KCTD10

Summary

KCTD10 (potassium channel tetramerization domain containing 10, HGNC:23236) is a protein-coding gene on chromosome 12q24.11, encoding BTB/POZ domain-containing adapter for CUL3-mediated RhoA degradation protein 3 (Q9H3F6). Substrate-specific adapter of a BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complex. It is a selective cancer dependency (DepMap: 30.0% of cell lines).

The protein encoded by this gene binds proliferating cell nuclear antigen (PCNA) and may be involved in DNA synthesis and cell proliferation. In addition, the encoded protein may be a tumor suppressor. Several protein-coding and non-protein coding transcript variants have been found for this gene.

Source: NCBI Gene 83892 — RefSeq curated summary.

At a glance

• Gene–disease (curated): multiple congenital anomalies/dysmorphic syndrome (Limited, GenCC)
• GWAS associations: 11
• Clinical variants (ClinVar): 35 total
• Cancer dependency (DepMap): dependent in 30.0% of screened cell lines
• MANE Select transcript: NM_031954

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:23236
Approved symbol	KCTD10
Name	potassium channel tetramerization domain containing 10
Location	12q24.11
Locus type	gene with protein product
Status	Approved
Aliases	MSTP028, BTBD28
Ensembl gene	ENSG00000110906
Ensembl biotype	protein_coding
OMIM	613421
Entrez	83892

Gene structure

Transcript identifiers

Ensembl transcripts: 18 — 10 protein_coding, 4 retained_intron, 3 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000228495, ENST00000440541, ENST00000535546, ENST00000535747, ENST00000537165, ENST00000538161, ENST00000538377, ENST00000540089, ENST00000540355, ENST00000540402, ENST00000540411, ENST00000541077, ENST00000542262, ENST00000542858, ENST00000542954, ENST00000545759, ENST00000927233, ENST00000948235

RefSeq mRNA: 3 — MANE Select: NM_031954 NM_001317395, NM_001317399, NM_031954

CCDS: CCDS9128

Canonical transcript exons

ENST00000228495 — 7 exons

Exon	Start	End
ENSE00001250971	109448655	109451813
ENSE00003462237	109469515	109469728
ENSE00003462325	109457630	109457682
ENSE00003475433	109457992	109458078
ENSE00003593430	109456118	109456313
ENSE00003651575	109460636	109460805
ENSE00003680955	109477260	109477300

Expression profiles

Bgee: expression breadth ubiquitous, 258 present calls, max score 97.97.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 23.1329 / max 188.6634, expressed in 1806 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
133191	21.3076	1802
133193	1.3572	997
133192	0.4681	237

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
epithelial cell of pancreas	CL:0000083	97.97	gold quality
tendon of biceps brachii	UBERON:0008188	97.82	gold quality
secondary oocyte	CL:0000655	97.73	gold quality
popliteal artery	UBERON:0002250	97.54	gold quality
tibial artery	UBERON:0007610	97.54	gold quality
aorta	UBERON:0000947	97.34	gold quality
descending thoracic aorta	UBERON:0002345	97.17	gold quality
visceral pleura	UBERON:0002401	97.15	gold quality
thoracic aorta	UBERON:0001515	97.14	gold quality
ascending aorta	UBERON:0001496	97.11	gold quality
right coronary artery	UBERON:0001625	96.99	gold quality
saphenous vein	UBERON:0007318	96.97	gold quality
oviduct epithelium	UBERON:0004804	96.93	gold quality
pancreatic ductal cell	CL:0002079	96.76	gold quality
smooth muscle tissue	UBERON:0001135	96.63	gold quality
oocyte	CL:0000023	96.36	gold quality
parietal pleura	UBERON:0002400	96.35	gold quality
left coronary artery	UBERON:0001626	96.20	gold quality
stromal cell of endometrium	CL:0002255	96.08	gold quality
coronary artery	UBERON:0001621	96.08	gold quality
lower esophagus muscularis layer	UBERON:0035833	95.41	gold quality
lower esophagus	UBERON:0013473	95.40	gold quality
mucosa of stomach	UBERON:0001199	95.39	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	94.68	gold quality
gingival epithelium	UBERON:0001949	94.43	gold quality
muscle layer of sigmoid colon	UBERON:0035805	94.33	gold quality
middle temporal gyrus	UBERON:0002771	94.18	gold quality
myometrium	UBERON:0001296	94.00	gold quality
gall bladder	UBERON:0002110	93.90	gold quality
vena cava	UBERON:0004087	93.86	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	9.85
E-GEOD-110499	no	637.91

