ZC3H14

Summary

ZC3H14 (zinc finger CCCH-type containing 14, HGNC:20509) is a protein-coding gene on chromosome 14q31.3, encoding Zinc finger CCCH domain-containing protein 14 (Q6PJT7). RNA-binding protein involved in the biogenesis of circular RNAs (circRNAs), which are produced by back-splicing circularization of pre-mRNAs.

The protein encoded by this gene is a poly(A)-binding protein that can affect gene expression and poly(A) tail length. The encoded protein may influence mRNA stability, nuclear export, and translation.

Source: NCBI Gene 79882 — RefSeq curated summary.

At a glance

• Gene–disease (curated): intellectual disability, autosomal recessive 56 (Moderate, GenCC) — +2 more curated relationships
• GWAS associations: 1
• Clinical variants (ClinVar): 156 total
• Phenotypes (HPO): 2
• MANE Select transcript: NM_024824

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:20509
Approved symbol	ZC3H14
Name	zinc finger CCCH-type containing 14
Location	14q31.3
Locus type	gene with protein product
Status	Approved
Aliases	FLJ11806, UKp68, NY-REN-37
Ensembl gene	ENSG00000100722
Ensembl biotype	protein_coding
OMIM	613279
Entrez	79882

Gene structure

Transcript identifiers

Ensembl transcripts: 48 — 41 protein_coding, 3 nonsense_mediated_decay, 2 retained_intron, 2 protein_coding_CDS_not_defined

ENST00000251038, ENST00000302216, ENST00000318308, ENST00000336693, ENST00000393514, ENST00000406216, ENST00000553495, ENST00000554020, ENST00000554602, ENST00000555120, ENST00000555755, ENST00000555792, ENST00000555799, ENST00000555851, ENST00000555900, ENST00000556000, ENST00000556110, ENST00000556158, ENST00000556945, ENST00000557047, ENST00000557491, ENST00000557605, ENST00000557607, ENST00000557693, ENST00000557737, ENST00000649731, ENST00000888713, ENST00000888714, ENST00000888715, ENST00000888716, ENST00000888717, ENST00000888718, ENST00000888719, ENST00000888720, ENST00000888721, ENST00000888722, ENST00000888723, ENST00000888724, ENST00000888725, ENST00000888726, ENST00000888727, ENST00000888728, ENST00000888729, ENST00000888730, ENST00000888731, ENST00000971947, ENST00000971948, ENST00000971949

RefSeq mRNA: 28 — MANE Select: NM_024824 NM_001160103, NM_001160104, NM_001326295, NM_001326296, NM_001326297, NM_001326298, NM_001326299, NM_001326300, NM_001326301, NM_001326302, NM_001326303, NM_001326304, NM_001326305, NM_001326306, NM_001326307, NM_001326308, NM_001326309, NM_001326310, NM_001326311, NM_001326312, NM_001326313, NM_001326314, NM_001326315, NM_001326316, NM_024824, NM_207660, NM_207661, NM_207662

CCDS: CCDS32133, CCDS32134, CCDS32135, CCDS32136, CCDS55938, CCDS86417, CCDS86418

Canonical transcript exons

ENST00000251038 — 17 exons

Exon	Start	End
ENSE00001197974	88609712	88609803
ENSE00001218981	88596734	88596808
ENSE00001334793	88601924	88602083
ENSE00002468535	88611745	88627596
ENSE00003469137	88610834	88610940
ENSE00003482536	88572030	88572225
ENSE00003490826	88563651	88563693
ENSE00003549582	88571084	88571124
ENSE00003554663	88607243	88607363
ENSE00003616335	88574693	88574853
ENSE00003619794	88568039	88568153
ENSE00003625563	88602828	88603060
ENSE00003641976	88575840	88575940
ENSE00003653636	88609267	88609403
ENSE00003677821	88563037	88563169
ENSE00003684283	88572578	88573007
ENSE00003716072	88577985	88578140

Expression profiles

Bgee: expression breadth ubiquitous, 298 present calls, max score 98.91.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 27.7652 / max 288.0773, expressed in 1806 samples.

