IKBKG

Summary

IKBKG (inhibitor of nuclear factor kappa B kinase regulatory subunit gamma, HGNC:5961) is a protein-coding gene on chromosome Xq28, encoding NF-kappa-B essential modulator (Q9Y6K9). Regulatory subunit of the IKK core complex which phosphorylates inhibitors of NF-kappa-B thus leading to the dissociation of the inhibitor/NF-kappa-B complex and ultimately the degradation of the inhibitor. It is haploinsufficient (ClinGen: sufficient evidence).

This gene encodes the regulatory subunit of the inhibitor of kappaB kinase (IKK) complex, which activates NF-kappaB resulting in activation of genes involved in inflammation, immunity, cell survival, and other pathways. Mutations in this gene result in incontinentia pigmenti, hypohidrotic ectodermal dysplasia, and several other types of immunodeficiencies. A pseudogene highly similar to this locus is located in an adjacent region of the X chromosome.

Source: NCBI Gene 8517 — RefSeq curated summary.

At a glance

• Gene–disease (curated): incontinentia pigmenti (Definitive, ClinGen) — +6 more curated relationships
• GWAS associations: 1
• Clinical variants (ClinVar): 168 total — 54 pathogenic, 20 likely-pathogenic
• Phenotypes (HPO): 150
• Druggable target: yes
• Dosage sensitivity (ClinGen): haploinsufficiency sufficient evidence, triplosensitivity no evidence
• MANE Select transcript: NM_001099857

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:5961
Approved symbol	IKBKG
Name	inhibitor of nuclear factor kappa B kinase regulatory subunit gamma
Location	Xq28
Locus type	gene with protein product
Status	Approved
Aliases	IKK-gamma, NEMO, Fip3p, FIP-3, FIP3, IKKAP1, IKKG
Ensembl gene	ENSG00000269335
Ensembl biotype	protein_coding
OMIM	300248
Entrez	8517

Gene structure

Transcript identifiers

Ensembl transcripts: 50 — 44 protein_coding, 3 retained_intron, 2 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000413620, ENST00000422680, ENST00000440286, ENST00000445622, ENST00000492469, ENST00000594239, ENST00000611071, ENST00000611176, ENST00000612051, ENST00000615186, ENST00000615874, ENST00000617207, ENST00000617838, ENST00000618670, ENST00000619941, ENST00000686378, ENST00000686774, ENST00000687445, ENST00000689906, ENST00000692816, ENST00000692948, ENST00000693029, ENST00000907133, ENST00000907134, ENST00000907135, ENST00000907136, ENST00000907137, ENST00000907138, ENST00000907139, ENST00000907140, ENST00000907141, ENST00000907142, ENST00000907143, ENST00000907144, ENST00000907145, ENST00000907146, ENST00000907147, ENST00000907148, ENST00000907149, ENST00000907150, ENST00000907151, ENST00000907152, ENST00000937260, ENST00000968073, ENST00000968074, ENST00000968075, ENST00000968076, ENST00000968077, ENST00000968078, ENST00000968079

RefSeq mRNA: 10 — MANE Select: NM_001099857 NM_001099856, NM_001099857, NM_001145255, NM_001321396, NM_001321397, NM_001377312, NM_001377313, NM_001377314, NM_001377315, NM_003639

CCDS: CCDS14757, CCDS48196, CCDS48197, CCDS83513

Canonical transcript exons

ENST00000594239 — 10 exons

Exon	Start	End
ENSE00003010193	154563959	154564020
ENSE00003119213	154563559	154563701
ENSE00003124430	154560407	154560559
ENSE00003145142	154562810	154562953
ENSE00003161596	154561688	154561784
ENSE00003223451	154547620	154547745
ENSE00003725857	154564319	154565033
ENSE00003738507	154551988	154552189
ENSE00003745581	154556165	154556376
ENSE00003790811	154558532	154558650

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 96.44.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 14.3112 / max 83.3943, expressed in 1805 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
198196	10.3829	1793
198197	2.8109	1436
198195	0.8071	441
198193	0.2245	95
198191	0.0428	17
198192	0.0260	11
198194	0.0170	5

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
granulocyte	CL:0000094	96.44	gold quality
blood	UBERON:0000178	95.61	gold quality
spleen	UBERON:0002106	95.32	gold quality
right lobe of liver	UBERON:0001114	94.98	gold quality
metanephros cortex	UBERON:0010533	93.32	gold quality
upper lobe of left lung	UBERON:0008952	93.29	gold quality
right adrenal gland cortex	UBERON:0035827	93.02	gold quality
right adrenal gland	UBERON:0001233	93.00	gold quality
left adrenal gland	UBERON:0001234	92.90	gold quality
left adrenal gland cortex	UBERON:0035825	92.90	gold quality
small intestine Peyer’s patch	UBERON:0003454	92.71	gold quality
monocyte	CL:0000576	92.67	gold quality
leukocyte	CL:0000738	92.57	gold quality
right lung	UBERON:0002167	92.45	gold quality
mucosa of stomach	UBERON:0001199	92.36	gold quality
mucosa of transverse colon	UBERON:0004991	92.19	gold quality
lower esophagus mucosa	UBERON:0035834	92.03	gold quality
right hemisphere of cerebellum	UBERON:0014890	91.97	gold quality
right lobe of thyroid gland	UBERON:0001119	91.95	gold quality
transverse colon	UBERON:0001157	91.88	gold quality
body of stomach	UBERON:0001161	91.86	gold quality
left uterine tube	UBERON:0001303	91.82	gold quality
small intestine	UBERON:0002108	91.76	gold quality
lower esophagus muscularis layer	UBERON:0035833	91.75	gold quality
lower esophagus	UBERON:0013473	91.74	gold quality
liver	UBERON:0002107	91.66	gold quality
pituitary gland	UBERON:0000007	91.62	gold quality
skin of leg	UBERON:0001511	91.58	gold quality
body of uterus	UBERON:0009853	91.58	gold quality
left lobe of thyroid gland	UBERON:0001120	91.57	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-CURD-112	yes	3.72
E-ANND-3	yes	3.30
E-GEOD-111727	no	143.73

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

1 targets.

