INTS1

Summary

INTS1 (integrator complex subunit 1, HGNC:24555) is a protein-coding gene on chromosome 7p22.3, encoding Integrator complex subunit 1 (Q8N201). Component of the integrator complex, a multiprotein complex that terminates RNA polymerase II (Pol II) transcription in the promoter-proximal region of genes. It is a common-essential gene (DepMap: required in 98.8% of cancer cell lines).

INTS1 is a subunit of the Integrator complex, which associates with the C-terminal domain of RNA polymerase II large subunit (POLR2A; MIM 180660) and mediates 3-prime end processing of small nuclear RNAs U1 (RNU1; MIM 180680) and U2 (RNU2; MIM 180690) (Baillat et al., 2005 [PubMed 16239144]).

Source: NCBI Gene 26173 — RefSeq curated summary.

At a glance

• Gene–disease (curated): neurodevelopmental disorder with cataracts, poor growth, and dysmorphic facies (Strong, GenCC)
• GWAS associations: 1
• Clinical variants (ClinVar): 803 total — 11 pathogenic, 13 likely-pathogenic
• Phenotypes (HPO): 40
• Cancer dependency (DepMap): dependent in 98.8% of screened cell lines (common-essential)
• MANE Select transcript: NM_001080453

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:24555
Approved symbol	INTS1
Name	integrator complex subunit 1
Location	7p22.3
Locus type	gene with protein product
Status	Approved
Aliases	DKFZp586J0619, KIAA1440, INT1, NET28
Ensembl gene	ENSG00000164880
Ensembl biotype	protein_coding
OMIM	611345
Entrez	26173

Gene structure

Transcript identifiers

Ensembl transcripts: 17 — 11 protein_coding, 3 retained_intron, 3 protein_coding_CDS_not_defined

ENST00000404767, ENST00000468115, ENST00000479671, ENST00000482994, ENST00000483196, ENST00000493446, ENST00000493531, ENST00000496988, ENST00000859087, ENST00000859088, ENST00000916001, ENST00000916002, ENST00000916003, ENST00000916004, ENST00000951928, ENST00000951929, ENST00000951930

RefSeq mRNA: 1 — MANE Select: NM_001080453 NM_001080453

CCDS: CCDS47526

Canonical transcript exons

ENST00000404767 — 48 exons

Exon	Start	End
ENSE00001156712	1473072	1473184
ENSE00001156716	1473566	1473693
ENSE00001156759	1478366	1478506
ENSE00001156766	1478726	1478885
ENSE00001156772	1479430	1479684
ENSE00001156778	1480317	1480441
ENSE00001156790	1481342	1481488
ENSE00001156849	1470277	1470692
ENSE00001211887	1475948	1476071
ENSE00001211914	1476794	1476918
ENSE00001211925	1477550	1477673
ENSE00001211979	1480835	1480933
ENSE00001211997	1482546	1482707
ENSE00001212080	1474168	1474360
ENSE00001362658	1477753	1477936
ENSE00001415597	1476229	1476455
ENSE00001505948	1476570	1476657
ENSE00001505950	1483742	1483853
ENSE00001600944	1496156	1496264
ENSE00001602560	1498975	1499161
ENSE00001611337	1498412	1498553
ENSE00001639120	1502901	1503191
ENSE00001645323	1493754	1493911
ENSE00001667843	1499255	1499360
ENSE00001668955	1498707	1498852
ENSE00001673516	1499473	1499632
ENSE00001778322	1497138	1497314
ENSE00001918046	1504323	1504389
ENSE00003463352	1494816	1494893
ENSE00003473912	1470846	1470955
ENSE00003477819	1489344	1489404
ENSE00003480146	1471571	1471641
ENSE00003483143	1500170	1500366
ENSE00003483598	1493010	1493106
ENSE00003511764	1489591	1489682
ENSE00003568945	1485098	1485202
ENSE00003571544	1503903	1504001
ENSE00003579434	1485290	1485469
ENSE00003601363	1499884	1500021
ENSE00003624694	1472273	1472386
ENSE00003635337	1487320	1487449
ENSE00003648892	1474705	1474838
ENSE00003673075	1495433	1495553
ENSE00003676630	1484003	1484170
ENSE00003677642	1486922	1487101
ENSE00003677726	1486625	1486774
ENSE00003680933	1487760	1487957
ENSE00003790680	1471133	1471224

