XAF1

Summary

XAF1 (XIAP associated factor 1, HGNC:30932) is a protein-coding gene on chromosome 17p13.2, encoding XIAP-associated factor 1 (Q6GPH4). Seems to function as a negative regulator of members of the IAP (inhibitor of apoptosis protein) family.

This gene encodes a protein which binds to and counteracts the inhibitory effect of a member of the IAP (inhibitor of apoptosis) protein family. IAP proteins bind to and inhibit caspases which are activated during apoptosis. The proportion of IAPs and proteins which interfere with their activity, such as the encoded protein, affect the progress of the apoptosis signaling pathway. Multiple transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 54739 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 62 total
• MANE Select transcript: NM_017523

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:30932
Approved symbol	XAF1
Name	XIAP associated factor 1
Location	17p13.2
Locus type	gene with protein product
Status	Approved
Aliases	BIRC4BP, XIAPAF1, HSXIAPAF1
Ensembl gene	ENSG00000132530
Ensembl biotype	protein_coding
OMIM	606717
Entrez	54739

Gene structure

Transcript identifiers

Ensembl transcripts: 30 — 15 protein_coding, 8 nonsense_mediated_decay, 4 retained_intron, 3 protein_coding_CDS_not_defined

ENST00000346752, ENST00000361842, ENST00000571135, ENST00000571217, ENST00000571673, ENST00000572107, ENST00000572495, ENST00000572546, ENST00000573518, ENST00000573760, ENST00000574394, ENST00000574907, ENST00000574962, ENST00000575147, ENST00000575267, ENST00000575369, ENST00000576341, ENST00000576459, ENST00000576724, ENST00000909300, ENST00000909301, ENST00000909302, ENST00000909303, ENST00000941934, ENST00000941935, ENST00000941936, ENST00000941937, ENST00000941938, ENST00000941939, ENST00000941940

RefSeq mRNA: 9 — MANE Select: NM_017523 NM_001353134, NM_001353135, NM_001353136, NM_001353137, NM_001353138, NM_001353139, NM_001353140, NM_017523, NM_199139

CCDS: CCDS11080, CCDS11081

Canonical transcript exons

ENST00000361842 — 7 exons

Exon	Start	End
ENSE00002637037	6773113	6775647
ENSE00003507723	6758089	6758224
ENSE00003554320	6759662	6759718
ENSE00003583456	6770643	6770984
ENSE00003618323	6756046	6756110
ENSE00003627289	6762155	6762240
ENSE00003665017	6760406	6760601

Expression profiles

Bgee: expression breadth ubiquitous, 269 present calls, max score 98.37.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 12.9970 / max 456.8134, expressed in 1010 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
159069	11.8631	951
159065	0.3963	234
159068	0.3611	219
159064	0.1148	41
159070	0.0990	32
159067	0.0827	30
159066	0.0800	25

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
apex of heart	UBERON:0002098	98.37	gold quality
right ovary	UBERON:0002118	98.01	gold quality
left ovary	UBERON:0002119	97.78	gold quality
gall bladder	UBERON:0002110	97.36	gold quality
right uterine tube	UBERON:0001302	97.34	gold quality
monocyte	CL:0000576	96.79	gold quality
right lobe of liver	UBERON:0001114	96.70	gold quality
mononuclear cell	CL:0000842	96.41	gold quality
visceral pleura	UBERON:0002401	96.24	gold quality
leukocyte	CL:0000738	96.22	gold quality
spleen	UBERON:0002106	95.93	gold quality
endothelial cell	CL:0000115	95.91	gold quality
granulocyte	CL:0000094	95.88	gold quality
body of uterus	UBERON:0009853	95.68	gold quality
endocervix	UBERON:0000458	95.65	gold quality
parietal pleura	UBERON:0002400	95.49	gold quality
omental fat pad	UBERON:0010414	95.41	gold quality
peritoneum	UBERON:0002358	95.40	gold quality
adipose tissue of abdominal region	UBERON:0007808	95.11	gold quality
right coronary artery	UBERON:0001625	95.03	gold quality
sural nerve	UBERON:0015488	94.95	gold quality
lymph node	UBERON:0000029	94.80	gold quality
colonic epithelium	UBERON:0000397	94.49	gold quality
right lung	UBERON:0002167	94.45	gold quality
ectocervix	UBERON:0012249	94.44	gold quality
left uterine tube	UBERON:0001303	94.40	gold quality
upper lobe of left lung	UBERON:0008952	94.28	gold quality
rectum	UBERON:0001052	94.09	gold quality
subcutaneous adipose tissue	UBERON:0002190	93.98	gold quality
ovary	UBERON:0000992	93.90	gold quality

Single-cell (SCXA)

Detected in 7 experiment(s), a significant marker in 5.

