TNPO2

Summary

TNPO2 (transportin 2, HGNC:19998) is a protein-coding gene on chromosome 19p13.13, encoding Transportin-2 (O14787). Probably functions in nuclear protein import as nuclear transport receptor.

Predicted to enable nuclear import signal receptor activity and nuclear localization sequence binding activity. Predicted to be involved in protein import into nucleus. Predicted to act upstream of or within negative regulation of muscle cell differentiation. Predicted to be active in cytoplasm and nucleus. Implicated in intellectual developmental disorder with hypotonia, impaired speech, and dysmorphic facies.

Source: NCBI Gene 30000 — RefSeq curated summary.

At a glance

• Gene–disease (curated): intellectual developmental disorder with hypotonia, impaired speech, and dysmorphic facies (Strong, GenCC)
• GWAS associations: 1
• Clinical variants (ClinVar): 152 total — 4 pathogenic, 12 likely-pathogenic
• Phenotypes (HPO): 34
• MANE Select transcript: NM_001382241

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:19998
Approved symbol	TNPO2
Name	transportin 2
Location	19p13.13
Locus type	gene with protein product
Status	Approved
Aliases	IPO3, KPNB2B, FLJ12155, TRN2
Ensembl gene	ENSG00000105576
Ensembl biotype	protein_coding
OMIM	603002
Entrez	30000

Gene structure

Transcript identifiers

Ensembl transcripts: 29 — 19 protein_coding, 4 nonsense_mediated_decay, 4 retained_intron, 1 non_stop_decay, 1 protein_coding_CDS_not_defined

ENST00000356861, ENST00000425528, ENST00000450764, ENST00000585886, ENST00000586775, ENST00000587068, ENST00000587155, ENST00000587654, ENST00000588151, ENST00000588216, ENST00000588484, ENST00000588491, ENST00000589149, ENST00000589337, ENST00000589572, ENST00000589956, ENST00000590781, ENST00000592287, ENST00000897696, ENST00000897697, ENST00000897698, ENST00000897699, ENST00000897700, ENST00000897701, ENST00000897702, ENST00000956332, ENST00000956333, ENST00000956334, ENST00000956335

RefSeq mRNA: 11 — MANE Select: NM_001382241 NM_001136195, NM_001136196, NM_001382236, NM_001382237, NM_001382238, NM_001382239, NM_001382240, NM_001382241, NM_001382242, NM_001382243, NM_013433

CCDS: CCDS45991, CCDS45992

Canonical transcript exons

ENST00000425528 — 26 exons

Exon	Start	End
ENSE00000681778	12711296	12711461
ENSE00000681784	12710621	12710773
ENSE00000681796	12706196	12706367
ENSE00000681812	12703714	12703801
ENSE00000681815	12703428	12703526
ENSE00000681821	12702823	12702918
ENSE00000681841	12701598	12701672
ENSE00001402379	12702072	12702177
ENSE00001410405	12701326	12701453
ENSE00001625763	12723249	12723365
ENSE00001634028	12723769	12723932
ENSE00001714220	12706570	12706795
ENSE00002873321	12699201	12701243
ENSE00003465560	12715047	12715169
ENSE00003465844	12715243	12715324
ENSE00003493357	12711553	12711613
ENSE00003519838	12715405	12715538
ENSE00003554530	12701752	12701851
ENSE00003555826	12719029	12719178
ENSE00003560036	12720879	12720990
ENSE00003565272	12705492	12705599
ENSE00003610798	12714821	12714939
ENSE00003644666	12705240	12705398
ENSE00003665989	12705682	12705768
ENSE00003667802	12715633	12715739
ENSE00003681675	12719261	12719336

Expression profiles

Bgee: expression breadth ubiquitous, 291 present calls, max score 97.86.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 61.5245 / max 3556.0653, expressed in 1818 samples.