FANTOM5 promoters (11 alternative TSS)

Promoter ID	TPM avg	Samples expressed
140961	21.6549	1801
140960	3.5060	1406
140958	1.0067	610
140962	0.6092	358
140959	0.4675	243
140963	0.3001	168
140970	0.0894	16
140967	0.0820	5
140968	0.0204	4
140969	0.0183	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
left testis	UBERON:0004533	98.91	gold quality
right testis	UBERON:0004534	98.79	gold quality
sperm	CL:0000019	98.40	gold quality
male germ cell	CL:0000015	98.13	gold quality
testis	UBERON:0000473	97.74	gold quality
secondary oocyte	CL:0000655	96.33	gold quality
colonic epithelium	UBERON:0000397	95.08	gold quality
corpus epididymis	UBERON:0004359	94.85	gold quality
caput epididymis	UBERON:0004358	94.84	gold quality
ventricular zone	UBERON:0003053	94.42	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	94.41	gold quality
rectum	UBERON:0001052	94.41	gold quality
right lobe of liver	UBERON:0001114	94.40	gold quality
endometrium epithelium	UBERON:0004811	94.27	gold quality
calcaneal tendon	UBERON:0003701	94.16	gold quality
stromal cell of endometrium	CL:0002255	93.85	gold quality
cauda epididymis	UBERON:0004360	93.78	gold quality
oocyte	CL:0000023	93.32	gold quality
body of pancreas	UBERON:0001150	93.30	gold quality
paraflocculus	UBERON:0005351	93.25	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	93.24	gold quality
adrenal tissue	UBERON:0018303	93.19	gold quality
frontal pole	UBERON:0002795	93.07	gold quality
islet of Langerhans	UBERON:0000006	93.04	gold quality
ganglionic eminence	UBERON:0004023	93.00	gold quality
smooth muscle tissue	UBERON:0001135	92.96	gold quality
right lung	UBERON:0002167	92.74	gold quality
embryo	UBERON:0000922	92.73	gold quality
pancreas	UBERON:0001264	92.63	gold quality
ovary	UBERON:0000992	92.52	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-GEOD-134144	yes	28.44
E-ANND-3	yes	7.41
E-MTAB-10290	no	108.49

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

89 targeting ZC3H14, 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-3613-3P	100.00	76.36	7965
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-568	99.98	69.86	2084
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-144-3P	99.94	73.98	2698
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-605-3P	99.88	69.22	1833
HSA-MIR-30A-3P	99.87	69.74	2928
HSA-MIR-30D-3P	99.87	69.92	2917
HSA-MIR-30E-3P	99.87	69.68	2942
HSA-MIR-548D-3P	99.87	70.67	4362
HSA-MIR-6124	99.87	69.78	3551
HSA-MIR-5582-3P	99.86	72.48	4221
HSA-MIR-548BB-3P	99.86	70.58	4354
HSA-MIR-548AC	99.84	70.77	4351
HSA-MIR-548H-3P	99.84	70.80	4349
HSA-MIR-548Z	99.84	70.80	4349
HSA-MIR-548AZ-5P	99.83	69.94	3230
HSA-MIR-548T-5P	99.83	69.91	3220
HSA-MIR-1323	99.83	69.89	2471
HSA-MIR-3180-5P	99.82	69.12	2422
HSA-MIR-4495	99.82	72.08	3080

Literature-anchored findings (GeneRIF, showing 9)

