AKAP6

Summary

AKAP6 (A-kinase anchoring protein 6, HGNC:376) is a protein-coding gene on chromosome 14q12, encoding A-kinase anchor protein 6 (Q13023). Binds to type II regulatory subunits of protein kinase A and anchors/targets them to the nuclear membrane or sarcoplasmic reticulum.

The A-kinase anchor proteins (AKAPs) are a group of structurally diverse proteins, which have the common function of binding to the regulatory subunit of protein kinase A (PKA) and confining the holoenzyme to discrete locations within the cell. This gene encodes a member of the AKAP family. The encoded protein is highly expressed in various brain regions and cardiac and skeletal muscle. It is specifically localized to the sarcoplasmic reticulum and nuclear membrane, and is involved in anchoring PKA to the nuclear membrane or sarcoplasmic reticulum.

Source: NCBI Gene 9472 — RefSeq curated summary.

At a glance

• Gene–disease (curated): neurodevelopmental disorder (Moderate, GenCC)
• GWAS associations: 58
• Clinical variants (ClinVar): 377 total — 8 pathogenic
• MANE Select transcript: NM_004274

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:376
Approved symbol	AKAP6
Name	A-kinase anchoring protein 6
Location	14q12
Locus type	gene with protein product
Status	Approved
Aliases	KIAA0311, mAKAP, AKAP100, PRKA6, ADAP6
Ensembl gene	ENSG00000151320
Ensembl biotype	protein_coding
OMIM	604691
Entrez	9472

Gene structure

Transcript identifiers

Ensembl transcripts: 18 — 11 protein_coding, 6 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000280979, ENST00000553547, ENST00000554410, ENST00000554449, ENST00000554740, ENST00000555207, ENST00000555950, ENST00000556037, ENST00000556540, ENST00000556638, ENST00000557102, ENST00000557272, ENST00000557354, ENST00000557396, ENST00000557708, ENST00000851220, ENST00000851221, ENST00000851222

RefSeq mRNA: 1 — MANE Select: NM_004274 NM_004274

CCDS: CCDS9644

Canonical transcript exons

ENST00000280979 — 14 exons

Exon	Start	End
ENSE00000998907	32599410	32599506
ENSE00000998908	32600629	32600792
ENSE00000998914	32773678	32773893
ENSE00000998915	32821402	32824815
ENSE00000999466	32545230	32546999
ENSE00000999467	32577120	32577242
ENSE00001289147	32829848	32837684
ENSE00002486850	32329298	32329408
ENSE00003517003	32678311	32678459
ENSE00003562715	32732454	32732600
ENSE00003596649	32535554	32535805
ENSE00003604313	32735658	32735882
ENSE00003660885	32695990	32696110
ENSE00003791340	32433460	32433817

Expression profiles

Bgee: expression breadth ubiquitous, 226 present calls, max score 90.74.

FANTOM5 (CAGE): breadth broad, TPM avg 14.6241 / max 1119.5819, expressed in 490 samples.

FANTOM5 promoters (19 alternative TSS)

Promoter ID	TPM avg	Samples expressed
139122	8.9405	261
139123	3.0385	217
139137	0.8167	163
139136	0.3981	126
139130	0.3309	97
139134	0.3166	51
139139	0.2826	127
139140	0.1452	87
139141	0.1246	49
139129	0.0417	22

