AKAP10

Summary

AKAP10 (A-kinase anchoring protein 10, HGNC:368) is a protein-coding gene on chromosome 17p11.2, encoding A-kinase anchor protein 10, mitochondrial (O43572). Differentially targeted protein that binds to type I and II regulatory subunits of protein kinase A and anchors them to the mitochondria or the plasma membrane.

This gene encodes a member of the A-kinase anchor protein family. A-kinase anchor proteins bind to the regulatory subunits of protein kinase A (PKA) and confine the holoenzyme to discrete locations within the cell. The encoded protein is localized to mitochondria and interacts with both the type I and type II regulatory subunits of PKA. Polymorphisms in this gene may be associated with increased risk of arrhythmias and sudden cardiac death.

Source: NCBI Gene 11216 — RefSeq curated summary.

At a glance

• GWAS associations: 11
• Clinical variants (ClinVar): 183 total — 57 pathogenic, 1 likely-pathogenic
• MANE Select transcript: NM_007202

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:368
Approved symbol	AKAP10
Name	A-kinase anchoring protein 10
Location	17p11.2
Locus type	gene with protein product
Status	Approved
Aliases	D-AKAP2, PRKA10, MGC9414
Ensembl gene	ENSG00000108599
Ensembl biotype	protein_coding
OMIM	604694
Entrez	11216

Gene structure

Transcript identifiers

Ensembl transcripts: 22 — 15 protein_coding, 5 nonsense_mediated_decay, 1 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000225737, ENST00000395536, ENST00000460046, ENST00000474245, ENST00000571858, ENST00000572155, ENST00000572341, ENST00000576896, ENST00000578898, ENST00000582611, ENST00000583951, ENST00000885388, ENST00000885389, ENST00000937766, ENST00000937767, ENST00000937768, ENST00000937769, ENST00000937770, ENST00000937771, ENST00000941090, ENST00000941091, ENST00000941092

RefSeq mRNA: 2 — MANE Select: NM_007202 NM_001330152, NM_007202

CCDS: CCDS11214, CCDS82091

Canonical transcript exons

ENST00000225737 — 15 exons

Exon	Start	End
ENSE00000694049	19940887	19941010
ENSE00000694051	19936286	19936430
ENSE00000694052	19931805	19931978
ENSE00000694054	19924408	19924517
ENSE00000881495	19958014	19958571
ENSE00001911446	19904302	19906232
ENSE00002672716	19977592	19977828
ENSE00003498905	19941826	19941910
ENSE00003504390	19947407	19947505
ENSE00003530810	19968414	19968461
ENSE00003546001	19962840	19963022
ENSE00003553700	19909926	19909978
ENSE00003568142	19920036	19920118
ENSE00003636585	19909181	19909276
ENSE00003693829	19939713	19939849

Expression profiles

Bgee: expression breadth ubiquitous, 287 present calls, max score 98.43.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 24.7448 / max 461.1191, expressed in 1817 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
164898	24.7448	1817

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
buccal mucosa cell	CL:0002336	98.43	gold quality
sural nerve	UBERON:0015488	94.37	gold quality
calcaneal tendon	UBERON:0003701	93.30	gold quality
trabecular bone tissue	UBERON:0002483	92.45	gold quality
adrenal tissue	UBERON:0018303	90.82	gold quality
monocyte	CL:0000576	90.73	gold quality
mononuclear cell	CL:0000842	90.48	gold quality
leukocyte	CL:0000738	90.28	gold quality
nipple	UBERON:0002030	89.78	gold quality
blood	UBERON:0000178	89.70	gold quality
cranial nerve II	UBERON:0000941	89.23	gold quality
colonic epithelium	UBERON:0000397	89.17	gold quality
tendon	UBERON:0000043	88.58	gold quality
bone marrow cell	CL:0002092	88.42	gold quality
visceral pleura	UBERON:0002401	87.80	gold quality
pancreatic ductal cell	CL:0002079	87.63	gold quality
pylorus	UBERON:0001166	87.58	gold quality
middle frontal gyrus	UBERON:0002702	87.22	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	87.15	gold quality
granulocyte	CL:0000094	87.15	gold quality
tonsil	UBERON:0002372	87.15	gold quality
paraflocculus	UBERON:0005351	87.08	gold quality
corpus callosum	UBERON:0002336	87.07	gold quality
cortical plate	UBERON:0005343	87.05	gold quality
penis	UBERON:0000989	86.53	gold quality
frontal pole	UBERON:0002795	86.48	gold quality
lymph node	UBERON:0000029	86.39	gold quality
cardia of stomach	UBERON:0001162	85.73	gold quality
primary visual cortex	UBERON:0002436	85.70	gold quality
right uterine tube	UBERON:0001302	85.52	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.83