Expression profiles

Bgee: expression breadth ubiquitous, 269 present calls, max score 97.31.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 19.5942 / max 110.0044, expressed in 1793 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
82417	18.9637	1792
82418	0.6305	364

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
left testis	UBERON:0004533	97.31	gold quality
right testis	UBERON:0004534	97.13	gold quality
apex of heart	UBERON:0002098	96.72	gold quality
right frontal lobe	UBERON:0002810	96.49	gold quality
right hemisphere of cerebellum	UBERON:0014890	96.49	gold quality
mucosa of transverse colon	UBERON:0004991	95.92	gold quality
cerebellar hemisphere	UBERON:0002245	95.85	gold quality
cerebellar cortex	UBERON:0002129	95.69	gold quality
adenohypophysis	UBERON:0002196	95.53	gold quality
right lobe of thyroid gland	UBERON:0001119	95.49	gold quality
left lobe of thyroid gland	UBERON:0001120	95.25	gold quality
right uterine tube	UBERON:0001302	95.15	gold quality
granulocyte	CL:0000094	94.97	gold quality
metanephros cortex	UBERON:0010533	94.96	gold quality
right lobe of liver	UBERON:0001114	94.80	gold quality
lower esophagus mucosa	UBERON:0035834	94.73	gold quality
hindlimb stylopod muscle	UBERON:0004252	94.69	gold quality
left ovary	UBERON:0002119	94.64	gold quality
gastrocnemius	UBERON:0001388	94.51	gold quality
pituitary gland	UBERON:0000007	94.38	gold quality
sural nerve	UBERON:0015488	94.35	gold quality
cingulate cortex	UBERON:0003027	94.29	gold quality
right ovary	UBERON:0002118	94.28	gold quality
anterior cingulate cortex	UBERON:0009835	94.25	gold quality
tibial nerve	UBERON:0001323	94.21	gold quality
thyroid gland	UBERON:0002046	94.15	gold quality
body of pancreas	UBERON:0001150	94.08	gold quality
body of uterus	UBERON:0009853	94.06	gold quality
endocervix	UBERON:0000458	93.99	gold quality
testis	UBERON:0000473	93.98	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.69

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

5 targeting INTS1, 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-6783-3P	99.89	67.92	2059
HSA-MIR-1343-3P	99.89	66.78	1815
HSA-MIR-939-3P	98.97	65.07	2347
HSA-MIR-663B	97.40	62.91	664
HSA-MIR-6784-5P	84.56	60.91	126

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 98.8% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 5)

• Mutations in INTS1 cause a severe neurodevelopmental syndrome. (PMID:28542170)
• The distinctive phenotype associated with biallelic variants in INTS1 points to dysfunction of the integrator complex as a mechanism for intellectual disability, eye defects and craniofacial anomalies (PMID:30622326)
• Biallelic INTS1 Mutations Cause a Rare Neurodevelopmental Disorder in Two Chinese Siblings. (PMID:31428919)
• A family of fuchs endothelial corneal dystrophy and anterior polar cataract with an analysis of whole exome sequencing. (PMID:32367751)
• A deleterious variant of INTS1 leads to disrupted sleep-wake cycles. (PMID:39189071)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	ints1	ENSDARG00000100419
mus_musculus	Ints1	ENSMUSG00000029547
rattus_norvegicus	Ints1	ENSRNOG00000047880
drosophila_melanogaster	IntS1	FBGN0034964
caenorhabditis_elegans	ints-1	WBGENE00015499

Protein

Protein identifiers

Integrator complex subunit 1 — Q8N201 (reviewed: Q8N201)