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cortical plate	UBERON:0005343	90.74	gold quality
gastrocnemius	UBERON:0001388	90.51	gold quality
muscle of leg	UBERON:0001383	90.45	gold quality
prefrontal cortex	UBERON:0000451	90.38	gold quality
hindlimb stylopod muscle	UBERON:0004252	90.27	gold quality
heart left ventricle	UBERON:0002084	90.20	gold quality
cardiac ventricle	UBERON:0002082	89.78	gold quality
ventricular zone	UBERON:0003053	87.99	gold quality
Brodmann (1909) area 9	UBERON:0013540	87.95	gold quality
popliteal artery	UBERON:0002250	87.89	gold quality
tibial artery	UBERON:0007610	87.87	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	87.83	gold quality
heart	UBERON:0000948	87.77	gold quality
cingulate cortex	UBERON:0003027	87.69	gold quality
anterior cingulate cortex	UBERON:0009835	87.54	gold quality
skeletal muscle organ	UBERON:0014892	87.32	gold quality
muscle organ	UBERON:0001630	87.31	gold quality
ganglionic eminence	UBERON:0004023	87.27	gold quality
neocortex	UBERON:0001950	86.89	gold quality
frontal cortex	UBERON:0001870	86.88	gold quality
aorta	UBERON:0000947	86.78	gold quality
apex of heart	UBERON:0002098	86.56	gold quality
right atrium auricular region	UBERON:0006631	86.54	gold quality
right frontal lobe	UBERON:0002810	86.53	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	86.41	gold quality
ascending aorta	UBERON:0001496	85.83	gold quality
thoracic aorta	UBERON:0001515	85.69	gold quality
colonic epithelium	UBERON:0000397	85.58	gold quality
cerebral cortex	UBERON:0000956	85.57	gold quality
cardiac atrium	UBERON:0002081	85.48	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-GEOD-75140	yes	1342.10
E-GEOD-100618	yes	259.12
E-MTAB-11268	no	2003.83
E-MTAB-2983	no	483.47
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

265 targeting AKAP6, 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-3646	100.00	73.56	5283
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-3120-5P	100.00	65.56	965
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-518D-5P	100.00	67.51	979
HSA-MIR-518E-5P	100.00	67.66	954
HSA-MIR-518F-5P	100.00	67.51	979
HSA-MIR-519A-5P	100.00	67.66	954
HSA-MIR-519B-5P	100.00	67.66	954
HSA-MIR-519C-5P	100.00	67.66	954
HSA-MIR-520C-5P	100.00	67.51	979
HSA-MIR-522-5P	100.00	67.66	954
HSA-MIR-523-5P	100.00	67.66	954
HSA-MIR-526A-5P	100.00	67.51	979
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-4500	99.99	72.72	2367
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

Literature-anchored findings (GeneRIF, showing 9)

• mAKAP organized ubiquitin E3 ligases that managed the stability of HIF-1alpha and optimally positioned it close to its site of action inside the nucleus (PMID:19109240)
• cAMP-stimulated protein phosphatase 2A activity associated with muscle A kinase-anchoring protein (mAKAP) signaling complexes inhibits the phosphorylation and activity of the cAMP-specific phosphodiesterase PDE4D3 (PMID:20106966)
• This study expands our understanding of the regulation of MEF2 in skeletal muscle and identifies the mAKAP scaffold as a facilitator of MEF2 transcription and myogenic differentiation. (PMID:22484155)
• Comparative analysis of the binding responses of mutations to mAKAP could provide important information about how these mutations modulate PKA and PDE4D3 signaling. (PMID:23806656)
• Findings indicate a interplay between A-kinase anchoring protein 6 (AKAP6) and myogenin. (PMID:26563778)
• Two single nucleotide polymorphisms (SNPs), MIR211-rs10457441 and AKAP6-rs17522122 were genotyped in 1570 non-demented older Australians of European ancestry. AKAP6-rs17522122*T was associated with worse baseline performance in episodic memory, working memory, vocabulary and perceptual speed, but it was not associated with cognitive change in any domain. (PMID:28067462)
• AKAP6 SNPs found in human patients with cardiovascular diseases significantly affect the cAMP/PKA signaling pathway. (PMID:29600899)
• Inherited variants in ARHGEF10L and AKAP6, with potential transcriptional regulatory function and association with Epithelial ovarian cancer risk, warrant investigation in independent Epithelial ovarian cancer study populations. (PMID:29979793)
• This study provided evidence for the impact of AKAP6 polymorphisms on susceptibility and prognosis of glioma, suggesting AKAP6 variants might have potential roles in the etiology of glioma. (PMID:31759389)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	akap6	ENSDARG00000077295
mus_musculus	Akap6	ENSMUSG00000061603
rattus_norvegicus	Akap6	ENSRNOG00000004841

Paralogs (1): CEP68 (ENSG00000011523)

Protein

Protein identifiers

A-kinase anchor protein 6 — Q13023 (reviewed: Q13023)

Alternative names: A-kinase anchor protein 100 kDa, Protein kinase A-anchoring protein 6, mAKAP

All UniProt accessions (7): Q13023, G3V3B5, G3V3H2, G3V3H6, G3V3H7, G3V569, H0YJT7

UniProt curated annotations — full annotation on UniProt →

Function. Binds to type II regulatory subunits of protein kinase A and anchors/targets them to the nuclear membrane or sarcoplasmic reticulum. May act as an adapter for assembling multiprotein complexes.

