DENND1A

Summary

DENND1A (DENN domain containing 1A, HGNC:29324) is a protein-coding gene on chromosome 9q33.3, encoding DENN domain-containing protein 1A (Q8TEH3). Guanine nucleotide exchange factor (GEF) regulating clathrin-mediated endocytosis through RAB35 activation.

Clathrin (see MIM 118955)-mediated endocytosis is a major mechanism for internalization of proteins and lipids. Members of the connecdenn family, such as DENND1A, 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 57706 — RefSeq curated summary.

At a glance

• GWAS associations: 30
• Clinical variants (ClinVar): 190 total
• MANE Select transcript: NM_001352964

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29324
Approved symbol	DENND1A
Name	DENN domain containing 1A
Location	9q33.3
Locus type	gene with protein product
Status	Approved
Aliases	FLJ21129, FAM31A
Ensembl gene	ENSG00000119522
Ensembl biotype	protein_coding
OMIM	613633
Entrez	57706

Gene structure

Transcript identifiers

Ensembl transcripts: 24 — 15 protein_coding, 8 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000373618, ENST00000373620, ENST00000373624, ENST00000394215, ENST00000462245, ENST00000473039, ENST00000474676, ENST00000475421, ENST00000475615, ENST00000479305, ENST00000491650, ENST00000497135, ENST00000699491, ENST00000866225, ENST00000866226, ENST00000866227, ENST00000866228, ENST00000937722, ENST00000937723, ENST00000937724, ENST00000937725, ENST00000937726, ENST00000937727, ENST00000937728

RefSeq mRNA: 10 — MANE Select: NM_001352964 NM_001352964, NM_001352965, NM_001352966, NM_001352967, NM_001352968, NM_001393654, NM_001400446, NM_001400449, NM_020946, NM_024820

CCDS: CCDS35133, CCDS35134, CCDS87687, CCDS94479

Canonical transcript exons

ENST00000394215 — 24 exons

Exon	Start	End
ENSE00001358207	123676720	123676789
ENSE00001924870	123929889	123930126
ENSE00003458981	123583169	123583270
ENSE00003460985	123757703	123757822
ENSE00003470940	123792587	123792630
ENSE00003475074	123403402	123403490
ENSE00003476742	123457793	123457897
ENSE00003479666	123457348	123457435
ENSE00003504935	123630376	123630476
ENSE00003509546	123454739	123454779
ENSE00003518536	123652013	123652123
ENSE00003534875	123878951	123879021
ENSE00003538307	123769514	123769563
ENSE00003554209	123452276	123452347
ENSE00003565422	123557570	123557695
ENSE00003576947	123671291	123671371
ENSE00003610242	123450693	123450749
ENSE00003617829	123609436	123609481
ENSE00003621417	123440360	123440491
ENSE00003681442	123383655	123383913
ENSE00003690431	123667026	123667079
ENSE00003926455	123387730	123387858
ENSE00003927398	123379658	123382625
ENSE00003933495	123411776	123411829

Expression profiles

Bgee: expression breadth ubiquitous, 213 present calls, max score 91.51.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 12.5090 / max 198.2184, expressed in 1793 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
102416	8.1264	1730
102415	4.3659	1585
102412	0.0167	4

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
monocyte	CL:0000576	91.51	gold quality
leukocyte	CL:0000738	91.33	gold quality
bone marrow cell	CL:0002092	90.21	gold quality
ventricular zone	UBERON:0003053	90.14	gold quality
ileal mucosa	UBERON:0000331	88.71	gold quality
granulocyte	CL:0000094	88.02	gold quality
right frontal lobe	UBERON:0002810	87.99	gold quality
anterior cingulate cortex	UBERON:0009835	87.82	gold quality
prefrontal cortex	UBERON:0000451	86.93	gold quality
blood	UBERON:0000178	86.77	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	86.49	gold quality
stromal cell of endometrium	CL:0002255	86.46	gold quality
neocortex	UBERON:0001950	86.29	gold quality
frontal cortex	UBERON:0001870	86.14	gold quality
amygdala	UBERON:0001876	86.03	gold quality
Brodmann (1909) area 9	UBERON:0013540	85.99	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	85.85	gold quality
pigmented layer of retina	UBERON:0001782	85.49	gold quality
colonic epithelium	UBERON:0000397	85.40	gold quality
ganglionic eminence	UBERON:0004023	85.27	gold quality
cerebral cortex	UBERON:0000956	85.23	gold quality
temporal lobe	UBERON:0001871	84.76	gold quality
tibialis anterior	UBERON:0001385	84.36	silver quality
gastrocnemius	UBERON:0001388	84.24	gold quality
forebrain	UBERON:0001890	84.19	gold quality
mucosa of transverse colon	UBERON:0004991	84.12	gold quality
muscle of leg	UBERON:0001383	84.08	gold quality
caudate nucleus	UBERON:0001873	84.06	gold quality
nucleus accumbens	UBERON:0001882	83.95	gold quality
entorhinal cortex	UBERON:0002728	83.64	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-GEOD-93593	yes	319.27
E-ANND-3	yes	8.36