All UniProt accessions (2): Q8N201, H7C582

UniProt curated annotations — full annotation on UniProt →

Function. Component of the integrator complex, a multiprotein complex that terminates RNA polymerase II (Pol II) transcription in the promoter-proximal region of genes. The integrator complex provides a quality checkpoint during transcription elongation by driving premature transcription termination of transcripts that are unfavorably configured for transcriptional elongation: the complex terminates transcription by (1) catalyzing dephosphorylation of the C-terminal domain (CTD) of Pol II subunit POLR2A/RPB1 and SUPT5H/SPT5, (2) degrading the exiting nascent RNA transcript via endonuclease activity and (3) promoting the release of Pol II from bound DNA. The integrator complex is also involved in terminating the synthesis of non-coding Pol II transcripts, such as enhancer RNAs (eRNAs), small nuclear RNAs (snRNAs), telomerase RNAs and long non-coding RNAs (lncRNAs). Within the integrator complex, INTS1 is involved in the post-termination step: INTS1 displaces INTS3 and the SOSS factors, allowing the integrator complex to return to the closed conformation, ready to bind to the paused elongation complex for another termination cycle. Mediates recruitment of cytoplasmic dynein to the nuclear envelope, probably as component of the integrator complex.

Subunit / interactions. Component of the Integrator complex, composed of core subunits INTS1, INTS2, INTS3, INTS4, INTS5, INTS6, INTS7, INTS8, INTS9/RC74, INTS10, INTS11/CPSF3L, INTS12, INTS13, INTS14 and INTS15. The core complex associates with protein phosphatase 2A subunits PPP2CA and PPP2R1A, to form the Integrator-PP2A (INTAC) complex. Interacts with ESRRB, ESRRB is not a core component of the Integrator complex and this association is a bridge for the interaction with the multiprotein complex Integrator; attracts the transcriptional machinery.

Subcellular location. Nucleus. Nucleus membrane.

Disease relevance. Neurodevelopmental disorder with cataracts, poor growth, and dysmorphic facies (NDCAGF) [MIM:618571] An autosomal recessive neurodevelopmental disorder characterized by severe global developmental delay with motor impairment, cognitive delays, absent or severely limited speech, dysmorphic features, hypotonia and cataracts. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the Integrator subunit 1 family.

RefSeq proteins (1): NP_001073922* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR016024	ARM-type_fold	Homologous_superfamily
IPR022145	INTS1_RPB2-bd	Domain
IPR038902	INTS1	Family
IPR053964	INT1_R3	Domain
IPR053965	INTS1_R4	Domain
IPR053966	INTS1_INTS2-bd	Domain

Pfam: PF12432, PF22927, PF22928, PF22929

UniProt features (171 total): helix 114, turn 14, strand 14, modified residue 10, sequence variant 7, sequence conflict 4, region of interest 3, compositionally biased region 3, chain 1, transmembrane region 1

Structure

Experimental structures (PDB)

8 structures.

PDB	Method	Resolution (Å)
8RC4	ELECTRON MICROSCOPY	3.1
7CUN	ELECTRON MICROSCOPY	3.5
7PKS	ELECTRON MICROSCOPY	3.6
8RBZ	ELECTRON MICROSCOPY	3.7
8RBX	ELECTRON MICROSCOPY	4.1
8YJB	ELECTRON MICROSCOPY	4.1
7YCX	ELECTRON MICROSCOPY	4.18
9VD9	ELECTRON MICROSCOPY	4.6

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8N201-F1	75.49	0.15

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 (10): 83, 87, 307, 924, 1318, 1326, 1327, 1395, 13, 47

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-6807505	RNA polymerase II transcribes snRNA genes
R-HSA-73857	RNA Polymerase II Transcription
R-HSA-74160	Gene expression (Transcription)

MSigDB gene sets: 204 (showing top): GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, GOBP_GROWTH, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, MODULE_453, chr7p22, GOBP_INNER_CELL_MASS_CELL_PROLIFERATION, GOBP_RNA_SURVEILLANCE, GOBP_IN_UTERO_EMBRYONIC_DEVELOPMENT, GOBP_BLASTOCYST_DEVELOPMENT, GOBP_DNA_TEMPLATED_TRANSCRIPTION_INITIATION, GOBP_TRANSCRIPTION_INITIATION_AT_RNA_POLYMERASE_II_PROMOTER, GOBP_MULTI_MULTICELLULAR_ORGANISM_PROCESS, GOBP_EMBRYO_DEVELOPMENT, GOBP_BLASTOCYST_GROWTH, MODULE_18