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): SP1, TFAP2A

miRNA regulators (miRDB)

121 targeting KCTD10, 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-3163	100.00	77.23	8605
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-2110	99.96	66.68	1930
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-185-3P	99.95	67.01	1743
HSA-MIR-144-3P	99.94	73.98	2698
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-1-3P	99.93	72.35	1914
HSA-MIR-206	99.93	72.50	1893
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-3119	99.92	71.34	2390
HSA-MIR-613	99.91	71.50	1710
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-6780A-5P	99.88	66.69	2776
HSA-MIR-4492	99.87	68.25	3611

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 30.0% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 12)

• KCTD10 may be associated with DNA synthesis and cell proliferation (PMID:19125419)
• binding of SP1 to the proximal promoter region stimulated the promoter activity and endogenous KCTD10 expression, whereas binding of AP-2alpha to this region showed opposite effects. (PMID:19154347)
• For the SNPs KCTD10_i5642G–>C and MVK_S52NG–>A, homozygotes for the major alleles (G) had lower HDL-cholesterol concentrations than did carriers of the minor alleles (P = 0.005 and P = 0.019, respectively). (PMID:19605566)
• KCTD10 inhibited the transcriptional activities of nuclear factor kappa B (NF-kappaB) and activating protein-1 reporters (PMID:22810651)
• The gastrointestinal stromal tumor-specific transcription factor ETV1 may have no prognostic potential, whereas its downstream gene KCTD10 is associated with a favorable prognosis. (PMID:23977394)
• These findings suggest that rs11066782 in KCTD10, rs11613718 in KCTD10 and rs11067233 in MMAB may contribute to the susceptibility of coronary heart disease by altering plasma HDL-C levels in Han Chinese. (PMID:27716295)
• identified the RING E3 ligase complex Cullin-3-Rbx1-KCTD10 as key modulator of endothelial barrier integrity via its regulation of the ubiquitination, localization, and activity of RhoB. (PMID:29358211)
• results suggest that CEP97 degradation by the cullin-3-RBX1-KCTD10 complex plays a crucial role in serum-starvation-induced CP110 removal and ciliogenesis (PMID:30404837)
• This novel molecular axis (CUL3/KCTD10/RhoB) positively regulates the activity of Rac1 in HER2-positive breast cancers. (PMID:30515933)
• EIF3D is a novel substrate of CUL3/KCTD10 ubiquitin ligase. The ubiquitin code of EIF3D is K27-polyubiquitination at the lysine 153 and 275 residues. (PMID:31280863)
• The study showed that ERCC6 and HTRA1single nucleotide polymorphisms rs3793784 and rs11200638 were associated with increased odds of early and exudative age-related macular degeneration, while the variant in KCTD10 (rs56209061) was found to be protective. (PMID:31583032)
• The CRL3[KCTD10] ubiquitin ligase-USP18 axis coordinately regulates cystine uptake and ferroptosis by modulating SLC7A11. (PMID:38959043)

Cross-species orthologs

33 orthologs

Organism	Symbol	Gene ID
danio_rerio	kctd10	ENSDARG00000017115
mus_musculus	Kctd10	ENSMUSG00000001098
rattus_norvegicus	Kctd10	ENSRNOG00000047896
drosophila_melanogaster	CG10465	FBGN0033017
caenorhabditis_elegans		WBGENE00008425
caenorhabditis_elegans		WBGENE00008932
caenorhabditis_elegans		WBGENE00011486
caenorhabditis_elegans		WBGENE00011621
caenorhabditis_elegans		WBGENE00015112
caenorhabditis_elegans		WBGENE00015113
caenorhabditis_elegans		WBGENE00015914
caenorhabditis_elegans		WBGENE00016545
caenorhabditis_elegans		WBGENE00016546
caenorhabditis_elegans		WBGENE00016547
caenorhabditis_elegans		WBGENE00016549
caenorhabditis_elegans		WBGENE00016550
caenorhabditis_elegans		WBGENE00017705
caenorhabditis_elegans		WBGENE00017707
caenorhabditis_elegans		WBGENE00017709
caenorhabditis_elegans		WBGENE00017710
caenorhabditis_elegans		WBGENE00019339
caenorhabditis_elegans		WBGENE00019342
caenorhabditis_elegans		WBGENE00022566
caenorhabditis_elegans		WBGENE00022567
caenorhabditis_elegans		WBGENE00022568
caenorhabditis_elegans		WBGENE00022569
caenorhabditis_elegans		WBGENE00022570
caenorhabditis_elegans		WBGENE00022571
caenorhabditis_elegans		WBGENE00022572
caenorhabditis_elegans		WBGENE00022573
caenorhabditis_elegans		WBGENE00022574
caenorhabditis_elegans		WBGENE00022575
caenorhabditis_elegans		WBGENE00044373