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

17 targeting DENND1A, 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-196A-1-3P	99.99	72.15	2772
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-96-5P	99.95	72.80	2140
HSA-MIR-12133	99.92	71.82	2006
HSA-MIR-1271-5P	99.91	71.99	1972
HSA-MIR-1323	99.83	69.89	2471
HSA-MIR-548AZ-5P	99.83	69.94	3230
HSA-MIR-548T-5P	99.83	69.91	3220
HSA-MIR-548O-3P	99.74	69.30	2228
HSA-MIR-888-3P	99.53	69.77	1057
HSA-MIR-6165	99.44	67.12	1389
HSA-MIR-29B-1-5P	98.86	68.35	1364
HSA-MIR-5089-5P	98.45	66.06	1388
HSA-MIR-7106-3P	97.33	65.33	644
HSA-MIR-125A-3P	97.04	66.92	902
HSA-MIR-6730-3P	97.03	67.54	889
HSA-MIR-4761-3P	96.27	66.26	524

Literature-anchored findings (GeneRIF, showing 20)

• At least two of the PCOS susceptibility loci identified in the Chinese PCOS GWAS (DENND1A and THADA) are also associated with PCOS in European derived populations. (PMID:22180642)
• The rs2479106 G allele was associated with decreased PCOS susceptibility (PMID:22504079)
• Variants in DENND1A are associated with polycystic ovary syndrome in women of European ancestry. (PMID:22547425)
• Our results suggest that SNPs rs2479106 in gene DENND1A and rs13405728 in gene LHCGR are associated with endometrioid adenocarcinoma. (PMID:22902918)
• THADA and DENND1A, carry risk alleles that are associated with endocrine and metabolic disturbances in PCOS patients of Han Chinese descent. (PMID:23208300)
• sequence analysis of the DENND1A gene of patients with PCOS did not identify alterations that alone could be responsible for the PCOS pathogenesis (PMID:24086769)
• DENND1A, plays a key role in the hyperandrogenemia associated with polycystic ovary syndrome. (PMID:24706793)
• We demonstrated lack of association of DENND1A SNPs rs10818854, rs2479106, and rs10986105, previously associated with PCOS in Asians, with PCOS in Bahraini Arab women. (PMID:25626177)
• 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)
• This meta-analysis suggested that rs2479106 and rs10818854 polymorphisms in the DENND1A gene were associated with increased risk of polycystic ovary syndrome (PMID:26757598)
• Genome-wide association studies have identified DENND1A as a candidate gene for polycystic ovary syndrome (PCOS). PCOS theca cells are shown to overexpress DENND1A splice variant 2 (V2), but not V1. Also, the genetic variation 330 bp upstream of exon 20A is not associated with VE variant expression. (PMID:27297658)
• DENND1A gene variant is likely to have influence on PCOS risk. (PMID:27488699)
• The association of DENND1A rs10818854 and rs10986105 variants with PCOS in Tunisian but not Bahraini women confirms the dependence of this association on the ethnic/racial origin of study subjects. (PMID:29325736)
• Genetic variants of PCOS (rs13405728 in LHCGR gene; rs13429458 in THADA gene and rs2479106 in DENND1A gene) may not be involved in the development of preeclampsia in Han Chinese women. (PMID:29727258)
• we evaluated the frequencies of CYP19A1 rs2414096 and DENND1A rs10818854 polymorphisms in overweight and normal individuals and didn’t find any significant difference between these groups which demonstrates a lack of association between obesity risk and these SNPs (PMID:30232779)
• decreased miR-130b-3p expression in PCOS theca cells, which was correlated with increased DENND1A.V2, cytochrome P450 17alpha-hydroxylase (CYP17A1) mRNA and androgen biosynthesis. (PMID:31184707)
• The tagging SNPs rs2479106 and rs2468819 in the DENND1A gene are associated with polycystic ovary syndrome (PCOS) in the Chinese population, whereas rs2670139, rs2536951 and rs2479102 are not correlated with PCOS in the same population (PMID:31941453)
• A Multi-center Genome-wide Association Study of Cervical Dystonia. (PMID:34320236)
• Association of FSHR and DENND1A polymorphisms with polycystic ovary syndrome: a meta-analysis. (PMID:36350975)
• Unraveling the Genetic Associations of DENND1A (rs9696009) and ERBB4 (rs2178575) with Infertile Polycystic Ovary Syndrome Females in Pakistan. (PMID:37870708)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	dennd1a	ENSDARG00000014592
mus_musculus	Dennd1a	ENSMUSG00000035392
rattus_norvegicus	Dennd1a	ENSRNOG00000010526
drosophila_melanogaster	CG18659	FBGN0027561
caenorhabditis_elegans		WBGENE00004375