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): MYCN

miRNA regulators (miRDB)

143 targeting AKAP10, 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-190A-3P	100.00	80.35	5520
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-574-5P	100.00	66.01	989
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-512-3P	99.97	67.35	1049
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-8075	99.97	67.20	962
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-4666A-3P	99.96	71.71	3434

Literature-anchored findings (GeneRIF, showing 19)

• deuterium exchange-mass spectrometry (DXMS) and limited proteolysis to probe the folded regions of D-AKAP2, providing for the first time insight into the intra-domain dynamics of a scaffold protein (PMID:12206784)
• A variant of the kinase-binding domain of this enzyme involves a disease susceptibility polymorphism. (PMID:12646697)
• Results describe the structural features of dual-specificity A kinase-anchoring protein 2 (D-AKAP2) and its interaction with protein kinase A (PKA). (PMID:15488188)
• These studies suggest a role for AKAP10 in heart rhythm control. (PMID:17485678)
• AKAP10 2073A>G variation is associated with an increased risk of colorectal cancer in the Chinese population. (PMID:19209010)
• There was a significant association between AKAP10 gene 2073A/G polymorphism and colorectal cancer. (PMID:19462906)
• the AKAP10 Val allele predicted greater resting heart rate and heart rate variability (PMID:19496216)
• D-AKAP2 promotes accumulation of recycling proteins in the Rab4/Rab11-positive endocytic recycling compartment (PMID:19797056)
• AKAP10 single nucleotide polymorphism is associated with increased risk of arrhythmia during kidney transplantation. (PMID:19857670)
• Results describe the structures of the protein kinase A RIalpha subunit D/D domain alone and in complex with D-AKAP2. (PMID:20159461)
• Results suggest G1936 polymorphism in A-kinase-anchoring protein is preventative factor against preterm birth, in contrast with previously asserted negative effects in adults. (PMID:21701445)
• There is possible association between a 1936G AKAP10 variant and blood pressure in Polish newborns. (PMID:22817328)
• No significant differences were found in AKAP10 genotype or allele distribution between the age groups (newborn vs. nonagenerian) for either gender. (PMID:23092224)
• Questioned whether 1936A>G is associated with metabolic changes in newborns that are predictive of the metabolic phenotype in adults. Demonstrate an association between 1936G variant and total cholesterol level in cord blood of Polish newborns. (PMID:23095189)
• Studied the clinicopathologic significance of A-kinase anchoring proteins 10 (AKAP 10) expression and the relationship with its polymorphism in colorectal cancer. (PMID:23468363)
• Its signaling pathway is associated with the progression and prognosis of colorectal neoplasms. (PMID:25213315)
• Described is a structure of D-AKAP2 in complex with two interacting partners and the exact mechanism by which a segment that on its own is disordered presents an alpha-helix to PKA and a beta-strand to PDZK1. (PMID:25348485)
• Significant association between the AKAP10 polymorphisms and reduced risk of Preterm birth in the Malays was observed. (PMID:26110499)
• Here, using zebrafish, murine, and human models, the authors show that erythropoietin (EPO) signaling, together with the GATA1 transcriptional target, AKAP10, regulates heme biosynthesis during erythropoiesis at the outer mitochondrial membrane. (PMID:28553927)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	akap10	ENSDARG00000059549
mus_musculus	Akap10	ENSMUSG00000047804
rattus_norvegicus	Akap10	ENSRNOG00000002899
drosophila_melanogaster	pkaap	FBGN0040079
caenorhabditis_elegans		WBGENE00004348