• these proteins are members of an evolutionarily conserved family of poly(A) RNA binding proteins (PMID:17630287)
• multiple transcripts encoding several ZC3H14 isoforms exist in vivo (PMID:19303045)
• New neuroprotective strategies targeting MSUT-2 that may be effective in modulating tau neurotoxicity in human tauopathy disorders. (PMID:20658987)
• MSUT2 levels may influence neuronal vulnerability to tau toxicity and aggregation. (PMID:21355046)
• report a intellectual disability disease locus on chromosome 14q31.3 corresponding to mutation of the ZC3H14 gene that encodes a conserved polyadenosine RNA binding protein (PMID:21734151)
• we show here that human ZC3H14 can functionally substitute for dNab2 in fly neurons and can rescue defects in development and locomotion that are present in dNab2 null flies (PMID:24671764)
• ATP5G1 turnover increases upon depletion of ZC3H14, double knockdown of ZC3H14 and the nonsense-mediated decay factor, UPF1, rescues ATP5G1 transcript levels. Furthermore, fractionation reveals an increase in the amount of ATP5G1 pre-mRNA that reaches the cytoplasm when ZC3H14 is depleted and that ZC3H14 binds to ATP5G1 pre-mRNA in the nucleus. (PMID:27563065)
• study suggests that ZC3H14 functions as a novel tumor suppressor and is a candidate prognostic biomarker for hepatocellular carcinoma patients (PMID:30371740)
• AlphaScreen Identifies MSUT2 Inhibitors for Tauopathy-Targeting Therapeutic Discovery. (PMID:32981422)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	zc3h14	ENSDARG00000041402
mus_musculus	Zc3h14	ENSMUSG00000021012
rattus_norvegicus	Zc3h14	ENSRNOG00000004083
drosophila_melanogaster	Nab2	FBGN0028471
caenorhabditis_elegans		WBGENE00022019

Protein

Protein identifiers

Zinc finger CCCH domain-containing protein 14 — Q6PJT7 (reviewed: Q6PJT7)

Alternative names: Mammalian suppressor of tau pathology-2, Renal carcinoma antigen NY-REN-37

All UniProt accessions (16): Q6PJT7, A0A087WTC9, A0A3B3IT62, G3V240, G3V256, G3V2X4, G3V3R9, G3V3Y4, G3V411, G3V473, G3V4R5, G3V572, G3V5I6, H0YJ51, H0YJ87, H0YJA2

UniProt curated annotations — full annotation on UniProt →

Function. RNA-binding protein involved in the biogenesis of circular RNAs (circRNAs), which are produced by back-splicing circularization of pre-mRNAs. Acts by binding to both exon-intron boundary and 3’-UTR of pre-mRNAs to promote circRNA biogenesis through dimerization and the association with the spliceosome. Required for spermatogenesis via involvement in circRNA biogenesis. Regulates the pre-mRNA processing of ATP5MC1; preventing its degradation. Also binds the poly(A) tail of mRNAs; controlling poly(A) length in neuronal cells.

Subunit / interactions. Homodimer; facilitating circular RNAs (circRNAs) formation. Associates with the spliceosome. Interacts with HOOK2. Interacts with ZFC3H1 in a RNase-sensitive manner.

Subcellular location. Nucleus speckle Nucleus speckle Nucleus speckle Cytoplasm.

Tissue specificity. Expressed in fetal and adult brain. Expressed in fetal and adult temporal lobe. Expressed in fetal and adult brain. Expressed in fetal and adult temporal lobe.

Disease relevance. Intellectual developmental disorder, autosomal recessive 56 (MRT56) [MIM:617125] A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. The disease is caused by variants affecting the gene represented in this entry.

Miscellaneous. ZC3H14 can functionally substitute for Nab2 in fly neurons and can rescue defects in development and locomotion that are present in dNab2 null flies.

Similarity. Belongs to the ZC3H14 family.

Isoforms (10)

UniProt ID	Names	Canonical?
Q6PJT7-1	1, Isoform 1	yes
Q6PJT7-2	2
Q6PJT7-3	3, Isoform 2
Q6PJT7-4	4, Isoform 3 short
Q6PJT7-5	5
Q6PJT7-6	6, Isoform 4
Q6PJT7-8	8
Q6PJT7-9	9
Q6PJT7-10	10
Q6PJT7-11	11

RefSeq proteins (28): NP_001153575, NP_001153576, NP_001313224, NP_001313225, NP_001313226, NP_001313227, NP_001313228, NP_001313229, NP_001313230, NP_001313231, NP_001313232, NP_001313233, NP_001313234, NP_001313235, NP_001313236, NP_001313237, NP_001313238, NP_001313239, NP_001313240, NP_001313241, NP_001313242, NP_001313243, NP_001313244, NP_001313245, NP_079100, NP_997543, NP_997544, NP_997545 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000571	Znf_CCCH	Domain
IPR040366	Nab2/ZC3H14	Family