Subunit / interactions. Interacts with RII subunit of PKA, phosphatase 2B (calcineurin) and AKAP79. Interacts with SYNPO2.

Subcellular location. Sarcoplasmic reticulum. Nucleus membrane.

Tissue specificity. Highly expressed in cardiac and skeletal muscle, followed by brain.

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.

Isoforms (2)

UniProt ID	Names	Canonical?
Q13023-1	1	yes
Q13023-2	2

RefSeq proteins (1): NP_004265* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002017	Spectrin_repeat	Repeat
IPR018159	Spectrin/alpha-actinin	Repeat

Pfam: PF00435

UniProt features (47 total): sequence variant 15, compositionally biased region 12, region of interest 11, modified residue 3, repeat 2, splice variant 2, chain 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q13023-F1	43.07	0.02

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): 1073, 1570, 1595

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 320 (showing top): GOBP_POTASSIUM_ION_TRANSPORT, GOBP_POSITIVE_REGULATION_OF_CALCIUM_ION_TRANSPORT, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_MUSCLE_TISSUE_DEVELOPMENT, GOBP_REGULATION_OF_CALCIUM_MEDIATED_SIGNALING, GOBP_RESPONSE_TO_PEPTIDE, GOBP_REGULATION_OF_DEVELOPMENTAL_GROWTH, GOBP_POSITIVE_REGULATION_OF_MUSCLE_CELL_DIFFERENTIATION, GOBP_GROWTH, GOBP_PROTEIN_TARGETING, GOBP_STRIATED_MUSCLE_CELL_DIFFERENTIATION, GOBP_POSITIVE_REGULATION_OF_HEART_GROWTH, GOBP_REGULATION_OF_STRIATED_MUSCLE_CELL_DIFFERENTIATION, GOBP_RELAXATION_OF_CARDIAC_MUSCLE, CTATGCA_MIR153

GO Biological Process (16): action potential (GO:0001508), protein targeting (GO:0006605), adenylate cyclase-activating G protein-coupled receptor signaling pathway (GO:0007189), obsolete positive regulation of protein kinase A signaling (GO:0010739), regulation of release of sequestered calcium ion into cytosol by sarcoplasmic reticulum (GO:0010880), positive regulation of cell growth (GO:0030307), positive regulation of release of sequestered calcium ion into cytosol (GO:0051281), regulation of membrane repolarization (GO:0060306), positive regulation of cell growth involved in cardiac muscle cell development (GO:0061051), positive regulation of calcineurin-NFAT signaling cascade (GO:0070886), cellular response to cAMP (GO:0071320), cellular response to cytokine stimulus (GO:0071345), regulation of cAMP/PKA signal transduction (GO:0141161), positive regulation of potassium ion transmembrane transport (GO:1901381), regulation of metal ion transport (GO:0010959), positive regulation of cation transmembrane transport (GO:1904064)

GO Molecular Function (7): adenylate cyclase binding (GO:0008179), protein kinase A regulatory subunit binding (GO:0034237), protein-membrane adaptor activity (GO:0043495), transmembrane transporter binding (GO:0044325), protein kinase A binding (GO:0051018), molecular adaptor activity (GO:0060090), protein binding (GO:0005515)