Paralogs (2): TNFAIP1 (ENSG00000109079), KCTD13 (ENSG00000174943)

Protein

Protein identifiers

BTB/POZ domain-containing adapter for CUL3-mediated RhoA degradation protein 3 — Q9H3F6 (reviewed: Q9H3F6)

Alternative names: BTB/POZ domain-containing protein KCTD10, Potassium channel tetramerization domain-containing protein 10

All UniProt accessions (11): Q9H3F6, B3KVY5, F5GWA4, F5GWK6, F5GY15, F5H268, F5H497, F5H6V0, F8W8I7, S4R3L9, S4R3Y7

UniProt curated annotations — full annotation on UniProt →

Function. Substrate-specific adapter of a BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complex. The BCR(BACURD3) E3 ubiquitin ligase complex mediates the ubiquitination of target proteins, leading to their degradation by the proteasome.

Subunit / interactions. Homotetramer; forms a two-fold symmetric tetramer in solution. Interacts with CUL3; interaction is direct and forms a 5:5 heterodecamer. Component of the BCR(BACURD3) E3 ubiquitin ligase complex, at least composed of CUL3, KCTD10/BACURD3 and RBX1. Interacts with DNA polymerase delta subunit 2/POLD2. Interacts with PCNA.

Subcellular location. Nucleus.

Pathway. Protein modification; protein ubiquitination.

Similarity. Belongs to the BACURD family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q9H3F6-1	1	yes
Q9H3F6-2	2
Q9H3F6-3	3

RefSeq proteins (3): NP_001304324, NP_001304328, NP_114160* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000210	BTB/POZ_dom	Domain
IPR003131	T1-type_BTB	Domain
IPR011333	SKP1/BTB/POZ_sf	Homologous_superfamily
IPR045068	BACURD1-3	Family

Pfam: PF02214

UniProt features (20 total): helix 5, strand 4, sequence conflict 3, splice variant 3, modified residue 2, chain 1, domain 1, short sequence motif 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
5FTA	X-RAY DIFFRACTION	2.64

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9H3F6-F1	82.73	0.61

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): 1, 23

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 203 (showing top): GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_UP, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_REGULATION_OF_SMALL_GTPASE_MEDIATED_SIGNAL_TRANSDUCTION, GOBP_NEGATIVE_REGULATION_OF_SMALL_GTPASE_MEDIATED_SIGNAL_TRANSDUCTION, GOBP_NEGATIVE_REGULATION_OF_INTRACELLULAR_SIGNAL_TRANSDUCTION, RICKMAN_TUMOR_DIFFERENTIATED_WELL_VS_POORLY_DN, MILI_PSEUDOPODIA_HAPTOTAXIS_UP, GOBP_NEGATIVE_REGULATION_OF_RHO_PROTEIN_SIGNAL_TRANSDUCTION, GOBP_POST_TRANSLATIONAL_PROTEIN_MODIFICATION, GOBP_REGULATION_OF_RHO_PROTEIN_SIGNAL_TRANSDUCTION, GOBP_PROTEIN_HOMOOLIGOMERIZATION, MILI_PSEUDOPODIA_CHEMOTAXIS_UP, GOBP_PROTEASOMAL_PROTEIN_CATABOLIC_PROCESS, GOMF_SIGNALING_RECEPTOR_BINDING

GO Biological Process (6): ubiquitin-dependent protein catabolic process (GO:0006511), protein ubiquitination (GO:0016567), negative regulation of Rho protein signal transduction (GO:0035024), proteasome-mediated ubiquitin-dependent protein catabolic process (GO:0043161), protein homooligomerization (GO:0051260), monoatomic ion transmembrane transport (GO:0034220)

GO Molecular Function (4): Notch binding (GO:0005112), identical protein binding (GO:0042802), ubiquitin-protein transferase activity (GO:0004842), protein binding (GO:0005515)

