SLX4IP

Summary

SLX4IP (SLX4 interacting protein, HGNC:16225) is a protein-coding gene on chromosome 20p12.2, encoding Protein SLX4IP (Q5VYV7).

At a glance

• GWAS associations: 10
• Clinical variants (ClinVar): 54 total — 1 pathogenic
• MANE Select transcript: NM_001009608

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16225
Approved symbol	SLX4IP
Name	SLX4 interacting protein
Location	20p12.2
Locus type	gene with protein product
Status	Approved
Aliases	dJ1099D15.3
Ensembl gene	ENSG00000149346
Ensembl biotype	protein_coding
OMIM	615958
Entrez	128710

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 2 protein_coding, 1 nonsense_mediated_decay

ENST00000334534, ENST00000488816, ENST00000931374

RefSeq mRNA: 1 — MANE Select: NM_001009608 NM_001009608

CCDS: CCDS33439

Canonical transcript exons

ENST00000334534 — 8 exons

Exon	Start	End
ENSE00000906751	10556231	10556320
ENSE00000906752	10560700	10560820
ENSE00000990108	10621314	10621414
ENSE00000990116	10598675	10598752
ENSE00000990117	10601731	10601819
ENSE00001175305	10458176	10458231
ENSE00001386017	10622659	10628030
ENSE00001536204	10435305	10435453

Expression profiles

Bgee: expression breadth ubiquitous, 236 present calls, max score 87.59.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 9.9996 / max 172.4219, expressed in 1710 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
183560	9.9996	1710

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
epithelial cell of pancreas	CL:0000083	87.59	silver quality
pancreatic ductal cell	CL:0002079	86.61	silver quality
corpus epididymis	UBERON:0004359	85.31	gold quality
oocyte	CL:0000023	85.28	gold quality
secondary oocyte	CL:0000655	84.84	gold quality
kidney epithelium	UBERON:0004819	83.84	silver quality
oviduct epithelium	UBERON:0004804	83.23	gold quality
left ventricle myocardium	UBERON:0006566	83.11	gold quality
cardiac muscle of right atrium	UBERON:0003379	83.00	gold quality
nasal cavity epithelium	UBERON:0005384	82.73	silver quality
sperm	CL:0000019	81.99	silver quality
epithelium of nasopharynx	UBERON:0001951	81.63	gold quality
gingiva	UBERON:0001828	80.93	gold quality
gingival epithelium	UBERON:0001949	80.92	gold quality
cauda epididymis	UBERON:0004360	80.83	gold quality
mammalian vulva	UBERON:0000997	80.59	gold quality
esophagus squamous epithelium	UBERON:0006920	80.52	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	80.51	gold quality
caput epididymis	UBERON:0004358	80.25	gold quality
bronchial epithelial cell	CL:0002328	79.86	gold quality
colonic mucosa	UBERON:0000317	79.57	gold quality
mucosa of sigmoid colon	UBERON:0004993	79.51	gold quality
bronchus	UBERON:0002185	79.50	gold quality
mucosa of paranasal sinus	UBERON:0005030	78.42	silver quality
seminal vesicle	UBERON:0000998	78.35	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	78.18	gold quality
pigmented layer of retina	UBERON:0001782	77.90	gold quality
visceral pleura	UBERON:0002401	77.87	gold quality
oral cavity	UBERON:0000167	77.82	gold quality
buccal mucosa cell	CL:0002336	77.28	silver quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.91

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

174 targeting SLX4IP, 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-4668-3P	100.00	68.74	2635
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-101-3P	99.94	75.03	2230
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-548A-5P	99.94	71.27	3482
HSA-MIR-548AD-5P	99.94	71.23	3502
HSA-MIR-548AE-5P	99.94	71.23	3502

Literature-anchored findings (GeneRIF, showing 6)

• C20orf94 is a target gene of the BACH1 transcription factor according to ChIP-seq analysis in HEK 293 cells. (PMID:21555518)
• The association of SLX4IP deletion with male sex suggest that differential illegitimate V(D)J-mediated recombination events contribute to the higher incidence rates of childhood acute lymphoblastic leukemia in boys compared with girls. (PMID:24045615)
• SLX4IP antagonizes promiscuous BLM Activity during alternative lengthening of telomeres maintenance in osteosarcoma cells. (PMID:31447390)
• The binding of SLX4IP to both SLX4 and XPF-ERCC1 not only is vital for maintaining the stability of SLX4IP protein, but also promotes the interaction between SLX4 and XPF-ERCC1, especially after DNA damage. Collectively, these results demonstrate a new regulatory role for SLX4IP in maintaining an efficient SLX4-XPF-ERCC1 complex in interstrand crosslinks (ICLs) repair. (PMID:31495888)
• SLX4IP and telomere dynamics dictate breast cancer metastasis and therapeutic responsiveness. (PMID:32071280)
• SLX4IP Promotes Telomere Maintenance in Androgen Receptor-Independent Castration-Resistant Prostate Cancer through ALT-like Telomeric PML Localization. (PMID:33188147)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	slx4ip	ENSDARG00000039069
mus_musculus	Slx4ip	ENSMUSG00000027281
rattus_norvegicus	Slx4ip	ENSRNOG00000007430