GO Cellular Component (13): nuclear envelope (GO:0005635), cytoplasm (GO:0005737), caveola (GO:0005901), junctional sarcoplasmic reticulum membrane (GO:0014701), intercalated disc (GO:0014704), sarcoplasmic reticulum (GO:0016529), T-tubule (GO:0030315), nuclear membrane (GO:0031965), calcium channel complex (GO:0034704), perinuclear region of cytoplasm (GO:0048471), nucleus (GO:0005634), membrane (GO:0016020), protein-containing complex (GO:0032991)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
regulation of membrane potential	2
regulation of release of sequestered calcium ion into cytosol	2
protein binding	2
binding	2
nucleus	2
establishment of protein localization	1
adenylate cyclase-modulating G protein-coupled receptor signaling pathway	1
adenylate cyclase activator activity	1
release of sequestered calcium ion into cytosol by sarcoplasmic reticulum	1
regulation of cell growth	1
cell growth	1
positive regulation of growth	1
positive regulation of cellular process	1
release of sequestered calcium ion into cytosol	1
positive regulation of calcium ion transmembrane transport	1
regulation of biological process	1
membrane repolarization	1
positive regulation of cardiac muscle hypertrophy	1
positive regulation of cell growth	1
positive regulation of striated muscle cell differentiation	1
positive regulation of cardiac muscle tissue growth	1
cell growth involved in cardiac muscle cell development	1
regulation of cell growth involved in cardiac muscle cell development	1
calcineurin-NFAT signaling cascade	1
regulation of calcineurin-NFAT signaling cascade	1
positive regulation of calcineurin-mediated signaling	1
response to cAMP	1
cellular response to nitrogen compound	1
cellular response to oxygen-containing compound	1
response to cytokine	1
cAMP/PKA signal transduction	1
regulation of intracellular signal transduction	1
positive regulation of potassium ion transport	1
potassium ion transmembrane transport	1
regulation of potassium ion transmembrane transport	1
positive regulation of cation transmembrane transport	1
metal ion transport	1
regulation of monoatomic ion transport	1
positive regulation of monoatomic ion transmembrane transport	1

Protein interactions and networks

STRING

1070 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
AKAP6	RYR2	Q92736	984
AKAP6	RAPGEF3	O95398	965
AKAP6	MAPK7	Q13164	958
AKAP6	PRKACA	P17612	951
AKAP6	PRKACG	P22612	951
AKAP6	PRKACB	P22694	951
AKAP6	AKAP1	Q92667	931
AKAP6	FKBP1B	P68106	929
AKAP6	PDE4D	Q08499	925
AKAP6	PDE4A	P27815	921
AKAP6	AKAP7	O43687	810
AKAP6	ALDH7A1	P49419	810
AKAP6	AKAP5	P24588	800
AKAP6	AKAP9	Q99996	753
AKAP6	PPP2R5D	Q14738	697

IntAct

21 interactions, top by confidence:

A	B	Type	Score
OPTN	AKAP6	psi-mi:“MI:2364”(proximity)	0.450
ABL1	AKAP6	psi-mi:“MI:0915”(physical association)	0.400
AKAP6	CRK	psi-mi:“MI:0915”(physical association)	0.400
AKAP6	SRC	psi-mi:“MI:0915”(physical association)	0.400
AKAP6	FYN	psi-mi:“MI:0915”(physical association)	0.400
GRB2	AKAP6	psi-mi:“MI:0915”(physical association)	0.400
AKAP6	NCK1	psi-mi:“MI:0915”(physical association)	0.400
AKAP6	PIK3R1	psi-mi:“MI:0915”(physical association)	0.400
Mecom	ESYT2	psi-mi:“MI:0914”(association)	0.350
AKAP6	RYR2	psi-mi:“MI:0403”(colocalization)	0.270
	AKAP6	psi-mi:“MI:0915”(physical association)	0.000
AKAP6	DTNBP1	psi-mi:“MI:0915”(physical association)	0.000
FMR1	AKAP6	psi-mi:“MI:0915”(physical association)	0.000
TRAF3IP1	AKAP6	psi-mi:“MI:0915”(physical association)	0.000
DISC1	AKAP6	psi-mi:“MI:0915”(physical association)	0.000
CDC5L	AKAP6	psi-mi:“MI:0915”(physical association)	0.000
AKAP6		psi-mi:“MI:0915”(physical association)	0.000
NRIP1	AKAP6	psi-mi:“MI:0915”(physical association)	0.000
PCNT	AKAP6	psi-mi:“MI:0915”(physical association)	0.000
AKAP6	OPTN	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (21): AKAP6 (Reconstituted Complex), AKAP6 (Reconstituted Complex), AKAP6 (Affinity Capture-RNA), AKAP6 (Protein-peptide), AKAP6 (Co-fractionation), AKAP6 (Two-hybrid), AKAP6 (Co-localization), PDE4A (Affinity Capture-Western), AKAP6 (Affinity Capture-Western), AKAP6 (Affinity Capture-Western), AKAP6 (Reconstituted Complex), AKAP6 (Two-hybrid), AKAP6 (Two-hybrid), AKAP6 (Affinity Capture-Western), EEA1 (Cross-Linking-MS (XL-MS))

