INTS6L

Summary

INTS6L (integrator complex subunit 6 like, HGNC:27334) is a protein-coding gene on chromosome Xq26.3, encoding Integrator complex subunit 6-like (Q5JSJ4).

Predicted to be involved in snRNA 3’-end processing. Predicted to be part of integrator complex.

Source: NCBI Gene 203522 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 174 total
• MANE Select transcript: NM_001351601

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:27334
Approved symbol	INTS6L
Name	integrator complex subunit 6 like
Location	Xq26.3
Locus type	gene with protein product
Status	Approved
Aliases	FLJ41215
Ensembl gene	ENSG00000165359
Ensembl biotype	protein_coding
Entrez	203522

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 7 protein_coding, 3 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000370752, ENST00000481429, ENST00000481908, ENST00000493637, ENST00000494957, ENST00000639893, ENST00000899998, ENST00000899999, ENST00000946955, ENST00000946956, ENST00000946957

RefSeq mRNA: 6 — MANE Select: NM_001351601 NM_001351601, NM_001351603, NM_001351604, NM_001351605, NM_001351606, NM_182540

CCDS: CCDS35401, CCDS87784

Canonical transcript exons

ENST00000639893 — 18 exons

Exon	Start	End
ENSE00001592431	135577193	135577427
ENSE00003465487	135579788	135580162
ENSE00003469651	135573939	135574062
ENSE00003474458	135547137	135547265
ENSE00003509615	135546702	135546885
ENSE00003520127	135556168	135556300
ENSE00003542975	135551994	135552146
ENSE00003544886	135581050	135581143
ENSE00003559024	135546380	135546469
ENSE00003559366	135545423	135545572
ENSE00003635838	135569337	135569431
ENSE00003638901	135575084	135575226
ENSE00003648218	135521241	135521318
ENSE00003650699	135572815	135573033
ENSE00003684516	135549642	135549805
ENSE00003805492	135570436	135570546
ENSE00003806068	135520660	135521103
ENSE00003810887	135581528	135582510

Expression profiles

Bgee: expression breadth ubiquitous, 210 present calls, max score 90.74.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 8.5330 / max 182.7254, expressed in 1486 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
197637	7.0260	1387
197639	1.5070	524

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cerebellar hemisphere	UBERON:0002245	90.74	gold quality
cerebellar cortex	UBERON:0002129	90.66	gold quality
right hemisphere of cerebellum	UBERON:0014890	90.37	gold quality
cerebellum	UBERON:0002037	89.78	gold quality
right uterine tube	UBERON:0001302	89.62	gold quality
granulocyte	CL:0000094	89.54	gold quality
calcaneal tendon	UBERON:0003701	89.21	gold quality
epithelial cell of pancreas	CL:0000083	88.48	silver quality
lymph node	UBERON:0000029	87.43	gold quality
mucosa of transverse colon	UBERON:0004991	86.88	gold quality
spleen	UBERON:0002106	86.55	gold quality
right adrenal gland	UBERON:0001233	86.01	gold quality
left adrenal gland cortex	UBERON:0035825	85.98	gold quality
right adrenal gland cortex	UBERON:0035827	85.87	gold quality
left ovary	UBERON:0002119	85.86	gold quality
right ovary	UBERON:0002118	85.72	gold quality
left adrenal gland	UBERON:0001234	85.53	gold quality
transverse colon	UBERON:0001157	85.50	gold quality
adenohypophysis	UBERON:0002196	85.10	gold quality
adrenal cortex	UBERON:0001235	85.03	gold quality
monocyte	CL:0000576	84.98	gold quality
leukocyte	CL:0000738	84.78	gold quality
tibia	UBERON:0000979	84.70	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	84.63	gold quality
rectum	UBERON:0001052	84.36	gold quality
thymus	UBERON:0002370	84.32	gold quality
pituitary gland	UBERON:0000007	84.20	gold quality
ileal mucosa	UBERON:0000331	83.89	gold quality
tonsil	UBERON:0002372	83.81	gold quality
adrenal gland	UBERON:0002369	83.80	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.93
E-GEOD-124858	no	47.97