Target	Regulation
OPA1	Activation

Upstream regulators (CollecTRI, top): CTNNB1, CUX1, E2F4

miRNA regulators (miRDB)

20 targeting IKBKG, 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-4283	100.00	66.42	2097
HSA-MIR-4650-5P	99.98	64.69	999
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-3912-5P	99.95	66.11	925
HSA-MIR-4694-3P	99.79	69.53	2640
HSA-MIR-7106-5P	99.53	67.47	3574
HSA-MIR-766-5P	99.47	67.91	2225
HSA-MIR-1276	99.36	68.18	1642
HSA-MIR-7515	99.31	68.22	1795
HSA-MIR-3064-5P	99.26	66.13	1497
HSA-MIR-3085-3P	99.26	66.16	1490
HSA-MIR-6504-5P	99.26	65.95	1487
HSA-MIR-939-3P	98.97	65.07	2347
HSA-MIR-7156-3P	98.25	67.66	859
HSA-MIR-4457	98.09	67.12	1274
HSA-MIR-5685	97.02	64.34	1004
HSA-MIR-7847-3P	96.63	64.58	952
HSA-MIR-324-5P	95.68	65.20	560
HSA-MIR-6750-5P	93.94	66.68	797
HSA-MIR-6822-5P	93.94	66.34	812

Functional genomics

ClinGen dosage: haploinsufficiency 3 (sufficient evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 40)

• survival of male patients with incontinentia pigmenti carrying a lethal mutation can be explained by somatic mosaicism or Klinefelter syndrome (PMID:11673821)
• An unusual and complex genomic region susceptible to various types of pathogenic and polymorphic rearrangements, including the recurrent lethal deletion associated with the The X-linked dominant and male-lethal disorder incontinentia pigmenti (IP). (PMID:11709543)
• The human herpes virus 8-encoded viral FLICE inhibitory protein physically associates with and persistently activates the Ikappa B kinase complex. (PMID:11830587)
• We also examined the interaction of NEMO with prokaryotic and eukaryotic Hsp70, and we showed that the Hsp70-NEMO complex forms a supramolecular structure probably corresponding to an assembly intermediate. (PMID:11877453)
• Deficient natural killer cell cytotoxicity in patients with IKK-gamma/NEMO mutations (PMID:12045264)
• Association of the adaptor TANK with the I kappa B kinase (IKK) regulator connects IKK complexes with IKK epsilon and TBK1 kinases (PMID:12133833)
• Data suggest that the zinc finger domain of NEMO likely represents a point of convergence for signaling pathways initiated by slow and weak NF-kappa B-activating conditions. (PMID:12138192)
• The carboxyl-terminal region of IKKgamma is required for full IKK activation (PMID:12192055)
• localization of NEMO to the immunological synapse is important for TCR-induced NF-kappaB activation (PMID:12530972)
• IKKgamma tetramerization enforces a spatial positioning of two kinase dimers to facilitate transautophosphorylation and NF-kappaB activation. (PMID:12612076)
• ubiquitination of NEMO mediated by c-IAP1 likely plays an important role in the activation of IKK by TNF-alpha. (PMID:12867425)
• IKKgamma is activated by CIKS (PMID:12943667)
• IKK gamma/NEMO has a critical role in regulating cytokine-induced IKK activity and is able to shuttle between the cytoplasm and the nucleus and to bind to CBP, leading to transcriptional repression of the NF-kappa B pathway (PMID:14597638)
• Genotoxic stress induces SUMO-1 modification and ATM activation, which work in concert to cause nuclear targeting and ubiquitylation of free NEMO to permit the NF-kappaB survival pathway. (PMID:14651848)
• Bcl10 targets NEMO for lysine-63-linked ubiquitination (PMID:14695475)
• NEMO is critical for T-cell development and/or survival in humans as well as in mice. (PMID:14726382)
• The zinc finger structure of IKK-gamma plays an essential role in tumor necrosis factor-induced NF-kappa B activation and may be an alternative target for inhibition of inflammation by modifying NF-kappa B activation. (PMID:14764716)
• NEMO mutation with immunodeficiency is a combined immunodeficiency with early susceptibility to pyogenic bacteria and later susceptibility to mycobacteria; specific features of NEMO mutations provide insight into the role of NEMO in immune function (PMID:15100680)
• Ikappa kinase gamma-NFkappaB binds to CARMA1 and CARMA3 in B and T lymphocytes (PMID:15184390)
• Data show that the third cytoskeleton-associated protein-glycine conserved domain of CYLD specifically interacts with one of the two proline-rich sequences of NEMO/IKKgamma. (PMID:15341735)
• Mutation of the gene encoding NEMO can result in immunodeficiency without ectodermal dysplasia (PMID:15356572)
• Data show that specific NEMO mutations impair CD40-mediated c-Rel activation and B cell terminal differentiation. (PMID:15578091)
• FIP-3 and Rab11 protein complex regulates recycling endosomes targeting to the cleavage furrow during late cytokinesis. (PMID:15601896)
• Incontinentia pigmenti in most cases were caused by NEMO Delta 4-10 deletion in NEMO gene. (PMID:15833158)
• findings suggest that CYLD serves as a novel target of IKK and that the site-specific phosphorylation of CYLD regulates its signaling function (PMID:15870263)
• FIP3 and FIP4 serve to couple Rab11-positive vesicle traffic from recycling endosomes to the cleavage furrow/midbody where they are tethered prior to fusion events via interactions with Arf6 and the Exocyst. (PMID:16148947)
• Point mutation in NEMO leads anhidrotic ectodermal dysplasia with immunodeficiency in relation to the NEMO-dependent mechanism of IKK activation. (PMID:16379012)
• results show that ATM phosphorylates Ser85 of NEMO in response to genotoxic stress & that this is required for ubiquitination of NEMO; this modification is essential for nuclear export of NEMO & ATM & their interaction with IKK in the cytoplasm (PMID:16497931)
• Longer NBD-containing peptides of IKK-2 may be required to give the NBD an appropriate conformation for recognition by NEMO and/or to provide for additional interactions with NEMO. (PMID:16583354)
• Differing levels of IKKgamma-delta expression, therefore, may affect signal transduction cascades coupling to IKK (PMID:16611882)
• ABIN-1 physically links A20 to NEMO/IKKgamma and facilitates A20-mediated de-ubiquitination of NEMO/IKKgamma, thus resulting in inhibition of NF-kappaB (PMID:16684768)
• TLR8-mediated MEKK3-dependent IKKgamma phosphorylation might play an important role in the activation of IKK complex, leading to IkappaBalpha phosphorylation (PMID:16737960)
• mutations in the zinc finger domain of NEMO can lead to pathway specific defects in NEMO ubiquitination and thus immune deficiency (PMID:16794254)
• PIASy is the first SUMO ligase for NEMO whose substrate specificity seems to be controlled by IKK interaction, subcellular targeting and oxidative stress conditions. (PMID:16906147)
• The amino terminus of NEMO contains important functional domains that not only mediate interaction with I-kappa B kinases (IKKs) but also regulate IKK activation by promoting oligomerization of NEMO. (PMID:17000764)
• Malignant cells in high-risk myeloid dysplastic syndome and acute myeloid leukemia cells critically depend on IKKgamma/NEMO to survive. (PMID:17043643)
• IKK-gamma is essential for ubiquitin-dependent subcellular relocalization of the IKK complex in Jurkat Tax-expressing T cells. (PMID:17145747)
• IL1 induced NF-kappaB activation is NEMO-dependent but does not require IKKbeta (PMID:17244613)
• protein phosphatase 2a recruitment to I-kappaB kinase gamma/NF-kappaB essential modulator is regulated by heptad repeats, which are targeted by HTLV-I tax (PMID:17314097)
• identification of a common exons 4-10 deletion of NEMO in a Japanese family with incontinentia pigmenti (PMID:17401323)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	ikbkg	ENSDARG00000017037
mus_musculus	Ikbkg	ENSMUSG00000004221
rattus_norvegicus	Ikbkg	ENSRNOG00000060936