Protein

Protein identifiers

A-kinase anchor protein 10, mitochondrial — O43572 (reviewed: O43572)

Alternative names: Dual specificity A kinase-anchoring protein 2, Protein kinase A-anchoring protein 10

All UniProt accessions (11): O43572, A0A0S2Z4Y8, A0A0S2Z4Z7, E7EMD6, I3L177, I3L479, I3NI04, J3QL61, J3QR74, J3QRM7, K7EM25

UniProt curated annotations — full annotation on UniProt →

Function. Differentially targeted protein that binds to type I and II regulatory subunits of protein kinase A and anchors them to the mitochondria or the plasma membrane. Although the physiological relevance between PKA and AKAPS with mitochondria is not fully understood, one idea is that BAD, a proapoptotic member, is phosphorylated and inactivated by mitochondria-anchored PKA. It cannot be excluded too that it may facilitate PKA as well as G protein signal transduction, by acting as an adapter for assembling multiprotein complexes. With its RGS domain, it could lead to the interaction to G-alpha proteins, providing a link between the signaling machinery and the downstream kinase.

Subcellular location. Mitochondrion. Membrane. Cytoplasm.

Domain organisation. RII-alpha binding site, predicted to form an amphipathic helix, could participate in protein-protein interactions with a complementary surface on the R-subunit dimer.

RefSeq proteins (2): NP_001317081, NP_009133* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR016137	RGS	Domain
IPR036305	RGS_sf	Homologous_superfamily
IPR037719	AKAP10_AKB_dom	Domain
IPR044926	RGS_subdomain_2	Homologous_superfamily
IPR052246	Cell_Polariz_PKAAnc	Family

Pfam: PF00615

UniProt features (18 total): region of interest 4, modified residue 3, sequence variant 2, sequence conflict 2, domain 2, compositionally biased region 2, transit peptide 1, chain 1, helix 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
3IM4	X-RAY DIFFRACTION	2.29
3TMH	X-RAY DIFFRACTION	3.8

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O43572-F1	65.23	0.31

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 (3): 52, 189, 281

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-983231	Factors involved in megakaryocyte development and platelet production
R-HSA-109582	Hemostasis

MSigDB gene sets: 145 (showing top): GGGACCA_MIR133A_MIR133B, RNGTGGGC_UNKNOWN, DACOSTA_UV_RESPONSE_VIA_ERCC3_XPCS_DN, FOXO4_01, USF_01, DEBIASI_APOPTOSIS_BY_REOVIRUS_INFECTION_UP, DANG_BOUND_BY_MYC, SPIELMAN_LYMPHOBLAST_EUROPEAN_VS_ASIAN_DN, TAANNYSGCG_UNKNOWN, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_DN, BUCKANOVICH_T_LYMPHOCYTE_HOMING_ON_TUMOR_UP, CHEN_HOXA5_TARGETS_9HR_UP, BENPORATH_MYC_MAX_TARGETS, SCGGAAGY_ELK1_02, GOMF_PROTEIN_KINASE_A_BINDING

GO Biological Process (2): signal transduction (GO:0007165), intracellular protein localization (GO:0008104)

GO Molecular Function (3): protein kinase A binding (GO:0051018), protein binding (GO:0005515), kinase activity (GO:0016301)

GO Cellular Component (6): mitochondrion (GO:0005739), cytosol (GO:0005829), plasma membrane (GO:0005886), protein-containing complex (GO:0032991), cytoplasm (GO:0005737), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Hemostasis	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
cytoplasm	2
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
macromolecule localization	1
protein binding	1
binding	1
transferase activity, transferring phosphorus-containing groups	1
intracellular membrane-bounded organelle	1
membrane	1
cell periphery	1
cellular_component	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