Paralogs (2): DENND1C (ENSG00000205744), DENND1B (ENSG00000213047)

Protein

Protein identifiers

DENN domain-containing protein 1A — Q8TEH3 (reviewed: Q8TEH3)

Alternative names: Connecdenn 1, Protein FAM31A

All UniProt accessions (3): A0A0A0MS48, A0A8V8TNT3, Q8TEH3

UniProt curated annotations — full annotation on UniProt →

Function. Guanine nucleotide exchange factor (GEF) regulating clathrin-mediated endocytosis through RAB35 activation. Promotes the exchange of GDP to GTP, converting inactive GDP-bound RAB35 into its active GTP-bound form. Regulates clathrin-mediated endocytosis of synaptic vesicles and mediates exit from early endosomes. Binds phosphatidylinositol-phosphates (PtdInsPs), with some preference for PtdIns(3)P.

Subunit / interactions. Interacts with RAB35. Interacts with clathrin and with the adapter protein complex 2, AP-2. Interacts with ITSN1 and SH3GL2. Interacts (when phosphorylated) with YWHAE.

Subcellular location. Cytoplasmic vesicle. Clathrin-coated vesicle membrane. Presynaptic cell membrane.

Post-translational modifications. Phosphorylated on serine and/or threonine in an Akt-dependent manner. Phosphorylation probably regulates the guanine nucleotide exchange factor (GEF) activity, possibly by disrupting an intramolecular interaction between the DENN domain and the C-terminus of the protein, thereby relieving the autoinhibition.

Disease relevance. Genetic variants in DENND1A may play a role in susceptibility to polycystic ovary syndrome (PCOS), the most common endocrine disease among premenopausal women. PCOS is a complex disorder characterized by infertility, hirsutism, obesity, various menstrual disturbances, and enlarged ovaries studded with atretic follicles.

Activity regulation. The guanine nucleotide exchange factor (GEF) activity is autoinhibited. Autoinhibition may be the result of intramolecular interaction between the DENN domain and the C-terminus, which is disrupted upon phosphorylation. Activation is regulated by Akt activation.

Isoforms (7)

UniProt ID	Names	Canonical?
Q8TEH3-1	1	yes
Q8TEH3-2	2
Q8TEH3-3	3
Q8TEH3-4	4
Q8TEH3-5	5
Q8TEH3-6	6
Q8TEH3-7	7

RefSeq proteins (10): NP_001339893, NP_001339894, NP_001339895, NP_001339896, NP_001339897, NP_001380583, NP_001387375, NP_001387378, NP_065997, NP_079096 (=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 (74 total): helix 17, strand 14, splice variant 11, modified residue 9, compositionally biased region 7, region of interest 4, turn 4, domain 3, short sequence motif 2, chain 1, mutagenesis site 1, sequence conflict 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
6EKK	X-RAY DIFFRACTION	1.82

