 1q31.3. (PMID:24347560)
• The guanine nucleotide exchange factor activity of connecdenn 1 and 2 are autoinhibited, and this is regulated by Akt activation downstream of insulin stimulation. (PMID:26055712)
• Study reveals a previously unrecognized mechanism by which DENND1B regulates surface TCR dynamics to fine-tune TH2 cell signaling and effector functions. Dennd1b-/- TH2 cells exhibit delayed TCR downmodulation following TCR activation that is associated with enhanced TCR signaling and greater transcriptional activation and secretion of TH2-associated cytokines. (PMID:26774822)
• polymorphisms in the DENND1B are significantly associated with development of asthma and atopy and these polymorphisms can influence DENND1B expression and consequently, asthma. (PMID:28668455)
• Variation at DENND1B and Asthma on the Island of Tristan da Cunha. (PMID:31608842)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	dennd1b	ENSDARG00000101868
mus_musculus	Dennd1b	ENSMUSG00000056268
rattus_norvegicus	Dennd1b	ENSRNOG00000011063
drosophila_melanogaster	CG18659	FBGN0027561
caenorhabditis_elegans		WBGENE00004375

Paralogs (2): DENND1A (ENSG00000119522), DENND1C (ENSG00000205744)

Protein

Protein identifiers

DENN domain-containing protein 1B — Q6P3S1 (reviewed: Q6P3S1)

Alternative names: Connecdenn 2, Protein FAM31B

All UniProt accessions (3): B3KR95, B7ZBL5, Q6P3S1

UniProt curated annotations — full annotation on UniProt →

Function. Guanine nucleotide exchange factor (GEF) for RAB35 that acts as a regulator of T-cell receptor (TCR) internalization in TH2 cells. Acts by promoting the exchange of GDP to GTP, converting inactive GDP-bound RAB35 into its active GTP-bound form. Plays a role in clathrin-mediated endocytosis. Controls cytokine production in TH2 lymphocytes by controlling the rate of TCR internalization and routing to endosomes: acts by mediating clathrin-mediated endocytosis of TCR via its interaction with the adapter protein complex 2 (AP-2) and GEF activity. Dysregulation leads to impaired TCR down-modulation and recycling, affecting cytokine production in TH2 cells.

Subunit / interactions. Interacts with RAB35. Interacts with clathrin heavy chain/CLTC. Interacts with components of the adapter protein complex 2 (AP-2) AP2A2 and AP2B1. Interacts with CD3E.

Subcellular location. Cytoplasm. Cytosol. Cytoplasmic vesicle. Clathrin-coated vesicle.

Tissue specificity. Highly expressed in dendritic and natural killer cells and at lower levels in other myeloid lineage cells and in pituitary. Significantly up-regulated in effector memory T-cells as compared with naive T-cells.

Post-translational modifications. Phosphorylated on serine and/or threonine, possibly regulating the guanine nucleotide exchange factor (GEF) activity.

Disease relevance. Asthma (ASTHMA) [MIM:600807] The most common chronic disease affecting children and young adults. It is a complex genetic disorder with a heterogeneous phenotype, largely attributed to the interactions among many genes and between these genes and the environment. It is characterized by recurrent attacks of paroxysmal dyspnea, with wheezing due to spasmodic contraction of the bronchi. Disease susceptibility is associated with variants affecting the gene represented in this entry. Asthma susceptibility is probably caused by decreased TCR down-modulation and recycling in TH2 cells, causing prolonged TCR signaling and increased cytokine production in TH2 lymphocytes.

Domain organisation. The FXDXF motif mediates interaction the AP-2 complex. The clathrin box motif mediates interaction with clathrin.

Isoforms (5)

UniProt ID	Names	Canonical?
Q6P3S1-1	5	yes
Q6P3S1-2	2
Q6P3S1-3	3
Q6P3S1-4	4
Q6P3S1-5	1, DENND1B-S

RefSeq proteins (3): NP_001182144, NP_001287787, NP_659414 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001194	cDENN_dom	Domain
IPR005112	dDENN_dom	Domain
IPR005113	uDENN_dom	Domain
IPR037516	Tripartite_DENN	Domain
IPR040032	DENND1A/B/C	Family
IPR043153	DENN_C	Homologous_superfamily

Pfam: PF02141, PF03455, PF03456

UniProt features (63 total): helix 18, strand 11, modified residue 7, mutagenesis site 6, splice variant 5, turn 4, domain 3, region of interest 2, short sequence motif 2, compositionally biased region 2, chain 1, sequence variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
3TW8	X-RAY DIFFRACTION	2.1

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6P3S1-F1	67.33	0.42

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 (7): 520, 535, 536, 549, 552, 652, 653

Mutagenesis-validated functional residues (6):

Position	Phenotype
489	causes only a slight reduction in ap2b1-binding.
500	greatly reduce ap2b1-binding.
501	no effect.
502	almost completely abolishes ap2b1-binding.
507	no effect.
509	greatly reduce ap2b1-binding.