ESM2 similar proteins: A2CG63, B8A5Y1, E1C213, E2RK09, F1N5V1, F1SRY5, G3V8T1, O60934, O75475, O94988, O96028, P29374, P46100, Q0VEE6, Q13023, Q2TB10, Q3TYA6, Q4LE39, Q5F363, Q5HYC2, Q5RCV3, Q5VYS8, Q62315, Q66T72, Q68FE9, Q6NVE8, Q6P7W0, Q7TP65, Q7YQM3, Q7YQM4, Q812D1, Q86T82, Q8BVE8, Q8C0R0, Q8IVF5, Q8IZM8, Q8MJG1, Q8N302, Q8NDB2, Q8VBW5

Diamond homologs: Q13023, Q8C0D9, Q9WVC7, Q5RCQ2, Q76N32

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 18 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
Downstream signal transduction	5	135.9×	3e-08
FCGR3A-mediated phagocytosis	6	80.2×	2e-08
VEGFA-VEGFR2 Pathway	5	49.7×	2e-06

GO biological processes:

GO term	Partners	Fold	FDR
ephrin receptor signaling pathway	5	107.5×	3e-07

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	8
Likely pathogenic	0
Uncertain significance	302
Likely benign	21
Benign	5

Top pathogenic / likely-pathogenic (8)

Variant ID	HGVS	Classification
146008	GRCh38/hg38 14q12-21.1(chr14:30382554-37712341)x1	Pathogenic
154183	GRCh38/hg38 14q12-13.1(chr14:28803988-33234266)x1	Pathogenic
154996	GRCh38/hg38 14q12-21.2(chr14:30792271-44685131)x1	Pathogenic
1809348	GRCh37/hg19 14q12-13.1(chr14:24959823-33415359)x1	Pathogenic
3063324	GRCh37/hg19 14q12-21.2(chr14:29190489-45325177)x1	Pathogenic
3391922	GRCh37/hg19 14q12-21.2(chr14:30935698-44461013)x1	Pathogenic
58523	GRCh38/hg38 14q12-21.2(chr14:30670314-44990595)x3	Pathogenic
688414	GRCh37/hg19 14q12-13.1(chr14:30448939-35017859)x1	Pathogenic

SpliceAI

5800 predictions. Top by Δscore:

Variant	Effect	Δscore
14:32329405:GATG:G	donor_gain	1.0000
14:32433459:GCT:G	acceptor_gain	1.0000
14:32433813:TAAAG:T	donor_loss	1.0000
14:32433814:AAAG:A	donor_loss	1.0000
14:32433818:GT:G	donor_loss	1.0000
14:32433819:T:A	donor_loss	1.0000
14:32443762:GGGA:G	donor_gain	1.0000
14:32443763:GGAG:G	donor_gain	1.0000
14:32535551:CAG:C	acceptor_loss	1.0000
14:32535552:AGGAC:A	acceptor_loss	1.0000
14:32535553:G:A	acceptor_loss	1.0000
14:32535553:GGAC:G	acceptor_gain	1.0000
14:32535802:AGAG:A	donor_gain	1.0000
14:32535803:GAG:G	donor_gain	1.0000
14:32535803:GAGG:G	donor_gain	1.0000
14:32535805:GGTG:G	donor_loss	1.0000
14:32535806:G:GA	donor_loss	1.0000
14:32535806:G:GG	donor_gain	1.0000
14:32535807:T:G	donor_loss	1.0000
14:32546997:GAG:G	donor_gain	1.0000
14:32546999:GGTAA:G	donor_loss	1.0000
14:32547000:G:GC	donor_loss	1.0000
14:32547001:T:G	donor_loss	1.0000
14:32577115:ACAAG:A	acceptor_gain	1.0000
14:32577117:A:AG	acceptor_gain	1.0000
14:32577117:AAG:A	acceptor_gain	1.0000
14:32577117:AAGG:A	acceptor_gain	1.0000
14:32577117:AAGGG:A	acceptor_gain	1.0000
14:32577118:A:G	acceptor_gain	1.0000
14:32577118:AGG:A	acceptor_gain	1.0000