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8TEH3-F1	61.57	0.35

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 (9): 473, 519, 520, 523, 536, 538, 546, 592, 749

Mutagenesis-validated functional residues (1):

Position	Phenotype
536–538	phosphomimetic mutant; abolishes the intramolecular interaction between the denn domain and the c-terminus of the protei

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: 146 (showing top): GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GOBP_REGULATION_OF_SMALL_GTPASE_MEDIATED_SIGNAL_TRANSDUCTION, GOBP_VESICLE_MEDIATED_TRANSPORT, REACTOME_MEMBRANE_TRAFFICKING, CACCAGC_MIR138, RICKMAN_METASTASIS_DN, SHETH_LIVER_CANCER_VS_TXNIP_LOSS_PAM4, GOCC_COATED_VESICLE, LIAO_METASTASIS, DODD_NASOPHARYNGEAL_CARCINOMA_UP, GOBP_ENDOCYTIC_RECYCLING, GOBP_LOCALIZATION_WITHIN_MEMBRANE, GOBP_IMPORT_INTO_CELL, GOBP_SMALL_GTPASE_MEDIATED_SIGNAL_TRANSDUCTION, ACEVEDO_METHYLATED_IN_LIVER_CANCER_DN

GO Biological Process (5): endocytosis (GO:0006897), protein transport (GO:0015031), endocytic recycling (GO:0032456), regulation of Rab protein signal transduction (GO:0032483), synaptic vesicle endocytosis (GO:0048488)

GO Molecular Function (6): guanyl-nucleotide exchange factor activity (GO:0005085), phosphatidylinositol-3-phosphate binding (GO:0032266), phosphatidylinositol phosphate binding (GO:1901981), lipid binding (GO:0008289), SH3 domain binding (GO:0017124), small GTPase binding (GO:0031267)

GO Cellular Component (12): cytosol (GO:0005829), clathrin-coated vesicle (GO:0030136), clathrin-coated vesicle membrane (GO:0030665), presynaptic membrane (GO:0042734), plasma membrane (GO:0005886), membrane (GO:0016020), dendrite (GO:0030425), cytoplasmic vesicle (GO:0031410), cell projection (GO:0042995), neuronal cell body (GO:0043025), synapse (GO:0045202), presynapse (GO:0098793)

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	4
cytoplasm	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
Rab protein signal transduction	1
regulation of small GTPase mediated signal transduction	1
synaptic vesicle recycling	1
presynaptic endocytosis	1
GTP binding	1
GDP binding	1
GTPase regulator activity	1
phosphatidylinositol phosphate binding	1
phospholipid binding	1
binding	1
protein domain specific binding	1
GTPase binding	1
coated vesicle	1
clathrin-coated vesicle	1
coated vesicle membrane	1
synaptic membrane	1
presynapse	1
membrane	1
cell periphery	1
neuron projection	1
dendritic tree	1
intracellular vesicle	1
somatodendritic compartment	1
cell body	1
cell junction	1
synapse	1

Protein interactions and networks

STRING

728 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DENND1A	RAB35	Q15286	988
DENND1A	MADD	Q8WXG6	939
DENND1A	CLTC	Q00610	754
DENND1A	AOPEP	Q8N6M6	737
DENND1A	NEK6	Q9HC98	728
DENND1A	LHCGR	P22888	722
DENND1A	TOX3	O15405	714
DENND1A	CRB2	Q5IJ48	707
DENND1A	RAB5B	P35239	702
DENND1A	NEK7	Q8TDX7	684
DENND1A	FSHR	P23945	673
DENND1A	SUOX	P51687	669
DENND1A	KRR1	Q13601	642
DENND1A	LHX2	P50458	640
DENND1A	THADA	Q6YHU6	640

IntAct

109 interactions, top by confidence:

A	B	Type	Score
YWHAG	BLTP3B	psi-mi:“MI:0914”(association)	0.640
YWHAG	BLTP3B	psi-mi:“MI:2364”(proximity)	0.640
YWHAB	BLTP3B	psi-mi:“MI:2364”(proximity)	0.610
YWHAB	BLTP3B	psi-mi:“MI:0914”(association)	0.610
YWHAH	BLTP3B	psi-mi:“MI:0914”(association)	0.570
YWHAH	BLTP3B	psi-mi:“MI:2364”(proximity)	0.570
SYNGAP1	IGF2BP3	psi-mi:“MI:0914”(association)	0.530
YWHAZ	BLTP3B	psi-mi:“MI:0914”(association)	0.530
LIMA1	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
Tmod3	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
Sec24c	SEC31A	psi-mi:“MI:0914”(association)	0.350
CLTB	WNK1	psi-mi:“MI:0914”(association)	0.350
GTSE1	HIP1	psi-mi:“MI:0914”(association)	0.350
PICALM	WNK1	psi-mi:“MI:0914”(association)	0.350
CLTC		psi-mi:“MI:0914”(association)	0.350
ANAPC15		psi-mi:“MI:0914”(association)	0.350
Myo1c	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
ATL2	ACRBP	psi-mi:“MI:0914”(association)	0.350
GAK	PARP10	psi-mi:“MI:0914”(association)	0.350
Xpo1	IFT56	psi-mi:“MI:0914”(association)	0.350
PLEKHA7	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
VAMP5	ESYT2	psi-mi:“MI:0914”(association)	0.350
ESR1	ESYT2	psi-mi:“MI:0914”(association)	0.350
ZDHHC5	IGKV2D-24	psi-mi:“MI:0914”(association)	0.350
YWHAE	DEPDC5	psi-mi:“MI:0914”(association)	0.350
PAAT	HIP1	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

BioGRID (114): DENND1A (Affinity Capture-MS), DENND1A (Affinity Capture-MS), DENND1A (Affinity Capture-MS), DENND1A (Affinity Capture-MS), DENND1A (Affinity Capture-MS), DENND1A (Affinity Capture-MS), DENND1A (Affinity Capture-MS), DENND1A (Affinity Capture-MS), DENND1A (Affinity Capture-MS), DENND1A (Affinity Capture-MS), DENND1A (Affinity Capture-MS), DENND1A (Affinity Capture-MS), KCTD3 (Affinity Capture-MS), KIF13B (Affinity Capture-MS), ZBTB21 (Affinity Capture-MS)

ESM2 similar proteins: A0A0U1RR37, A1L170, A1L1I3, A1L260, A2AMM0, A4IFJ0, B5G1P1, D3ZQL6, E7F5E1, G5BQH4, O08919, O54724, O60237, O75420, P06759, P33622, P53814, P85125, Q2KI85, Q2TAL5, Q3T044, Q3UMT1, Q4RTJ5, Q4V882, Q5I1X5, Q5U2R6, Q63312, Q6NZI2, Q75AS0, Q80VC9, Q8BG95, Q8BGT6, Q8C0J6, Q8CI12, Q8IV56, Q8K382, Q8N3F8, Q8TEH3, Q8WUF5, Q91VJ2

Diamond homologs: E9PXF8, G2WWH6, I1RQE2, O02626, O75064, O95248, P78524, Q3U1T9, Q3U1Y4, Q5VZ89, Q68D51, Q68F67, Q6NTN5, Q6P3S1, Q6ZPE2, Q7Z401, Q86WG5, Q8C4S8, Q8CFK6, Q8IV53, Q8K382, Q8TEH3, Q91VV4, Q924W7, Q9H6A0, Q9TXP3, Q9ULE3, Q9Y7Q7, X0JZ91, A6H8H2, Q80U28, Q9VXY2, Q9W3D3, Q6NXD8, A2RSQ0, G3V7Q0, Q6IQ26, Q6PAL8, Q6ZUT9, Q6P9P8

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 106 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
Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex	9	82.8×	9e-14
Activation of BAD and translocation to mitochondria	7	73.0×	2e-10
SARS-CoV-1 targets host intracellular signalling and regulatory pathways	7	64.4×	5e-10
Activation of BH3-only proteins	7	47.6×	4e-09
RHO GTPases activate PKNs	8	34.8×	4e-09
Intrinsic Pathway for Apoptosis	7	28.1×	2e-07
FOXO-mediated transcription	5	23.0×	3e-05
SARS-CoV-1-host interactions	7	16.9×	3e-06