Paralogs (1): OPTN (ENSG00000123240)

Protein

Protein identifiers

NF-kappa-B essential modulator — Q9Y6K9 (reviewed: Q9Y6K9)

Alternative names: FIP-3, IkB kinase-associated protein 1, Inhibitor of nuclear factor kappa-B kinase subunit gamma, NF-kappa-B essential modifier

All UniProt accessions (15): A0A087WUW6, A0A087WWQ9, A0A087X0G7, A0A087X1B1, A0A087X1K7, A0A8I5KQX1, A0A8I5KQX5, A0A8I5KRU9, A0A8I5KYQ7, C9J2V2, C9JCG6, C9JH59, C9JN51, D3DWY0, Q9Y6K9

UniProt curated annotations — full annotation on UniProt →

Function. Regulatory subunit of the IKK core complex which phosphorylates inhibitors of NF-kappa-B thus leading to the dissociation of the inhibitor/NF-kappa-B complex and ultimately the degradation of the inhibitor. Its binding to scaffolding polyubiquitin plays a key role in IKK activation by multiple signaling receptor pathways. Can recognize and bind both ‘Lys-63’-linked and linear polyubiquitin upon cell stimulation, with a much higher affinity for linear polyubiquitin. Could be implicated in NF-kappa-B-mediated protection from cytokine toxicity. Essential for viral activation of IRF3. Involved in TLR3- and IFIH1-mediated antiviral innate response; this function requires ‘Lys-27’-linked polyubiquitination. (Microbial infection) Also considered to be a mediator for HTLV-1 Tax oncoprotein activation of NF-kappa-B.

Subunit / interactions. Homodimer; disulfide-linked. Component of the I-kappa-B-kinase (IKK) core complex consisting of CHUK, IKBKB and IKBKG; probably four alpha/CHUK-beta/IKBKB dimers are associated with four gamma/IKBKG subunits. The IKK core complex seems to associate with regulatory or adapter proteins to form a IKK-signalosome holo-complex. The IKK complex associates with TERF2IP/RAP1, leading to promote IKK-mediated phosphorylation of RELA/p65. Part of a complex composed of NCOA2, NCOA3, CHUK/IKKA, IKBKB, IKBKG and CREBBP. Interacts with COPS3, CYLD, NALP2, TRPC4AP and PIDD1. Interacts with ATM; the complex is exported from the nucleus. Interacts with TRAF6. Interacts with IKBKE. Interacts with TANK; the interaction is enhanced by IKBKE and TBK1. Part of a ternary complex consisting of TANK, IKBKB and IKBKG. Interacts with ZFAND5. Interacts with RIPK2. Interacts with TNIP1 and TNFAIP3; TNIP1 facilitates the TNFAIP3-mediated de-ubiquitination of IKBKG. Interacts with TNFAIP3; the interaction is induced by TNF stimulation and by polyubiquitin. Binds (via UBAN region) polyubiquitin; binds both ‘Lys-63’-linked and linear polyubiquitin, with higher affinity for linear ubiquitin. Interacts with NLRP10. Interacts with TANK; this interaction increases in response to DNA damage. Interacts with USP10; this interaction increases in response to DNA damage. Interacts with ZC3H12A; this interaction increases in response to DNA damage. Interacts with IFIT5; the interaction synergizes the recruitment of IKK to MAP3K7 and enhances IKK phosphorylation. Interacts with TRIM29; this interaction induces IKBKG/NEMO ubiquitination and proteolytic degradation. Interacts with TRIM13; this interaction leads to IKBKG/NEMO ubiquitination. Interacts with ARFIP2. Interacts with RIPK1. Interacts with (ubiquitinated) BCL10; interaction with polyubiquitinated BCL10 via both ‘Lys-63’-linked and linear ubiquitin is required for TCR-induced NF-kappa-B activation. Interacts with MARCHF2; during the late stages of macrophage viral and bacterial infection; the interaction leads to ubiquitination and degradation of IKBKG/NEMO. (Microbial infection) Interacts with Molluscum contagiosum virus protein MC005; this interaction inhibits NF-kappa-B activation. (Microbial infection) Interacts with HTLV-1 Tax oncoprotein; the interaction activates IKBKG. (Microbial infection) Interacts with Shigella flexneri ipah9.8; the interaction promotes TNIP1-dependent ‘Lys-27’-linked polyubiquitination of IKBKG which perturbs NF-kappa-B activation during bacterial infection. (Microbial infection) Interacts with SARS coronavirus-2/SARS-CoV-2 virus protein ORF9B (via N-terminus); the interaction inhibits polyubiquitination through ‘Lys-63’ and NF-kappa-B activation.

Subcellular location. Cytoplasm. Nucleus.

Tissue specificity. Heart, brain, placenta, lung, liver, skeletal muscle, kidney and pancreas.

Post-translational modifications. Phosphorylation at Ser-68 attenuates aminoterminal homodimerization. Polyubiquitinated on Lys-285 via ‘Lys-63’-linked ubiquitin; the ubiquitination is mediated downstream of NOD2 and RIPK2 and probably plays a role in signaling by facilitating interactions with ubiquitin domain-containing proteins and activates the NF-kappa-B pathway. Polyubiquitinated on Lys-285 and Lys-399 through ‘Lys-63’-linked ubiquitin; the ubiquitination is mediated by BCL10, MALT1 and TRAF6 and probably plays a role in signaling by facilitating interactions with ubiquitin domain-containing proteins and activates the NF-kappa-B pathway. Monoubiquitinated on Lys-277 and Lys-309; promotes nuclear export. Polyubiquitinated through ‘Lys-27’ by TRIM23; involved in antiviral innate and inflammatory responses. Linear polyubiquitinated on Lys-111, Lys-143, Lys-226, Lys-246, Lys-264, Lys-277, Lys-285, Lys-292, Lys-302, Lys-309 and Lys-326; the head-to-tail polyubiquitination is mediated by the LUBAC complex and plays a key role in NF-kappa-B activation. Deubiquitinated by USP10 in a TANK-dependent and -independent manner, leading to the negative regulation of NF-kappa-B signaling upon DNA damage. Ubiquitinated at Lys-326 by MARCHF2 following bacterial and viral infection which leads to its degradation. Polyubiquitinated via ‘Lys-29’-linked ubiquitin; leading to lysosomal degradation. Sumoylated on Lys-277 and Lys-309 with SUMO1; the modification results in phosphorylation of Ser-85 by ATM leading to a replacement of the sumoylation by mono-ubiquitination on these residues. Neddylated by TRIM40, resulting in stabilization of NFKBIA and down-regulation of NF-kappa-B activity. (Microbial infection) Cleaved by hepatitis A virus (HAV) protease 3C allowing the virus to disrupt the host innate immune signaling. (Microbial infection) Deubiquitinated by Epstein-Barr virus BPLF1 on both ‘Lys-48’ and ‘Lys-63’-linked ubiquitin chains; leading to NF-kappa-B signaling inhibition. (Microbial infection) Polyubiquitinated on Lys-309 and Lys-321 via ‘Lys-27’-linked ubiquitin by Shigella flexneri E3 ubiquitin-protein ligase ipah9.8, leading to its degradation by the proteasome. (Microbial infection) Polyubiquitination through ‘Lys-63’ is interrupted by interaction with SARS coronavirus-2/SARS-CoV-2 virus protein ORF9B which inhibits the NF-kappa-B pathway.