1436 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
AKAP10	PRKACG	P22612	874
AKAP10	PRKACB	P22694	874
AKAP10	PRKACA	P17612	873
AKAP10	RAB4A	P20338	820
AKAP10	AKAP1	Q92667	744
AKAP10	RAB11A	P24410	734
AKAP10	PRKAR2B	P31323	711
AKAP10	AKAP8	O43823	707
AKAP10	RGS6	P49758	676
AKAP10	RGS21	Q2M5E4	673
AKAP10	RGS12	O14924	672
AKAP10	RGS17	Q9UGC6	671
AKAP10	RGS11	O94810	668
AKAP10	RGS7	P49802	665
AKAP10	RGS20	O76081	662

IntAct

154 interactions, top by confidence:

A	B	Type	Score
EIF4E	EIF4G3	psi-mi:“MI:0914”(association)	0.810
NHERF2	PODXL	psi-mi:“MI:0914”(association)	0.770
AKAP10	NHERF2	psi-mi:“MI:0407”(direct interaction)	0.590
PRKAR1A	AKAP10	psi-mi:“MI:0407”(direct interaction)	0.560
AKAP10	PDZK1	psi-mi:“MI:0407”(direct interaction)	0.440
AKAP10	MAST2	psi-mi:“MI:0407”(direct interaction)	0.440
AKAP10	SHANK1	psi-mi:“MI:0407”(direct interaction)	0.440
AKAP10	SNX27	psi-mi:“MI:0407”(direct interaction)	0.440
AKAP10	ARHGEF12	psi-mi:“MI:0407”(direct interaction)	0.440
AKAP10	GRID2IP	psi-mi:“MI:0407”(direct interaction)	0.440
AKAP10	PTPN3	psi-mi:“MI:0407”(direct interaction)	0.440
MAST1	AKAP10	psi-mi:“MI:0407”(direct interaction)	0.440
AKAP10	PDZD7	psi-mi:“MI:0407”(direct interaction)	0.440
AKAP10	NHERF4	psi-mi:“MI:0407”(direct interaction)	0.440
AKAP10	PDZD2	psi-mi:“MI:0407”(direct interaction)	0.440
AKAP10	ARHGEF11	psi-mi:“MI:0407”(direct interaction)	0.440
AKAP10	PARD3B	psi-mi:“MI:0407”(direct interaction)	0.440
AKAP10	DLG3	psi-mi:“MI:0407”(direct interaction)	0.440
AKAP10	SCRIB	psi-mi:“MI:0407”(direct interaction)	0.440
AKAP10	FRMPD4	psi-mi:“MI:0407”(direct interaction)	0.440
AKAP10	TAMALIN	psi-mi:“MI:0407”(direct interaction)	0.440
TIAM2	AKAP10	psi-mi:“MI:0407”(direct interaction)	0.440
AKAP10	MAGI2	psi-mi:“MI:0407”(direct interaction)	0.440
AKAP10	SNTB1	psi-mi:“MI:0407”(direct interaction)	0.440
AKAP10	RHPN1	psi-mi:“MI:0407”(direct interaction)	0.440
AKAP10	PDZRN4	psi-mi:“MI:0407”(direct interaction)	0.440
APBA3	AKAP10	psi-mi:“MI:0407”(direct interaction)	0.440

BioGRID (54): AKAP10 (Two-hybrid), AKAP10 (Two-hybrid), AKAP10 (Affinity Capture-RNA), PRKAR2B (Two-hybrid), IKZF3 (Two-hybrid), AKAP10 (Reconstituted Complex), AKAP10 (Affinity Capture-MS), AKAP10 (Two-hybrid), AKAP10 (Affinity Capture-MS), AKAP10 (Two-hybrid), AKAP10 (Affinity Capture-MS), AKAP10 (Proximity Label-MS), AKAP10 (Affinity Capture-RNA), AKAP10 (Reconstituted Complex), AKAP10 (Proximity Label-MS)