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: 455 (showing top): TGGTGCT_MIR29A_MIR29B_MIR29C, WANG_CLIM2_TARGETS_UP, GOBP_POSITIVE_REGULATION_OF_ADAPTIVE_IMMUNE_RESPONSE, GOBP_REGULATION_OF_ADAPTIVE_IMMUNE_RESPONSE, GCANCTGNY_MYOD_Q6, GOBP_POSITIVE_REGULATION_OF_CYTOKINE_PRODUCTION_INVOLVED_IN_IMMUNE_RESPONSE, GOZGIT_ESR1_TARGETS_DN, GOBP_ANTIGEN_RECEPTOR_MEDIATED_SIGNALING_PATHWAY, MITSIADES_RESPONSE_TO_APLIDIN_DN, GOBP_POSITIVE_REGULATION_OF_CYTOKINE_PRODUCTION, GOBP_VESICLE_MEDIATED_TRANSPORT, REACTOME_MEMBRANE_TRAFFICKING, GOMF_GTPASE_BINDING, GOBP_LEUKOCYTE_MEDIATED_IMMUNITY, GOBP_REGULATION_OF_IMMUNE_RESPONSE

GO Biological Process (6): endocytosis (GO:0006897), protein transport (GO:0015031), endocytic recycling (GO:0032456), regulation of immune response (GO:0050776), T cell receptor signaling pathway (GO:0050852), positive regulation of T-helper 2 cell cytokine production (GO:2000553)

GO Molecular Function (4): guanyl-nucleotide exchange factor activity (GO:0005085), small GTPase binding (GO:0031267), phosphatidylinositol phosphate binding (GO:1901981), protein binding (GO:0005515)

GO Cellular Component (5): cytosol (GO:0005829), nuclear speck (GO:0016607), clathrin-coated vesicle (GO:0030136), cytoplasm (GO:0005737), cytoplasmic vesicle (GO:0031410)

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
cytoplasm	2
cellular anatomical structure	2
vesicle budding from membrane	1
membrane invagination	1
vesicle-mediated transport	1
import into cell	1
transport	1
intracellular protein localization	1
establishment of protein localization	1
endosomal transport	1
vesicle-mediated transport to the plasma membrane	1
regulation of immune system process	1
immune response	1
regulation of response to stimulus	1
antigen receptor-mediated signaling pathway	1
positive regulation of T cell cytokine production	1
positive regulation of type 2 immune response	1
T-helper 2 cell cytokine production	1
regulation of T-helper 2 cell cytokine production	1
GTP binding	1
GDP binding	1
GTPase regulator activity	1
GTPase binding	1
phospholipid binding	1
binding	1
nuclear ribonucleoprotein granule	1
coated vesicle	1
intracellular anatomical structure	1
intracellular vesicle	1

Protein interactions and networks

STRING

798 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DENND1B	RAB35	Q15286	995
DENND1B	LHX9	Q9NQ69	723
DENND1B	ORMDL3	Q8N138	680
DENND1B	CLTC	Q00610	660
DENND1B	MADD	Q8WXG6	656
DENND1B	NEK7	Q8TDX7	650
DENND1B	NEK6	Q9HC98	602
DENND1B	GSDMB	Q8TAX9	576
DENND1B	PDE4D	Q08499	573
DENND1B	CRB2	Q5IJ48	570
DENND1B	CHP1	Q99653	547
DENND1B	CLEC16A	Q2KHT3	523
DENND1B	C1orf53	Q5VUE5	522
DENND1B	RAB21	Q9UL25	521
DENND1B	LHX2	P50458	497

IntAct

12 interactions, top by confidence:

A	B	Type	Score
DENND1B	SERPINA12	psi-mi:“MI:0915”(physical association)	0.400
DENND1B	FKBP8	psi-mi:“MI:0915”(physical association)	0.400
Xpo1	IFT56	psi-mi:“MI:0914”(association)	0.350
S100A6	VWA8	psi-mi:“MI:0914”(association)	0.350
SFN	BLTP3B	psi-mi:“MI:2364”(proximity)	0.270
YWHAB	E2F8	psi-mi:“MI:2364”(proximity)	0.270
YWHAE	E2F8	psi-mi:“MI:2364”(proximity)	0.270
YWHAH	E2F8	psi-mi:“MI:2364”(proximity)	0.270
YWHAQ	E2F8	psi-mi:“MI:2364”(proximity)	0.270
YWHAZ	E2F8	psi-mi:“MI:2364”(proximity)	0.270
YWHAG	E2F8	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (27): SERPINA12 (Affinity Capture-MS), DENND1B (Affinity Capture-MS), SERPINA12 (Affinity Capture-MS), DENND1B (Affinity Capture-RNA), DENND1B (Affinity Capture-RNA), DENND1B (Two-hybrid), SERPINA12 (Affinity Capture-MS), DENND1B (Affinity Capture-MS), FKBP8 (Affinity Capture-MS), ARF1 (Reconstituted Complex), ARF4 (Reconstituted Complex), ARF5 (Reconstituted Complex), RAB35 (Reconstituted Complex), HOOK1 (Two-hybrid), RBFOX2 (Two-hybrid)

ESM2 similar proteins: A0A096MJN4, A2A3N6, A3KMI0, A6H8H2, B7ZC32, D3ZSI8, F1M4A4, F4IJV4, O14986, O43236, O48709, O73630, O80452, P08487, P10686, P19174, P19838, P23678, P25799, P33173, P41230, P70181, P70182, Q04861, Q12756, Q17BU3, Q3B8D5, Q5CZZ9, Q5VZ89, Q5XUN4, Q5ZJ58, Q62077, Q63369, Q6F3J0, Q6P3S1, Q6P5D3, Q7PHR1, Q7YTB0, Q7Z401, Q80UP5

Diamond homologs: A2RSQ0, C8YR32, G3V7Q0, Q5FVJ0, Q6IQ26, Q6NXD8, Q6P3S1, Q6PAL8, Q6ZUT9, Q8BIJ7, Q8C4S8, Q8CFK6, Q8IV53, Q8IVV2, Q8RXA7, Q8WXG6, Q96T51, Q9TXP3, E9PXF8, G2WWH6, I1RQE2, O02626, O75064, O95248, P78524, Q3U1T9, Q3U1Y4, Q5VZ89, Q68D51, Q68F67, Q6NTN5, Q6ZPE2, Q7Z401, Q86WG5, Q8K382, Q8TEH3, Q91VV4, Q924W7, Q9H6A0, Q9ULE3

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 15 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
Activation of BAD and translocation to mitochondria	7	484.5×	3e-17
Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex	7	427.5×	4e-17
SARS-CoV-1 targets host intracellular signalling and regulatory pathways	7	427.5×	4e-17
Activation of BH3-only proteins	7	316.0×	4e-16
RHO GTPases activate PKNs	7	201.9×	1e-14
Intrinsic Pathway for Apoptosis	7	186.3×	2e-14
FOXO-mediated transcription	5	152.7×	4e-10
SARS-CoV-1-host interactions	7	111.8×	7e-13

GO biological processes:

GO term	Partners	Fold	FDR
protein targeting	5	140.9×	1e-08
intracellular protein localization	7	56.4×	1e-09

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	44
Likely benign	3
Benign	3

Top pathogenic / likely-pathogenic (0)

SpliceAI

3511 predictions. Top by Δscore:

Variant	Effect	Δscore
1:197583147:CTTA:C	donor_loss	1.0000
1:197583149:TA:T	donor_loss	1.0000
1:197583151:CCTG:C	donor_gain	1.0000
1:197583249:TCACC:T	acceptor_gain	1.0000
1:197583250:CACC:C	acceptor_gain	1.0000
1:197583250:CACCC:C	acceptor_gain	1.0000
1:197583251:ACC:A	acceptor_gain	1.0000
1:197583252:CC:C	acceptor_gain	1.0000
1:197583252:CCC:C	acceptor_gain	1.0000
1:197583253:CC:C	acceptor_gain	1.0000
1:197583254:C:CC	acceptor_gain	1.0000
1:197595206:A:AC	donor_gain	1.0000
1:197595207:C:CC	donor_gain	1.0000
1:197595207:CA:C	donor_gain	1.0000
1:197595207:CAG:C	donor_gain	1.0000
1:197595207:CAGG:C	donor_gain	1.0000
1:197595207:CAGGT:C	donor_gain	1.0000
1:197607067:ACTT:A	donor_loss	1.0000
1:197607068:CTTA:C	donor_loss	1.0000
1:197607069:TTACC:T	donor_loss	1.0000
1:197607070:T:TG	donor_loss	1.0000
1:197607071:A:AC	donor_gain	1.0000
1:197607071:A:AG	donor_loss	1.0000
1:197607072:C:CC	donor_gain	1.0000
1:197607072:CCA:C	donor_gain	1.0000
1:197607170:ACTCT:A	acceptor_gain	1.0000
1:197607171:CTCT:C	acceptor_gain	1.0000
1:197607171:CTCTC:C	acceptor_gain	1.0000
1:197607172:TCTCT:T	acceptor_gain	1.0000
1:197607173:CT:C	acceptor_gain	1.0000

AlphaMissense

5112 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:197611953:C:T	G266E	0.999
1:197611959:A:G	L264P	0.999
1:197611963:A:C	Y263D	0.999
1:197617711:A:G	W241R	0.999
1:197617711:A:T	W241R	0.999
1:197642748:T:A	E212V	0.999
1:197553096:A:G	L389P	0.998
1:197553099:C:G	R388P	0.998
1:197553110:A:C	F384L	0.998
1:197553110:A:T	F384L	0.998
1:197553111:A:G	F384S	0.998
1:197553112:A:G	F384L	0.998
1:197595221:A:G	L345P	0.998
1:197595311:A:G	L315P	0.998
1:197611954:C:G	G266R	0.998
1:197611954:C:T	G266R	0.998
1:197617674:A:G	L253P	0.998
1:197617709:C:A	W241C	0.998
1:197617709:C:G	W241C	0.998
1:197642744:C:A	R213S	0.998
1:197642744:C:G	R213S	0.998
1:197642745:C:A	R213M	0.998
1:197642745:C:G	R213T	0.998
1:197642814:A:G	L190P	0.998
1:197645700:A:T	I184K	0.998
1:197658334:A:G	L111P	0.998
1:197658359:A:G	W103R	0.998
1:197658359:A:T	W103R	0.998
1:197658369:A:C	S99R	0.998
1:197658369:A:T	S99R	0.998

dbSNP variants (sampled 300 via entrez): RS1000024831 (1:197621492 C>A), RS1000028489 (1:197726604 G>A), RS1000064958 (1:197575609 G>A), RS1000067846 (1:197528164 T>G), RS1000069461 (1:197723353 G>A), RS1000079573 (1:197575253 A>C), RS1000098616 (1:197527903 C>A,T), RS1000099988 (1:197696766 G>A), RS1000104233 (1:197646245 G>T), RS1000107742 (1:197702075 A>G), RS1000111428 (1:197595079 T>G), RS1000130186 (1:197733304 T>C), RS1000132790 (1:197694377 G>C), RS1000133391 (1:197582219 T>C), RS1000150836 (1:197697192 C>T)

Disease associations

OMIM: gene MIM:613292 | disease phenotypes: MIM:209850

GenCC curated gene-disease

Mondo (1): autism (MONDO:0005260)

Orphanet (0):

HPO phenotypes

1 total (1 of 1 shown, HPO-id order):

HPO	Term
HP:0000717	Autism

GWAS associations

27 associations (top):

