TANC2

Summary

TANC2 (tetratricopeptide repeat, ankyrin repeat and coiled-coil containing 2, HGNC:30212) is a protein-coding gene on chromosome 17q23.2-q23.3, encoding Protein TANC2 (Q9HCD6). Scaffolding protein in the dendritic spines which acts as immobile postsynaptic posts able to recruit KIF1A-driven dense core vesicles to dendritic spines.

Predicted to be a structural constituent of postsynaptic density. Predicted to be involved in dense core granule cytoskeletal transport; regulation of dendritic spine development; and regulation of dendritic spine morphogenesis. Predicted to act upstream of or within in utero embryonic development. Located in dendritic spine. Implicated in intellectual developmental disorder with autistic features and language delay, with or without seizures.

Source: NCBI Gene 26115 — RefSeq curated summary.

At a glance

• Gene–disease (curated): intellectual developmental disorder with autistic features and language delay, with or without seizures (Definitive, ClinGen) — +1 more curated relationship
• GWAS associations: 5
• Clinical variants (ClinVar): 580 total — 13 pathogenic, 25 likely-pathogenic
• Phenotypes (HPO): 19
• MANE Select transcript: NM_001394998

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:30212
Approved symbol	TANC2
Name	tetratricopeptide repeat, ankyrin repeat and coiled-coil containing 2
Location	17q23.2-q23.3
Locus type	gene with protein product
Status	Approved
Aliases	DKFZP564D166, FLJ10215, FLJ11824, KIAA1148, KIAA1636, rols, ROLSA
Ensembl gene	ENSG00000170921
Ensembl biotype	protein_coding
OMIM	615047
Entrez	26115

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 7 protein_coding, 4 retained_intron

ENST00000389520, ENST00000424789, ENST00000579541, ENST00000580068, ENST00000580466, ENST00000581143, ENST00000581424, ENST00000583016, ENST00000583356, ENST00000583545, ENST00000689528

RefSeq mRNA: 3 — MANE Select: NM_001394998 NM_001394998, NM_001411076, NM_025185

CCDS: CCDS45754, CCDS92375, CCDS92376

Canonical transcript exons

ENST00000689528 — 28 exons

Exon	Start	End
ENSE00001136901	63411511	63411686
ENSE00001136907	63405122	63405255
ENSE00001136999	63415528	63415674
ENSE00001137006	63413543	63413634
ENSE00001137017	63411998	63412130
ENSE00001137037	63406154	63406277
ENSE00001137057	63398821	63398914
ENSE00001232426	63395743	63395928
ENSE00001468752	63412680	63412709
ENSE00001506098	63354783	63355390
ENSE00001506099	63351250	63351416
ENSE00001506100	63340101	63340332
ENSE00001506101	63318957	63319090
ENSE00001530099	63314388	63314669
ENSE00001530101	63267748	63267873
ENSE00001530105	63237814	63238077
ENSE00001530106	63200771	63200957
ENSE00001552721	63193991	63194139
ENSE00001558906	63073943	63074014
ENSE00002436383	63418307	63418407
ENSE00002706171	63151270	63151380
ENSE00002724510	63099175	63099357
ENSE00003487812	63379718	63379826
ENSE00003540349	63389308	63389544
ENSE00003585791	63388635	63388757
ENSE00003922761	63419999	63427703
ENSE00003935073	63009537	63009626
ENSE00003937525	62966235	62966749

Expression profiles

Bgee: expression breadth ubiquitous, 246 present calls, max score 95.47.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 34.1320 / max 1232.5620, expressed in 1771 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
162144	16.2644	1725
162147	9.8862	1574
162148	2.6992	888
162145	2.6064	870
162146	1.7256	560
162177	0.3635	176
162172	0.3440	166
162170	0.2427	116