GO Biological Process (8): inner cell mass cell proliferation (GO:0001833), embryo implantation (GO:0007566), snRNA processing (GO:0016180), regulation of transcription elongation by RNA polymerase II (GO:0034243), U2 snRNA 3’-end processing (GO:0034474), negative regulation of apoptotic process (GO:0043066), RNA polymerase II transcription initiation surveillance (GO:0160240), blastocyst growth (GO:0001832)

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

GO Cellular Component (6): nucleus (GO:0005634), nucleoplasm (GO:0005654), membrane (GO:0016020), nuclear membrane (GO:0031965), integrator complex (GO:0032039), INTAC complex (GO:0160232)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
RNA Polymerase II Transcription	1
Gene expression (Transcription)	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
nuclear protein-containing complex	2
blastocyst growth	1
cell population proliferation	1
multicellular organism development	1
female pregnancy	1
reproductive process	1
RNA processing	1
snRNA metabolic process	1
transcription elongation by RNA polymerase II	1
regulation of DNA-templated transcription elongation	1
snRNA 3’-end processing	1
apoptotic process	1
regulation of apoptotic process	1
negative regulation of programmed cell death	1
transcription initiation at RNA polymerase II promoter	1
nuclear RNA surveillance	1
blastocyst development	1
developmental growth	1
binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
nucleus	1
nuclear envelope	1
organelle membrane	1
integrator complex	1

Protein interactions and networks

STRING

1452 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
INTS1	INTS11	Q5TA45	970
INTS1	INTS2	Q9H0H0	897
INTS1	INTS4	Q96HW7	888
INTS1	INTS9	Q9NV88	887
INTS1	INTS12	Q96CB8	884
INTS1	INTS3	Q68E01	883
INTS1	INTS14	Q96SY0	843
INTS1	INTS7	Q9NVH2	823
INTS1	POLR2A	P24928	788
INTS1	INTS5	Q6P9B9	775
INTS1	INTS8	Q75QN2	775
INTS1	INTS6	Q9UL03	773
INTS1	INTS13	Q9NVM9	734
INTS1	INTS10	Q9NVR2	690
INTS1	SYMPK	Q92797	654

IntAct

176 interactions, top by confidence:

A	B	Type	Score
PPP2R1A	STRN	psi-mi:“MI:0914”(association)	0.880
PPP2R1A	STRN	psi-mi:“MI:2364”(proximity)	0.880
INTS10	INTS11	psi-mi:“MI:0915”(physical association)	0.740
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
INTS12	INTS1	psi-mi:“MI:0915”(physical association)	0.690
INTS13	INTS11	psi-mi:“MI:0914”(association)	0.690
POLR2C	SUPT5H	psi-mi:“MI:0914”(association)	0.640
ILVBL	COG7	psi-mi:“MI:0914”(association)	0.640
NDUFS7	NDUFS8	psi-mi:“MI:0914”(association)	0.640
APLNR	METTL15	psi-mi:“MI:0914”(association)	0.530
NPY2R	RTL8C	psi-mi:“MI:0914”(association)	0.530
CBX1	KPNA3	psi-mi:“MI:0914”(association)	0.530
SUPT5H	POLR2D	psi-mi:“MI:0914”(association)	0.530
TGOLN2	DENND11	psi-mi:“MI:0914”(association)	0.530
MAS1	POTEF	psi-mi:“MI:0914”(association)	0.530
IL13RA2	METTL15	psi-mi:“MI:0914”(association)	0.530
KIR2DS2	RHOBTB3	psi-mi:“MI:0914”(association)	0.530
ILVBL	EIF2B5	psi-mi:“MI:0914”(association)	0.530
FAM174A	BLTP3B	psi-mi:“MI:0914”(association)	0.530
STK16	UNC119B	psi-mi:“MI:0914”(association)	0.530
CD70	METTL15	psi-mi:“MI:0914”(association)	0.530
ILVBL	SLC33A1	psi-mi:“MI:0914”(association)	0.530
APLNR	SLC33A1	psi-mi:“MI:0914”(association)	0.530

BioGRID (239): INTS1 (Affinity Capture-MS), INTS1 (Affinity Capture-MS), INTS1 (Affinity Capture-MS), INTS1 (Affinity Capture-MS), INTS1 (Affinity Capture-MS), INTS1 (Affinity Capture-MS), INTS1 (Affinity Capture-MS), INTS1 (Affinity Capture-MS), INTS1 (Co-fractionation), INTS1 (Co-fractionation), INTS1 (Co-fractionation), INTS1 (Co-fractionation), INTS7 (Co-fractionation), INTS1 (Affinity Capture-MS), INTS1 (Affinity Capture-MS)