Study	Trait	p-value
GCST000548_1	Asthma	2.000000e-13
GCST000548_2	Asthma	9.000000e-11
GCST000879_18	Crohn’s disease	9.000000e-09
GCST001010_1	Primary biliary cholangitis	2.000000e-14
GCST002166_11	Serum protein levels (sST2)	2.000000e-07
GCST003129_11	Primary biliary cholangitis	1.000000e-11
GCST004131_92	Inflammatory bowel disease	4.000000e-11
GCST004132_61	Crohn’s disease	5.000000e-11
GCST005537_146	Chronic inflammatory diseases (ankylosing spondylitis, Crohn’s disease, psoriasis, primary sclerosing cholangitis, ulcerative colitis) (pleiotropy)	2.000000e-09
GCST005581_41	Primary biliary cirrhosis	4.000000e-12
GCST005839_25	Depression	3.000000e-08
GCST006041_28	Major depressive disorder	5.000000e-07
GCST010101_1	White matter hyperintensities	6.000000e-09
GCST010108_1	Coffee consumption (cups per day)	2.000000e-08
GCST010697_27	Cortical surface area (min-P)	2.000000e-08
GCST010698_5	Subcortical volume (min-P)	5.000000e-08
GCST010699_10	Brain morphology (min-P)	2.000000e-10
GCST010700_57	Cortical thickness (MOSTest)	7.000000e-10
GCST010701_135	Cortical surface area (MOSTest)	5.000000e-10
GCST010702_59	Subcortical volume (MOSTest)	5.000000e-12
GCST010703_246	Brain morphology (MOSTest)	1.000000e-11
GCST012061_1	Chin morphology	1.000000e-12
GCST012063_1	Eye morphology	6.000000e-09
GCST012354_3	Anxiety	8.000000e-19
GCST90002388_634	Lymphocyte count	4.000000e-11
GCST90002389_91	Lymphocyte percentage of white cells	3.000000e-15
GCST90002399_15	Neutrophil percentage of white cells	3.000000e-10

EFO canonical traits (9, from GWAS)

EFO ID	Trait name
EFO:0004267	biliary liver cirrhosis
EFO:0005665	white matter hyperintensity measurement
EFO:0006782	cups of coffee per day measurement
EFO:0004346	neuroimaging measurement
EFO:0004840	cortical thickness
EFO:0009863	anxiety measurement
EFO:0004587	lymphocyte count
EFO:0007993	lymphocyte percentage of leukocytes
EFO:0007990	neutrophil percentage of leukocytes

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D001321	Autistic Disorder	F03.625.164.113.500