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cortical plate	UBERON:0005343	95.47	gold quality
middle temporal gyrus	UBERON:0002771	93.62	gold quality
Brodmann (1909) area 23	UBERON:0013554	92.44	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	91.46	gold quality
sural nerve	UBERON:0015488	90.22	gold quality
adrenal tissue	UBERON:0018303	89.95	gold quality
stromal cell of endometrium	CL:0002255	89.78	gold quality
postcentral gyrus	UBERON:0002581	89.67	gold quality
superior frontal gyrus	UBERON:0002661	89.42	gold quality
primary visual cortex	UBERON:0002436	89.24	gold quality
parietal lobe	UBERON:0001872	89.23	gold quality
entorhinal cortex	UBERON:0002728	88.31	gold quality
occipital lobe	UBERON:0002021	88.05	gold quality
sperm	CL:0000019	87.02	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	86.69	gold quality
lateral nuclear group of thalamus	UBERON:0002736	86.40	gold quality
ventricular zone	UBERON:0003053	86.36	gold quality
endothelial cell	CL:0000115	86.27	gold quality
corpus callosum	UBERON:0002336	85.83	gold quality
prefrontal cortex	UBERON:0000451	85.80	gold quality
testis	UBERON:0000473	85.04	gold quality
islet of Langerhans	UBERON:0000006	84.57	gold quality
lateral globus pallidus	UBERON:0002476	84.41	gold quality
ganglionic eminence	UBERON:0004023	84.39	gold quality
mucosa of paranasal sinus	UBERON:0005030	84.39	gold quality
frontal cortex	UBERON:0001870	84.19	gold quality
left testis	UBERON:0004533	84.16	gold quality
neocortex	UBERON:0001950	84.09	gold quality
right testis	UBERON:0004534	84.02	gold quality
nucleus accumbens	UBERON:0001882	84.00	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-HCAD-35	yes	49.51
E-CURD-119	yes	24.91
E-ANND-3	yes	16.80

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 5)

• A protein encoded by this locus was found to be differentially expressed in postmortem brains from patients with atypical frontotemporal lobar degeneration. (PMID:22360420)
• -RAD21 and EIF3H, both on chromosome 8q23, CHRAC1 on chromosome 8q24.3 and TANC2 on chromosome 17q23-were confirmed to be driver genes regulating the proliferation/survival of clonogenic breast cancer cells (PMID:24148822)
• Pediatric patients with disruptive TANC2 mutations present with autism, intellectual disability, and delayed language and motor development. In addition to a variable degree of epilepsy and facial dysmorphism, we observe a pattern of more complex psychiatric dysfunction or behavioral problems in adult probands or carrier parents. (PMID:31616000)
• Tanc2-mediated mTOR inhibition balances mTORC1/2 signaling in the developing mouse brain and human neurons. (PMID:33976205)
• HPV-18E6 Inhibits Interactions between TANC2 and SNX27 in a PBM-Dependent Manner and Promotes Increased Cell Proliferation. (PMID:36326272)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	tanc2a	ENSDARG00000079097
danio_rerio	tanc2b	ENSDARG00000107441
mus_musculus	Tanc2	ENSMUSG00000053580
rattus_norvegicus	Tanc2	ENSRNOG00000052840

Paralogs (4): CTTNBP2 (ENSG00000077063), TANC1 (ENSG00000115183), ANKRD63 (ENSG00000230778), ANKRD65 (ENSG00000235098)

Protein

Protein identifiers

Protein TANC2 — Q9HCD6 (reviewed: Q9HCD6)

Alternative names: Tetratricopeptide repeat, ankyrin repeat and coiled-coil domain-containing protein 2

All UniProt accessions (6): A0A8I5KXR5, Q9HCD6, J3KRP9, J3KTM5, J3QQY7, J3QRF0

UniProt curated annotations — full annotation on UniProt →

Function. Scaffolding protein in the dendritic spines which acts as immobile postsynaptic posts able to recruit KIF1A-driven dense core vesicles to dendritic spines.

Subunit / interactions. Interacts with KIF1A; the interaction decreases in presence of calcium.

Subcellular location. Cell projection. Dendritic spine.

Disease relevance. Intellectual developmental disorder with autistic features and language delay, with or without seizures (IDDALDS) [MIM:618906] An autosomal dominant neurodevelopmental disorder characterized by global developmental delay, varying degrees of intellectual disability, autism spectrum disorder, and delayed language. Some patients develop seizures. The disease is caused by variants affecting the gene represented in this entry. Defects in TANC2 has been found in a patient with isolated coloboma, a defect of the eye characterized by the absence of ocular structures due to abnormal morphogenesis of the optic cup and stalk, and the fusion of the fetal fissure (optic fissure). Isolated colobomas may be associated with an abnormally small eye (microphthalmia) or small cornea.

Similarity. Belongs to the TANC family.