Protein

Protein identifiers

Protein SLX4IP — Q5VYV7 (reviewed: Q5VYV7)

Alternative names: SLX4-interacting protein

All UniProt accessions (2): Q5VYV7, H0YD23

UniProt curated annotations — full annotation on UniProt →

Subunit / interactions. Interacts with SLX4/BTBD12; subunit of different structure-specific endonucleases.

Disease relevance. Chromosomal aberrations involving SLX4IP are found in acute lymphoblastic leukemia. A site-specific deletion within the 5’ region of SLX4IP is found in 30% of childhood acute lymphoblastic leukemia in general and more than 60% of ETV6/RUNX1-rearranged acute lymphoblastic leukemia. Breakpoints within SLX4IP reveal junctions with typical characteristics of illegitimate V(D)J mediated recombination. SLX4IP deletions are significantly associated with male gender and ETV6/RUNX1-rearranged acute lymphoblastic leukemia.

Similarity. Belongs to the SLX4IP family.

RefSeq proteins (1): NP_001009608* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR031479	SLX4IP	Family

Pfam: PF15744

UniProt features (24 total): cross-link 12, compositionally biased region 4, region of interest 3, modified residue 3, chain 1, sequence variant 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
9QED	ELECTRON MICROSCOPY	3.2
9QEE	ELECTRON MICROSCOPY	3.4

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q5VYV7-F1	55.33	0.08

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 (15): 392, 61, 79, 167, 176, 239, 242, 256, 291, 347, 356, 372, 399, 130, 213

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 84 (showing top): BERTUCCI_MEDULLARY_VS_DUCTAL_BREAST_CANCER_DN, CREIGHTON_ENDOCRINE_THERAPY_RESISTANCE_1, FOSTER_TOLERANT_MACROPHAGE_DN, SENESE_HDAC3_TARGETS_DN, NUYTTEN_EZH2_TARGETS_DN, CHIANG_LIVER_CANCER_SUBCLASS_UNANNOTATED_UP, WANG_RESPONSE_TO_GSK3_INHIBITOR_SB216763_UP, FIGUEROA_AML_METHYLATION_CLUSTER_3_UP, FIGUEROA_AML_METHYLATION_CLUSTER_7_UP, BRUINS_UVC_RESPONSE_EARLY_LATE, KOINUMA_TARGETS_OF_SMAD2_OR_SMAD3, BANP_TARGET_GENES, BARX1_TARGET_GENES, CIITA_TARGET_GENES, DMRT1_TARGET_GENES

GO Biological Process (0):

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

GO Cellular Component (0):

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
binding	1

Protein interactions and networks

STRING

562 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SLX4IP	SLX4	Q8IY92	960
SLX4IP	SLX1A	Q9BQ83	897
SLX4IP	MUS81	Q96NY9	879
SLX4IP	TERF2IP	Q9NYB0	823
SLX4IP	EME1	Q96AY2	822
SLX4IP	MSH3	P20585	702
SLX4IP	TERF2	Q15554	683
SLX4IP	ERCC4	Q92889	678
SLX4IP	ERCC1	P07992	630
SLX4IP	PCED1A	Q9H1Q7	589
SLX4IP	PLK1	P53350	536
SLX4IP	MSH2	P43246	506
SLX4IP	RAD54L2	Q9Y4B4	461
SLX4IP	ESF1	Q9H501	460
SLX4IP	LAMP5	Q9UJQ1	432

IntAct

35 interactions, top by confidence:

A	B	Type	Score
DLD	PDHX	psi-mi:“MI:0914”(association)	0.880
MAPK14	OBSL1	psi-mi:“MI:0914”(association)	0.790
KRT34	TXLNA	psi-mi:“MI:0914”(association)	0.670
MAPK14	RPS6KA5	psi-mi:“MI:0914”(association)	0.660
SLX4	ERCC1	psi-mi:“MI:0914”(association)	0.640
KPNA1	TCERG1	psi-mi:“MI:0914”(association)	0.640
PLK1	C1orf226	psi-mi:“MI:0914”(association)	0.560
IFI30	PRC1	psi-mi:“MI:0914”(association)	0.530
PDCD2L	PRMT3	psi-mi:“MI:0914”(association)	0.530
SLX4IP	SLX4	psi-mi:“MI:0915”(physical association)	0.480
GORASP1	CLASP2	psi-mi:“MI:0914”(association)	0.350
MAPK14	PRKY	psi-mi:“MI:0914”(association)	0.350
PDCD2L	PRMT3	psi-mi:“MI:0914”(association)	0.350
ERCC1	SLX4IP	psi-mi:“MI:0914”(association)	0.350
SLX4	MYO1C	psi-mi:“MI:0914”(association)	0.350
SLX4IP	RNASEH1	psi-mi:“MI:0914”(association)	0.350
SLX1A	PSMD11	psi-mi:“MI:0914”(association)	0.350
PLK1	ERCC6L	psi-mi:“MI:0914”(association)	0.350
FBLN5	ZNF320	psi-mi:“MI:0914”(association)	0.350
GORASP1	RTCA	psi-mi:“MI:0914”(association)	0.350
FEM1A	RNF113A	psi-mi:“MI:0914”(association)	0.350
AJUBA	DTNB	psi-mi:“MI:0914”(association)	0.350
vpr	ERCC1	psi-mi:“MI:0914”(association)	0.350
TP53BP1	PSMD14	psi-mi:“MI:2364”(proximity)	0.270
BRCA1	SMCHD1	psi-mi:“MI:2364”(proximity)	0.270
MDC1	SMCHD1	psi-mi:“MI:2364”(proximity)	0.270
HNF4A	TAF4	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (98): SLX4IP (Reconstituted Complex), SLX4IP (Affinity Capture-MS), SLX4IP (Affinity Capture-MS), SLX4IP (Affinity Capture-MS), SLX4IP (Affinity Capture-MS), SLX4IP (Affinity Capture-MS), SLX4IP (Reconstituted Complex), SLX4IP (Affinity Capture-MS), SLX4IP (Affinity Capture-MS), SLX4IP (Affinity Capture-MS), SLX4IP (Affinity Capture-MS), SLX4IP (Affinity Capture-MS), SLX4IP (Affinity Capture-MS), SLX4IP (Affinity Capture-RNA), SLX4IP (Affinity Capture-MS)

ESM2 similar proteins: A0A087WXM9, A0A2K1JJ00, A0JM83, A4IGL8, E1BC15, E9Q5F9, O14513, O35923, O60673, O88491, P46013, P97929, Q14B71, Q28DZ0, Q29RT4, Q3MHH3, Q3TNU4, Q3ZBP0, Q4QY64, Q4V7J0, Q5DTT3, Q5E9A0, Q5F2C3, Q5RD08, Q5VWN6, Q5VYV7, Q61493, Q69YH5, Q6NS59, Q703I1, Q80U59, Q86XD8, Q8IXS0, Q8IYL3, Q8L7I1, Q8N7Z5, Q8NFU7, Q8TEP8, Q92628, Q96BU1

Diamond homologs: A4IGL8, Q5VYV7, Q7T2B3, Q9D7Y9

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 47 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
mRNA Splicing - Major Pathway	6	8.2×	5e-03

GO biological processes:

GO term	Partners	Fold	FDR
DNA repair	7	10.4×	5e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	44
Likely benign	5
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
1526684	GRCh37/hg19 20p12.2(chr20:10573642-10778864)x1	Pathogenic

SpliceAI

2376 predictions. Top by Δscore:

Variant	Effect	Δscore
20:10458232:G:GG	donor_gain	1.0000
20:10556229:A:AG	acceptor_gain	1.0000
20:10556229:AGTGT:A	acceptor_gain	1.0000
20:10556230:G:GG	acceptor_gain	1.0000
20:10556230:GT:G	acceptor_gain	1.0000
20:10556230:GTGTG:G	acceptor_gain	1.0000
20:10558928:A:T	donor_gain	1.0000
20:10558946:G:GT	donor_gain	1.0000
20:10560589:C:G	donor_gain	1.0000
20:10598669:TTCCA:T	acceptor_loss	1.0000
20:10598671:CCA:C	acceptor_loss	1.0000
20:10598672:CAG:C	acceptor_loss	1.0000
20:10598673:A:AC	acceptor_loss	1.0000
20:10598749:GCTG:G	donor_gain	1.0000
20:10598752:GGTA:G	donor_loss	1.0000
20:10598753:G:C	donor_loss	1.0000
20:10601729:A:AG	acceptor_gain	1.0000
20:10601730:G:GG	acceptor_gain	1.0000
20:10556221:T:G	acceptor_loss	0.9900
20:10556222:GTCTT:G	acceptor_loss	0.9900
20:10556223:TCTT:T	acceptor_loss	0.9900
20:10556224:CTTTC:C	acceptor_loss	0.9900
20:10556225:TTTC:T	acceptor_loss	0.9900
20:10556226:TTCA:T	acceptor_loss	0.9900
20:10556227:TCAG:T	acceptor_loss	0.9900
20:10556228:CAGTG:C	acceptor_loss	0.9900
20:10556229:A:C	acceptor_loss	0.9900
20:10556229:AGT:A	acceptor_gain	0.9900
20:10556230:GTG:G	acceptor_gain	0.9900
20:10556230:GTGT:G	acceptor_gain	0.9900