ESM2 similar proteins: A0A088MLT8, A2AFR3, A5PMU4, F1LXF1, O08873, O15034, O43572, O88845, O94967, P0C6S7, P11274, P22681, P22682, P49797, Q01826, Q13905, Q14161, Q14CM0, Q5F3F2, Q5F3L9, Q60611, Q66H91, Q6DRP4, Q6PAJ1, Q6ZM86, Q6ZWB6, Q70E73, Q7Z6G8, Q80U28, Q80U40, Q80U62, Q80YA9, Q86UL8, Q8BIE6, Q8BIZ1, Q8CGF6, Q8K2Y9, Q8QFX1, Q8TEK3, Q8WXG6

Diamond homologs: O43572, O88845, P57770, Q10955

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 117 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
Ras activation upon Ca2+ influx through NMDA receptor	5	38.6×	1e-05
Assembly and cell surface presentation of NMDA receptors	11	37.7×	1e-12
Unblocking of NMDA receptors, glutamate binding and activation	5	36.7×	1e-05
Negative regulation of NMDA receptor-mediated neuronal transmission	5	36.7×	1e-05
Dopamine Neurotransmitter Release Cycle	5	33.5×	1e-05
Long-term potentiation	5	32.1×	2e-05
Neurexins and neuroligins	11	29.3×	1e-11
Protein-protein interactions at synapses	7	25.1×	1e-06

GO biological processes:

GO term	Partners	Fold	FDR
establishment or maintenance of epithelial cell apical/basal polarity	11	57.1×	1e-14
protein localization to synapse	6	41.0×	9e-07
receptor clustering	7	39.0×	1e-07
regulation of postsynaptic membrane neurotransmitter receptor levels	7	31.0×	5e-07
protein-containing complex assembly	9	9.2×	5e-05
cell-cell adhesion	10	9.1×	2e-05
exocytosis	6	8.1×	3e-03
chemical synaptic transmission	9	6.2×	9e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	57
Likely pathogenic	1
Uncertain significance	96
Likely benign	5
Benign	3

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1047866	GRCh37/hg19 17p11.2(chr17:16601603-20063369)	Pathogenic
1330162	GRCh37/hg19 17p11.2(chr17:16829153-20361747)x3	Pathogenic
144213	GRCh38/hg38 17p11.2(chr17:16879232-20316151)x3	Pathogenic
144242	GRCh38/hg38 17p11.2(chr17:18872617-20316151)x1	Pathogenic
146614	GRCh38/hg38 17p11.2(chr17:17331511-20022528)x1	Pathogenic
146753	GRCh38/hg38 17p11.2(chr17:16879233-20390697)x1	Pathogenic
146754	GRCh38/hg38 17p11.2(chr17:16734558-20390697)x3	Pathogenic
146755	GRCh38/hg38 17p11.2(chr17:16734558-20390697)x1	Pathogenic
147756	GRCh38/hg38 17p11.2(chr17:16734588-20390725)x1	Pathogenic
147821	GRCh38/hg38 17p11.2(chr17:16734588-20316151)x1	Pathogenic
148912	GRCh38/hg38 17p11.2(chr17:16699816-20390725)x1	Pathogenic
150319	GRCh38/hg38 17p11.2(chr17:16854250-20560048)x3	Pathogenic
150743	GRCh38/hg38 17p11.2(chr17:16656162-20390697)x1	Pathogenic
151506	GRCh38/hg38 17p11.2(chr17:16699694-20530646)x3	Pathogenic
152261	GRCh38/hg38 17p11.2(chr17:16699816-20492214)x3	Pathogenic
153671	GRCh38/hg38 17p11.2(chr17:16838097-20436415)x1	Pathogenic
153822	GRCh38/hg38 17p11.2(chr17:16858500-20570955)x3	Pathogenic
155114	GRCh38/hg38 17p11.2(chr17:16699816-20428292)x1	Pathogenic
155314	GRCh38/hg38 17p11.2(chr17:16696708-20492860)x3	Pathogenic
155350	GRCh38/hg38 17p11.2(chr17:16718415-20546210)x3	Pathogenic
1703565	GRCh37/hg19 17p11.2(chr17:16651292-20286898)	Pathogenic
1703566	GRCh37/hg19 17p11.2(chr17:17151140-20187953)	Pathogenic
2506529	GRCh37/hg19 17p11.2(chr17:16664739-20370783)	Pathogenic
253426	GRCh37/hg19 17p11.2(chr17:17053390-19893098)x1	Pathogenic
2685598	GRCh37/hg19 17p11.2(chr17:16651293-20450566)x1	Pathogenic
393812	GRCh37/hg19 17p11.2(chr17:16740141-20261191)x3	Pathogenic
393895	GRCh37/hg19 17p11.2(chr17:16603130-20261191)x1	Pathogenic
394152	GRCh37/hg19 17p11.2(chr17:16757564-20261191)x1	Pathogenic
395659	GRCh37/hg19 17p11.2(chr17:16637902-20261250)x1	Pathogenic
441841	GRCh37/hg19 17p11.2(chr17:16727264-20413564)x1	Pathogenic