Isoforms (4)

UniProt ID	Names	Canonical?
Q9HCD6-1	1	yes
Q9HCD6-2	2
Q9HCD6-3	3
Q9HCD6-4	4

RefSeq proteins (3): NP_001381927, NP_001398005, NP_079461 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002110	Ankyrin_rpt	Repeat
IPR011990	TPR-like_helical_dom_sf	Homologous_superfamily
IPR019734	TPR_rpt	Repeat
IPR027417	P-loop_NTPase	Homologous_superfamily
IPR036770	Ankyrin_rpt-contain_sf	Homologous_superfamily
IPR050889	Dendritic_Spine_Reg/Scaffold	Family
IPR058018	AAA_lid_TANC1/2	Domain
IPR058056	WH_TANC1/2	Domain

Pfam: PF00023, PF12796, PF13181, PF13637, PF25520, PF25521

UniProt features (61 total): repeat 14, modified residue 14, region of interest 9, sequence variant 9, splice variant 5, compositionally biased region 4, sequence conflict 4, chain 1, glycosylation site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9HCD6-F1	59.92	0.28

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 (14): 169, 238, 294, 400, 1442, 1458, 1530, 1545, 1563, 1576, 1579, 1722, 1824, 1827

Glycosylation sites (1): 1928

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 337 (showing top): MORF_ITGA2, GOBP_DENDRITE_DEVELOPMENT, GCM_MAP4K4, MORF_MSH3, GOBP_VESICLE_LOCALIZATION, MORF_BRCA1, GOZGIT_ESR1_TARGETS_DN, GOBP_DENDRITIC_SPINE_DEVELOPMENT, GOBP_CELLULAR_COMPONENT_MAINTENANCE, GOBP_NEUROGENESIS, ACEVEDO_LIVER_CANCER_WITH_H3K27ME3_UP, MORF_RAD51L3, GOBP_REGULATION_OF_CELL_PROJECTION_ORGANIZATION, GOBP_CELL_JUNCTION_ORGANIZATION, MODULE_205

GO Biological Process (4): regulation of dendritic spine development (GO:0060998), regulation of dendritic spine morphogenesis (GO:0061001), dense core granule cytoskeletal transport (GO:0099519), in utero embryonic development (GO:0001701)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (5): axon (GO:0030424), dendritic spine (GO:0043197), cell projection (GO:0042995), synapse (GO:0045202), postsynapse (GO:0098794)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
regulation of developmental process	1
dendritic spine development	1
regulation of neuron projection development	1
regulation of anatomical structure morphogenesis	1
dendritic spine morphogenesis	1
regulation of postsynapse organization	1
axon	1
vesicle cytoskeletal trafficking	1
dense core granule transport	1
chordate embryonic development	1
binding	1
neuron projection	1
dendrite	1
neuron spine	1
postsynapse	1
cell junction	1
synapse	1

Protein interactions and networks

STRING

1420 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TANC2	KIF1A	Q12756	606
TANC2	ARMC6	Q6NXE6	485
TANC2	PPFIA1	Q13136	477
TANC2	DCLK2	Q8N568	471
TANC2	ZYX	Q15942	463
TANC2	CEP120	Q8N960	457
TANC2	LATS2	Q9NRM7	451
TANC2	PPFIA3	O75145	444
TANC2	CBY1	Q9Y3M2	441
TANC2	DCAF17	Q5H9S7	439
TANC2	CAPN9	O14815	425
TANC2	FJX1	Q86VR8	421
TANC2	RIC8A	Q9NPQ8	409
TANC2	DCAF7	P61962	396
TANC2	DOHH	Q9BU89	390

IntAct

214 interactions, top by confidence:

A	B	Type	Score
MAPRE1	CLASP2	psi-mi:“MI:0914”(association)	0.850
PPP1CC	CCDC85C	psi-mi:“MI:0914”(association)	0.740
TANC2	TAX1BP3	psi-mi:“MI:0914”(association)	0.690
TAX1BP3	ARVCF	psi-mi:“MI:0914”(association)	0.690
TAX1BP3	TANC2	psi-mi:“MI:0407”(direct interaction)	0.690
PPP1CA	CCDC85C	psi-mi:“MI:0914”(association)	0.670
YWHAG	BLTP3B	psi-mi:“MI:2364”(proximity)	0.640
YWHAH	PLEKHG3	psi-mi:“MI:0914”(association)	0.610
YWHAE	RGS12	psi-mi:“MI:0914”(association)	0.610
YWHAB	BLTP3B	psi-mi:“MI:2364”(proximity)	0.610
TANC2	SNX27	psi-mi:“MI:0407”(direct interaction)	0.590
YWHAH	BLTP3B	psi-mi:“MI:2364”(proximity)	0.570
YWHAE	SRSF10	psi-mi:“MI:0914”(association)	0.560
PTPN13	TANC2	psi-mi:“MI:0407”(direct interaction)	0.550
ZYX	TBC1D10B	psi-mi:“MI:0914”(association)	0.530
BAG2	HGS	psi-mi:“MI:0914”(association)	0.530
PPP1R13L	HSPA8	psi-mi:“MI:0914”(association)	0.530
YWHAB	PLEKHG3	psi-mi:“MI:0914”(association)	0.480
YWHAQ	PLEKHG3	psi-mi:“MI:0914”(association)	0.480
TANC2	SYNJ2BP	psi-mi:“MI:0407”(direct interaction)	0.440
MAST2	TANC2	psi-mi:“MI:0407”(direct interaction)	0.440
TANC2	SNTG1	psi-mi:“MI:0407”(direct interaction)	0.440
SCRIB	TANC2	psi-mi:“MI:0407”(direct interaction)	0.440
TANC2	SCRIB	psi-mi:“MI:0407”(direct interaction)	0.440
TANC2	ERBIN	psi-mi:“MI:0407”(direct interaction)	0.440
TANC2	IL16	psi-mi:“MI:0407”(direct interaction)	0.440

BioGRID (104): TANC2 (Affinity Capture-MS), TANC2 (Affinity Capture-MS), TANC2 (Affinity Capture-MS), TANC2 (Affinity Capture-MS), TANC2 (Affinity Capture-MS), TANC2 (Affinity Capture-MS), TANC2 (Affinity Capture-MS), TANC2 (Two-hybrid), TANC2 (Affinity Capture-MS), TANC2 (Affinity Capture-MS), TANC2 (Affinity Capture-MS), TANC2 (Affinity Capture-MS), TANC2 (Affinity Capture-MS), KCTD3 (Affinity Capture-MS), KIF13B (Affinity Capture-MS)

ESM2 similar proteins: A2A690, A2AWP8, A6QL63, F1LTE0, O08873, O14795, O43312, O70585, P0C7A6, P84060, Q08BT5, Q0VGY8, Q14161, Q15139, Q1LVW0, Q3KR37, Q5T6S3, Q62101, Q66H91, Q68FF6, Q6DFZ1, Q6GQW0, Q6IQ26, Q6P6Y1, Q6PAL8, Q6ZWH5, Q80TI0, Q80U28, Q80YA9, Q86UE8, Q8BG18, Q8BIE6, Q8R1S4, Q8WXG6, Q8WXI2, Q92538, Q9BZ71, Q9C0D5, Q9D2N4, Q9ESB5

Diamond homologs: A2A690, F1LTE0, Q0VGY8, Q38931, Q43207, Q6F6B3, Q9C0D5, Q9FJL3, Q9HCD6, A4K2V0, A6ZRW3, D7REX8, F1RBN2, F4K487, O13797, O14217, O16259, O35814, O48802, O54981, P07213, P0CT30, P15705, P25407, P31948, P38825, P53041, P53042, Q07617, Q08752, Q15785, Q2U919, Q3KRD5, Q3ZBZ8, Q4R8N7, Q54DA8, Q5U2X2, Q5VJS5, Q5WA76, Q5XEP2

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
TANC2	“up-regulates activity”	KIF1A	binding
DLG4	“up-regulates activity”	TANC2	binding
TANC2	up-regulates	Dendritic_spine_morphogenesis

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 161 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	8	49.8×	5e-10
Activation of BAD and translocation to mitochondria	7	49.4×	2e-09
SARS-CoV-1 targets host intracellular signalling and regulatory pathways	7	43.5×	5e-09
Activation of BH3-only proteins	7	32.2×	5e-08
Dopamine Neurotransmitter Release Cycle	6	27.6×	2e-06
RHO GTPases activate PKNs	9	26.4×	2e-09
Ras activation upon Ca2+ influx through NMDA receptor	5	26.4×	2e-05
Unblocking of NMDA receptors, glutamate binding and activation	5	25.2×	3e-05

GO biological processes:

GO term	Partners	Fold	FDR
establishment or maintenance of epithelial cell apical/basal polarity	11	43.2×	5e-13
receptor clustering	8	33.7×	3e-08
protein localization to synapse	5	25.9×	1e-04
regulation of postsynaptic membrane neurotransmitter receptor levels	7	23.4×	3e-06
protein targeting	8	19.8×	1e-06
establishment of cell polarity	5	12.9×	3e-03
intracellular protein localization	13	9.2×	5e-07
protein-containing complex assembly	9	6.9×	6e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	13
Likely pathogenic	25
Uncertain significance	408
Likely benign	95
Benign	9

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1316038	NM_001394998.1(TANC2):c.94C>T (p.Arg32Ter)	Pathogenic
1318856	NM_001394998.1(TANC2):c.864G>A (p.Trp288Ter)	Pathogenic
1325789	NM_001394998.1(TANC2):c.1048_1060dup (p.Leu354fs)	Pathogenic
1385449	NM_001394998.1(TANC2):c.91del (p.Asp31fs)	Pathogenic
1454576	NM_001394998.1(TANC2):c.4632del (p.Gly1545fs)	Pathogenic
3235167	NM_001394998.1(TANC2):c.2583-1G>A	Pathogenic
3359000	NM_001394998.1(TANC2):c.1938G>A (p.Trp646Ter)	Pathogenic
3900676	NM_001394998.1(TANC2):c.2691+1G>T	Pathogenic
3965326	NM_001394998.1(TANC2):c.4687del (p.Arg1563fs)	Pathogenic
4687274	NM_001394998.1(TANC2):c.2653G>T (p.Glu885Ter)	Pathogenic
4718010	NM_001394998.1(TANC2):c.2419G>T (p.Glu807Ter)	Pathogenic
4727463	NM_001394998.1(TANC2):c.5275C>T (p.Gln1759Ter)	Pathogenic
922129	NM_001394998.1(TANC2):c.1441+1G>A	Pathogenic
1297027	NM_001394998.1(TANC2):c.5350C>T (p.Arg1784Ter)	Likely pathogenic
1342072	NM_001394998.1(TANC2):c.2662_2665dup (p.His889fs)	Likely pathogenic
2578806	GRCh37/hg19 17q23.3(chr17:61151304-61457187)x1	Likely pathogenic
2692534	NM_001394998.1(TANC2):c.587C>G (p.Ser196Ter)	Likely pathogenic
3024265	NM_001394998.1(TANC2):c.1123_1124del (p.Ser375fs)	Likely pathogenic
3065508	NM_001394998.1(TANC2):c.2044del (p.Gln682fs)	Likely pathogenic
3173744	NM_001394998.1(TANC2):c.5233C>T (p.Gln1745Ter)	Likely pathogenic
3173747	NM_001394998.1(TANC2):c.5738_5742del (p.Thr1913fs)	Likely pathogenic
3235923	NM_001394998.1(TANC2):c.1808del (p.Glu603fs)	Likely pathogenic
3362510	NM_001394998.1(TANC2):c.2582+2T>G	Likely pathogenic
3774893	NM_001394998.1(TANC2):c.139+2T>A	Likely pathogenic
3776373	NM_001394998.1(TANC2):c.5368C>T (p.Arg1790Ter)	Likely pathogenic
4076238	NM_001394998.1(TANC2):c.4146_4147del (p.Arg1383fs)	Likely pathogenic
4077682	NM_001394998.1(TANC2):c.1108C>T (p.Arg370Ter)	Likely pathogenic
4293202	NM_001394998.1(TANC2):c.2205dup (p.Asp736Ter)	Likely pathogenic
4294473	NM_001394998.1(TANC2):c.2413del (p.Ser805fs)	Likely pathogenic
4684993	NM_001394998.1(TANC2):c.1441+5G>A	Likely pathogenic

SpliceAI

5735 predictions. Top by Δscore:

Variant	Effect	Δscore
17:63028668:A:T	donor_gain	1.0000
17:63028699:TTTTC:T	donor_gain	1.0000
17:63073931:A:AG	acceptor_gain	1.0000
17:63073932:A:G	acceptor_gain	1.0000
17:63073941:AGAT:A	acceptor_gain	1.0000
17:63073942:GATG:G	acceptor_gain	1.0000
17:63074011:CAAG:C	donor_loss	1.0000
17:63074012:AAG:A	donor_loss	1.0000
17:63074013:AGGTA:A	donor_loss	1.0000
17:63074014:GGTA:G	donor_loss	1.0000
17:63074015:GTAA:G	donor_loss	1.0000
17:63074016:T:G	donor_loss	1.0000
17:63099170:A:AG	acceptor_gain	1.0000
17:63099170:AACAG:A	acceptor_gain	1.0000
17:63099171:A:G	acceptor_gain	1.0000
17:63099173:A:T	acceptor_loss	1.0000
17:63193983:T:A	acceptor_gain	1.0000
17:63193986:TACA:T	acceptor_loss	1.0000
17:63193988:CAGG:C	acceptor_loss	1.0000
17:63193989:A:AG	acceptor_gain	1.0000
17:63193989:AG:A	acceptor_gain	1.0000
17:63193989:AGG:A	acceptor_loss	1.0000
17:63193989:AGGT:A	acceptor_gain	1.0000
17:63193990:G:GG	acceptor_gain	1.0000
17:63193990:GG:G	acceptor_gain	1.0000
17:63193990:GGT:G	acceptor_gain	1.0000
17:63193990:GGTG:G	acceptor_gain	1.0000
17:63193990:GGTGA:G	acceptor_gain	1.0000
17:63194119:G:GT	donor_gain	1.0000
17:63194135:ATCAG:A	donor_gain	1.0000

AlphaMissense

13499 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:63194048:T:A	L90H	1.000
17:63194048:T:C	L90P	1.000
17:63200943:A:T	D178V	1.000
17:63200945:A:C	S179R	1.000
17:63200947:T:A	S179R	1.000
17:63200947:T:G	S179R	1.000
17:63200952:T:C	I181T	1.000
17:63200955:T:A	I182N	1.000
17:63314438:T:C	F330L	1.000
17:63314440:T:A	F330L	1.000
17:63314440:T:G	F330L	1.000
17:63314568:G:A	G373E	1.000
17:63314574:G:A	G375D	1.000
17:63314609:A:C	S387R	1.000
17:63314611:C:A	S387R	1.000
17:63314611:C:G	S387R	1.000
17:63340119:T:C	C458R	1.000
17:63340121:T:G	C458W	1.000
17:63340143:T:C	C466R	1.000
17:63340162:T:A	V472D	1.000
17:63354880:G:C	R617P	1.000
17:63354955:T:C	L642P	1.000
17:63354967:T:C	L646P	1.000
17:63355000:T:C	L657P	1.000
17:63355006:T:C	L659P	1.000
17:63355018:T:C	L663P	1.000
17:63355021:T:A	I664K	1.000
17:63355036:T:A	L669Q	1.000
17:63355036:T:C	L669P	1.000
17:63355042:T:C	L671S	1.000

dbSNP variants (sampled 300 via entrez): RS1000005085 (17:62986542 G>A), RS1000009012 (17:63030263 A>T), RS1000017308 (17:63258638 C>T), RS1000023463 (17:63408761 C>T), RS1000031228 (17:63091177 A>G), RS1000037321 (17:63353541 A>G), RS1000037824 (17:63268282 C>A), RS1000037863 (17:63002083 T>C), RS1000053413 (17:63310423 G>C), RS1000064163 (17:63133526 A>T), RS1000069011 (17:63364736 A>G), RS1000075026 (17:62987954 C>T), RS1000077888 (17:63046736 G>A), RS1000098418 (17:63173253 T>A), RS1000110800 (17:63168235 T>G)

Disease associations

OMIM: gene MIM:615047 | disease phenotypes: MIM:618906, MIM:181500

GenCC curated gene-disease

Disease	Classification	Inheritance
intellectual developmental disorder with autistic features and language delay, with or without seizures	Strong	Autosomal dominant
syndromic intellectual disability	Supportive	Autosomal dominant

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
intellectual developmental disorder with autistic features and language delay, with or without seizures	Definitive	AD

Mondo (7): intellectual developmental disorder with autistic features and language delay, with or without seizures (MONDO:0030051), autism spectrum disorder (MONDO:0005258), intellectual disability (MONDO:0001071), neurodevelopmental disorder (MONDO:0700092), schizophrenia (MONDO:0005090), epilepsy (MONDO:0005027), syndromic intellectual disability (MONDO:0000508)

Orphanet (3): NON RARE IN EUROPE: Autism (Orphanet:106), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658), NON RARE IN EUROPE: Schizophrenia (Orphanet:3140)