AlphaMissense

2676 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
20:10601761:T:A	V116D	0.982
20:10601742:T:C	F110L	0.978
20:10601744:C:A	F110L	0.978
20:10601744:C:G	F110L	0.978
20:10556247:T:A	V15D	0.976
20:10598696:C:A	A87D	0.976
20:10556301:T:C	F33S	0.972
20:10598701:T:C	F89L	0.972
20:10598703:C:A	F89L	0.972
20:10598703:C:G	F89L	0.972
20:10556300:T:C	F33L	0.971
20:10556302:T:A	F33L	0.971
20:10556302:T:G	F33L	0.971
20:10560716:T:C	L45S	0.969
20:10556240:T:C	F13L	0.967
20:10556242:T:A	F13L	0.967
20:10556242:T:G	F13L	0.967
20:10556244:C:A	A14D	0.966
20:10601743:T:C	F110S	0.965
20:10601743:T:G	F110C	0.963
20:10556297:T:A	W32R	0.960
20:10556297:T:C	W32R	0.960
20:10598702:T:C	F89S	0.960
20:10560740:T:A	V53D	0.956
20:10556259:T:C	L19P	0.952
20:10560820:G:C	G80R	0.950
20:10598695:G:C	A87P	0.950
20:10601767:T:A	V118D	0.950
20:10598690:T:C	I85T	0.949
20:10556253:T:A	V17E	0.947

dbSNP variants (sampled 300 via entrez): RS1000006587 (20:10503348 G>A), RS1000019716 (20:10538724 A>C), RS1000040488 (20:10491028 CAA>C), RS1000073403 (20:10552282 C>T), RS1000110248 (20:10459658 T>C), RS1000144774 (20:10453207 A>G), RS1000153665 (20:10594752 C>T), RS1000154379 (20:10492675 T>A), RS1000155050 (20:10462604 A>C,G,T), RS1000159337 (20:10621465 G>A,C), RS1000164362 (20:10606635 CAATA>C), RS1000186219 (20:10602226 A>G), RS1000192304 (20:10576868 A>G,T), RS1000201573 (20:10531758 G>A), RS1000219702 (20:10599542 T>C)

Disease associations

OMIM: gene MIM:615958 | disease phenotypes: MIM:118450

GenCC curated gene-disease

Mondo (1): Alagille syndrome due to a JAG1 point mutation (MONDO:0016862)

Orphanet (2): Alagille syndrome due to a JAG1 point mutation (Orphanet:261619), Alagille syndrome (Orphanet:52)

HPO phenotypes

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

GWAS associations

10 associations (top):

Study	Trait	p-value
GCST000960_19	Cardiac hypertrophy	9.000000e-06
GCST004105_5	Body mass index (change over time) in chronic obstructive pulmonary disease	6.000000e-06
GCST004761_1	Fasting blood glucose adjusted for BMI	1.000000e-08
GCST006288_402	Heel bone mineral density	8.000000e-14
GCST006288_679	Heel bone mineral density	9.000000e-21
GCST006288_78	Heel bone mineral density	3.000000e-09
GCST006629_21	Pulse pressure	7.000000e-42
GCST006979_696	Heel bone mineral density	2.000000e-14
GCST007268_67	Diastolic blood pressure	4.000000e-16
GCST008153_2	Lean body mass	5.000000e-06

EFO canonical traits (7, from GWAS)

EFO ID	Trait name
EFO:0002503	cardiac hypertrophy
EFO:0005937	longitudinal BMI measurement
EFO:0008036	BMI-adjusted fasting blood glucose measurement
EFO:0009270	heel bone mineral density
EFO:0005763	pulse pressure measurement
EFO:0006336	diastolic blood pressure
EFO:0004995	lean body mass

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

19 total (human), top 19 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
FR900359	decreases phosphorylation	1
TAK-243	affects sumoylation	1
bisphenol A	increases methylation	1
sodium arsenite	decreases expression	1
manganese chloride	increases expression, increases abundance	1
benzo(e)pyrene	increases methylation	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
nickel sulfate	decreases expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
ICG 001	increases 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
Amiodarone	increases expression	1
Benzo(a)pyrene	decreases expression	1
Manganese	increases abundance, increases expression	1
Methapyrilene	increases methylation	1
Quercetin	increases expression	1
Thiram	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Aflatoxin B1	increases methylation	1

Clinical trials (associated diseases)

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