SpliceAI

2734 predictions. Top by Δscore:

Variant	Effect	Δscore
17:19906228:CATAA:C	acceptor_gain	1.0000
17:19906230:TAA:T	acceptor_gain	1.0000
17:19906233:C:CC	acceptor_gain	1.0000
17:19909175:CCTTA:C	donor_loss	1.0000
17:19909176:CTTA:C	donor_loss	1.0000
17:19909177:TTA:T	donor_loss	1.0000
17:19909178:TACCT:T	donor_loss	1.0000
17:19909180:C:T	donor_loss	1.0000
17:19909276:CCTAA:C	acceptor_loss	1.0000
17:19909277:C:CA	acceptor_loss	1.0000
17:19909277:C:CC	acceptor_gain	1.0000
17:19909278:T:G	acceptor_loss	1.0000
17:19920115:CTTC:C	acceptor_gain	1.0000
17:19920118:CCTAA:C	acceptor_loss	1.0000
17:19920119:C:CC	acceptor_gain	1.0000
17:19920120:T:A	acceptor_loss	1.0000
17:19924401:AGCTT:A	donor_loss	1.0000
17:19924402:GCTTA:G	donor_loss	1.0000
17:19924403:CTTA:C	donor_loss	1.0000
17:19924404:TTA:T	donor_loss	1.0000
17:19924405:TACCC:T	donor_loss	1.0000
17:19924406:A:AT	donor_loss	1.0000
17:19924406:AC:A	donor_gain	1.0000
17:19924407:C:A	donor_loss	1.0000
17:19924407:CC:C	donor_gain	1.0000
17:19924407:CCCGG:C	donor_gain	1.0000
17:19924513:CTGGA:C	acceptor_gain	1.0000
17:19924514:TGGA:T	acceptor_gain	1.0000
17:19924515:GGA:G	acceptor_gain	1.0000
17:19924518:C:CC	acceptor_gain	1.0000