GO Cellular Component (5): nucleoplasm (GO:0005654), cytosol (GO:0005829), plasma membrane (GO:0005886), Cul3-RING ubiquitin ligase complex (GO:0031463), nucleus (GO:0005634)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
protein ubiquitination	1
modification-dependent protein catabolic process	1
protein modification by small protein conjugation	1
Rho protein signal transduction	1
regulation of Rho protein signal transduction	1
negative regulation of small GTPase mediated signal transduction	1
ubiquitin-dependent protein catabolic process	1
proteasomal protein catabolic process	1
protein complex oligomerization	1
monoatomic ion transport	1
transmembrane transport	1
signaling receptor binding	1
protein binding	1
ubiquitin-like protein transferase activity	1
binding	1
nuclear lumen	1
cytoplasm	1
membrane	1
cell periphery	1
cullin-RING ubiquitin ligase complex	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

1136 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
KCTD10	CUL3	Q13618	923
KCTD10	POLD2	P49005	786
KCTD10	RBX1	P62877	762
KCTD10	CEP97	Q8IW35	645
KCTD10	KCTD20	Q7Z5Y7	619
KCTD10	KCTD11	Q693B1	588
KCTD10	BTBD10	Q9BSF8	563
KCTD10	EIF3D	O15371	556
KCTD10	TBX5	Q99593	531
KCTD10	CCDC27	Q2M243	523
KCTD10	EPS8	Q12929	512
KCTD10	KCTD19	Q17RG1	477
KCTD10	RND2	P52198	459
KCTD10	KCTD13	Q8WZ19	453
KCTD10	DDX6	P26196	451

IntAct

112 interactions, top by confidence:

A	B	Type	Score
LSM3	LSM1	psi-mi:“MI:0914”(association)	0.950
TNFAIP1	KCTD13	psi-mi:“MI:0914”(association)	0.900
KCTD13	CUL3	psi-mi:“MI:0914”(association)	0.870
EXOSC1	EXOSC10	psi-mi:“MI:0914”(association)	0.810
KCTD13	KCTD10	psi-mi:“MI:0915”(physical association)	0.800
CUL3	KCTD10	psi-mi:“MI:0915”(physical association)	0.800
NRP1	CSNK2A2	psi-mi:“MI:0914”(association)	0.790
NHERF2	PODXL	psi-mi:“MI:0914”(association)	0.770
COPS6	RHOBTB1	psi-mi:“MI:0914”(association)	0.730
TNFAIP1	KCTD10	psi-mi:“MI:0915”(physical association)	0.670
DCX	ZBTB5	psi-mi:“MI:0914”(association)	0.670
HSPB2	BAG3	psi-mi:“MI:0914”(association)	0.670
CUL3	ENC1	psi-mi:“MI:0914”(association)	0.640
GLMN	FKBP5	psi-mi:“MI:0914”(association)	0.640
CFAP36	SNTB2	psi-mi:“MI:0914”(association)	0.620
DVL3	KCTD10	psi-mi:“MI:0915”(physical association)	0.560
TCEA2	KCTD10	psi-mi:“MI:0915”(physical association)	0.560
NTAQ1	KCTD10	psi-mi:“MI:0915”(physical association)	0.560
KCTD10	KCTD10	psi-mi:“MI:0915”(physical association)	0.560
TEX11	KCTD10	psi-mi:“MI:0915”(physical association)	0.560
PDIA6	TXNRD1	psi-mi:“MI:0914”(association)	0.560
CUL3	RHOBTB1	psi-mi:“MI:0914”(association)	0.530
CUL3	ZSWIM8	psi-mi:“MI:0914”(association)	0.530
KIR3DL2	METTL15	psi-mi:“MI:0914”(association)	0.530
SOST	KPNA4	psi-mi:“MI:0914”(association)	0.530
CIMAP1D	NMT2	psi-mi:“MI:0914”(association)	0.530
TNFAIP3	UBB	psi-mi:“MI:0914”(association)	0.530

BioGRID (292): KCTD10 (Affinity Capture-MS), KCTD10 (Affinity Capture-MS), KCTD10 (Affinity Capture-MS), KCTD10 (Affinity Capture-MS), KCTD10 (Affinity Capture-MS), KCTD10 (Affinity Capture-MS), KCTD10 (Affinity Capture-MS), KCTD10 (Affinity Capture-MS), KCTD10 (Affinity Capture-MS), KCTD10 (Affinity Capture-MS), KCTD10 (Affinity Capture-MS), KCTD10 (Affinity Capture-MS), KCTD10 (Affinity Capture-MS), KCTD10 (Affinity Capture-MS), KCTD10 (Affinity Capture-MS)