FANTOM5 promoters (11 alternative TSS)

Promoter ID	TPM avg	Samples expressed
179347	23.4381	1752
179343	17.9590	1788
179342	7.7292	1671
179344	7.2920	1706
179338	1.3653	802
179341	1.3065	522
179346	0.9086	528
179345	0.8477	292
179339	0.3680	174
179336	0.2696	87

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	97.86	gold quality
cervix squamous epithelium	UBERON:0006922	97.83	gold quality
inferior olivary complex	UBERON:0002127	97.77	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	97.76	gold quality
entorhinal cortex	UBERON:0002728	97.53	gold quality
lateral nuclear group of thalamus	UBERON:0002736	97.49	gold quality
pons	UBERON:0000988	97.44	gold quality
medulla oblongata	UBERON:0001896	97.39	gold quality
Brodmann (1909) area 46	UBERON:0006483	97.37	gold quality
nipple	UBERON:0002030	97.36	gold quality
ventral tegmental area	UBERON:0002691	97.31	gold quality
superior vestibular nucleus	UBERON:0007227	97.22	gold quality
orbitofrontal cortex	UBERON:0004167	97.19	gold quality
parietal lobe	UBERON:0001872	97.06	gold quality
dorsal plus ventral thalamus	UBERON:0001897	96.95	gold quality
lateral globus pallidus	UBERON:0002476	96.89	gold quality
olfactory bulb	UBERON:0002264	96.88	gold quality
postcentral gyrus	UBERON:0002581	96.88	gold quality
superior frontal gyrus	UBERON:0002661	96.76	gold quality
middle temporal gyrus	UBERON:0002771	96.74	gold quality
CA1 field of hippocampus	UBERON:0003881	96.70	gold quality
subthalamic nucleus	UBERON:0001906	96.69	gold quality
inferior vagus X ganglion	UBERON:0005363	96.66	gold quality
ganglionic eminence	UBERON:0004023	96.64	gold quality
ventricular zone	UBERON:0003053	96.54	gold quality
substantia nigra pars reticulata	UBERON:0001966	96.51	gold quality
temporal lobe	UBERON:0001871	96.45	gold quality
right frontal lobe	UBERON:0002810	96.38	gold quality
substantia nigra pars compacta	UBERON:0001965	96.21	gold quality
tongue squamous epithelium	UBERON:0006919	96.21	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.49

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

79 targeting TNPO2, 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-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-1-3P	99.93	72.35	1914
HSA-MIR-206	99.93	72.50	1893
HSA-MIR-613	99.91	71.50	1710
HSA-MIR-9902	99.89	69.15	2250
HSA-MIR-5582-3P	99.86	72.48	4221
HSA-MIR-4779	99.86	66.50	1583
HSA-MIR-6764-5P	99.75	67.89	2304
HSA-MIR-670-5P	99.67	69.94	1565
HSA-MIR-3175	99.65	66.30	2031
HSA-MIR-3177-5P	99.65	70.38	1174
HSA-MIR-1249-5P	99.61	66.55	2049
HSA-MIR-6797-5P	99.61	66.55	2084
HSA-MIR-802	99.61	67.70	1254
HSA-MIR-1915-3P	99.58	66.79	1988
HSA-MIR-3136-3P	99.57	66.59	781
HSA-MIR-7155-3P	99.57	66.48	794
HSA-MIR-12117	99.50	67.57	868
HSA-MIR-5584-5P	99.49	68.22	2814
HSA-MIR-4441	99.49	66.56	3216
HSA-MIR-1207-5P	99.49	69.11	2983
HSA-MIR-6081	99.48	66.07	1446

Literature-anchored findings (GeneRIF, showing 10)

• Karyopherin beta 2B participates in mRNA export from the nucleus (PMID:12384575)
• Transportin-2 mediates nuclear import of HuR protein in vitro (PMID:14981248)
• The structure of Kap beta 2 (also known as Transportin) bound to one of its substrates, the NLS of hnRNP A1, that we report here explains the mechanism of substrate displacement by Ran GTPase. (PMID:16901787)
• Nuclear import of fused in sarcoma (FUS) is dependent on Transportin, and interference with this transport pathway leads to cytoplasmic redistribution and recruitment of fused in sarcoma (FUS) into stress granules. (PMID:20606625)
• a role for the nuclear trafficking factor TRN2 (transportin 2) through HuR in cell death (PMID:21646354)
• Studies indicate potential roles of Tranportin-1 and Transportin-2 beyond protein nuclear import. (PMID:24780099)
• IPO3 binds NEMO, promotes its nuclear import, and is critical for DNA damage-dependent NF-kappaB activation. (PMID:26060253)
• TNPO2 operates downstream of DYNC1I1 and promotes gastric cancer cell proliferation and inhibits apoptosis. (PMID:31605449)
• Transportin-2 plays a critical role in nucleocytoplasmic shuttling of oestrogen receptor-alpha. (PMID:33122699)
• TNPO2 variants associate with human developmental delays, neurologic deficits, and dysmorphic features and alter TNPO2 activity in Drosophila. (PMID:34314705)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	tnpo2a	ENSDARG00000038239
danio_rerio	tnpo2b	ENSDARG00000042887
danio_rerio	tnpo2b	ENSDARG00000113296
mus_musculus	Tnpo2	ENSMUSG00000031691
rattus_norvegicus	Tnpo2	ENSRNOG00000003970
drosophila_melanogaster	Tnpo	FBGN0024921
caenorhabditis_elegans		WBGENE00002076