HPO phenotypes

19 total (20 of 19 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000252	Microcephaly
HP:0000687	Widely spaced teeth
HP:0000729	Autistic behavior
HP:0000733	Motor stereotypy
HP:0000739	Anxiety
HP:0000750	Delayed speech and language development
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001270	Motor delay
HP:0001290	Generalized hypotonia
HP:0001363	Craniosynostosis
HP:0001382	Joint hypermobility
HP:0002360	Sleep disturbance
HP:0002376	Developmental regression
HP:0002497	Spastic ataxia
HP:0002650	Scoliosis
HP:0007018	Attention deficit hyperactivity disorder
HP:0012450	Chronic constipation
HP:0100753	Schizophrenia

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST005316_217	Intelligence (MTAG)	2.000000e-08
GCST007576_59	Chronotype	2.000000e-11
GCST009462_89	Optic disc size	6.000000e-11
GCST012337_14	Nonsyndromic cleft lip with or without cleft palate	1.000000e-08
GCST90000025_606	Appendicular lean mass	5.000000e-11

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004337	intelligence
EFO:0008328	chronotype measurement
EFO:0004980	appendicular lean mass

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D004827	Epilepsy	C10.228.140.490
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D065886	Neurodevelopmental Disorders	F03.625

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

PharmGKB clinical annotations

1 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs2429427	Efficacy	3	Calcium channel blockers	Hypertension

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs2429427	TANC2	3	2.25	1	Calcium channel blockers

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, decreases expression	5
trichostatin A	affects cotreatment, increases expression	3
Benzo(a)pyrene	affects expression, affects methylation, increases methylation	3
methylmercuric chloride	increases expression	2
sodium arsenite	decreases expression, increases abundance	2
Arsenic	decreases expression, increases abundance, affects methylation	2
Cisplatin	affects cotreatment, decreases expression	2
Estradiol	increases expression, affects cotreatment	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Tobacco Smoke Pollution	decreases expression, increases expression	2
aristolochic acid I	decreases expression	1
OTX015	increases expression	1
FR900359	decreases phosphorylation	1
mivebresib	increases expression	1
bisphenol A	increases methylation, affects cotreatment	1
arsenite	affects binding, decreases reaction	1
sulforaphane	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
benzo(e)pyrene	increases methylation	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, decreases expression	1
aflatoxin B2	decreases methylation, increases methylation	1
coumarin	affects phosphorylation	1
epigallocatechin gallate	increases expression, affects cotreatment, decreases expression	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	increases expression	1
pentabromodiphenyl ether	increases 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
2,2’,4,4’-tetrabromodiphenyl ether	increases expression	1