ESM2 similar proteins: A3KMV1, A4IFB4, A5PKG7, A9ULR9, B1WC97, B5DEL1, O70479, O73916, P0C5J9, Q01820, Q0VD00, Q0VFV7, Q12259, Q13829, Q28DC9, Q2HJ48, Q2T9W0, Q2TUM3, Q3URF8, Q4G0X4, Q5EAX2, Q5F3E8, Q5M956, Q5RBH4, Q5XJ34, Q5ZJP7, Q6DC02, Q6DCX3, Q6DG99, Q6P3P4, Q6P7W2, Q719H9, Q7TNY1, Q7TPL3, Q7Z3E5, Q863D4, Q8BGV7, Q8BJK1, Q8BNL5, Q8K0E1

Diamond homologs: A3KMV1, A4IFB4, A5PKG7, A6H6X4, A9ULR9, B1WC97, B5DEL1, D5SHR0, O70479, P0C5J9, Q03607, Q0VD00, Q0VFV7, Q13829, Q14681, Q28DC9, Q29RJ0, Q2HJ48, Q2T9W0, Q2TUM3, Q3URF8, Q4G0X4, Q50H33, Q54KH0, Q58DF7, Q5DTY9, Q5EAX2, Q5F3E8, Q5M956, Q5RBH4, Q5XJ34, Q5ZJP7, Q68DU8, Q693B1, Q6DC02, Q6DCX3, Q6DG99, Q6DK85, Q6P3P4, Q6P7W2

SIGNOR signaling

4 interactions.

A	Effect	B	Mechanism
CUL3	“up-regulates activity”	KCTD10	binding
KCTD10	“down-regulates quantity”	RHOA	binding
KCTD10	“down-regulates quantity by destabilization”	CEP97	binding
KCTD10	“up-regulates activity”	“Cullin 3-RBX1-Skp1”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 126 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
DNA Damage Recognition in GG-NER	6	21.1×	2e-04
Formation of TC-NER Pre-Incision Complex	6	15.7×	5e-04
Cargo recognition for clathrin-mediated endocytosis	6	7.8×	8e-03
Neddylation	9	5.3×	5e-03

GO biological processes:

GO term	Partners	Fold	FDR
protein neddylation	6	39.0×	6e-06
protein deubiquitination	6	9.8×	6e-03
proteasome-mediated ubiquitin-dependent protein catabolic process	11	5.3×	2e-03
cell migration	9	5.1×	8e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	25
Likely benign	0
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

1049 predictions. Top by Δscore:

Variant	Effect	Δscore
12:109456112:TCTTA:T	donor_loss	1.0000
12:109456113:CTTAC:C	donor_loss	1.0000
12:109456114:TTA:T	donor_loss	1.0000
12:109456115:TACCT:T	donor_loss	1.0000
12:109456116:A:T	donor_loss	1.0000
12:109456117:C:CG	donor_loss	1.0000
12:109456311:TTG:T	acceptor_gain	1.0000
12:109456312:TG:T	acceptor_gain	1.0000
12:109456314:C:CC	acceptor_gain	1.0000
12:109457690:T:C	acceptor_gain	1.0000
12:109457690:T:TC	acceptor_gain	1.0000
12:109457693:T:C	acceptor_gain	1.0000
12:109457693:T:TC	acceptor_gain	1.0000
12:109457695:T:C	acceptor_gain	1.0000
12:109457695:T:TC	acceptor_gain	1.0000
12:109460630:GCCTA:G	donor_loss	1.0000
12:109460633:TACTT:T	donor_loss	1.0000
12:109460634:A:AC	donor_gain	1.0000
12:109460634:ACTTG:A	donor_loss	1.0000
12:109460635:C:CC	donor_gain	1.0000
12:109460635:C:G	donor_loss	1.0000
12:109460655:TCTTC:T	donor_gain	1.0000
12:109460656:CTTCC:C	donor_gain	1.0000
12:109460658:TCC:T	donor_gain	1.0000
12:109460801:CCAGC:C	acceptor_gain	1.0000
12:109460802:CAGC:C	acceptor_gain	1.0000
12:109460802:CAGCC:C	acceptor_gain	1.0000
12:109460803:AGC:A	acceptor_gain	1.0000
12:109460806:C:CA	acceptor_loss	1.0000
12:109460806:C:CC	acceptor_gain	1.0000