Experiment	Marker?	Max mean expression
E-CURD-53	yes	1062.21
E-MTAB-11011	yes	1043.64
E-CURD-119	yes	26.71
E-GEOD-130148	yes	5.94
E-ANND-3	yes	4.50
E-MTAB-6379	no	2323.04
E-MTAB-5061	no	3.09

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): HSF1, IFNB1, IRF1, SPI1, STAT1, STAT3, TP53

miRNA regulators (miRDB)

88 targeting XAF1, 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-6748-5P	100.00	65.81	1057
HSA-MIR-196A-5P	100.00	68.16	684
HSA-MIR-196B-5P	100.00	68.16	681
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-6758-5P	100.00	66.21	1470
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-9983-3P	99.94	71.48	3631
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-3671	99.90	73.04	3897
HSA-MIR-6499-3P	99.90	66.38	1212
HSA-MIR-3140-3P	99.88	68.47	2069
HSA-MIR-129-5P	99.88	70.26	3273
HSA-LET-7A-2-3P	99.87	70.53	1921
HSA-LET-7G-3P	99.85	70.43	1929
HSA-MIR-5010-3P	99.83	70.60	2357
HSA-MIR-548AZ-5P	99.83	69.94	3230
HSA-MIR-548T-5P	99.83	69.91	3220
HSA-MIR-6844	99.82	70.69	2423
HSA-MIR-3680-3P	99.75	72.51	3095
HSA-MIR-6885-3P	99.75	70.36	3187
HSA-MIR-4677-5P	99.70	70.09	1940
HSA-MIR-29B-2-5P	99.67	68.98	1726
HSA-MIR-1303	99.65	69.77	1662
HSA-MIR-651-5P	99.64	68.49	1104

Literature-anchored findings (GeneRIF, showing 40)