GO biological processes:

GO term	Partners	Fold	FDR
protein targeting	6	22.7×	2e-04
negative regulation of translation	5	10.1×	9e-03
intracellular protein localization	8	8.6×	9e-04
protein phosphorylation	8	5.6×	8e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	150
Likely benign	7
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

7408 predictions. Top by Δscore:

Variant	Effect	Δscore
9:123382622:GCCT:G	acceptor_gain	1.0000
9:123382622:GCCTC:G	acceptor_loss	1.0000
9:123382623:CCTC:C	acceptor_gain	1.0000
9:123382623:CCTCT:C	acceptor_loss	1.0000
9:123382624:CT:C	acceptor_gain	1.0000
9:123382625:TC:T	acceptor_loss	1.0000
9:123382626:C:CA	acceptor_loss	1.0000
9:123382626:C:CC	acceptor_gain	1.0000
9:123383649:CCATA:C	donor_loss	1.0000
9:123383650:CATA:C	donor_loss	1.0000
9:123383651:ATACC:A	donor_loss	1.0000
9:123383652:TACCT:T	donor_loss	1.0000
9:123383653:ACCTG:A	donor_loss	1.0000
9:123383654:C:CT	donor_loss	1.0000
9:123383681:C:CA	donor_gain	1.0000
9:123403400:A:AC	donor_gain	1.0000
9:123403401:C:CT	donor_gain	1.0000
9:123403401:CTG:C	donor_gain	1.0000
9:123403401:CTGCT:C	donor_gain	1.0000
9:123440357:CA:C	donor_loss	1.0000
9:123440358:A:AC	donor_gain	1.0000
9:123440358:ACC:A	donor_loss	1.0000
9:123440359:C:CC	donor_gain	1.0000
9:123440359:CCTGT:C	donor_gain	1.0000
9:123440487:ATGTC:A	acceptor_gain	1.0000
9:123440488:TGTC:T	acceptor_gain	1.0000
9:123440489:GTC:G	acceptor_gain	1.0000
9:123440489:GTCC:G	acceptor_loss	1.0000
9:123440490:TC:T	acceptor_gain	1.0000
9:123440491:CCTG:C	acceptor_gain	1.0000

AlphaMissense

7180 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:123450703:A:G	L449S	1.000
9:123452298:G:T	A426D	1.000
9:123454756:A:G	W404R	1.000
9:123454756:A:T	W404R	1.000
9:123583233:A:G	L268P	1.000
9:123609458:C:T	G248E	1.000
9:123609459:C:G	G248R	1.000
9:123609459:C:T	G248R	1.000
9:123609464:A:G	L246P	1.000
9:123609479:G:T	A241D	1.000
9:123630391:A:G	L235P	1.000
9:123630428:A:G	W223R	1.000
9:123630428:A:T	W223R	1.000
9:123630458:C:A	G213W	1.000
9:123630469:G:T	A209D	1.000
9:123652050:T:A	E194V	1.000
9:123652098:G:T	A178D	1.000
9:123667036:A:T	I166K	1.000
9:123757781:A:G	L75P	1.000
9:123769537:A:C	F53L	1.000
9:123769537:A:T	F53L	1.000
9:123769539:A:G	F53L	1.000
9:123450706:C:G	R448P	0.999
9:123450724:A:G	I442T	0.999
9:123450736:G:T	A438E	0.999
9:123450744:T:A	K435N	0.999
9:123450744:T:G	K435N	0.999
9:123450748:G:T	A434E	0.999
9:123452284:A:C	Y431D	0.999
9:123452286:A:T	V430D	0.999

dbSNP variants (sampled 300 via entrez): RS1000010232 (9:123389346 G>A), RS1000023983 (9:123812763 TA>T), RS1000026697 (9:123722334 T>C), RS1000035749 (9:123675495 G>A), RS1000040471 (9:123402956 G>A), RS1000050787 (9:123611956 C>T), RS1000051590 (9:123571214 A>G), RS1000054147 (9:123450511 AAG>A), RS1000062866 (9:123545677 C>T), RS1000063808 (9:123790139 T>C), RS1000067268 (9:123766598 G>A,C), RS1000071102 (9:123655333 G>T), RS1000075024 (9:123727038 T>C), RS1000080163 (9:123722028 G>C), RS1000083264 (9:123478925 T>C,G)