AlphaMissense

15401 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
14:32433683:T:A	W64R	1.000
14:32433683:T:C	W64R	1.000
14:32433719:T:A	W76R	1.000
14:32433719:T:C	W76R	1.000
14:32433723:T:C	L77P	1.000
14:32433753:T:C	L87P	1.000
14:32433804:T:C	L104P	1.000
14:32433813:T:C	L107P	1.000
14:32535582:T:A	V118D	1.000
14:32535600:T:C	L124P	1.000
14:32535603:T:C	L125P	1.000
14:32535680:T:A	W151R	1.000
14:32535680:T:C	W151R	1.000
14:32535682:G:C	W151C	1.000
14:32535682:G:T	W151C	1.000
14:32535690:T:C	L154P	1.000
14:32535711:T:C	L161P	1.000
14:32433685:G:C	W64C	0.999
14:32433685:G:T	W64C	0.999
14:32433693:T:A	V67D	0.999
14:32433696:T:C	L68P	0.999
14:32433702:T:C	L70S	0.999
14:32433721:G:C	W76C	0.999
14:32433721:G:T	W76C	0.999
14:32433723:T:A	L77H	0.999
14:32433744:T:A	V84D	0.999
14:32433817:G:C	K108N	0.999
14:32433817:G:T	K108N	0.999
14:32535560:T:C	C111R	0.999
14:32535562:T:G	C111W	0.999

dbSNP variants (sampled 300 via entrez): RS1000001830 (14:32659263 C>G), RS1000008881 (14:32507158 T>A), RS1000012293 (14:32594265 A>G), RS1000014896 (14:32465761 A>C,G), RS1000018660 (14:32465459 G>A), RS1000022011 (14:32416656 G>A), RS1000022679 (14:32825774 C>A,T), RS1000026249 (14:32636907 T>C), RS1000026555 (14:32459475 A>G), RS1000028647 (14:32332275 A>C), RS1000045475 (14:32412718 C>T), RS1000049167 (14:32768424 A>C), RS1000050219 (14:32807086 A>C,G), RS1000050237 (14:32785073 C>A), RS1000050647 (14:32612132 C>T)

Disease associations

OMIM: gene MIM:604691 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
neurodevelopmental disorder	Moderate	Autosomal dominant

Mondo (1): neurodevelopmental disorder (MONDO:0700092)

Orphanet (0):

HPO phenotypes

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

GWAS associations

58 associations (top):

Study	Trait	p-value
GCST000873_3	Anorexia nervosa	6.000000e-06
GCST001512_5	Economic and political preferences (environmentalism)	6.000000e-06
GCST001526_15	Fasting blood insulin (BMI interaction)	5.000000e-07
GCST002774_26	Cognitive function	3.000000e-08
GCST002783_299	Body mass index	3.000000e-06
GCST002783_31	Body mass index	6.000000e-06
GCST002783_555	Body mass index	3.000000e-06
GCST002875_136	Diisocyanate-induced asthma	2.000000e-06
GCST003542_58	Night sleep phenotypes	7.000000e-06
GCST003992_41	Photic sneeze reflex	6.000000e-16
GCST004347_5	Glioma	2.000000e-06
GCST004348_19	Non-glioblastoma glioma	5.000000e-11
GCST004557_237	Body mass index	3.000000e-08
GCST004557_25	Body mass index	2.000000e-08
GCST004557_66	Body mass index	4.000000e-06
GCST004558_157	Body mass index (joint analysis main effects and physical activity interaction)	7.000000e-08
GCST004558_22	Body mass index (joint analysis main effects and physical activity interaction)	3.000000e-08
GCST004559_101	Body mass index in physically active individuals	6.000000e-08
GCST004559_18	Body mass index in physically active individuals	3.000000e-08
GCST004904_117	Body mass index	4.000000e-09
GCST004946_18	Schizophrenia	2.000000e-08
GCST005212_24	Asthma	4.000000e-06
GCST005316_411	Intelligence (MTAG)	1.000000e-09
GCST005316_528	Intelligence (MTAG)	1.000000e-10
GCST005316_529	Intelligence (MTAG)	2.000000e-09
GCST005316_530	Intelligence (MTAG)	2.000000e-12
GCST006014_20	Creatine kinase levels	1.000000e-10
GCST006061_149	Atrial fibrillation	1.000000e-13
GCST006061_156	Atrial fibrillation	2.000000e-21
GCST006061_157	Atrial fibrillation	2.000000e-17