Pfam: PF14608

UniProt features (56 total): modified residue 14, splice variant 12, cross-link 11, sequence conflict 6, zinc finger region 5, compositionally biased region 3, region of interest 3, chain 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6PJT7-F1	56.87	0.11

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 (25): 1, 85, 240, 281, 327, 343, 357, 390, 409, 421, 498, 515, 527, 620, 99, 139, 175, 198, 245, 283 …

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 179 (showing top): GOBP_REGULATION_OF_MRNA_CATABOLIC_PROCESS, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_MALE_GAMETE_GENERATION, GOBP_POST_TRANSCRIPTIONAL_REGULATION_OF_GENE_EXPRESSION, GOBP_REGULATION_OF_CATABOLIC_PROCESS, GOBP_RNA_SPLICING, ZHOU_INFLAMMATORY_RESPONSE_LIVE_DN, FLECHNER_BIOPSY_KIDNEY_TRANSPLANT_REJECTED_VS_OK_DN, GOBP_DEVELOPMENTAL_PROCESS_INVOLVED_IN_REPRODUCTION, GOCC_NEURON_PROJECTION, FOXJ2_02, GOBP_NEGATIVE_REGULATION_OF_CATABOLIC_PROCESS, chr14q31, GOCC_CYTOPLASMIC_REGION, GOCC_NUCLEAR_SPECK

GO Biological Process (5): spermatogenesis (GO:0007283), cell differentiation (GO:0030154), regulation of mRNA stability (GO:0043488), mRNA stabilization (GO:0048255), spliceosome-depend formation of circular RNA (GO:0160091)

GO Molecular Function (7): RNA binding (GO:0003723), mRNA 3’-UTR binding (GO:0003730), poly(A) binding (GO:0008143), zinc ion binding (GO:0008270), pre-mRNA binding (GO:0036002), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (7): nucleus (GO:0005634), nucleolus (GO:0005730), cytoplasm (GO:0005737), nuclear speck (GO:0016607), dendrite cytoplasm (GO:0032839), axon cytoplasm (GO:1904115), ribonucleoprotein complex (GO:1990904)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
neuron projection cytoplasm	2
developmental process involved in reproduction	1
male gamete generation	1
cellular developmental process	1
regulation of RNA stability	1
regulation of mRNA catabolic process	1
regulation of mRNA stability	1
RNA stabilization	1
negative regulation of mRNA catabolic process	1
mRNA splicing, via spliceosome	1
nucleic acid binding	1
mRNA binding	1
poly-purine tract binding	1
transition metal ion binding	1
RNA binding	1
binding	1
cation binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
intracellular membraneless organelle	1
intracellular anatomical structure	1
cellular anatomical structure	1
nuclear ribonucleoprotein granule	1
dendrite	1
axon	1
protein-containing complex	1

Protein interactions and networks

STRING

2238 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ZC3H14	PABPN1	Q86U42	870
ZC3H14	NAB2	Q15742	845
ZC3H14	HOOK2	Q96ED9	838
ZC3H14	MARK1	Q9P0L2	639
ZC3H14	MAPT	P10636	606
ZC3H14	PCF11	O94913	572
ZC3H14	ALYREF	Q86V81	551
ZC3H14	YWHAQ	P27348	549
ZC3H14	LRP8	Q14114	545
ZC3H14	THOC1	Q96FV9	520
ZC3H14	PRPF38A	Q8NAV1	518
ZC3H14	VLDLR	P98155	511
ZC3H14	NPEPPS	P55786	495
ZC3H14	MTMR14	Q8NCE2	495
ZC3H14	GLE1	Q53GS7	490
ZC3H14	AMMECR1L	Q6DCA0	490

IntAct

147 interactions, top by confidence:

A	B	Type	Score
PNN	PRP4K	psi-mi:“MI:0914”(association)	0.790
SARNP	DDX39A	psi-mi:“MI:0914”(association)	0.740
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
NCBP1	KPNA3	psi-mi:“MI:0914”(association)	0.640
CAMKV	AP3B1	psi-mi:“MI:0914”(association)	0.640
SNRPA1	HTATSF1	psi-mi:“MI:0914”(association)	0.640
PNN	CASC3	psi-mi:“MI:0914”(association)	0.640
SLC39A5	FAM171A2	psi-mi:“MI:0914”(association)	0.640
DDIT3	ZC3H14	psi-mi:“MI:0915”(physical association)	0.560
KPNB1	POM121C	psi-mi:“MI:0914”(association)	0.530
NCBP3	SAP18	psi-mi:“MI:0914”(association)	0.530
SNRNP70	GTPBP1	psi-mi:“MI:0914”(association)	0.530
ELAVL2	IGF2BP3	psi-mi:“MI:0914”(association)	0.530
SNIP1	CASC3	psi-mi:“MI:0914”(association)	0.530
ZC3H18	AQR	psi-mi:“MI:0914”(association)	0.530
RALYL	CDC40	psi-mi:“MI:0914”(association)	0.530
WSB2	UBB	psi-mi:“MI:0914”(association)	0.530
SNRPC	SNRPGP15	psi-mi:“MI:0914”(association)	0.530
CDKL1	TRIP6	psi-mi:“MI:0914”(association)	0.530
SLC30A2	ESYT2	psi-mi:“MI:0914”(association)	0.530
CPSF6	DDX39A	psi-mi:“MI:0914”(association)	0.480
THRAP3	HNRNPC	psi-mi:“MI:0914”(association)	0.480
ITCH	ZC3H14	psi-mi:“MI:0407”(direct interaction)	0.440
ZC3H14	PCNA	psi-mi:“MI:0915”(physical association)	0.370
EXOC7	ZC3H14	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (228): ZC3H14 (Two-hybrid), ZC3H14 (Affinity Capture-MS), ZC3H14 (Affinity Capture-MS), ZC3H14 (Affinity Capture-MS), ZC3H14 (Affinity Capture-MS), ZC3H14 (Affinity Capture-MS), ZC3H14 (Affinity Capture-MS), ZC3H14 (Affinity Capture-MS), ZC3H14 (Affinity Capture-MS), ZC3H14 (Two-hybrid), ZC3H14 (Two-hybrid), ZC3H14 (Affinity Capture-MS), ZC3H14 (Proximity Label-MS), ZC3H14 (Affinity Capture-MS), ZC3H14 (Affinity Capture-MS)

ESM2 similar proteins: A0A1B0GTU1, A2AUY4, B7ZS37, D3Z8Y2, D4A4L4, D4A666, E1B7L7, O46385, O60293, O75152, O95425, P0DQW0, Q08AZ1, Q3KQW7, Q3U1C4, Q3UH68, Q3ZC82, Q4G0F8, Q4V9H5, Q5F3Z9, Q5NBX1, Q5REG6, Q5ZJJ1, Q5ZM88, Q61464, Q62394, Q68FE9, Q6NZF1, Q6PJT7, Q6ZQ03, Q6ZU65, Q76L83, Q7TMD5, Q8BHZ4, Q8BJ05, Q8BLG0, Q8BZ32, Q8C9B9, Q8CCJ9, Q8K298

Diamond homologs: Q08AZ1, Q3ZC82, Q4R6F6, Q5F3Z9, Q5TYQ8, Q6PJT7, Q7TMD5, Q8BJ05, Q95XU6

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 187 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
Transport of Mature Transcript to Cytoplasm	12	36.0×	1e-14
mRNA 3’-end processing	21	32.6×	5e-25
Transport of Mature mRNA derived from an Intron-Containing Transcript	22	26.4×	5e-24
RNA Polymerase II Transcription Termination	15	25.9×	5e-16
Metal ion SLC transporters	5	23.7×	9e-05
mRNA Splicing	27	23.3×	5e-28
mRNA Polyadenylation	29	20.1×	5e-28
Processing of Capped Intron-Containing Pre-mRNA	31	20.1×	7e-30