ESM2 similar proteins: A0A0R4ITC5, A1L1F4, A4L9P7, E9Q8I9, F1MKX4, F1QFR9, F1R2X6, F8VPU6, O94915, P21359, P42345, P42346, P51593, P97526, Q04690, Q14997, Q29RF7, Q2HJG5, Q498H0, Q4KLU7, Q4QXM3, Q4VA53, Q5F3U9, Q5F3V3, Q5R6J0, Q5SSW2, Q5TBA9, Q5U241, Q5VYK3, Q6A026, Q6DDM4, Q6GP04, Q6NRP2, Q6P4S8, Q6PDI5, Q6TRW4, Q7PX35, Q7TMY8, Q7Z3U7, Q7Z6Z7

Diamond homologs: Q6P4S8, Q8N201, Q9W1C5

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
INTS1	“form complex”	“Integrator complex”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 222 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
FGFR2 mutant receptor activation	6	29.7×	1e-06
Abortive elongation of HIV-1 transcript in the absence of Tat	9	29.0×	1e-09
Pausing and recovery of Tat-mediated HIV elongation	10	23.9×	1e-09
Tat-mediated HIV elongation arrest and recovery	10	23.9×	1e-09
Signaling by FGFR2 IIIa TM	6	23.4×	4e-06
HIV elongation arrest and recovery	10	22.5×	1e-09
Pausing and recovery of HIV elongation	10	22.5×	1e-09
MicroRNA (miRNA) biogenesis	7	20.8×	1e-06

GO biological processes:

GO term	Partners	Fold	FDR
RNA polymerase II transcription initiation surveillance	9	40.3×	3e-10
snRNA processing	7	37.2×	1e-07
regulation of transcription elongation by RNA polymerase II	8	32.4×	3e-08
adenylate cyclase-modulating G protein-coupled receptor signaling pathway	7	11.9×	3e-04
G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger	6	9.5×	6e-03
phospholipase C-activating G protein-coupled receptor signaling pathway	11	7.3×	6e-05
G protein-coupled receptor signaling pathway	22	4.0×	9e-06

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	11
Likely pathogenic	13
Uncertain significance	507
Likely benign	135
Benign	51

Top pathogenic / likely-pathogenic (24)

Variant ID	HGVS	Classification
1699498	NM_001080453.3(INTS1):c.5572C>T (p.Arg1858Ter)	Pathogenic
2142869	NM_001080453.3(INTS1):c.4932del (p.Arg1645fs)	Pathogenic
2194809	NM_001080453.3(INTS1):c.1927_1928del (p.Cys643fs)	Pathogenic
2264258	NM_001080453.3(INTS1):c.789dup (p.Arg264fs)	Pathogenic
2285823	NM_001080453.3(INTS1):c.2197del (p.Leu733fs)	Pathogenic
643062	NM_001080453.3(INTS1):c.6381C>G (p.Tyr2127Ter)	Pathogenic
689520	NM_001080453.3(INTS1):c.5351C>A (p.Ser1784Ter)	Pathogenic
689522	NM_001080453.3(INTS1):c.5398dup (p.Arg1800fs)	Pathogenic
689523	NM_001080453.3(INTS1):c.5621C>T (p.Pro1874Leu)	Pathogenic
689524	NM_001080453.3(INTS1):c.1645A>G (p.Met549Val)	Pathogenic
689525	NM_001080453.3(INTS1):c.5881C>T (p.Gln1961Ter)	Pathogenic
1064555	NM_001080453.3(INTS1):c.2402delinsTT (p.Arg801fs)	Likely pathogenic
1342412	NM_001080453.3(INTS1):c.3424_3429+20del	Likely pathogenic
1690772	NM_001080453.3(INTS1):c.544G>T (p.Glu182Ter)	Likely pathogenic
2288312	NM_001080453.3(INTS1):c.1711+1G>A	Likely pathogenic
3065918	NM_001080453.3(INTS1):c.-42+1G>C	Likely pathogenic
3891394	NM_001080453.3(INTS1):c.301C>T (p.Arg101Ter)	Likely pathogenic
3893349	NM_001080453.3(INTS1):c.3084G>A (p.Trp1028Ter)	Likely pathogenic
4056800	NM_001080453.3(INTS1):c.5776G>T (p.Glu1926Ter)	Likely pathogenic
4813368	NM_001080453.3(INTS1):c.6184+1G>T	Likely pathogenic
4845466	NM_001080453.3(INTS1):c.536dup (p.Val180fs)	Likely pathogenic
816897	NM_001080453.3(INTS1):c.3036del (p.Met1013fs)	Likely pathogenic
816898	NM_001080453.3(INTS1):c.3430-2A>C	Likely pathogenic
977211	NM_001080453.3(INTS1):c.1855G>T (p.Glu619Ter)	Likely pathogenic