AlphaMissense

2045 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:109451776:A:G	L254P	1.000
12:109451785:T:A	E251V	1.000
12:109451791:A:C	I249S	1.000
12:109451791:A:G	I249T	1.000
12:109451791:A:T	I249N	1.000
12:109451794:C:G	R248P	1.000
12:109451804:G:A	P245S	1.000
12:109451804:G:T	P245T	1.000
12:109451805:A:C	F244L	1.000
12:109451805:A:T	F244L	1.000
12:109451807:A:G	F244L	1.000
12:109456118:C:A	K241N	1.000
12:109456118:C:G	K241N	1.000
12:109456120:T:C	K241E	1.000
12:109456127:T:A	K238N	1.000
12:109456127:T:G	K238N	1.000
12:109456128:T:A	K238I	1.000
12:109456129:T:C	K238E	1.000
12:109456143:T:C	Y233C	1.000
12:109456144:A:C	Y233D	1.000
12:109456144:A:G	Y233H	1.000
12:109456146:A:T	V232D	1.000
12:109456149:A:C	I231S	1.000
12:109456149:A:G	I231T	1.000
12:109456149:A:T	I231N	1.000
12:109456152:G:A	S230F	1.000
12:109456153:A:G	S230P	1.000
12:109456157:A:C	C228W	1.000
12:109456158:C:A	C228F	1.000
12:109456158:C:G	C228S	1.000

dbSNP variants (sampled 300 via entrez): RS1000656628 (12:109450270 T>C), RS1000721947 (12:109462620 G>A), RS1000794545 (12:109462279 T>A), RS1000805943 (12:109473666 C>G,T), RS1000947110 (12:109469133 G>A), RS1001148503 (12:109449501 C>T), RS1001178269 (12:109460262 G>A,C), RS1001306373 (12:109476361 A>C), RS1001460354 (12:109467125 A>G), RS1001562973 (12:109473386 C>T), RS1001653110 (12:109475851 A>G), RS1001730993 (12:109458623 A>G), RS1001827929 (12:109466812 C>G,T), RS1001841356 (12:109448896 G>A), RS1001872453 (12:109449049 T>C)

Disease associations

OMIM: gene MIM:613421 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
multiple congenital anomalies/dysmorphic syndrome	Limited	Autosomal dominant

Mondo (1): multiple congenital anomalies/dysmorphic syndrome (MONDO:0019042)

Orphanet (0):

HPO phenotypes

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

GWAS associations

11 associations (top):

Study	Trait	p-value
GCST000805_11	HDL cholesterol	3.000000e-06
GCST010134_6	Non-oily fish consumption	6.000000e-11
GCST010135_11	Oily fish consumption	6.000000e-11
GCST010135_3	Oily fish consumption	7.000000e-17
GCST010140_3	Pork consumption	6.000000e-11
GCST010140_47	Pork consumption	7.000000e-17
GCST010142_62	Fish- and plant-related diet	4.000000e-13
GCST010142_83	Fish- and plant-related diet	4.000000e-08
GCST010142_87	Fish- and plant-related diet	2.000000e-19
GCST010142_94	Fish- and plant-related diet	5.000000e-13
GCST010866_97	Coronary artery disease	8.000000e-17

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0008111	diet measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases expression, affects expression	2
aristolochic acid I	increases expression	1
bisphenol F	affects cotreatment, increases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	increases abundance, affects cotreatment, increases oxidation	1
bisphenol A	affects cotreatment, increases expression	1
potassium chromate(VI)	affects cotreatment, increases expression	1
coumarin	decreases phosphorylation	1
methacrylaldehyde	increases abundance, affects cotreatment, increases oxidation	1
epigallocatechin gallate	affects cotreatment, increases expression	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	decreases expression	1
CGP 52608	affects binding, increases reaction	1
bisphenol S	affects cotreatment, increases expression	1
Bortezomib	increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Sunitinib	decreases expression	1
Acetaminophen	increases expression	1
Acrolein	affects cotreatment, increases oxidation, increases abundance	1
Air Pollutants	affects cotreatment, increases abundance, increases oxidation	1
Atrazine	decreases expression	1
Dexamethasone	affects cotreatment, increases expression	1
Doxorubicin	increases expression	1
Indomethacin	affects cotreatment, increases expression	1
Lead	affects expression	1
Methotrexate	decreases expression	1
Ozone	affects cotreatment, increases oxidation, increases abundance	1
Plant Extracts	affects cotreatment, increases expression	1
Rotenone	decreases expression	1
Tobacco Smoke Pollution	increases expression	1

Clinical trials (associated diseases)

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