GO biological processes:

GO term	Partners	Fold	FDR
negative regulation of mRNA splicing, via spliceosome	9	41.5×	8e-11
U2-type prespliceosome assembly	9	33.8×	6e-10
RNA export from nucleus	5	28.2×	6e-05
RNA splicing, via transesterification reactions	7	26.3×	8e-07
regulation of alternative mRNA splicing, via spliceosome	14	20.6×	2e-12
alternative mRNA splicing, via spliceosome	5	20.3×	3e-04
mRNA splicing, via spliceosome	36	19.9×	8e-34
positive regulation of mRNA splicing, via spliceosome	6	19.6×	5e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	97
Likely benign	26
Benign	7

Top pathogenic / likely-pathogenic (0)

SpliceAI

4749 predictions. Top by Δscore:

Variant	Effect	Δscore
14:88568037:A:AG	acceptor_gain	1.0000
14:88568038:G:GG	acceptor_gain	1.0000
14:88568149:GTATG:G	donor_gain	1.0000
14:88568977:TTTC:T	donor_gain	1.0000
14:88571069:T:TA	acceptor_gain	1.0000
14:88571080:TCA:T	acceptor_loss	1.0000
14:88571081:CAGGC:C	acceptor_loss	1.0000
14:88571082:A:AG	acceptor_gain	1.0000
14:88571082:AG:A	acceptor_gain	1.0000
14:88571083:G:GT	acceptor_gain	1.0000
14:88571083:GG:G	acceptor_gain	1.0000
14:88571121:ACTG:A	donor_gain	1.0000
14:88571122:CTGGT:C	donor_loss	1.0000
14:88571123:TGG:T	donor_loss	1.0000
14:88571124:GGTAA:G	donor_loss	1.0000
14:88571125:G:GG	donor_gain	1.0000
14:88571126:T:A	donor_loss	1.0000
14:88572028:A:AG	acceptor_gain	1.0000
14:88572029:G:GA	acceptor_gain	1.0000
14:88572029:GA:G	acceptor_gain	1.0000
14:88572029:GAA:G	acceptor_gain	1.0000
14:88572029:GAAC:G	acceptor_gain	1.0000
14:88572029:GAACC:G	acceptor_gain	1.0000
14:88572221:GTCAG:G	donor_gain	1.0000
14:88572224:AGGT:A	donor_loss	1.0000
14:88572225:GGTAA:G	donor_loss	1.0000
14:88572226:G:GG	donor_gain	1.0000
14:88572573:A:G	acceptor_gain	1.0000
14:88572576:A:AG	acceptor_gain	1.0000
14:88572577:G:GA	acceptor_gain	1.0000

AlphaMissense

4881 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
14:88563153:T:G	I7S	1.000
14:88563165:T:A	I11N	1.000
14:88563165:T:C	I11T	1.000
14:88563165:T:G	I11S	1.000
14:88563654:G:C	A14P	1.000
14:88563655:C:A	A14D	1.000
14:88563658:T:A	I15N	1.000
14:88563668:A:C	K18N	1.000
14:88563668:A:T	K18N	1.000
14:88563670:T:C	L19S	1.000
14:88568044:G:A	E29K	1.000
14:88568048:T:A	L30H	1.000
14:88568048:T:C	L30P	1.000
14:88568051:C:A	P31H	1.000
14:88568051:C:G	P31R	1.000
14:88568053:G:C	D32H	1.000
14:88568056:T:C	Y33H	1.000
14:88568057:A:G	Y33C	1.000
14:88568060:T:A	I34N	1.000
14:88568060:T:G	I34S	1.000
14:88568063:T:A	M35K	1.000
14:88568063:T:G	M35R	1.000
14:88568064:G:A	M35I	1.000
14:88568064:G:C	M35I	1.000
14:88568064:G:T	M35I	1.000
14:88568066:T:A	V36E	1.000
14:88568069:T:A	M37K	1.000
14:88568069:T:C	M37T	1.000
14:88568069:T:G	M37R	1.000
14:88568070:G:A	M37I	1.000