Disease relevance. Ectodermal dysplasia and immunodeficiency 1 (EDAID1) [MIM:300291] A form of ectoderma dysplasia, a heterogeneous group of disorders due to abnormal development of two or more ectodermal structures. EDAID1 is an X-linked recessive disorder characterized by absence of sweat glands, sparse scalp hair, rare conical teeth and immunological abnormalities resulting in severe infectious diseases. Severely affected individuals may also show lymphedema, osteopetrosis, and, rarely, hematologic abnormalities. The phenotype is highly variable, and may be fatal in childhood. The disease is caused by variants affecting the gene represented in this entry. Immunodeficiency 33 (IMD33) [MIM:300636] An X-linked recessive disorder characterized by variably impaired immunologic function and early-onset recurrent infections, usually due to pneumococcus, H.influenzae, and atypical mycobacteria. Features of hypohidrotic ectodermal dysplasia are generally not present, although some patients may have conical teeth or hypodontia. Disease susceptibility is associated with variants affecting the gene represented in this entry. Incontinentia pigmenti (IP) [MIM:308300] A genodermatosis usually prenatally lethal in males. In affected females, it causes abnormalities of the skin, hair, eyes, nails, teeth, skeleton, heart, and central nervous system. The prominent skin signs occur in four classic cutaneous stages: perinatal inflammatory vesicles, verrucous patches, a distinctive pattern of hyperpigmentation and dermal scarring. The disease is caused by variants affecting the gene represented in this entry. Autoinflammatory disease, systemic, X-linked (SAIDX) [MIM:301081] An X-linked disorder characterized by systemic autoinflammation appearing in the first months of life. Clinical manifestations are variable, including lymphadenopathy, hepatosplenomegaly, fever, panniculitis, and nodular skin rash. Additional features may include inflammation of the optic nerve, intracranial hemorrhage, and lipodystrophy. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. The leucine-zipper domain and the CCHC NOA-type zinc-fingers constitute the UBAN region and are essential for polyubiquitin binding and for the activation of IRF3.

Isoforms (3)

UniProt ID	Names	Canonical?
Q9Y6K9-1	1	yes
Q9Y6K9-2	2
Q9Y6K9-3	3

RefSeq proteins (10): NP_001093326, NP_001093327, NP_001138727, NP_001308325, NP_001308326, NP_001364241, NP_001364242, NP_001364243, NP_001364244, NP_003630 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR021063	NEMO_N	Domain
IPR032419	CC2-LZ_dom	Domain
IPR034735	NEMO_ZF	Domain
IPR051301	Optineurin/NFkB_EssMod	Family

Pfam: PF11577, PF16516, PF18414

UniProt features (117 total): mutagenesis site 35, sequence variant 24, cross-link 18, region of interest 9, helix 6, modified residue 6, binding site 4, splice variant 3, sequence conflict 2, turn 2, strand 2, disulfide bond 2, chain 1, zinc finger region 1, coiled-coil region 1, compositionally biased region 1

Structure

Experimental structures (PDB)

17 structures.

PDB	Method	Resolution (Å)
8U7C	X-RAY DIFFRACTION	1.44
6MI3	X-RAY DIFFRACTION	1.78
7T2U	X-RAY DIFFRACTION	2.1
3BRV	X-RAY DIFFRACTION	2.2
3BRT	X-RAY DIFFRACTION	2.25
4BWN	X-RAY DIFFRACTION	2.27
6MI4	X-RAY DIFFRACTION	2.5
6XX0	X-RAY DIFFRACTION	2.6
3CL3	X-RAY DIFFRACTION	3.2
3FX0	X-RAY DIFFRACTION	3.2
6YEK	X-RAY DIFFRACTION	3.2
9AZJ	X-RAY DIFFRACTION	3.32
5LDE	X-RAY DIFFRACTION	3.38
7TV4	X-RAY DIFFRACTION	4.2
2JVX	SOLUTION NMR
2JVY	SOLUTION NMR
5AAY	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9Y6K9-F1	82.75	0.63

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (4): 397; 400; 413; 417

Post-translational modifications (24): 31, 43, 68, 85, 376, 387, 111, 139, 143, 226, 246, 264, 277, 277, 283, 285, 292, 302, 309, 309 …

Disulfide bonds (2): 54, 347

Mutagenesis-validated functional residues (35):

Position	Phenotype
344	no effect on march2f-mediated k48-linked ubiquitination.
358	no effect on march2f-mediated k48-linked ubiquitination.
399	abolishes bcl10-mediated but not ripk2-mediated ubiquitination. important decrease in the ubiquitination level; when ass
414	abolishes binding to polyubiquitin.
415	impairs binding to polyubiquitin.
68	increases formation of homodimers.
68	abolishes interaction with ikbkb; abolishes tnf induced nf-kappa-b activity.
85	decreases ubiquitination and abolishes nuclear export.
115	no change in the ubiquitination level; when associated with r-399.
224	no change in the ubiquitination level; when associated with r-399.
277	partial abolition of sumoylation. abolishes sumoylation and ikk activation; when associated with a-309.
285	decreased ability to activate nf-kappa-b. important decrease in the ubiquitination level; when associated with r-399.
296	no effet on oligomerization,impairs binding of ’lys-63’-linked ubiuitin and linear tetra-ubiquitin, impairs tnf-induced
300	greatly impairs tandem ubiquitin binding.
301	impairs tandem ubiquitin binding.
302	no effect on march2f-mediated k48-linked ubiquitination.
304	complete loss of cleavage by hav protease 3c.
304	impairs tandem ubiquitin binding.
307	greatly impairs tandem ubiquitin binding.
308	greatly impairs tandem ubiquitin binding.
309	partial abolition of sumoylation. abolishes sumoylation and ikk activation; when associated with a-277. no effect on mar
312	greatly impairs tandem ubiquitin binding,impairs oligomerization, impairs tnf-induced nf-kappa-b activation.
312	mno effet on oligomerization, preferentially binds tri-ubiquitin chains (’lys-48’ or ’lys-63’-linked).
312	impairs tandem ubiquitin binding.
313	impairs tandem ubiquitin binding.