AlphaMissense

4385 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:19909248:G:T	A639D	1.000
17:19920104:C:T	G589E	1.000
17:19931923:A:G	L508P	1.000
17:19936326:A:G	F476S	1.000
17:19936328:A:C	C475W	1.000
17:19936329:C:T	C475Y	1.000
17:19936330:A:G	C475R	1.000
17:19936341:G:T	P471Q	1.000
17:19936359:A:C	I465S	1.000
17:19936359:A:T	I465N	1.000
17:19936367:T:A	E462D	1.000
17:19936367:T:G	E462D	1.000
17:19939731:G:T	A435D	1.000
17:19939732:C:G	A435P	1.000
17:19939779:A:G	L419P	1.000
17:19939791:A:G	F415S	1.000
17:19939801:C:G	A412P	1.000
17:19940954:A:G	L373P	1.000
17:19947466:A:T	I306K	1.000
17:19909249:C:G	A639P	0.999
17:19920079:G:C	F597L	0.999
17:19920079:G:T	F597L	0.999
17:19920080:A:G	F597S	0.999
17:19920081:A:G	F597L	0.999
17:19920086:C:T	G595E	0.999
17:19920105:C:G	G589R	0.999
17:19920105:C:T	G589R	0.999
17:19924429:A:G	L577S	0.999
17:19931932:A:G	L505S	0.999
17:19931936:A:C	Y504D	0.999

dbSNP variants (sampled 300 via entrez): RS1000032878 (17:19959475 T>C), RS1000094371 (17:19959006 C>G,T), RS1000147763 (17:19918036 A>G), RS1000168898 (17:19968693 A>T), RS1000220922 (17:19969071 C>A,T), RS1000263377 (17:19917986 C>T), RS1000311322 (17:19930668 G>A,C), RS1000342015 (17:19930912 C>T), RS1000353177 (17:19923661 G>A), RS1000366859 (17:19939478 C>T), RS1000409781 (17:19974337 G>A), RS1000433026 (17:19947022 G>A), RS1000451151 (17:19911690 C>T), RS1000529696 (17:19959253 A>C), RS1000597571 (17:19919284 C>T)

Disease associations

OMIM: gene MIM:604694 | disease phenotypes: MIM:610883, MIM:182290, MIM:115080

GenCC curated gene-disease

Mondo (3): Potocki-Lupski syndrome (MONDO:0012574), Smith-Magenis syndrome (MONDO:0008434), cardiac conduction defect (MONDO:0100042)

Orphanet (3): 17p11.2 microduplication syndrome (Orphanet:1713), Smith-Magenis syndrome (Orphanet:819), Hereditary progressive cardiac conduction defect (Orphanet:871)

HPO phenotypes

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

GWAS associations

11 associations (top):

Study	Trait	p-value
GCST001337_49	Platelet count	2.000000e-09
GCST004599_116	Mean platelet volume	5.000000e-14
GCST004603_175	Platelet count	3.000000e-11
GCST004946_7	Schizophrenia	4.000000e-08
GCST006100_1	Strenuous sports or other exercises	3.000000e-11
GCST008128_2	Body mass index	1.000000e-07
GCST008129_28	Body mass index	2.000000e-07
GCST010083_71	Hemoglobin levels	2.000000e-09
GCST010703_51	Brain morphology (MOSTest)	1.000000e-08
GCST90002398_265	Neutrophil count	2.000000e-09
GCST90002402_442	Platelet count	2.000000e-18

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:0004309	platelet count
EFO:0008002	physical activity measurement
EFO:0004340	body mass index
EFO:0004509	hemoglobin measurement
EFO:0004346	neuroimaging measurement
EFO:0004833	neutrophil count

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D058496	Smith-Magenis Syndrome	C10.281.900; C16.131.077.879; C16.131.260.887; C16.320.180.887