Cellosaurus cell lines

1 cell lines: 1 induced pluripotent stem cell

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_C0F0	GWCMCi005-A	Induced pluripotent stem cell	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00391261	PHASE4	COMPLETED	An Open-label Trial of Metformin for Weight Control of Pediatric Patients on Antipsychotic Medications.
NCT01028820	PHASE4	COMPLETED	FMRI Brain Activation of Aripiprazole Treatment in Autism Spectrum Disorders
NCT01333865	PHASE4	COMPLETED	A Study of Memantine Hydrochloride (Namenda®) for Cognitive and Behavioral Impairment in Adults With Autism Spectrum Disorders
NCT01337700	PHASE4	COMPLETED	Milnacipran in Autism and the Functional Locus Coeruleus and Noradrenergic Model of Autism
NCT01695200	PHASE4	COMPLETED	Omega-3 Fatty Acids in Autism Spectrum Disorders
NCT02096952	PHASE4	COMPLETED	Methylphenidate ER Liquid Formulation in Adults With ASD and ADHD
NCT02235467	PHASE4	COMPLETED	Multisite Study: Parental Training Using Video Modelling to Develop Social Skills in Children With Autism
NCT02940574	PHASE4	COMPLETED	Neural and Behavioral Effects of Oxytocin in Autism Spectrum Disorders
NCT03333629	PHASE4	COMPLETED	Promoting Positive Outcomes for Individuals With ASD: Linking Early Detection, Treatment, and Long-term Outcomes
NCT03337646	PHASE4	COMPLETED	Evaluation of the Effect and Safety of Lisdexamfetamine in Children Aged 6-12 With ADHD and Autism
NCT03538431	PHASE4	COMPLETED	Improving Driving in Young People With Autism Spectrum Disorders
NCT03757585	PHASE4	COMPLETED	Natural Treatments for the Management of Emotional Dysregulation in Youth With Non-verbal Learning Disability (NVLD) and/or Autism Spectrum Disorders (ASD)
NCT04903353	PHASE4	COMPLETED	Pragmatic Trial Comparing Weight Gain in Children With Autism Taking Risperidone Versus Aripiprazole
NCT05063656	PHASE4	COMPLETED	Biomarker-Driven Pharmacological Treatment of Adolescents With Autism Spectrum Disorder With Gabapentin
NCT05146245	PHASE4	UNKNOWN	Safety and Pharmacokinetics of Antipsychotics in Children 2: Studying TDM in an RCT
NCT05916339	PHASE4	RECRUITING	AWARE: Management of ADHD in Autism Spectrum Disorder
NCT05954052	PHASE4	TERMINATED	A Study of Glutathione in Children With Autism Spectrum Disorder
NCT06853665	PHASE4	RECRUITING	The TEAM Study - Treatment Efficacy for Autism/Attention Using Mixed Amphetamine
NCT07054697	PHASE4	COMPLETED	Pilot-RCT With Individualized Homeopathic Treatment in the Children With Autism Spectrum Disorder
NCT07161804	PHASE4	COMPLETED	Pilot RCT Using Homeopathic Medicines in ASD
NCT07439042	PHASE4	NOT_YET_RECRUITING	Buspirone for Anxiety in Autistic Youth
NCT01302964	PHASE3	COMPLETED	Mirtazapine Treatment of Anxiety in Children and Adolescents With Pervasive Developmental Disorders
NCT01706523	PHASE3	TERMINATED	Open Label Extension Study of STX209 (Arbaclofen) in Autism Spectrum Disorders
NCT01825798	PHASE3	COMPLETED	Treatment of Overweight Induced by Antipsychotic Medication in Young People With Autism Spectrum Disorders (ASD)
NCT01972074	PHASE3	COMPLETED	Behavioral and Neural Response to Memantine in Adolescents With Autism Spectrum Disorder
NCT02985749	PHASE3	COMPLETED	A Study of Oxytocin for the Treatment of Social Impairment in Individuals With High Functioning Autism Spectrum Disorder
NCT03197922	PHASE3	COMPLETED	Treatment of Encopresis in Children With Autism Spectrum Disorders
NCT03504917	PHASE3	TERMINATED	A Study of Balovaptan in Adults With Autism Spectrum Disorder With a 2-Year Open-Label Extension
NCT03553875	PHASE3	TERMINATED	Memantine for the Treatment of Social Deficits in Youth With Disorders of Impaired Social Interactions
NCT03640156	PHASE3	COMPLETED	Modulating Socially Adaptive Mirror System Functioning in Autism by Oxytocin
NCT03715153	PHASE3	TERMINATED	Efficacy and Safety of Bumetanide Oral Liquid Formulation in Children Aged From 2 to Less Than 7 Years Old With Autism Spectrum Disorder.
NCT03715166	PHASE3	TERMINATED	Efficacy and Safety of Bumetanide Oral Liquid Formulation in Children and Adolescents Aged From 7 to Less Than 18 Years Old With Autism Spectrum Disorder
NCT04233502	PHASE3	WITHDRAWN	Efficacy and Safety of Slenyto for Insomnia in Children With ASD
NCT04578756	PHASE3	COMPLETED	Open-Label, Flexible-dose Study to Evaluate the Long-Term Safety and Tolerability of Cariprazine in the Treatment of Pediatric Participants With Schizophrenia, Bipolar I Disorder, or Autism Spectrum Disorder
NCT04623398	PHASE3	COMPLETED	Effect of Lithium in Patients With Autism Spectrum Disorder and Phelan-McDermid Syndrome (SHANK3 Haploinsufficiency)
NCT04725383	PHASE3	TERMINATED	Amitriptyline for Repetitive Behaviors in Autism Spectrum Disorders
NCT05212493	PHASE3	COMPLETED	The Effects of Medical Cannabis in Children With Autistic Spectrum Disorder
NCT05361707	PHASE3	UNKNOWN	Evaluating the Effects of Tasimelteon in Individuals With Autism Spectrum Disorder (ASD) and Sleep Disturbances
NCT05439616	PHASE3	COMPLETED	Study of Cariprazine Oral Capsules or Solution to Assess Adverse Events and Change in Irritability Due to Autism Spectrum Disorder (ASD) in Participants Aged 5-17 Years With ASD
NCT06229210	PHASE3	RECRUITING	Safety and Tolerability Trial of Lumateperone in Pediatric Patients With Schizophrenia, Bipolar Disorder or Autism Spectrum Disorder