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression, decreases methylation, increases expression	7
methylmercuric chloride	decreases expression, affects cotreatment	3
trichostatin A	affects cotreatment, decreases expression, increases expression	3
Benzo(a)pyrene	increases expression, decreases expression, decreases methylation	3
bisphenol A	affects cotreatment, increases methylation, increases expression	2
mercuric bromide	decreases expression, affects cotreatment	2
entinostat	decreases expression, affects cotreatment	2
Panobinostat	affects cotreatment, decreases expression	2
Nickel	increases expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
p-Chloromercuribenzoic Acid	affects cotreatment, decreases expression	2
aristolochic acid I	decreases expression	1
bisphenol F	increases expression, affects cotreatment	1
urushiol	increases expression	1
triphenyl phosphate	affects expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
sodium arsenite	increases expression	1
cobaltous chloride	increases expression	1
butyraldehyde	decreases expression	1
nickel sulfate	increases expression	1
S-(1,2-dichlorovinyl)cysteine	affects cotreatment, decreases expression	1
pentanal	decreases expression	1
perfluorooctane sulfonic acid	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
ICG 001	increases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
eprenetapopt	affects expression, affects reaction	1
jinfukang	decreases expression, affects cotreatment	1
(+)-JQ1 compound	decreases expression	1
Fulvestrant	affects cotreatment, increases methylation	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00211796	PHASE4	COMPLETED	Divalproex Sodium ER in Adult Autism
NCT00391261	PHASE4	COMPLETED	An Open-label Trial of Metformin for Weight Control of Pediatric Patients on Antipsychotic Medications.
NCT00409747	PHASE4	COMPLETED	Minocycline to Treat Childhood Regressive Autism
NCT00576732	PHASE4	COMPLETED	A Study of the Effectiveness and Safety of Two Doses of Risperidone in the Treatment of Children and Adolescents With Autistic Disorder
NCT00844753	PHASE4	COMPLETED	Atomoxetine, Placebo and Parent Management Training in Autism
NCT01028820	PHASE4	COMPLETED	FMRI Brain Activation of Aripiprazole Treatment in Autism Spectrum Disorders
NCT01098383	PHASE4	UNKNOWN	Treatment With Acetyl-Choline Esterase Inhibitors in Children With Autism Spectrum Disorders
NCT01333865	PHASE4	COMPLETED	A Study of Memantine Hydrochloride (Namenda®) for Cognitive and Behavioral Impairment in Adults With Autism Spectrum Disorders
NCT01337700	PHASE4	COMPLETED	Milnacipran in Autism and the Functional Locus Coeruleus and Noradrenergic Model of Autism
NCT01695200	PHASE4	COMPLETED	Omega-3 Fatty Acids in Autism Spectrum Disorders
NCT02069977	PHASE4	UNKNOWN	Study to Evaluate the Efficacy and Safety of Aripiprazole
NCT02096952	PHASE4	COMPLETED	Methylphenidate ER Liquid Formulation in Adults With ASD and ADHD
NCT02199925	PHASE4	UNKNOWN	An Open-Label Study to Evaluate the Efficacy of High-Dose Gammaplex in Children on the Autism Spectrum
NCT02235467	PHASE4	COMPLETED	Multisite Study: Parental Training Using Video Modelling to Develop Social Skills in Children With Autism
NCT02255565	PHASE4	COMPLETED	Dose Response Effects of Quillivant XR in Children With ADHD and Autism: A Pilot Study
NCT02940574	PHASE4	COMPLETED	Neural and Behavioral Effects of Oxytocin in Autism Spectrum Disorders
NCT03333629	PHASE4	COMPLETED	Promoting Positive Outcomes for Individuals With ASD: Linking Early Detection, Treatment, and Long-term Outcomes
NCT03337646	PHASE4	COMPLETED	Evaluation of the Effect and Safety of Lisdexamfetamine in Children Aged 6-12 With ADHD and Autism
NCT03538431	PHASE4	COMPLETED	Improving Driving in Young People With Autism Spectrum Disorders
NCT03757585	PHASE4	COMPLETED	Natural Treatments for the Management of Emotional Dysregulation in Youth With Non-verbal Learning Disability (NVLD) and/or Autism Spectrum Disorders (ASD)
NCT04903353	PHASE4	COMPLETED	Pragmatic Trial Comparing Weight Gain in Children With Autism Taking Risperidone Versus Aripiprazole
NCT05063656	PHASE4	COMPLETED	Biomarker-Driven Pharmacological Treatment of Adolescents With Autism Spectrum Disorder With Gabapentin
NCT05146245	PHASE4	UNKNOWN	Safety and Pharmacokinetics of Antipsychotics in Children 2: Studying TDM in an RCT
NCT05916339	PHASE4	RECRUITING	AWARE: Management of ADHD in Autism Spectrum Disorder
NCT05954052	PHASE4	TERMINATED	A Study of Glutathione in Children With Autism Spectrum Disorder
NCT06853665	PHASE4	RECRUITING	The TEAM Study - Treatment Efficacy for Autism/Attention Using Mixed Amphetamine
NCT07054697	PHASE4	COMPLETED	Pilot-RCT With Individualized Homeopathic Treatment in the Children With Autism Spectrum Disorder
NCT07161804	PHASE4	COMPLETED	Pilot RCT Using Homeopathic Medicines in ASD
NCT07439042	PHASE4	NOT_YET_RECRUITING	Buspirone for Anxiety in Autistic Youth
NCT00036231	PHASE3	TERMINATED	Synthetic Human Secretin in Children With Autism and Gastrointestinal Dysfunction
NCT00036244	PHASE3	COMPLETED	Synthetic Human Secretin in Children With Autism
NCT00065884	PHASE3	UNKNOWN	Valproate Response in Aggressive Autistic Adolescents
NCT00065962	PHASE3	COMPLETED	Secretin for the Treatment of Autism
NCT00252603	PHASE3	COMPLETED	Galantamine Versus Placebo in Childhood Autism
NCT00346736	PHASE3	COMPLETED	Use of Acupuncture In Children With Autistic Spectrum Disorder
NCT00352248	PHASE3	COMPLETED	Randomized Controlled Trial of Acupuncture Versus Sham Acupuncture in Autistic Spectrum Disorder
NCT00352352	PHASE3	COMPLETED	Use of Acupuncture In Children With Autistic Spectrum Disorder
NCT00355329	PHASE3	COMPLETED	Randomized Control Trial of Using Tongue Acupuncture in Autistic Spectrum Disorder Using PET Scan for Clinical Correlation
NCT00498173	PHASE3	COMPLETED	Effectiveness of Atomoxetine in Treating ADHD Symptoms in Children and Adolescents With Autism
NCT00541346	PHASE3	COMPLETED	A Pilot Study of Daytrana TM in Children With Autism Co-Morbid for Attention Deficit Hyperactivity Disorder (ADHD) Symptoms