Function

Pathways and Gene Ontology

Reactome pathways

88 pathways

ID	Pathway
R-HSA-1169091	Activation of NF-kappaB in B cells
R-HSA-1236974	ER-Phagosome pathway
R-HSA-168638	NOD1/2 Signaling Pathway
R-HSA-168927	TICAM1, RIP1-mediated IKK complex recruitment
R-HSA-1810476	RIP-mediated NFkB activation via ZBP1
R-HSA-202424	Downstream TCR signaling
R-HSA-2871837	FCERI mediated NF-kB activation
R-HSA-445989	TAK1-dependent IKK and NF-kappa-B activation
R-HSA-450302	activated TAK1 mediates p38 MAPK activation
R-HSA-450321	JNK (c-Jun kinases) phosphorylation and activation mediated by activated human TAK1
R-HSA-4755510	SUMOylation of immune response proteins
R-HSA-5357905	Regulation of TNFR1 signaling
R-HSA-5357956	TNFR1-induced NF-kappa-B signaling pathway
R-HSA-5602636	IKBKB deficiency causes SCID
R-HSA-5603027	IKBKG deficiency causes anhidrotic ectodermal dysplasia with immunodeficiency (EDA-ID) (via TLR)
R-HSA-5603029	IkBA variant leads to EDA-ID
R-HSA-5607764	CLEC7A (Dectin-1) signaling
R-HSA-5684264	MAP3K8 (TPL2)-dependent MAPK1/3 activation
R-HSA-5689880	Ub-specific processing proteases
R-HSA-5689896	Ovarian tumor domain proteases
R-HSA-9020702	Interleukin-1 signaling
R-HSA-933542	TRAF6 mediated NF-kB activation
R-HSA-933543	NF-kB activation through FADD/RIP-1 pathway mediated by caspase-8 and -10
R-HSA-937039	IRAK1 recruits IKK complex
R-HSA-937041	IKK complex recruitment mediated by RIP1
R-HSA-9705671	SARS-CoV-2 activates/modulates innate and adaptive immune responses
R-HSA-975144	IRAK1 recruits IKK complex upon TLR7/8 or 9 stimulation
R-HSA-9758274	Regulation of NF-kappa B signaling
R-HSA-9833482	PKR-mediated signaling
R-HSA-9860276	SLC15A4:TASL-dependent IRF5 activation

MSigDB gene sets: 727 (showing top): PID_BCR_5PATHWAY, REACTOME_DDX58_IFIH1_MEDIATED_INDUCTION_OF_INTERFERON_ALPHA_BETA, REACTOME_IKK_COMPLEX_RECRUITMENT_MEDIATED_BY_RIP1, MORF_RAGE, GOBP_REGULATION_OF_T_CELL_RECEPTOR_SIGNALING_PATHWAY, GOBP_NEGATIVE_REGULATION_OF_RESPONSE_TO_ENDOPLASMIC_RETICULUM_STRESS, BIOCARTA_TNFR2_PATHWAY, GOBP_REGULATION_OF_ANTIGEN_RECEPTOR_MEDIATED_SIGNALING_PATHWAY, BIOCARTA_RELA_PATHWAY, MODULE_52, GOBP_REGULATION_OF_AUTOPHAGY, REACTOME_INNATE_IMMUNE_SYSTEM, GOBP_B_CELL_HOMEOSTASIS, KEGG_ADIPOCYTOKINE_SIGNALING_PATHWAY, GOBP_VESICLE_LOCALIZATION

GO Biological Process (23): B cell homeostasis (GO:0001782), apoptotic process (GO:0006915), inflammatory response (GO:0006954), immune response (GO:0006955), DNA damage response (GO:0006974), canonical NF-kappaB signal transduction (GO:0007249), response to virus (GO:0009615), positive regulation of gene expression (GO:0010628), positive regulation of macroautophagy (GO:0016239), defense response to bacterium (GO:0042742), positive regulation of canonical NF-kappaB signal transduction (GO:0043123), negative regulation of canonical NF-kappaB signal transduction (GO:0043124), anoikis (GO:0043276), innate immune response (GO:0045087), positive regulation of transcription by RNA polymerase II (GO:0045944), T cell receptor signaling pathway (GO:0050852), positive regulation of T cell receptor signaling pathway (GO:0050862), obsolete positive regulation of NF-kappaB transcription factor activity (GO:0051092), establishment of vesicle localization (GO:0051650), protein-containing complex assembly (GO:0065003), negative regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway (GO:1902236), positive regulation of ubiquitin-dependent protein catabolic process (GO:2000060), regulation of transcription by RNA polymerase II (GO:0006357)

GO Molecular Function (14): zinc ion binding (GO:0008270), protein domain specific binding (GO:0019904), polyubiquitin modification-dependent protein binding (GO:0031593), ubiquitin protein ligase binding (GO:0031625), signaling adaptor activity (GO:0035591), identical protein binding (GO:0042802), protein homodimerization activity (GO:0042803), protein heterodimerization activity (GO:0046982), K63-linked polyubiquitin modification-dependent protein binding (GO:0070530), linear polyubiquitin binding (GO:1990450), transferrin receptor binding (GO:1990459), protein binding (GO:0005515), kinase activity (GO:0016301), metal ion binding (GO:0046872)

GO Cellular Component (9): ubiquitin ligase complex (GO:0000151), spindle pole (GO:0000922), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), cytosol (GO:0005829), IkappaB kinase complex (GO:0008385), protein-containing complex (GO:0032991), mitotic spindle (GO:0072686)

Reactome top-level categories

Rollup of top-18 pathways:

Category	Pathways
MAP kinase activation	3
Diseases associated with the TLR signaling cascade	3
Toll Like Receptor 3 (TLR3) Cascade	2
Interleukin-1 signaling	2
TNF signaling	2
Deubiquitination	2
Downstream signaling events of B Cell Receptor (BCR)	1
Antigen processing-Cross presentation	1
Nucleotide-binding domain, leucine rich repeat containing receptor (NLR) signaling pathways	1
ZBP1(DAI) mediated induction of type I IFNs	1
TCR signaling	1
Fc epsilon receptor (FCERI) signaling	1
MyD88:MAL(TIRAP) cascade initiated on plasma membrane	1
TRIF (TICAM1)-mediated TLR4 signaling	1
TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
defense response	2
canonical NF-kappaB signal transduction	2
regulation of canonical NF-kappaB signal transduction	2
protein binding	2
protein dimerization activity	2
spindle	2
lymphocyte homeostasis	1
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
immune system process	1
response to stimulus	1
cellular response to stress	1
intracellular signaling cassette	1
response to other organism	1
gene expression	1
regulation of gene expression	1
positive regulation of macromolecule biosynthetic process	1
positive regulation of autophagy	1
macroautophagy	1
regulation of macroautophagy	1
response to bacterium	1
positive regulation of intracellular signal transduction	1
negative regulation of intracellular signal transduction	1
apoptotic process	1
immune response	1
defense response to symbiont	1
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
positive regulation of DNA-templated transcription	1
antigen receptor-mediated signaling pathway	1
T cell receptor signaling pathway	1
regulation of T cell receptor signaling pathway	1
positive regulation of antigen receptor-mediated signaling pathway	1
vesicle localization	1
establishment of localization in cell	1
establishment of organelle localization	1
cellular component assembly	1
protein-containing complex organization	1

Protein interactions and networks

STRING

3164 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
IKBKG	CHUK	O15111	999
IKBKG	IKBKB	O14920	999
IKBKG	TRAF6	Q9Y4K3	997
IKBKG	RIPK1	Q13546	994
IKBKG	CYLD	Q9NQC7	992
IKBKG	IKBKE	Q14164	992
IKBKG	RAB11A	P24410	991
IKBKG	TANK	Q92844	990
IKBKG	ERC1	Q8IUD2	984
IKBKG	TAB2	Q9NYJ8	984
IKBKG	BCL10	O95999	981
IKBKG	ASAP1	Q9ULH1	970
IKBKG	CARD11	Q9BXL7	960
IKBKG	TRAF2	Q12933	958
IKBKG	NFKB1	P19838	953

IntAct

658 interactions, top by confidence:

A	B	Type	Score
IKBKG	IKBKB	psi-mi:“MI:0914”(association)	0.980
IKBKG	IKBKB	psi-mi:“MI:0407”(direct interaction)	0.980
IKBKG	IKBKB	psi-mi:“MI:0915”(physical association)	0.980
IKBKB	IKBKG	psi-mi:“MI:0915”(physical association)	0.980
CHUK	IKBKG	psi-mi:“MI:0915”(physical association)	0.980
IKBKB	CHUK	psi-mi:“MI:0914”(association)	0.960
SHARPIN	RNF31	psi-mi:“MI:0914”(association)	0.960
CHUK	IKBKB	psi-mi:“MI:0915”(physical association)	0.960
CHUK	IKBKB	psi-mi:“MI:0914”(association)	0.960
MAP3K14	CHUK	psi-mi:“MI:0914”(association)	0.950
RBCK1	IKBKG	psi-mi:“MI:0915”(physical association)	0.900
IKBKG	RBCK1	psi-mi:“MI:0914”(association)	0.900
IKBKG	RBCK1	psi-mi:“MI:0915”(physical association)	0.900
IKBKG	RIPK1	psi-mi:“MI:0914”(association)	0.890
RIPK1	IKBKG	psi-mi:“MI:0915”(physical association)	0.890
IKBKG	IKBKG	psi-mi:“MI:0407”(direct interaction)	0.880
IKBKG	IKBKG	psi-mi:“MI:0915”(physical association)	0.880
CDC37	IKBKB	psi-mi:“MI:0914”(association)	0.850
IKBKG		psi-mi:“MI:0915”(physical association)	0.830

BioGRID (1159): IKBKG (Affinity Capture-Western), IKBKG (Affinity Capture-Western), NFKBIA (Biochemical Activity), RELA (Biochemical Activity), IKBKG (Co-purification), IKBKG (Affinity Capture-Western), TRIM13 (Affinity Capture-Western), ATM (Affinity Capture-Western), PIAS4 (Affinity Capture-Western), UBC (Reconstituted Complex), IKBKG (Biochemical Activity), CHUK (Affinity Capture-Western), IKBKB (Affinity Capture-Western), IKBKB (Affinity Capture-Western), IKBKG (Two-hybrid)

ESM2 similar proteins: A0A140LIT1, A0A1B0GVG4, A0JNH6, A1A5D9, A6NC98, A6NGB0, A6NJZ7, A6NNM3, F6XLV1, O15049, O54887, P0C7N4, P58660, P60531, Q0D2H9, Q0P5D1, Q2KJ21, Q2TAC2, Q3LUD3, Q3T1I3, Q3TMW1, Q3V0F0, Q4QRL3, Q5JTB6, Q5RD60, Q66HR5, Q6NSJ2, Q6PHN1, Q6QZQ4, Q80VM7, Q8BP01, Q8C7U1, Q8CB62, Q8CGU1, Q8CHW5, Q8K2I2, Q8N137, Q8N283, Q8N6Y0, Q8R370

Diamond homologs: A9QT41, O88522, Q5M7B7, Q5R923, Q5RI56, Q6TMG5, Q7YS99, Q861Q8, Q8R5M4, Q90Z16, Q95KA2, Q95KU9, Q96CV9, Q9Y6K9, Q8K3K8

SIGNOR signaling

34 interactions.

A	Effect	B	Mechanism
IKBKG	“up-regulates activity”	RELA	phosphorylation
ATM	“down-regulates activity”	IKBKG	phosphorylation
RIPK1	“up-regulates activity”	IKBKG	binding
IKBKB	unknown	IKBKG	phosphorylation
IKBKB	“down-regulates activity”	IKBKG	phosphorylation
BCL10	up-regulates	IKBKG	binding
MAP3K7	“up-regulates activity”	IKBKG	binding
IKBKG	“up-regulates activity”	IKBKB	binding
IKK-complex	“down-regulates activity”	IKBKG	phosphorylation
IKK-complex	unknown	IKBKG	phosphorylation
IKBKG	up-regulates	NfKb-p65/p50	phosphorylation
IKBKG	“form complex”	IKK-complex	binding
RIPK2	“up-regulates activity”	IKBKG
EGLN3	“down-regulates activity”	IKBKG	binding
BPLF1	“down-regulates activity”	IKBKG	deubiquitination
RNF31	“up-regulates activity”	IKBKG	polyubiquitination
RUSC1	“up-regulates quantity by stabilization”	IKBKG
IKBKG	“up-regulates activity”	BCL10	ubiquitination
FGR	“down-regulates activity”	IKBKG	phosphorylation
LYN	“down-regulates activity”	IKBKG	phosphorylation
SRC	“down-regulates activity”	IKBKG	phosphorylation
FYN	“down-regulates activity”	IKBKG	phosphorylation
GSK3B	“down-regulates quantity”	IKBKG	phosphorylation
hsamir7085p	“down-regulates quantity by repression”	IKBKG	“post transcriptional regulation”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 109 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
TNFR1-induced NF-kappa-B signaling pathway	10	39.1×	2e-11
RIP-mediated NFkB activation via ZBP1	5	39.1×	5e-06
TNFR1-induced proapoptotic signaling	7	35.8×	1e-07
Regulation of necroptotic cell death	6	30.6×	2e-06
TNF signaling	6	29.5×	2e-06
RIPK1-mediated regulated necrosis	5	26.6×	3e-05
Regulation of TNFR1 signaling	10	26.0×	1e-09
Eukaryotic Translation Elongation	7	22.7×	1e-06