EFO canonical traits (16, from GWAS)

EFO ID	Trait name
EFO:0004827	economic and social preference
EFO:0004340	body mass index
EFO:0004337	intelligence
EFO:0006995	response to diisocyanate
EFO:0007887	autosomal dominant compelling helio-ophthalmic outburst syndrome
EFO:0008002	physical activity measurement
EFO:0004534	creatine kinase measurement
EFO:0004847	age at onset
EFO:0006781	coffee consumption measurement
EFO:0004784	self reported educational attainment
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0004462	PR interval
EFO:0009819	comparative body size at age 10, self-reported
EFO:0006335	systolic blood pressure
EFO:0004531	urate measurement
EFO:0009749	age at first sexual intercourse measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D065886	Neurodevelopmental Disorders	F03.625

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases expression, increases methylation	2
aristolochic acid I	decreases expression	1
methyleugenol	decreases expression	1
bisphenol A	decreases methylation, affects cotreatment	1
beta-lapachone	decreases expression	1
arsenite	affects binding, decreases reaction	1
sodium arsenite	increases expression	1
zinc chromate	increases abundance, increases expression	1
aflatoxin B2	increases methylation	1
S-(1,2-dichlorovinyl)cysteine	affects cotreatment, affects response to substance, increases expression	1
chromium hexavalent ion	increases expression, increases abundance	1
CGP 52608	affects binding, increases reaction	1
bisphenol S	decreases methylation	1
incobotulinumtoxinA	decreases expression	1
Sunitinib	decreases expression	1
Fulvestrant	affects cotreatment, decreases methylation	1
Air Pollutants	increases abundance, increases expression	1
Curcumin	increases expression	1
Cycloheximide	decreases expression, decreases reaction	1
Diethylhexyl Phthalate	decreases expression	1
Doxorubicin	decreases expression	1
Estradiol	decreases expression, affects cotreatment	1
Lead	affects expression	1
Lipopolysaccharides	affects response to substance, increases expression, affects cotreatment	1
N-Nitrosopyrrolidine	decreases expression	1
Testosterone	decreases expression	1
Tetrachlorodibenzodioxin	decreases expression, decreases reaction	1
Tobacco Smoke Pollution	decreases expression	1
Triclosan	decreases expression	1
Cadmium Chloride	increases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT04586348	PHASE4	UNKNOWN	Prenatal Iodine Supplementation and Early Childhood Neurodevelopment
NCT04873115	PHASE4	UNKNOWN	Double-blind, Placebo-controlled, Randomized Clinical Trial Comparing the Efficacy and Safety of Sialanar Plus orAl rehabiLitation Against Placebo Plus Oral Rehabilitation for chIldren and Adolescents With seVere Sialorrhoea and Neurodisabilties,
NCT02559102	PHASE3	COMPLETED	Dexmedetomidine Sedation Versus General Anaesthesia for Inguinal Hernia Surgery in Infants
NCT02757079	PHASE3	COMPLETED	Study of the Efficacy and Safety of NPC-15 for Sleep Disorders of Children With Neurodevelopmental Disorders
NCT06915480	PHASE3	RECRUITING	Reducing Missed Appointments
NCT07377032	PHASE3	RECRUITING	TAP-GRIN: Interventional Study on Patients With GRIN-related Neurodevelopmental Disorders
NCT02909959	PHASE2	COMPLETED	Sulforaphane for the Treatment of Young Men With Autism Spectrum Disorder
NCT06081348	PHASE2	RECRUITING	Sertraline vs. Placebo in the Treatment of Anxiety in Children and AdoLescents With NeurodevelopMental Disorders
NCT06352372	PHASE2	COMPLETED	Safety and Efficacy of tPBM for Epileptiform Activity in Autism