Paralogs (5): IPO5 (ENSG00000065150), TNPO1 (ENSG00000083312), KPNB1 (ENSG00000108424), RANBP6 (ENSG00000137040), IPO4 (ENSG00000196497)

Protein

Protein identifiers

Transportin-2 — O14787 (reviewed: O14787)

Alternative names: Karyopherin beta-2b

All UniProt accessions (8): O14787, A0A075B780, K7ELC3, K7EMA3, K7ENW1, K7ESC1, K7ESG1, K7ESJ3

UniProt curated annotations — full annotation on UniProt →

Function. Probably functions in nuclear protein import as nuclear transport receptor. Serves as receptor for nuclear localization signals (NLS) in cargo substrates. Is thought to mediate docking of the importin/substrate complex to the nuclear pore complex (NPC) through binding to nucleoporin and the complex is subsequently translocated through the pore by an energy requiring, Ran-dependent mechanism. At the nucleoplasmic side of the NPC, Ran binds to the importin, the importin/substrate complex dissociates and importin is re-exported from the nucleus to the cytoplasm where GTP hydrolysis releases Ran. The directionality of nuclear import is thought to be conferred by an asymmetric distribution of the GTP- and GDP-bound forms of Ran between the cytoplasm and nucleus.

Subcellular location. Cytoplasm. Nucleus.

Disease relevance. Intellectual developmental disorder with hypotonia, impaired speech, and dysmorphic facies (IDDHISD) [MIM:619556] An autosomal dominant disorder characterized by global developmental delay, impaired intellectual development, poor or absent speech, hypotonia, ophthalmologic abnormalities, and non-specific dysmorphic features. Some affected individuals have seizures, and a few have involvement of other organ systems. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the importin beta family. Importin beta-2 subfamily.

Isoforms (2)

UniProt ID	Names	Canonical?
O14787-1	1	yes
O14787-2	2, beta2b

RefSeq proteins (11): NP_001129667, NP_001129668, NP_001369165, NP_001369166, NP_001369167, NP_001369168, NP_001369169, NP_001369170, NP_001369171, NP_001369172, NP_038461 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000357	HEAT	Repeat
IPR001494	Importin-beta_N	Domain
IPR011989	ARM-like	Homologous_superfamily
IPR016024	ARM-type_fold	Homologous_superfamily
IPR040122	Importin_beta	Family
IPR058584	IMB1_TNPO1-like_TPR	Domain

Pfam: PF02985, PF03810, PF13513, PF25574

UniProt features (55 total): repeat 20, sequence conflict 16, sequence variant 13, chain 1, domain 1, region of interest 1, compositionally biased region 1, modified residue 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O14787-F1	91.28	0.77

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 (1): 862

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 272 (showing top): RNGTGGGC_UNKNOWN, MYAATNNNNNNNGGC_UNKNOWN, TONKS_TARGETS_OF_RUNX1_RUNX1T1_FUSION_MONOCYTE_UP, E2F_Q4_01, GCM_GSPT1, GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, GOBP_NEGATIVE_REGULATION_OF_MUSCLE_CELL_DIFFERENTIATION, PEREZ_TP63_TARGETS, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, MODULE_352, GOBP_ESTABLISHMENT_OF_PROTEIN_LOCALIZATION_TO_ORGANELLE, GOMF_GTPASE_BINDING, GGGTGGRR_PAX4_03, GCM_BCL2L1, AACWWCAANK_UNKNOWN

GO Biological Process (4): protein import into nucleus (GO:0006606), negative regulation of muscle cell differentiation (GO:0051148), intracellular protein transport (GO:0006886), protein transport (GO:0015031)

GO Molecular Function (4): nuclear localization sequence binding (GO:0008139), small GTPase binding (GO:0031267), nuclear import signal receptor activity (GO:0061608), protein binding (GO:0005515)