GO biological processes:

GO term	Partners	Fold	FDR
non-canonical NF-kappaB signal transduction	6	53.2×	3e-07
negative regulation of necroptotic process	5	52.2×	4e-06
canonical NF-kappaB signal transduction	12	46.3×	1e-14
protein refolding	5	32.9×	3e-05
tumor necrosis factor-mediated signaling pathway	7	24.4×	2e-06
cellular response to heat	5	18.1×	5e-04
negative regulation of canonical NF-kappaB signal transduction	9	16.3×	8e-07
obsolete positive regulation of NF-kappaB transcription factor activity	7	15.1×	3e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	54
Likely pathogenic	20
Uncertain significance	45
Likely benign	18
Benign	9

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
11447	NC_000023.11:g.(154556377_154558531)(154565046?)del	Pathogenic
11448	NM_001099857.5(IKBKG):c.1110dup (p.Ala371fs)	Pathogenic
11450	NM_001099857.5(IKBKG):c.1259A>G (p.Ter420Trp)	Pathogenic
11451	NM_001099857.5(IKBKG):c.120_129dup (p.Glu44fs)	Pathogenic
11452	NM_001099857.5(IKBKG):c.184C>T (p.Arg62Ter)	Pathogenic
11453	NM_001099857.5(IKBKG):c.1171G>T (p.Glu391Ter)	Pathogenic
11454	NM_001099857.5(IKBKG):c.1249T>C (p.Cys417Arg)	Pathogenic
11456	NM_001099857.5(IKBKG):c.1250G>T (p.Cys417Phe)	Pathogenic
11458	NM_001099857.5(IKBKG):c.1166_1178dup (p.Asp394fs)	Pathogenic
11459	NG_009896.1:g.19984_24446dup	Pathogenic
11460	NM_001099857.5(IKBKG):c.458T>G (p.Leu153Arg)	Pathogenic
11461	NM_001099857.5(IKBKG):c.1207C>T (p.Gln403Ter)	Pathogenic
11463	NM_001099857.5(IKBKG):c.1049dup (p.Ala351fs)	Pathogenic
11464	NM_001099857.5(IKBKG):c.1056-1G>A	Pathogenic
11465	NM_001099857.5(IKBKG):c.111dup (p.Met38fs)	Pathogenic
11466	NM_001099857.5(IKBKG):c.863C>G (p.Ala288Gly)	Pathogenic
11468	NM_001099857.5(IKBKG):c.956G>A (p.Arg319Gln)	Pathogenic
11469	NM_001099857.5(IKBKG):c.517C>G (p.Arg173Gly)	Pathogenic
1220510	NM_001099857.5(IKBKG):c.1167del (p.Glu390fs)	Pathogenic
1684047	NM_001099857.5(IKBKG):c.519-19_519-2del	Pathogenic
1687109	NM_001099857.5(IKBKG):c.519-2A>G	Pathogenic
1687111	NM_001099857.5(IKBKG):c.671+2T>G	Pathogenic
1687112	NM_001099857.5(IKBKG):c.671+5G>A	Pathogenic
2663721	NM_001099857.5(IKBKG):c.1116del (p.Ala373fs)	Pathogenic
3109022	NM_001099857.5(IKBKG):c.187+1G>A	Pathogenic
3242266	NM_001099857.5(IKBKG):c.373del (p.Val125fs)	Pathogenic
3340352	NM_001099857.5(IKBKG):c.256C>T (p.Gln86Ter)	Pathogenic
3381371	NM_001099857.5(IKBKG):c.518+2T>G	Pathogenic
372385	NM_001099857.5(IKBKG):c.672-2A>G	Pathogenic
372387	NM_001099857.5(IKBKG):c.1167dup (p.Glu390fs)	Pathogenic

SpliceAI

2539 predictions. Top by Δscore:

Variant	Effect	Δscore
X:154546028:ATACT:A	donor_loss	1.0000
X:154546030:ACTC:A	donor_loss	1.0000
X:154546032:TCA:T	donor_loss	1.0000
X:154546033:CA:C	donor_loss	1.0000
X:154546034:A:AC	donor_gain	1.0000
X:154546034:ACCGA:A	donor_loss	1.0000
X:154546035:C:CG	donor_gain	1.0000
X:154546035:CCG:C	donor_gain	1.0000
X:154546035:CCGA:C	donor_gain	1.0000
X:154546160:CTGT:C	acceptor_gain	1.0000
X:154551987:GCCC:G	acceptor_gain	1.0000
X:154551987:GCCCT:G	acceptor_gain	1.0000
X:154552187:GAGGT:G	donor_loss	1.0000
X:154552188:AGG:A	donor_loss	1.0000
X:154552189:GGTGA:G	donor_loss	1.0000
X:154552190:GTGAG:G	donor_loss	1.0000
X:154552191:T:A	donor_loss	1.0000
X:154552196:A:T	donor_gain	1.0000
X:154556347:G:GT	donor_gain	1.0000
X:154556347:G:T	donor_gain	1.0000
X:154558628:G:GT	donor_gain	1.0000
X:154560402:GCCAG:G	acceptor_loss	1.0000
X:154560404:CAG:C	acceptor_loss	1.0000
X:154560405:A:AG	acceptor_gain	1.0000
X:154560405:AG:A	acceptor_gain	1.0000
X:154560405:AGG:A	acceptor_gain	1.0000
X:154560406:G:A	acceptor_gain	1.0000
X:154560406:G:GA	acceptor_gain	1.0000
X:154560406:GGG:G	acceptor_gain	1.0000
X:154560555:GAGAA:G	donor_gain	1.0000