NCT00503191	PHASE1	COMPLETED	NeuroModulation Technique Treatment of Autism
NCT04475848	PHASE1	COMPLETED	A Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Food Effect of RO6953958 in Healthy Participants
NCT06300398	PHASE1	COMPLETED	IAMA-6 Oral Dose Study in Healthy Adults
NCT01783041	PHASE2/PHASE3	COMPLETED	Effect of Early L-Carnitine Supplementation on Neurodevelopmental Outcomes in Very Preterm Infants
NCT05767385	PHASE2/PHASE3	RECRUITING	Fetal Cerebrovascular Autoregulation in Congenital Heart Disease and Association With Neonatal Neurobehavior
NCT05675098	EARLY_PHASE1	NOT_YET_RECRUITING	Central Nervous System Stimulants and Physical Function in Children With Cerebral Palsy
NCT00783783	Not specified	COMPLETED	CYP2D6 Pharmacogenetics in Risperidone-Treated Children
NCT01778504	Not specified	RECRUITING	Studying Childhood-onset Behavioral, Psychiatric, and Developmental Disorders
NCT01850784	Not specified	UNKNOWN	High Energy Formula Feeding in Infants With Congenital Heart Disease
NCT01922791	Not specified	COMPLETED	Nutrition and Pregnancy Intervention Study
NCT01942525	Not specified	UNKNOWN	Influence of Intrauterine Growth Restriction on Amplitude-integrated EEG in Preterm Infants
NCT02003170	Not specified	COMPLETED	Etiology and Early Diagnosis of Neurodevelopmental Disorders
NCT02118649	Not specified	ACTIVE_NOT_RECRUITING	Enhancing Behavior and Brain Response to Visual Targets Using a Computer Game
NCT02557191	Not specified	TERMINATED	Biomarkers, Neurodevelopment and Preterm Infants
NCT02690675	Not specified	COMPLETED	Iron Supplement Effect on Child Development
NCT02694003	Not specified	COMPLETED	Better Nights, Better Days for Children With Neurodevelopment Disorders
NCT02792894	Not specified	COMPLETED	Family Networks (FaNs) for Children With Developmental Disorders and Delays
NCT02871674	Not specified	UNKNOWN	Good Night Project: Behavioural Sleep Interventions for Children With ADHD: A Randomised Controlled Trial
NCT02887157	Not specified	COMPLETED	Analyzing Retinal Microanatomy in ROP
NCT02898298	Not specified	COMPLETED	Positive Emotion Regulation Training in Children, Adolescents and Young Adults With and Without Developmental Disorder
NCT02912780	Not specified	UNKNOWN	Introduction of Microsystems in a Level 3 Neonatal Intensive Care Unit
NCT03023293	Not specified	COMPLETED	n-3 PUFAs, Irisin and Maternal Glucose Metabolism From Pregnancy to Postpartum
NCT03023644	Not specified	COMPLETED	Improving Neurodevelopmental Outcomes in Children With Congenital Heart Disease: An Intervention Study
NCT03032991	Not specified	UNKNOWN	Early Biomarkers of Neurodevelopment in Offspring of Diabetic Mothers
NCT03088189	Not specified	TERMINATED	Effect of Parental Peri-conceptional Vitamin B12 Supplementation on Infant Neurocognitive Development in Offspring
NCT03096028	Not specified	COMPLETED	Developmental Origins of Mental Health Disorders
NCT03148782	Not specified	COMPLETED	Brain Plasticity Underlying Acquisition of New Organizational Skills in Children-R61 Phase
NCT03172104	Not specified	COMPLETED	Neurobehavioural Development of Infants Born <30 Weeks Gestational Age Between Birth and Five Years of Age
NCT03222375	Not specified	RECRUITING	SQUED™ Series 28.1 Home-use and Treatment of Autowave Reverberator of Autism
NCT03229928	Not specified	COMPLETED	Clinical Testing of a Real-Time Behavior Measurement Tool: Measuring Outcomes for CHAnge
NCT03232489	Not specified	UNKNOWN	Study for the Evaluation of the Feasibility of Applying Advanced MRI Scanning in Pediatric Clinical Practice