dbSNP variants (sampled 300 via entrez): RS1000016786 (14:88625207 G>A,T), RS1000042940 (14:88575969 G>A,C), RS1000089220 (14:88617697 G>C,T), RS1000168191 (14:88601193 A>G), RS1000237947 (14:88619925 A>G), RS1000242292 (14:88612013 G>A), RS1000290251 (14:88619672 T>C), RS1000290848 (14:88588240 G>A,T), RS1000313428 (14:88570736 G>A,C), RS1000398071 (14:88582356 C>G), RS1000441227 (14:88627260 C>A,T), RS1000450596 (14:88582026 C>T), RS1000478471 (14:88604286 A>T), RS1000638643 (14:88606415 C>T), RS1000703346 (14:88576444 C>G)

Disease associations

OMIM: gene MIM:613279 | disease phenotypes: MIM:617125

GenCC curated gene-disease

Disease	Classification	Inheritance
intellectual disability, autosomal recessive 56	Moderate	Autosomal recessive
autosomal recessive non-syndromic intellectual disability	Supportive	Autosomal recessive

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
intellectual disability	Limited	AR

Mondo (3): intellectual disability, autosomal recessive 56 (MONDO:0014930), intellectual disability (MONDO:0001071), autosomal recessive non-syndromic intellectual disability (MONDO:0019502)

Orphanet (1): NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

2 total (2 of 2 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0001249	Intellectual disability

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST008473_36	Visceral fat	3.000000e-06

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: other protein — RNA-binding proteins (RBPs)