• XAF1 augments TRAIL-induced apoptosis (PMID:12029096)
• Epigenetic silencing of XAF1 by aberrant promoter methylation may contribute to the malignant progression of human gastric tumors. (PMID:14612497)
• XAF1 expression in melanoma tissues was significantly reduced compared with benign melanocytic nevi (PMID:15610524)
• endogenous stress pressure in cancer cells sustained the high level expression of HSF1 and subsequently suppressed XAF1 expression, implicating the synergized effect of two anti-apoptotic protein families in cytoprotection under stress circumstances (PMID:16303760)
• The ratio of XAF1(A) and XAF1C mRNA expression differs amongst the cell lines tested, suggesting differential mRNA stabilities and/or the existence of tissue- or cell type-specific splicing regulation. (PMID:16343440)
• alternative splicing of XAF1 mRNA leads to formation of truncated XAF1 protein, which likely affects its functional interaction with XIAP, and consequently, contributes to pathogenesis of prostate cancers by disrupting balance of apoptosis machinery (PMID:16353137)
• Gene expression incresed in multiple sclerosis patients treated with interferon-beta. (PMID:16459719)
• siRNA to XAF1 inhibited IFN-induced apoptosis; conversely, overexpression of XAF1 overcame resistance to apoptosis induction by IFN-beta. (PMID:16801630)
• Epigenetic alteration of XAF1 is frequent in human urogenital cancers and may contribute to the malignant progression of tumors by rendering tumor cells a survival advantage partially through the attenuated p53 response. (PMID:16909101)
• Down-regulation of XAF1 in association with hypermethylation was detected in 3 of 4 human gastric cancer cell lines and 6 of 8 colon cancer cell lines. (PMID:17087954)
• In cancerization of oral mucosa, XIAP protein could play an important antiapoptotic role by overexpression, while XAF1 protein does not appear to antagonize effectively the role of XIAP. (PMID:17331366)
• Our study provides evidence that XAF1 is a crucial interferon-stimulated gene (ISG) mediator of IFN-induced sensitization to TRAIL in cancer. (PMID:17376236)
• Low XAF1 mRNA expression levels relate to an unfavorable clinical course in renal cell carcinoma. (PMID:17449173)
• An increased expression ratio of XIAP to XAF1 in combination with a disturbed expression of the XAF1 splice variants could be shown in gastric adenocarcinomas. (PMID:17471152)
• Genetic and epigenetic alteration of XAF1 is a common event in colorectal tumorigenesis and contributes to the malignant tumor progression by providing survival advantages for tumor cells under various stress conditions. (PMID:17570219)
• XAF1 mediates Survivin down-regulation through a complex containing XIAP, supporting dual roles for XAF1 in apoptosis (PMID:17613533)
• The high expression of HSF1 in gastro-intestinal cancer is associated with suppressed expression of XAF1. (PMID:17884799)
• Induction of XAF1 by IFNbeta was mediated by the transcription regulator Stat1 through the ISRE site within the promoter region of XAF1 gene in colon cancer. (PMID:18035482)
• Interferon gamma induces XAF1 and Noxa expression and potentiates apoptosis by STAT3 activation (PMID:18192275)
• INFalpha and 5-AZA-CdR can induce Xaf1 mRNA expressions in HL-60 and K562 cells. (PMID:18250043)
• CBP is a novel binding partner of XAF1, and the interaction between XAF1 and CBP and their functional consequence were mediated by adaptor-related protein complex 1. (PMID:18362468)
• XAF1 may have a role as a tumor suppressor gene in advanced bladder cancer treated with neoadjuvant chemotherapy (PMID:18555708)
• Promoter hypermethylation and down regulation of XAF1 is associated with liver tumor recurrence after liver transplantation. (PMID:18830757)
• These data suggest that a down-regulation of Smac/DIABLO and HtrA2 is implicated in the development and progression of TGCT, whereas overexpression of XAF1 in TGCT might contribute to their extraordinary sensitivity to chemotherapy. (PMID:18979398)
• JNK1 stimulated and mediated the effects of IFN and TNF-alpha on XAF1 expression through transcriptional regulation by induction of IRF-1. (PMID:19056926)
• results document that the restoration of XAF1 inhibits gastric tumorigenesis and tumor growth and that XAF1 is a promising candidate for cancer gene therapy. (PMID:19358264)
• imbalance in XIAP/XAF1 mRNA expression levels correlated to overall patient survival, and that high XIAP immunoreactivity was a poor prognostic factor. (PMID:19397802)
• 5-AZA treatment can induce the expression of XAF1 mRNA and protein in myeloma. (PMID:19549372)
• XAF1 as a novel cell cycle regulator through modulating G(2)/M checkpoint and interaction with checkpoint kinase 1 in gastrointestinal cancer. (PMID:19628579)
• XIAP associated factor-1 (XAF1) is downregulated during progression of clear-cell renal cancer (PMID:19664236)
• 5-azacytidine treatment led to XAF1 promoter CpG islands hypomethylation and showed anti-myeloma activity in a time- and concentration-dependent manner. (PMID:19731821)
• The expression levels of the pro-apoptotic XAF-1 gene modulate the cytotoxic response to Nutlin-3 in B chronic lymphocytic leukemia. (PMID:19847196)
• XAF1 is a valuable prognostic marker in pancreatic cancer and could be a potential candidate for cancer gene therapy. (PMID:19922503)
• Demonstrate that p53 could suppress the transcription of XAF1 through interaction with a high affinity responsive element (-95 to -86 nt) within XAF1 promoter in gastrointestinal cancer cells. (PMID:20198350)
• XAF1 down-regulation may contribute to the prostate cancer development (PMID:21143993)
• These findings suggest that a potential novel feedback loop exists between XAF1 and wild-type p53 (PMID:21678496)
• The levels of XAF1 protein and mRNA in cancer tissues were significantly lower than those in cancer adjacent and normal lung tissues. (PMID:22088514)
• XAF1 is frequently methylated in esophageal cancer, and XAF1 expression is regulated by promoter region hypermethylation. (PMID:22719195)
• XAF1 may be involved in ovarian cancer development and up-regulation of XAF1 may confer sensitivity of ovarian cancer cells to cisplatin-mediated apoptosis. (PMID:22759793)
• The search of XIAP binding region within XAF1 revealed a modest affinity XIAP(RING) binding site is located at the C-terminal portion of XAF1.We also mapped the interaction sites for XAF1(RBD) on XIAP(RING) by using NMR. (PMID:22811387)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	xaf1	ENSDARG00000068939
mus_musculus	Xaf1	ENSMUSG00000040483
rattus_norvegicus	Xaf1	ENSRNOG00000037371