GO Cellular Component (3): nucleus (GO:0005634), cytoplasm (GO:0005737), nuclear lumen (GO:0031981)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
import into nucleus	2
intracellular protein localization	2
intracellular protein transport	1
protein localization to nucleus	1
establishment of protein localization to organelle	1
muscle cell differentiation	1
negative regulation of cell differentiation	1
regulation of muscle cell differentiation	1
protein transport	1
intracellular transport	1
transport	1
establishment of protein localization	1
signal sequence receptor activity	1
GTPase binding	1
nucleocytoplasmic carrier activity	1
binding	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
cellular anatomical structure	1
nucleus	1
intracellular organelle lumen	1

Protein interactions and networks

STRING

1420 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TNPO2	IPO9	Q96P70	874
TNPO2	NXF1	Q9UBU9	868
TNPO2	IPO7	O95373	805
TNPO2	NUP62	P37198	797
TNPO2	NUTF2	P13662	747
TNPO2	NXT2	Q9NPJ8	712
TNPO2	IPO13	O94829	692
TNPO2	NUP153	P49790	692
TNPO2	NXT1	Q9UKK6	685
TNPO2	IPO11	Q9UI26	680
TNPO2	TNPO3	Q9Y5L0	679
TNPO2	NUP214	P35658	658
TNPO2	XPOT	O43592	642
TNPO2	NXF2B	Q9GZY0	638
TNPO2	HNRNPA1	P09651	637

IntAct

164 interactions, top by confidence:

A	B	Type	Score
TNPO2	KLHL2	psi-mi:“MI:0915”(physical association)	0.670
TNPO2	CAMK2D	psi-mi:“MI:0915”(physical association)	0.670
TNPO2	EXOC5	psi-mi:“MI:0915”(physical association)	0.670
APIP	TNPO2	psi-mi:“MI:0915”(physical association)	0.670
CAMK2D	TNPO2	psi-mi:“MI:0915”(physical association)	0.670
TNPO2	APIP	psi-mi:“MI:0915”(physical association)	0.670
EXOC5	TNPO2	psi-mi:“MI:0915”(physical association)	0.670
SCN2B	EXOC5	psi-mi:“MI:0914”(association)	0.640
FAM234B	ABCD4	psi-mi:“MI:0914”(association)	0.620
TNPO2	NME1	psi-mi:“MI:0915”(physical association)	0.560
TNPO2	C1orf94	psi-mi:“MI:0915”(physical association)	0.560
TNPO2	PNMA5	psi-mi:“MI:0915”(physical association)	0.560
HEL-S-101	TNPO2	psi-mi:“MI:0915”(physical association)	0.560
NME1	TNPO2	psi-mi:“MI:0915”(physical association)	0.560
PNMA5	TNPO2	psi-mi:“MI:0915”(physical association)	0.560
C1orf94	TNPO2	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (292): TNPO2 (Two-hybrid), TNPO2 (Two-hybrid), TNPO2 (Two-hybrid), TNPO2 (Two-hybrid), TNPO2 (Two-hybrid), APIP (Two-hybrid), C1orf94 (Two-hybrid), PNMA5 (Two-hybrid), TNPO2 (Affinity Capture-RNA), TNPO2 (Affinity Capture-RNA), TNPO2 (Affinity Capture-MS), TNPO2 (Affinity Capture-MS), TNPO2 (Affinity Capture-MS), TNPO2 (Affinity Capture-MS), TNPO2 (Affinity Capture-MS)

ESM2 similar proteins: A0JN27, A6H7F7, B2RYU6, B5FXJ6, B5FYY5, B5X7X4, F1LTR1, F6RQL9, O14787, O43504, P22234, P61201, P61202, P61203, Q13126, Q13888, Q17QI2, Q2TBV5, Q2YDH6, Q3SZ68, Q3T132, Q4KLK9, Q4R9A8, Q4VC33, Q5F398, Q5R532, Q5RKJ1, Q5SP67, Q5ZJQ7, Q63ZJ2, Q66X52, Q6DEG4, Q6DF40, Q6IQT4, Q6IR75, Q6P1K8, Q7L5Y9, Q7ZXB7, Q92572, Q99LG2

Diamond homologs: B8ARW2, B9FDR3, O14089, O14787, Q3SYU7, Q55CQ7, Q8BFY9, Q8H0U4, Q92973, Q99LG2, P38217, P52296, P70168

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 159 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
Nuclear import of Rev protein	5	18.2×	2e-03
Rev-mediated nuclear export of HIV RNA	5	17.2×	2e-03

GO biological processes:

GO term	Partners	Fold	FDR
T cell costimulation	8	22.4×	2e-06
positive regulation of T cell proliferation	7	13.5×	4e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	4
Likely pathogenic	12
Uncertain significance	76
Likely benign	23
Benign	7

Top pathogenic / likely-pathogenic (16)

Variant ID	HGVS	Classification
1299679	NM_001382241.1(TNPO2):c.466G>A (p.Asp156Asn)	Pathogenic
1299680	NM_001382241.1(TNPO2):c.1108T>C (p.Trp370Arg)	Pathogenic
1299681	NM_001382241.1(TNPO2):c.1110G>C (p.Trp370Cys)	Pathogenic
1299682	NM_001382241.1(TNPO2):c.1637C>T (p.Ala546Val)	Pathogenic
1308660	NM_001382241.1(TNPO2):c.2048G>C (p.Ser683Thr)	Likely pathogenic
1321960	NM_001382241.1(TNPO2):c.1471_1474delinsCAAT (p.Lys491_Arg492delinsGlnTrp)	Likely pathogenic
1333639	NM_001382241.1(TNPO2):c.2110+1G>C	Likely pathogenic
1690646	NM_001382241.1(TNPO2):c.1643C>T (p.Ser548Phe)	Likely pathogenic
2225477	NM_001382241.1(TNPO2):c.466G>T (p.Asp156Tyr)	Likely pathogenic
2635269	NM_001382241.1(TNPO2):c.1541C>T (p.Pro514Leu)	Likely pathogenic
2691004	NM_001382241.1(TNPO2):c.826G>A (p.Glu276Lys)	Likely pathogenic
3024520	NM_001382241.1(TNPO2):c.890+1G>T	Likely pathogenic
3776150	NM_001382241.1(TNPO2):c.2174C>A (p.Ala725Asp)	Likely pathogenic
3778670	NM_001382241.1(TNPO2):c.1708T>G (p.Trp570Gly)	Likely pathogenic
4755458	NM_001382241.1(TNPO2):c.191C>T (p.Ser64Phe)	Likely pathogenic
4845653	NM_001382241.1(TNPO2):c.82C>A (p.Gln28Lys)	Likely pathogenic

SpliceAI

3580 predictions. Top by Δscore:

Variant	Effect	Δscore
19:12701190:T:TA	donor_gain	1.0000
19:12701320:CCTTA:C	donor_loss	1.0000
19:12701321:CTTA:C	donor_loss	1.0000
19:12701322:TTA:T	donor_loss	1.0000
19:12701323:TA:T	donor_loss	1.0000
19:12701324:A:AG	donor_loss	1.0000
19:12701449:AGAAT:A	acceptor_gain	1.0000
19:12701450:GAAT:G	acceptor_gain	1.0000
19:12701451:AAT:A	acceptor_gain	1.0000
19:12701451:AATC:A	acceptor_loss	1.0000
19:12701452:AT:A	acceptor_gain	1.0000
19:12701454:C:CC	acceptor_gain	1.0000
19:12701455:T:C	acceptor_loss	1.0000
19:12701593:CTCA:C	donor_loss	1.0000
19:12701594:TCACC:T	donor_loss	1.0000
19:12701595:CACCT:C	donor_loss	1.0000
19:12701596:A:C	donor_loss	1.0000
19:12701654:C:CT	acceptor_gain	1.0000
19:12701762:C:CA	donor_gain	1.0000
19:12701763:C:A	donor_gain	1.0000
19:12701781:T:C	donor_gain	1.0000
19:12702145:TGG:T	acceptor_gain	1.0000
19:12702148:C:CC	acceptor_gain	1.0000
19:12702818:CCCA:C	donor_loss	1.0000
19:12702819:CCA:C	donor_loss	1.0000
19:12702820:CAC:C	donor_loss	1.0000
19:12702822:CCTG:C	donor_loss	1.0000
19:12702916:CCC:C	acceptor_gain	1.0000
19:12702917:CC:C	acceptor_gain	1.0000
19:12702917:CCC:C	acceptor_gain	1.0000