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases expression, decreases methylation, increases expression	3
Acetaminophen	increases expression, decreases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
FR900359	decreases phosphorylation	1
bisphenol F	affects cotreatment, decreases expression	1
dicrotophos	decreases expression	1
trichostatin A	increases expression	1
beta-lapachone	decreases expression	1
arsenite	affects binding, decreases reaction	1
di-n-butylphosphoric acid	affects expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
abrine	increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
Irinotecan	decreases expression	1
Resveratrol	affects cotreatment, increases expression	1
Leflunomide	increases expression	1
Atrazine	increases expression	1
Benzo(a)pyrene	decreases methylation	1
Caffeine	decreases phosphorylation	1
Demecolcine	increases expression	1
Dexamethasone	decreases expression, affects cotreatment	1
Doxorubicin	decreases expression	1
Formaldehyde	decreases expression	1
Indomethacin	affects cotreatment, decreases expression	1
Lead	affects expression	1
Methyl Methanesulfonate	increases expression	1
Plant Extracts	affects cotreatment, increases expression	1
Tretinoin	increases expression	1
Vincristine	increases expression	1
1-Methyl-3-isobutylxanthine	affects cotreatment, decreases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT02776215	PHASE1	COMPLETED	Study of the Pharmacokinetics and Safety of Tasimelteon in Children and Adolescents
NCT02231008	PHASE2/PHASE3	COMPLETED	Evaluating the Effects of Tasimelteon vs Placebo on Sleep Disturbances in SMS
NCT00004351	Not specified	COMPLETED	Study of Phenotype and Genotype Correlations in Patients With Contiguous Gene Deletion Syndromes
NCT00013559	Not specified	ACTIVE_NOT_RECRUITING	Natural History Study of Smith-Magenis Syndrome
NCT01837121	Not specified	COMPLETED	a Trial of Using SMS Reminder Among Diabetic Retinopathy Patients in Rural China
NCT02180451	Not specified	UNKNOWN	Observational Study to Investigate the Melatonin and Cortisol Circadian Rhythms of Individuals With Smith-Magenis Syndrome (SMS)
NCT02400671	Not specified	COMPLETED	Mobile Strategies for Women’s and Children’s Health: Optimizing Adherence and Efficacy of PMTCT/ART
NCT03346616	Not specified	COMPLETED	Text4Peds: Short Message Service Evaluating Medical Student Education
NCT03379467	Not specified	COMPLETED	Use of SMS and Interactive Reminders to Improve Timely Immunization Coverage
NCT03492970	Not specified	COMPLETED	Melatonin in Adults With SMS
NCT03836300	Not specified	ENROLLING_BY_INVITATION	Parent and Infant Inter(X)Action Intervention (PIXI)
NCT04768803	Not specified	UNKNOWN	Ghrelin in Patients With a Rare Disease Associated With Intellectual Disability, and Hyperphagia, and/or Overweight, and/or Obesity
NCT05116904	Not specified	RECRUITING	Smith Magenis Syndrome and Autism Spectrum Disorders
NCT06247852	Not specified	COMPLETED	Persistent Pain After Cesarean Delivery - A Danish Multicenter Cohort Study
NCT07510971	Not specified	NOT_YET_RECRUITING	mHealth Intervention for Improving Vaccination Coverage in Bangladesh
NCT01609738	Not specified	COMPLETED	Left Ventricular Septum Pacing in Patients by Transvenous Approach Through the Inter-ventricular Septum
NCT02881671	Not specified	UNKNOWN	Identification of Genetic Basis of Atrioventricular Conduction Defects: From Congenital Forms to Degenerative Forms
NCT03024047	Not specified	UNKNOWN	Cohort Description of Younger With AV-block
NCT03947021	Not specified	UNKNOWN	Developing Methods for Reconstructing Electrical Heart Activity
NCT04776642	Not specified	RECRUITING	Biobank for Arrhythmia and Conduction Disorders: TowArd Pathophysiology Based Treatment
NCT06278844	Not specified	RECRUITING	Exercise Capacity Improvement by Conduction System Pacing in heArt Failure patieNts Without Compelling CRT inDication
NCT06371846	Not specified	UNKNOWN	Comparative Study of the Surface Electrocardiogram Signals During the Implantation of Conduction System Pacing Devices
NCT06620237	Not specified	ACTIVE_NOT_RECRUITING	BIO|MASTER.CSP Study
NCT06857201	Not specified	WITHDRAWN	RAFT-TAVR PACE: LBBAP vs. RVP Post-TAVR in Patients Requiring PPI
NCT07201363	Not specified	RECRUITING	Biomarkers of Inflammation and Fibrosis in Conduction Disorders After TAVI