SpliceAI

8742 predictions. Top by Δscore:

Variant	Effect	Δscore
7:1470689:TGCT:T	acceptor_gain	1.0000
7:1470691:CT:C	acceptor_gain	1.0000
7:1470693:C:CA	acceptor_loss	1.0000
7:1470693:C:CC	acceptor_gain	1.0000
7:1470842:TCA:T	donor_loss	1.0000
7:1470844:A:C	donor_loss	1.0000
7:1470845:C:CG	donor_loss	1.0000
7:1470951:CAATG:C	acceptor_gain	1.0000
7:1470953:ATG:A	acceptor_gain	1.0000
7:1470954:TG:T	acceptor_gain	1.0000
7:1470956:C:CC	acceptor_gain	1.0000
7:1471129:TCACC:T	donor_loss	1.0000
7:1471130:CAC:C	donor_loss	1.0000
7:1471131:A:AG	donor_loss	1.0000
7:1471132:C:CG	donor_loss	1.0000
7:1471220:TTGGT:T	acceptor_gain	1.0000
7:1471221:TGGT:T	acceptor_gain	1.0000
7:1471222:GGT:G	acceptor_gain	1.0000
7:1471223:GT:G	acceptor_gain	1.0000
7:1471224:TCTGA:T	acceptor_loss	1.0000
7:1471225:C:CC	acceptor_gain	1.0000
7:1471230:C:CT	acceptor_gain	1.0000
7:1471230:C:T	acceptor_gain	1.0000
7:1471231:G:T	acceptor_gain	1.0000
7:1471565:GCTCA:G	donor_loss	1.0000
7:1471566:CTCA:C	donor_loss	1.0000
7:1471567:TCA:T	donor_loss	1.0000
7:1471568:CA:C	donor_loss	1.0000
7:1471569:A:AC	donor_gain	1.0000
7:1471570:C:CC	donor_gain	1.0000

AlphaMissense

14227 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:1480918:A:G	L1289P	1.000
7:1481398:A:G	L1265P	1.000
7:1481407:A:G	L1262P	1.000
7:1481410:A:G	L1261P	1.000
7:1481439:A:C	F1251L	1.000
7:1481439:A:T	F1251L	1.000
7:1481441:A:G	F1251L	1.000
7:1481451:G:C	F1247L	1.000
7:1481451:G:T	F1247L	1.000
7:1481453:A:G	F1247L	1.000
7:1481461:A:G	L1244P	1.000
7:1482587:A:G	L1221P	1.000
7:1482593:A:G	L1219P	1.000
7:1482595:C:A	W1218C	1.000
7:1482595:C:G	W1218C	1.000
7:1482597:A:G	W1218R	1.000
7:1482597:A:T	W1218R	1.000
7:1482672:A:G	W1193R	1.000
7:1482672:A:T	W1193R	1.000
7:1483823:A:G	W1154R	1.000
7:1483823:A:T	W1154R	1.000
7:1485364:A:G	W1028R	1.000
7:1485364:A:T	W1028R	1.000
7:1486740:A:G	L954P	1.000
7:1487009:G:C	F913L	1.000
7:1487009:G:T	F913L	1.000
7:1487011:A:G	F913L	1.000
7:1487019:A:G	L910P	1.000
7:1487023:A:G	C909R	1.000
7:1487034:A:G	L905P	1.000