Paralogs (1): TRAFD1 (ENSG00000135148)

Protein

Protein identifiers

XIAP-associated factor 1 — Q6GPH4 (reviewed: Q6GPH4)

Alternative names: BIRC4-binding protein

All UniProt accessions (8): Q6GPH4, C9J7Z8, I3L2B3, I3L3B3, I3L3D9, I3L3Q2, I3L509, I3L534

UniProt curated annotations — full annotation on UniProt →

Function. Seems to function as a negative regulator of members of the IAP (inhibitor of apoptosis protein) family. Inhibits anti-caspase activity of BIRC4. Induces cleavage and inactivation of BIRC4 independent of caspase activation. Mediates TNF-induced apoptosis and is involved in apoptosis in trophoblast cells. May inhibit BIRC4 indirectly by activating the mitochondrial apoptosis pathway. After translocation to mitochondria, promotes translocation of BAX to mitochondria and cytochrome c release from mitochondria. Seems to promote the redistribution of BIRC4 from the cytoplasm to the nucleus, probably independent of BIRC4 inactivation which seems to occur in the cytoplasm. The BIRC4-XAF1 complex mediates down-regulation of BIRC5/survivin; the process requires the E3 ligase activity of BIRC4. Seems to be involved in cellular sensitivity to the proapoptotic actions of TRAIL. May be a tumor suppressor by mediating apoptosis resistance of cancer cells.

Subunit / interactions. Interacts with BIRC4; the interaction is not detected in. Interacts with BIRC1, BIRC2, BIRC3, BIRC7 and BIRC8. Part of an complex consisting of BIRC4, XAF1 and BIRC5; the complex formation requires IFN-beta stimulation. Interacts with RNF114, the interaction increases XAF1 stability and proapoptotic effects, and may regulate IFN signaling.

Subcellular location. Cytoplasm. Nucleus. Mitochondrion Nucleus Nucleus.

Tissue specificity. Widely expressed. Expression is frequently down-regulated in cancer cell lines. Isoform 5 is widely expressed. Expressed in placenta (at protein level).

Induction. Up-regulated by IFNB1/IFN-beta in cell lines sensitive to the proapoptotic effects of IFNB1 but not in apoptosis-resistant cells. Up-regulated by TNF in trophoblast cells.

Isoforms (7)

UniProt ID	Names	Canonical?
Q6GPH4-1	1, XAF1(A)	yes
Q6GPH4-2	2, XAF1B
Q6GPH4-3	3, D
Q6GPH4-4	4, E
Q6GPH4-5	5, XAF1C
Q6GPH4-6	6
Q6GPH4-7	7

RefSeq proteins (9): NP_001340063, NP_001340064, NP_001340065, NP_001340066, NP_001340067, NP_001340068, NP_001340069, NP_059993, NP_954590 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001293	Znf_TRAF	Domain
IPR013083	Znf_RING/FYVE/PHD	Homologous_superfamily
IPR031220	XAF1_C_sf	Homologous_superfamily
IPR041386	XAF1_C	Domain
IPR049439	TRAFD1-XIAF1_Znf	Domain
IPR051986	Innate_Immune_Apopt_Reg	Family

Pfam: PF18608, PF21366, PF23580

UniProt features (21 total): splice variant 6, sequence variant 4, sequence conflict 3, turn 2, chain 1, zinc finger region 1, strand 1, region of interest 1, helix 1, compositionally biased region 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
2LXW	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6GPH4-F1	73.13	0.38