AlphaMissense

5956 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:12701368:A:G	L891P	1.000
19:12701412:C:A	W876C	1.000
19:12701412:C:G	W876C	1.000
19:12701414:A:G	W876R	1.000
19:12701414:A:T	W876R	1.000
19:12701449:A:G	L864P	1.000
19:12701617:A:G	L856P	1.000
19:12701639:A:G	W849R	1.000
19:12701639:A:T	W849R	1.000
19:12701644:G:T	A847D	1.000
19:12701650:G:T	A845D	1.000
19:12701651:C:G	A845P	1.000
19:12701655:G:C	C843W	1.000
19:12701656:C:T	C843Y	1.000
19:12701657:A:G	C843R	1.000
19:12701790:A:G	C825R	1.000
19:12701795:C:A	G823V	1.000
19:12701795:C:T	G823D	1.000
19:12701796:C:A	G823C	1.000
19:12701796:C:G	G823R	1.000
19:12701798:C:G	R822P	1.000
19:12701800:G:C	F821L	1.000
19:12701800:G:T	F821L	1.000
19:12701802:A:G	F821L	1.000
19:12701804:G:T	A820D	1.000
19:12701812:C:A	K817N	1.000
19:12701812:C:G	K817N	1.000
19:12701814:T:C	K817E	1.000
19:12701814:T:G	K817Q	1.000
19:12701837:C:A	R809M	1.000

dbSNP variants (sampled 300 via entrez): RS1000007871 (19:12717540 G>A,C), RS1000018073 (19:12699254 G>A), RS1000292235 (19:12720208 G>A), RS1000509369 (19:12703176 A>T), RS1000683253 (19:12713826 G>A,C), RS1000756908 (19:12714133 T>A), RS1001247431 (19:12711193 C>A,G), RS1001353098 (19:12716714 G>A,T), RS1001740008 (19:12705870 C>T), RS1001851629 (19:12721567 C>A,T), RS1001947229 (19:12700102 G>A), RS1002196782 (19:12710294 G>A), RS1002333062 (19:12703147 T>C,G), RS1002367838 (19:12721963 T>C), RS1002502757 (19:12725557 C>G,T)

Disease associations

OMIM: gene MIM:603002 | disease phenotypes: MIM:619556

GenCC curated gene-disease

Disease	Classification	Inheritance
intellectual developmental disorder with hypotonia, impaired speech, and dysmorphic facies	Strong	Autosomal dominant

Mondo (2): intellectual developmental disorder with hypotonia, impaired speech, and dysmorphic facies (MONDO:0859197), neurodevelopmental disorder (MONDO:0700092)

Orphanet (0):

HPO phenotypes

34 total (30 of 34 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000232	Everted lower lip vermilion
HP:0000252	Microcephaly
HP:0000278	Retrognathia
HP:0000280	Coarse facial features
HP:0000322	Short philtrum
HP:0000341	Narrow forehead
HP:0000343	Long philtrum
HP:0000426	Prominent nasal bridge
HP:0000431	Wide nasal bridge
HP:0000483	Astigmatism
HP:0000486	Strabismus
HP:0000540	Hypermetropia
HP:0000545	Myopia
HP:0000729	Autistic behavior
HP:0000750	Delayed speech and language development
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001251	Ataxia
HP:0001252	Hypotonia
HP:0001263	Global developmental delay
HP:0001276	Hypertonia
HP:0001321	Cerebellar hypoplasia
HP:0001337	Tremor
HP:0001344	Absent speech
HP:0001508	Failure to thrive
HP:0002058	Myopathic facies
HP:0002119	Ventriculomegaly
HP:0002188	Delayed CNS myelination
HP:0002265	Large fleshy ears

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST008722_3	Diffuse large B-cell lymphoma or multiple sclerosis	9.000000e-08

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

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases expression, increases expression	4
sodium arsenite	decreases expression	2
Calcitriol	decreases expression	2
Tretinoin	decreases expression	2
aristolochic acid I	increases expression	1
FR900359	increases phosphorylation	1
bisphenol F	increases expression	1
dicrotophos	increases expression	1
decabromobiphenyl ether	decreases expression	1
cobaltous chloride	decreases expression	1
tetrabromobisphenol A	decreases expression	1
coumarin	increases phosphorylation	1
2-palmitoylglycerol	increases expression	1
torcetrapib	increases expression	1
abrine	increases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
pentabrominated diphenyl ether 100	decreases expression	1
hexabrominated diphenyl ether 153	decreases expression	1
bisphenol S	increases expression	1
Sunitinib	decreases expression	1
Acetaminophen	increases expression	1
Atrazine	increases expression	1
Vehicle Emissions	increases abundance, increases expression	1
Benzo(a)pyrene	affects methylation	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Estradiol	increases expression	1
Lead	affects expression	1
Selenium	decreases expression	1
Smoke	decreases expression	1
Thiram	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_D6Z2	GM28888	Induced pluripotent stem cell	Male

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