dbSNP variants (sampled 300 via entrez): RS1000152558 (7:1475736 G>A,T), RS1000169688 (7:1486544 C>A,G,T), RS1000193707 (7:1500962 C>A,G,T), RS1000250817 (7:1473175 G>A,C), RS1000321940 (7:1472473 G>A), RS1000478181 (7:1493695 T>A,C,G), RS1000497998 (7:1502234 C>G), RS1000551822 (7:1502384 C>A,T), RS1000617270 (7:1479743 G>A,T), RS1000627396 (7:1482023 G>A), RS1000654665 (7:1483978 C>T), RS1000766128 (7:1469952 G>A), RS1000817138 (7:1495266 C>T), RS1000831063 (7:1492462 G>A,T), RS1000835928 (7:1490958 G>A)

Disease associations

OMIM: gene MIM:611345 | disease phenotypes: MIM:618571, MIM:135900

GenCC curated gene-disease

Disease	Classification	Inheritance
neurodevelopmental disorder with cataracts, poor growth, and dysmorphic facies	Strong	Autosomal recessive

Mondo (2): neurodevelopmental disorder with cataracts, poor growth, and dysmorphic facies (MONDO:0032817), Coffin-Siris syndrome (MONDO:0015452)

Orphanet (1): Coffin-Siris syndrome (Orphanet:1465)

HPO phenotypes

40 total (30 of 40 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000110	Renal dysplasia
HP:0000175	Cleft palate
HP:0000268	Dolichocephaly
HP:0000286	Epicanthus
HP:0000293	Full cheeks
HP:0000308	Microretrognathia
HP:0000316	Hypertelorism
HP:0000343	Long philtrum
HP:0000369	Low-set ears
HP:0000411	Protruding ear
HP:0000414	Bulbous nose
HP:0000431	Wide nasal bridge
HP:0000470	Short neck
HP:0000480	Retinal coloboma
HP:0000483	Astigmatism
HP:0000486	Strabismus
HP:0000518	Cataract
HP:0000568	Microphthalmia
HP:0000729	Autistic behavior
HP:0000767	Pectus excavatum
HP:0001250	Seizure
HP:0001252	Hypotonia
HP:0001263	Global developmental delay
HP:0001288	Gait disturbance
HP:0001344	Absent speech
HP:0001627	Abnormal heart morphology
HP:0001845	Overlapping toe
HP:0002002	Deep philtrum
HP:0002007	Frontal bossing

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST004336_1	Executive inhibition (Stroop WIT and CIT) in attention deficit hyperactivity disorder	5.000000e-09

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0007969	cognitive inhibition measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C536436	Coffin-Siris syndrome (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, affects cotreatment, increases abundance, increases expression	4
Air Pollutants	affects expression, increases abundance, increases expression	3
bisphenol A	affects cotreatment, increases methylation, decreases expression, decreases methylation	2
Benzo(a)pyrene	affects methylation, increases methylation	2
Cisplatin	decreases expression	2
Smoke	increases expression, decreases expression, increases abundance	2
Aflatoxin B1	decreases expression, increases methylation, decreases reaction	2
Cadmium Chloride	increases expression	2
FR900359	affects phosphorylation	1
bisphenol F	decreases methylation	1
dicrotophos	increases expression	1
arsenite	affects binding, decreases reaction	1
manganese chloride	decreases expression, increases abundance, affects cotreatment	1
beta-methylcholine	affects expression	1
ICG 001	increases expression	1
Grape Seed Proanthocyanidins	affects cotreatment, decreases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	increases expression	1
Decitabine	decreases expression, decreases reaction	1
Fulvestrant	affects cotreatment, increases methylation	1
Acetaminophen	increases expression	1
Arsenic	affects cotreatment, decreases expression, increases abundance	1
Caffeine	decreases phosphorylation	1
Catechin	affects cotreatment, decreases expression	1
Hydrogen Peroxide	affects expression	1
Lipopolysaccharides	affects expression, affects response to substance	1
Manganese	decreases expression, increases abundance, affects cotreatment	1
Ozone	increases abundance, affects expression	1
Selenium	increases expression	1
Valproic Acid	increases methylation	1
Acrylamide	decreases expression	1

Clinical trials (associated diseases)

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