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-909733	Interferon alpha/beta signaling

MSigDB gene sets: 286 (showing top): RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, WALLACE_PROSTATE_CANCER_RACE_UP, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, GOBP_RESPONSE_TO_PEPTIDE, GOZGIT_ESR1_TARGETS_DN, GOBP_NEGATIVE_REGULATION_OF_TYPE_I_INTERFERON_PRODUCTION, BROWNE_HCMV_INFECTION_12HR_UP, GOBP_RESPONSE_TO_INTERFERON_BETA, BENNETT_SYSTEMIC_LUPUS_ERYTHEMATOSUS, IRF7_01, GOBP_NEGATIVE_REGULATION_OF_MULTICELLULAR_ORGANISMAL_PROCESS, FOSTER_TOLERANT_MACROPHAGE_DN, MILI_PSEUDOPODIA_HAPTOTAXIS_UP, GOBP_CYTOKINE_PRODUCTION, TAKEDA_TARGETS_OF_NUP98_HOXA9_FUSION_10D_UP

GO Biological Process (5): apoptotic process (GO:0006915), negative regulation of type I interferon production (GO:0032480), response to interferon-beta (GO:0035456), ubiquitin-dependent protein catabolic process (GO:0006511), positive regulation of type I interferon production (GO:0032481)

GO Molecular Function (4): zinc ion binding (GO:0008270), molecular sequestering activity (GO:0140313), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (5): nucleoplasm (GO:0005654), cytoplasm (GO:0005737), mitochondrion (GO:0005739), cytosol (GO:0005829), nucleus (GO:0005634)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Interferon Signaling	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
regulation of type I interferon production	2
type I interferon production	2
cytoplasm	2
intracellular membrane-bounded organelle	2
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
negative regulation of cytokine production	1
response to cytokine	1
protein ubiquitination	1
modification-dependent protein catabolic process	1
positive regulation of cytokine production	1
transition metal ion binding	1
molecular_function	1
binding	1
cation binding	1
nuclear lumen	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

1592 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
XAF1	XIAP	P98170	997
XAF1	IFI44L	Q53G44	726
XAF1	IFI44	Q8TCB0	725
XAF1	IFI6	P09912	723
XAF1	IFIT3	O14879	716
XAF1	OAS2	P29728	710
XAF1	IFI27	P40305	696
XAF1	TP53	P04637	694
XAF1	MX1	P20591	675
XAF1	IRF1	P10914	656
XAF1	IFIT1	P09914	650
XAF1	DIABLO	Q9NR28	648
XAF1	IFITM3	Q01628	617
XAF1	IRF7	Q92985	587
XAF1	TRIM22	Q8IYM9	579

IntAct

57 interactions, top by confidence:

A	B	Type	Score
XAF1	RNF114	psi-mi:“MI:0915”(physical association)	0.670
AKT1	XAF1	psi-mi:“MI:0915”(physical association)	0.670
XAF1	RNF166	psi-mi:“MI:0915”(physical association)	0.670
XAF1	AKT1	psi-mi:“MI:0914”(association)	0.670
TRIM50	XAF1	psi-mi:“MI:0915”(physical association)	0.560
XAF1	TRIM54	psi-mi:“MI:0915”(physical association)	0.560
XAF1	BIRC7	psi-mi:“MI:0915”(physical association)	0.560
VCP	XAF1	psi-mi:“MI:0915”(physical association)	0.560
UBXN2B	XAF1	psi-mi:“MI:0915”(physical association)	0.560
TRIM21	XAF1	psi-mi:“MI:0915”(physical association)	0.560
XAF1	TRIM50	psi-mi:“MI:0915”(physical association)	0.560
XAF1	GLS2	psi-mi:“MI:0915”(physical association)	0.560
RFC5	XAF1	psi-mi:“MI:0915”(physical association)	0.560
XAF1	TRIML2	psi-mi:“MI:0915”(physical association)	0.560
SEPHS1	XAF1	psi-mi:“MI:0915”(physical association)	0.560
XAF1	LRSAM1	psi-mi:“MI:0915”(physical association)	0.560
TSPY3	TSPY8	psi-mi:“MI:0914”(association)	0.350
TSGA10IP	BRCA2	psi-mi:“MI:0914”(association)	0.350
OR4X2	PCBP3	psi-mi:“MI:0914”(association)	0.350
PDSS1	PCBP3	psi-mi:“MI:0914”(association)	0.350
XAF1	TRIM54	psi-mi:“MI:0915”(physical association)	0.000
XAF1	BIRC7	psi-mi:“MI:0915”(physical association)	0.000
XAF1	VCP	psi-mi:“MI:0915”(physical association)	0.000
XAF1	RNF114	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (89): XAF1 (Affinity Capture-Western), XAF1 (Phenotypic Enhancement), TP53 (Affinity Capture-Western), TP53 (Reconstituted Complex), XAF1 (Affinity Capture-Western), XAF1 (Affinity Capture-Western), XAF1 (Phenotypic Suppression), SIAH2 (Two-hybrid), SIAH2 (Affinity Capture-Western), HIPK2 (Phenotypic Suppression), XAF1 (Affinity Capture-Western), XAF1 (Reconstituted Complex), XAF1 (Reconstituted Complex), XAF1 (Affinity Capture-Western), XIAP (Affinity Capture-Western)

ESM2 similar proteins: A0JPN4, A6H5X4, F1MGG3, O15553, P22934, P25118, P48778, Q08288, Q13077, Q14684, Q1XHT8, Q3TYG6, Q4R747, Q4R8T4, Q58DH1, Q5I0E2, Q5I0J8, Q5NBU8, Q5ND28, Q5NVA9, Q5SXM2, Q5XFX8, Q60953, Q66H85, Q69Z99, Q6AXZ2, Q6GPH4, Q6P9F5, Q6S9Z5, Q6ZUX3, Q80UU1, Q80VR2, Q8BIY3, Q8BJW7, Q8BP86, Q8BSI6, Q8BVM9, Q8C1F5, Q8IX06, Q91YK2

Diamond homologs: O14545, Q3UDK1, Q4R970, Q58D05, Q5NBU8, Q6GPH4, Q99MM4, Q60803, Q58DH1

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
XAF1	down-regulates	BIRC3	binding
XAF1	down-regulates	XIAP	binding
XAF1	down-regulates	BIRC2	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 22 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.

GO biological processes:

GO term	Partners	Fold	FDR
protein ubiquitination	5	10.3×	5e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	43
Likely benign	7
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

1208 predictions. Top by Δscore:

Variant	Effect	Δscore
17:6758074:A:AG	acceptor_gain	1.0000
17:6758074:ACCTT:A	acceptor_gain	1.0000
17:6758075:C:G	acceptor_gain	1.0000
17:6758088:G:GA	acceptor_gain	1.0000
17:6758088:GT:G	acceptor_gain	1.0000
17:6758088:GTA:G	acceptor_gain	1.0000
17:6760597:GAAAG:G	donor_gain	1.0000
17:6760599:AAGG:A	donor_loss	1.0000
17:6760600:AGGT:A	donor_loss	1.0000
17:6760602:G:GC	donor_loss	1.0000
17:6760602:G:GG	donor_gain	1.0000
17:6760603:T:A	donor_loss	1.0000
17:6756108:CTGGT:C	donor_loss	0.9900
17:6756110:GGT:G	donor_loss	0.9900
17:6756111:GT:G	donor_loss	0.9900
17:6756112:T:C	donor_loss	0.9900
17:6757098:TTC:T	donor_gain	0.9900
17:6758072:A:AG	acceptor_gain	0.9900
17:6758078:T:A	acceptor_gain	0.9900
17:6758085:GTAGT:G	acceptor_loss	0.9900
17:6758086:TAGTA:T	acceptor_loss	0.9900
17:6758087:A:AG	acceptor_gain	0.9900
17:6758087:A:T	acceptor_loss	0.9900
17:6758088:GTAA:G	acceptor_gain	0.9900
17:6758088:GTAAA:G	acceptor_gain	0.9900
17:6758221:GCAG:G	donor_gain	0.9900
17:6758222:CAGGT:C	donor_loss	0.9900
17:6758223:AG:A	donor_loss	0.9900
17:6758224:GG:G	donor_loss	0.9900
17:6758225:G:A	donor_loss	0.9900