CTD chemical–gene interactions

25 total (human), top 25 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression, decreases methylation	4
GSK-J4	increases expression	1
FR900359	affects phosphorylation	1
TAK-243	decreases sumoylation	1
triphenyl phosphate	affects expression	1
bisphenol A	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
sodium arsenite	increases expression	1
ochratoxin A	decreases expression	1
coumarin	increases phosphorylation	1
nivalenol	increases expression	1
K 7174	increases expression	1
bisphenol S	affects expression	1
Air Pollutants, Occupational	affects expression	1
Benzo(a)pyrene	affects methylation	1
Caffeine	increases phosphorylation	1
Doxorubicin	decreases expression	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Ivermectin	decreases expression	1
Ribonucleotides	affects binding	1
Rotenone	increases expression	1
Tretinoin	decreases expression	1
Cyclosporine	decreases expression	1
Aflatoxin B1	increases methylation	1
Cadmium Chloride	decreases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT05657860	PHASE4	COMPLETED	Guanfacine Extended Release for the Reduction of Aggression and Self-injurious Behavior Associated With Prader-Willi Syndrome
NCT05744479	PHASE4	RECRUITING	Metformin for Antipsychotic-induced Weight Gain in Adults With Intellectual Disability
NCT06107829	PHASE4	WITHDRAWN	Valbenazine Treatment of Tardive Dyskinesia in Adults With Intellectual/Developmental Disabilities
NCT06997198	PHASE4	NOT_YET_RECRUITING	Deutetrabenazine Treatment for Tardive Dyskinesia in Intellectual/Developmental Disabilities
NCT02270736	PHASE3	COMPLETED	Clinical Study to Investigate the Efficacy and Safety of NT 201 Compared to Placebo in the Treatment of Chronic Troublesome Drooling Associated With Neurological Disorders and/or Intellectual Disability
NCT02304302	PHASE2	COMPLETED	Down Syndrome Memantine Follow-up Study
NCT03862950	PHASE2	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome (Met)
NCT04529226	PHASE2	UNKNOWN	Study to Compare Clozapine vs Treatment as Usual in People With Intellectual Disability & Treatment-resistant Psychosis
NCT04821856	PHASE2	COMPLETED	Evaluation of the Effectiveness of Cannabidiol in Treating Severe Behavioural Problems in Children and Adolescents With Intellectual Disability
NCT05273320	PHASE1	COMPLETED	Clinical Trial of Nabilone for Aggression in Adults With Intellectual and Developmental Disabilities
NCT05301361	PHASE1	ENROLLING_BY_INVITATION	Sensitivity of the NIH Toolbox to Stimulant Treatment in Intellectual Disabilities
NCT06016764	PHASE1	COMPLETED	Use of MRI and cTBS for Catatonia in Autism
NCT06586827	PHASE1	COMPLETED	Impact of Competency-Based Training and Technical Assistance Employment Outcomes of Individuals With ID/DD
NCT07531940	PHASE1	NOT_YET_RECRUITING	Escalating Doses of Memantine in Down Syndrome (MEDS-123)
NCT03479476	PHASE2/PHASE3	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome
NCT02616796	PHASE1/PHASE2	COMPLETED	Effects of Social Gaze Training on Brain and Behavior in Fragile X Syndrome
NCT06860672	EARLY_PHASE1	RECRUITING	Clinical Trial of the Dual Vector Base Editor for the Treatment of the CHD3-R1025W Mutation
NCT00597948	Not specified	COMPLETED	Healthy Lifestyles for People With Intellectual Disabilities
NCT01087320	Not specified	RECRUITING	Genome Medical Sequencing for Gene Discovery
NCT01652963	Not specified	UNKNOWN	Picture-based Computerised Assessment and Training of Cognitive Behaviour Therapy Skills
NCT01695395	Not specified	COMPLETED	Mental Health Care Provision for Adults With Intellectual Disability and a Mental Disorder
NCT01867554	Not specified	COMPLETED	Research and Characterization of New Genes Involved in Intellectual Disability
NCT01915381	Not specified	COMPLETED	Improving Adherence Healthy Lifestyle With a Smartphone Application Based on Adults With Intellectual Disabilities
NCT01988623	Not specified	COMPLETED	Pivotal Response Treatment for Individuals With Intellectual Disabilities
NCT02099773	Not specified	COMPLETED	Support Staff-client Interactions With Augmentative and Alternative Communication
NCT02136849	Not specified	COMPLETED	Inter-regional Project of the Great Western Exploration Approach for Exome Molecular Causes Severe Intellectual Disability Isolated or Syndromic
NCT02225041	Not specified	COMPLETED	Sedation Strategy and Cognitive Outcome After Critical Illness in Early Childhood
NCT02414438	Not specified	COMPLETED	Establishing the Clinical Utility of First StepDx PLUS and NextStepDx PLUS Study
NCT02451761	Not specified	COMPLETED	Apparently Balanced Chromosomal Translocation/ Next-generation Sequencing/ Intellectual Disability
NCT02461420	Not specified	ACTIVE_NOT_RECRUITING	Mapping the Genotype, Phenotype, and Natural History of Phelan-McDermid Syndrome
NCT02461459	Not specified	ACTIVE_NOT_RECRUITING	Autism Spectrum Disorder (ASD) and Intellectual Disability (ID) Determinants in Tuberous Sclerosis Complex (TSC)
NCT02486081	Not specified	COMPLETED	Development and Application-Smart Football for Movement Evaluation and Training in the Special Education Population
NCT02504502	Not specified	COMPLETED	Enhancing Genomic Laboratory Reports to Enhance Communication and Empower Patients
NCT02513277	Not specified	COMPLETED	Diabetes Screening & Prevention for People With Learning (Intellectual) Disabilities:STOP Diabetes Study
NCT02561754	Not specified	COMPLETED	Weight Management for Adolescents With IDD
NCT02591446	Not specified	COMPLETED	Transcranial Magnetic Stimulation Studies in Autism Spectrum Disorders
NCT02714868	Not specified	COMPLETED	Evaluation of Project TEAM (Teens Making Environmental and Activity Modifications)
NCT02721394	Not specified	UNKNOWN	FCT With Young Children With ID in the UK: A Feasibility Project V.1
NCT02746614	Not specified	COMPLETED	Psychomotor Therapy Effects in Adaptive Behavior and Motor Proficiency in Intellectual Disability
NCT02836405	Not specified	COMPLETED	TMS for the Investigation of Brain Plasticity in Autism Spectrum Disorders