Disease associations

OMIM: gene MIM:613633 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

30 associations (top):

Study	Trait	p-value
GCST000754_4	Personality dimensions	9.000000e-06
GCST000914_2	Polycystic ovary syndrome	9.000000e-18
GCST000914_3	Polycystic ovary syndrome	8.000000e-19
GCST001712_35	Myopia (pathological)	2.000000e-11
GCST001935_2	Body mass index in non-asthmatics	2.000000e-07
GCST002137_7	Waist circumference	2.000000e-08
GCST002178_4	Adverse response to chemotherapy in breast cancer (alopecia) (cyclophosphamide+doxorubicin+/-5FU)	2.000000e-06
GCST003144_9	Polycystic ovary syndrome	1.000000e-06
GCST005273_1	Polycystic ovary syndrome	2.000000e-06
GCST005411_9	Thrombin-activatable fibrinolysis inhibitor activation peptide	4.000000e-07
GCST005839_1	Depression	3.000000e-08
GCST005951_64	Body mass index	2.000000e-10
GCST006041_38	Major depressive disorder	2.000000e-06
GCST006810_18	Self-reported risk-taking behaviour	2.000000e-08
GCST006948_52	Feeling nervous	1.000000e-08
GCST006949_12	Suffering from nerves	4.000000e-08
GCST006976_44	Macular thickness	3.000000e-15
GCST006979_175	Heel bone mineral density	9.000000e-12
GCST007089_7	Polycystic ovary syndrome	8.000000e-11
GCST007324_11	Adventurousness	5.000000e-11
GCST007325_217	General risk tolerance (MTAG)	3.000000e-09
GCST007325_303	General risk tolerance (MTAG)	5.000000e-15
GCST007576_260	Chronotype	5.000000e-12
GCST007843_15	Rheumatoid arthritis	2.000000e-16
GCST008529_51	Tea consumption	8.000000e-07
GCST010703_296	Brain morphology (MOSTest)	2.000000e-14
GCST012490_122	Femur bone mineral density x serum urate levels interaction	1.000000e-08
GCST012490_556	Femur bone mineral density x serum urate levels interaction	6.000000e-12
GCST90044902_3	Polycystic ovary syndrome (adjusted for age)	3.000000e-12
GCST90044903_3	Polycystic ovary syndrome (adjusted for age and BMI)	1.000000e-08

EFO canonical traits (10, from GWAS)

EFO ID	Trait name
EFO:0004365	personality trait
EFO:0004207	pathological myopia
EFO:0004340	body mass index
EFO:0008579	risk-taking behaviour
EFO:0009597	feeling nervous measurement
EFO:0009270	heel bone mineral density
EFO:0008328	chronotype measurement
EFO:0010091	tea consumption measurement
EFO:0004346	neuroimaging measurement
EFO:0004531	urate measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases expression	8
Valproic Acid	affects cotreatment, decreases expression, affects expression	4
trichostatin A	affects cotreatment, decreases expression	3
Aflatoxin B1	decreases expression, increases methylation	3
entinostat	decreases expression, affects cotreatment	2
belinostat	decreases expression, affects cotreatment	2
Vorinostat	affects cotreatment, decreases expression	2
Panobinostat	decreases expression, affects cotreatment	2
Nickel	increases expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Tretinoin	decreases expression	2
aristolochic acid I	decreases expression	1
FR900359	increases phosphorylation	1
dicrotophos	increases expression	1
methylmercuric chloride	decreases expression	1
methyleugenol	decreases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	decreases methylation, affects methylation, affects cotreatment	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
zinc chromate	increases abundance, decreases expression	1
benzo(e)pyrene	increases methylation	1
isobutyl alcohol	affects cotreatment, decreases expression, increases abundance	1
di-n-butylphosphoric acid	affects expression	1
chromium hexavalent ion	decreases expression, increases abundance	1
perfluorooctane sulfonic acid	increases expression	1
CGP 52608	increases reaction, affects binding	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
Sunitinib	increases expression	1
Fulvestrant	affects cotreatment, decreases methylation	1

Clinical trials (associated diseases)

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