AlphaMissense

2009 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:6760442:T:C	F88L	0.961
17:6760444:C:A	F88L	0.961
17:6760444:C:G	F88L	0.961
17:6770943:T:A	C270S	0.944
17:6770944:G:C	C270S	0.944
17:6770934:T:C	C267R	0.914
17:6770979:C:G	H282D	0.913
17:6770981:T:A	H282Q	0.913
17:6770981:T:G	H282Q	0.913
17:6773119:T:A	C286S	0.911
17:6773120:G:C	C286S	0.911
17:6770934:T:A	C267S	0.899
17:6770935:G:C	C267S	0.899
17:6770950:T:C	I272T	0.899
17:6758137:C:G	C27W	0.894
17:6770943:T:C	C270R	0.893
17:6758144:T:C	F30L	0.889
17:6758146:C:A	F30L	0.889
17:6758146:C:G	F30L	0.889
17:6773119:T:C	C286R	0.879
17:6770956:T:C	L274P	0.878
17:6770956:T:A	L274H	0.866
17:6770971:T:C	L279P	0.862
17:6756109:T:A	C11S	0.860
17:6756110:G:C	C11S	0.860
17:6770936:T:G	C267W	0.858
17:6770944:G:T	C270F	0.855
17:6758123:C:G	H23D	0.853
17:6756100:T:A	C8S	0.847
17:6756101:G:C	C8S	0.847

dbSNP variants (sampled 300 via entrez): RS1000272217 (17:6753591 C>T), RS1000328839 (17:6764712 T>A), RS1000440989 (17:6771334 C>T), RS1000444193 (17:6758674 A>G), RS1000490335 (17:6775389 C>T), RS1000524398 (17:6772549 C>A,T), RS1000644479 (17:6771051 A>C,G), RS1000902516 (17:6765960 A>G), RS1001007814 (17:6755582 T>A,C), RS1001129752 (17:6755187 C>T), RS1001290875 (17:6760692 C>A,G,T), RS1001311758 (17:6761857 C>T), RS1001490532 (17:6774215 C>G), RS1001746098 (17:6757730 A>G), RS1001864015 (17:6756527 G>A)

Disease associations

OMIM: gene MIM:606717 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases abundance	4
Decitabine	decreases methylation, increases expression	4
Etoposide	increases cleavage, increases response to substance, increases expression, affects reaction, decreases expression	3
Fluorouracil	decreases reaction, increases expression, affects reaction, increases response to substance	3
Tobacco Smoke Pollution	decreases expression	3
Cyclosporine	decreases expression, increases expression	3
monomethylarsonous acid	affects expression, decreases expression	2
(+)-JQ1 compound	decreases expression	2
Temozolomide	increases phosphorylation, increases response to substance, increases expression, decreases expression, increases reaction	2
Acetaminophen	decreases expression	2
Azacitidine	decreases methylation, increases expression, decreases expression	2
Benzo(a)pyrene	decreases expression, increases methylation	2
Copper	decreases expression, increases expression, affects reaction, affects expression, affects cotreatment	2
Nickel	increases expression	2
Tretinoin	increases reaction, affects binding, increases expression	2
Cadmium Chloride	decreases expression	2
OTX015	decreases expression	1
sotorasib	affects cotreatment, increases expression	1
alpha phellandrene	increases expression	1
triphenyl phosphate	affects expression	1
2,5,2’,5’-tetrachlorobiphenyl	decreases expression	1
arsenite	increases methylation	1
sulforaphane	decreases expression	1
butyraldehyde	increases expression	1
nickel chloride	increases expression, affects cotreatment	1
3,4,5,3’,4’-pentachlorobiphenyl	decreases expression	1
perfluorooctanoic acid	decreases expression	1
ochratoxin A	decreases expression	1
nickel sulfate	increases expression	1
hydroquinone	decreases expression	1

Clinical trials (associated diseases)

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