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

66 targeting INTS6L, 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-3163	100.00	77.23	8605
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-568	99.98	69.86	2084
HSA-LET-7G-5P	99.98	72.37	1784
HSA-LET-7I-5P	99.98	72.37	1788
HSA-LET-7A-5P	99.98	72.29	1790
HSA-LET-7B-5P	99.98	72.31	1790
HSA-LET-7C-5P	99.98	72.29	1790
HSA-LET-7E-5P	99.98	72.29	1790
HSA-LET-7F-5P	99.98	72.56	1784
HSA-MIR-98-5P	99.98	72.33	1787
HSA-MIR-485-3P	99.98	70.68	1585
HSA-MIR-539-3P	99.98	70.74	1616
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-548AN	99.97	70.91	2817
HSA-LET-7D-5P	99.96	71.76	1632
HSA-MIR-4458	99.96	71.64	1650
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-4760-3P	99.93	70.50	2385
HSA-MIR-6835-3P	99.93	70.49	2904
HSA-MIR-3682-5P	99.93	67.97	1163
HSA-MIR-450B-5P	99.92	71.48	3175
HSA-MIR-8063	99.91	69.76	3146
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-95-5P	99.89	72.17	3973

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	ints6l	ENSDARG00000017931
mus_musculus	Ints6l	ENSMUSG00000035967
rattus_norvegicus	Ints6l	ENSRNOG00000046662
drosophila_melanogaster	IntS6	FBGN0261383
caenorhabditis_elegans		WBGENE00000994

Paralogs (11): INTS6 (ENSG00000102786), SAGE1 (ENSG00000181433), CT45A5 (ENSG00000228836), CT45A1 (ENSG00000268940), CT45A3 (ENSG00000269096), CT45A10 (ENSG00000269586), CT45A9 (ENSG00000270946), CT45A2 (ENSG00000271449), CT45A7 (ENSG00000273696), CT45A8 (ENSG00000278085), CT45A6 (ENSG00000278289)

Protein

Protein identifiers

Integrator complex subunit 6-like — Q5JSJ4 (reviewed: Q5JSJ4)

Alternative names: Protein DDX26B

All UniProt accessions (2): A0A1W2PPI5, Q5JSJ4

Isoforms (2)

UniProt ID	Names	Canonical?
Q5JSJ4-1	1	yes
Q5JSJ4-4	3

RefSeq proteins (6): NP_001338530, NP_001338532, NP_001338533, NP_001338534, NP_001338535, NP_872346 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002035	VWF_A	Domain
IPR029307	INT_SG_DDX_CT_C	Domain
IPR036465	vWFA_dom_sf	Homologous_superfamily
IPR051113	Integrator_subunit6	Family
IPR057413	Beta-barrel_INTS6	Domain

Pfam: PF13519, PF15300, PF25462

UniProt features (8 total): sequence conflict 2, chain 1, domain 1, region of interest 1, modified residue 1, splice variant 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q5JSJ4-F1	68.53	0.19

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): 617

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 134 (showing top): IVANOVA_HEMATOPOIESIS_MATURE_CELL, GOCC_MICROTUBULE_ORGANIZING_CENTER, MARTINEZ_RB1_TARGETS_DN, GOCC_CENTROSOME, YAMAZAKI_TCEB3_TARGETS_UP, GOBP_SNRNA_PROCESSING, GOCC_INTEGRATOR_COMPLEX, BILD_MYC_ONCOGENIC_SIGNATURE, GREGORY_SYNTHETIC_LETHAL_WITH_IMATINIB, chrXq26, GOBP_SNRNA_METABOLIC_PROCESS, GSE5503_MLN_DC_VS_SPLEEN_DC_ACTIVATED_ALLOGENIC_TCELL_UP, NABA_ECM_GLYCOPROTEINS, NCOA6_TARGET_GENES, RYBP_TARGET_GENES

GO Biological Process (1): snRNA 3’-end processing (GO:0034472)

GO Molecular Function (0):

GO Cellular Component (1): integrator complex (GO:0032039)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
snRNA processing	1
RNA 3’-end processing	1
nuclear protein-containing complex	1

Protein interactions and networks

STRING

518 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
INTS6L	INTS14	Q96SY0	709
INTS6L	OR6C65	A6NJZ3	621
INTS6L	INTS3	Q68E01	501
INTS6L	ITIH6	Q6UXX5	478
INTS6L	INTS6	Q9UL03	449
INTS6L	RBMX2	Q9Y388	416
INTS6L	INTS2	Q9H0H0	406
INTS6L	INTS13	Q9NVM9	404
INTS6L	ZNF630	Q2M218	401
INTS6L	INTS12	Q96CB8	401
INTS6L	INTS15	Q96N11	398
INTS6L	PABIR2	Q7Z309	394
INTS6L	INTS10	Q9NVR2	393
INTS6L	HTATSF1	O43719	393
INTS6L	INTS9	Q9NV88	378

IntAct

21 interactions, top by confidence:

A	B	Type	Score
SUPT5H	POLR2D	psi-mi:“MI:0914”(association)	0.530
	MYO9A	psi-mi:“MI:0914”(association)	0.350
RYBP	PIPSL	psi-mi:“MI:0914”(association)	0.350
H2BC21	SMCHD1	psi-mi:“MI:0914”(association)	0.350
POLR2B	PALM3	psi-mi:“MI:0914”(association)	0.350
POLR2E	BDP1	psi-mi:“MI:0914”(association)	0.350
POLR2F	BDP1	psi-mi:“MI:0914”(association)	0.350
POLR2K	BDP1	psi-mi:“MI:0914”(association)	0.350
SSRP1	DDX39A	psi-mi:“MI:0914”(association)	0.350
ATG16L1	ESYT2	psi-mi:“MI:0914”(association)	0.350
S100A2	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
S100P	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
S100A6	VWA8	psi-mi:“MI:0914”(association)	0.350
MRFAP1L1	MYO9A	psi-mi:“MI:0914”(association)	0.350
NABP2	PSMD11	psi-mi:“MI:0914”(association)	0.350
INTS5	INTS6L	psi-mi:“MI:0914”(association)	0.350
NABP2	INTS6L	psi-mi:“MI:0914”(association)	0.350
INTS6L	CEP63	psi-mi:“MI:0915”(physical association)	0.000
CEP63	INTS6L	psi-mi:“MI:0915”(physical association)	0.000
MAPK14	INTS6L	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (21): DDX26B (Co-fractionation), DDX26B (Affinity Capture-MS), DDX26B (Affinity Capture-MS), DDX26B (Affinity Capture-MS), DDX26B (Affinity Capture-MS), DDX26B (Affinity Capture-MS), DDX26B (Affinity Capture-MS), DDX26B (Affinity Capture-MS), DDX26B (Affinity Capture-MS), DDX26B (Affinity Capture-MS), DDX26B (Affinity Capture-MS), DDX26B (Affinity Capture-MS), DDX26B (Affinity Capture-MS), DDX26B (Affinity Capture-MS), DDX26B (Proximity Label-MS)

ESM2 similar proteins: A0AUQ6, A2BE76, O14645, O18973, O35427, O35473, O55003, O88447, O88597, P50503, Q05B58, Q12983, Q13901, Q14457, Q14AM7, Q14CZ0, Q28HY5, Q32KN2, Q32PE4, Q4A1L3, Q4A1L4, Q4A1L5, Q4R3K5, Q4R8N2, Q4RLT3, Q52LA3, Q5JSJ4, Q5NVP8, Q5R878, Q5RBU4, Q5TKA1, Q5ZHS3, Q5ZJQ3, Q68FJ8, Q6DKA1, Q6GMH0, Q6GP52, Q6PAX8, Q6X4M3, Q7TSU0

Diamond homologs: A6NJ88, P0DMU7, P0DMU8, P0DMU9, P0DMV0, P0DMV1, P0DMV2, Q2TAF4, Q5DJT8, Q5HYN5, Q5JSJ4, Q5U4W6, Q6PCM2, Q7SYD9, Q8BND4, Q8NHU0, Q9NXZ1, Q9UL03, Q54Z23, Q9W485

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 28 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	5	181.3×	5e-10
Signaling by FGFR2 IIIa TM	5	143.1×	2e-09
Abortive elongation of HIV-1 transcript in the absence of Tat	6	141.9×	5e-11
Pausing and recovery of Tat-mediated HIV elongation	7	122.8×	7e-12
Tat-mediated HIV elongation arrest and recovery	7	122.8×	7e-12
RNA Pol II CTD phosphorylation and interaction with CE during HIV infection	6	116.5×	2e-10
RNA Pol II CTD phosphorylation and interaction with CE	6	116.5×	2e-10
HIV elongation arrest and recovery	7	115.3×	7e-12

GO biological processes:

GO term	Partners	Fold	FDR
transcription by RNA polymerase II	6	16.9×	2e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	5
Likely benign	3
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

3003 predictions. Top by Δscore:

Variant	Effect	Δscore
X:135545504:GCTC:G	donor_gain	1.0000
X:135546883:G:GT	donor_gain	1.0000
X:135549803:CTA:C	donor_gain	1.0000
X:135549806:G:GG	donor_gain	1.0000
X:135550182:G:GT	donor_gain	1.0000
X:135569398:C:G	donor_gain	1.0000
X:135569432:G:GG	donor_gain	1.0000
X:135572811:TTA:T	acceptor_loss	1.0000
X:135572812:TA:T	acceptor_loss	1.0000
X:135572813:A:AC	acceptor_loss	1.0000
X:135572813:A:AG	acceptor_gain	1.0000
X:135572814:G:GA	acceptor_gain	1.0000
X:135572814:GACC:G	acceptor_gain	1.0000
X:135572814:GACCA:G	acceptor_gain	1.0000
X:135573031:AAGG:A	donor_loss	1.0000
X:135573034:G:GC	donor_loss	1.0000
X:135573933:A:AG	acceptor_gain	1.0000
X:135573934:A:G	acceptor_gain	1.0000
X:135573936:TAGG:T	acceptor_loss	1.0000
X:135573937:A:AG	acceptor_gain	1.0000
X:135573937:A:G	acceptor_loss	1.0000
X:135573937:AG:A	acceptor_gain	1.0000
X:135573938:G:GA	acceptor_gain	1.0000
X:135573938:GG:G	acceptor_gain	1.0000
X:135573938:GGATT:G	acceptor_gain	1.0000
X:135574058:TGAAG:T	donor_loss	1.0000
X:135574059:GAAGG:G	donor_loss	1.0000
X:135574060:AAG:A	donor_loss	1.0000
X:135574062:GGT:G	donor_loss	1.0000
X:135574064:T:A	donor_loss	1.0000

AlphaMissense

5881 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:135521075:C:A	A28D	1.000
X:135521079:A:C	K29N	1.000
X:135521079:A:T	K29N	1.000
X:135521244:C:A	R39S	1.000
X:135521271:G:C	D48H	1.000
X:135521284:T:A	L52Q	1.000
X:135521284:T:C	L52P	1.000
X:135545429:T:A	W66R	1.000
X:135545429:T:C	W66R	1.000
X:135545431:G:C	W66C	1.000
X:135545431:G:T	W66C	1.000
X:135545451:T:C	F73S	1.000
X:135545463:T:C	L77P	1.000
X:135545508:T:C	L92P	1.000
X:135545533:T:A	N100K	1.000
X:135545533:T:G	N100K	1.000
X:135545541:G:C	R103T	1.000
X:135545541:G:T	R103I	1.000
X:135545542:A:C	R103S	1.000
X:135545542:A:T	R103S	1.000
X:135545568:G:A	G112E	1.000
X:135546380:G:A	G114R	1.000
X:135546380:G:C	G114R	1.000
X:135546380:G:T	G114W	1.000
X:135546381:G:A	G114E	1.000
X:135546385:A:C	R115S	1.000
X:135546385:A:T	R115S	1.000
X:135546390:C:A	P117Q	1.000
X:135546733:G:A	G154E	1.000
X:135546742:T:C	L157P	1.000

dbSNP variants (sampled 300 via entrez): RS1000263349 (X:135567934 A>G), RS1000447403 (X:135580572 G>A), RS1000507609 (X:135528664 G>C), RS1000538752 (X:135528221 C>T), RS1000687157 (X:135538501 C>T), RS1001102091 (X:135559406 G>T), RS1001283084 (X:135566104 A>G), RS1001296512 (X:135555844 C>T), RS1001418473 (X:135566675 A>G), RS1001535014 (X:135558932 C>T), RS1001644604 (X:135555330 T>C), RS1001948759 (X:135526916 T>C), RS1002047017 (X:135579070 A>G), RS1002095306 (X:135536851 A>C), RS1002241192 (X:135557883 A>T)

Disease associations

OMIM: gene `` | disease phenotypes: MIM:157900

GenCC curated gene-disease

Mondo (1): Mobius syndrome (MONDO:0008006)

Orphanet (1): Moebius syndrome (Orphanet:570)

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST008162_46	Hip circumference	5.000000e-06

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D020331	Mobius Syndrome	C07.465.299.825; C10.292.319.825; C10.292.562.700.375.750; C11.590.436.400.750; C16.131.077.578; C16.614.595

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

20 total (human), top 20 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
triphenyl phosphate	affects expression	1
propionaldehyde	increases expression	1
2-methyl-4-isothiazolin-3-one	increases expression	1
butyraldehyde	increases expression	1
potassium chromate(VI)	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
bisphenol S	increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Sunitinib	increases expression	1
Arsenic	increases methylation	1
Atrazine	increases expression	1
Cadmium	decreases expression	1
Calcitriol	increases expression	1
Doxorubicin	affects expression	1
Plant Extracts	increases expression, affects cotreatment	1
Rotenone	decreases expression	1
Thiram	increases expression	1
Tobacco Smoke Pollution	decreases expression	1
Aflatoxin B1	decreases methylation	1
Acrylamide	decreases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT03059420	Not specified	RECRUITING	Genetic Studies of Strabismus, Congenital Cranial Dysinnervation Disorders (CCDDs), and Their Associated Anomalies