AlphaMissense

2770 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:154564390:T:C	C397R	1.000
X:154563559:G:C	A305P	0.999
X:154563580:T:C	F312L	0.999
X:154563581:T:C	F312S	0.999
X:154563582:C:A	F312L	0.999
X:154563582:C:G	F312L	0.999
X:154563602:G:C	R319P	0.999
X:154564392:T:G	C397W	0.999
X:154564399:T:A	C400S	0.999
X:154564399:T:C	C400R	0.999
X:154564400:G:C	C400S	0.999
X:154564430:T:C	L410P	0.999
X:154564436:T:C	I412T	0.999
X:154564438:C:G	H413D	0.999
X:154564442:T:A	V414D	0.999
X:154564450:T:A	C417S	0.999
X:154564450:T:C	C417R	0.999
X:154564451:G:C	C417S	0.999
X:154561726:T:C	L237P	0.998
X:154562892:T:C	L284P	0.998
X:154562943:T:C	L301P	0.998
X:154563598:G:C	A318P	0.998
X:154564390:T:A	C397S	0.998
X:154564391:G:A	C397Y	0.998
X:154564391:G:C	C397S	0.998
X:154564401:C:G	C400W	0.998
X:154564423:G:C	D408H	0.998
X:154564430:T:A	L410Q	0.998
X:154564436:T:A	I412K	0.998
X:154564438:C:A	H413N	0.998

dbSNP variants (sampled 300 via entrez): RS1000020544 (X:154550384 C>T), RS1000053124 (X:154550888 G>A), RS1000300912 (X:154542862 G>A), RS1000781286 (X:154544389 T>A), RS1000907549 (X:154544711 A>G), RS1001035466 (X:154552243 C>A,T), RS1001466603 (X:154552688 T>G), RS1001576945 (X:154541190 G>C), RS1001700933 (X:154548452 C>T), RS1001726961 (X:154548896 A>G), RS1002529060 (X:154552774 G>A), RS1002633724 (X:154553394 G>A), RS1003012327 (X:154553001 C>T), RS1003376621 (X:154546505 G>A,T), RS1003607884 (X:154555009 G>T)

Disease associations

OMIM: gene MIM:300248 | disease phenotypes: MIM:308300, MIM:300291, MIM:300584, MIM:300636, MIM:301081, MIM:302060, MIM:607594

GenCC curated gene-disease

Disease	Classification	Inheritance
incontinentia pigmenti	Definitive	X-linked
ectodermal dysplasia and immunodeficiency 1	Definitive	X-linked
IKBKG-related immunodeficiency with or without ectodermal dysplasia	Strong	X-linked
autoinflammatory disease, X-linked	Strong	X-linked
immunodeficiency 33	Supportive	X-linked
anhidrotic ectodermal dysplasia-immunodeficiency-osteopetrosis-lymphedema syndrome	Supportive	X-linked
ectodermal dysplasia and immune deficiency	Supportive	Autosomal dominant

ClinGen Gene-Disease Validity (2)

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

Disease	Classification	Inheritance
incontinentia pigmenti	Definitive	XL
IKBKG-related immunodeficiency with or without ectodermal dysplasia	Definitive	XL

Mondo (9): incontinentia pigmenti (MONDO:0010631), ectodermal dysplasia and immunodeficiency 1 (MONDO:0020740), immunodeficiency 33 (MONDO:0010386), autoinflammatory disease, X-linked (MONDO:0800129), Barth syndrome (MONDO:0010543), common variable immunodeficiency (MONDO:0015517), anhidrotic ectodermal dysplasia-immunodeficiency-osteopetrosis-lymphedema syndrome (MONDO:0010295), ectodermal dysplasia and immune deficiency (MONDO:0010293), IKBKG-related immunodeficiency with or without ectodermal dysplasia (MONDO:0100162)

Orphanet (8): Incontinentia pigmenti (Orphanet:464), Hypohidrotic ectodermal dysplasia (Orphanet:238468), Hypohidrotic ectodermal dysplasia with immunodeficiency (Orphanet:98813), X-linked mendelian susceptibility to mycobacterial diseases (Orphanet:319605), OBSOLETE: X-linked mendelian susceptibility to mycobacterial diseases due to IKBKG deficiency (Orphanet:319612), NEMO deleted exon 5 autoinflammatory syndrome (Orphanet:699605), Barth syndrome (Orphanet:111), OBSOLETE: Common variable immunodeficiency (Orphanet:1572)

HPO phenotypes

150 total (30 of 150 shown, HPO-id order):

HPO	Term
HP:0000202	Orofacial cleft
HP:0000252	Microcephaly
HP:0000364	Hearing abnormality
HP:0000403	Recurrent otitis media
HP:0000486	Strabismus
HP:0000491	Keratitis
HP:0000505	Visual impairment
HP:0000518	Cataract
HP:0000532	Abnormal chorioretinal morphology
HP:0000541	Retinal detachment
HP:0000554	Uveitis
HP:0000568	Microphthalmia
HP:0000573	Retinal hemorrhage
HP:0000592	Blue sclerae
HP:0000648	Optic atrophy
HP:0000668	Hypodontia
HP:0000677	Oligodontia
HP:0000682	Abnormal dental enamel morphology
HP:0000684	Delayed eruption of teeth
HP:0000698	Conical tooth
HP:0000938	Osteopenia
HP:0000962	Hyperkeratosis
HP:0000964	Eczematoid dermatitis
HP:0000966	Hypohidrosis
HP:0000968	Ectodermal dysplasia
HP:0000975	Hyperhidrosis
HP:0000980	Pallor
HP:0000988	Skin rash
HP:0001000	Abnormality of skin pigmentation
HP:0001004	Lymphedema

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST003122_2	Hemoglobin levels	3.000000e-11

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004509	hemoglobin measurement
EFO:0007629	hemoglobin A1 measurement

MeSH disease descriptors (6)

Descriptor	Name	Tree numbers
D056889	Barth Syndrome	C14.240.400.172; C14.280.400.172; C16.131.077.121; C16.131.240.400.172; C16.320.322.068; C16.320.565.398.224; C18.452.584.563.224; C18.452.648.398.224
D017074	Common Variable Immunodeficiency	C20.673.330
D007184	Incontinentia Pigmenti	C16.131.077.445; C16.131.831.580; C16.320.850.420; C17.800.621.497; C17.800.804.580; C17.800.827.420
C564538	Ectodermal Dysplasia, Anhidrotic, with Immunodeficiency, Osteopetrosis, and Lymphedema (supp.)
C536181	Ectodermal dysplasia, hypohidrotic, with immune deficiency (supp.)
C536289	Immunodeficiency without anhidrotic ectodermal dysplasia (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL2111328 (PROTEIN COMPLEX), CHEMBL4967 (SINGLE PROTEIN)

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

PharmGKB clinical annotations

1 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs1050828	Toxicity	3	artesunate;primaquine;pyrimethamine;sulfadoxine

PharmGKB variants

3 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs1050828	G6PD, IKBKG	3	5.50	13	amodiaquine;pyrimethamine;sulfadoxine;artesunate;primaquine;pyrimethamine;sulfadoxine;artesunate;chlorproguanil;dapsone
rs5030868	G6PD, IKBKG	3	0.25	8	glyburide
rs137852340	G6PD, IKBKG		0.00	0

ChEMBL bioactivities

55 potent at pChembl≥5 of 61 total, top 46 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.52	IC50	30	nM	CHEMBL382945
7.40	IC50	40	nM	CHEMBL199837
7.40	IC50	40	nM	CHEMBL200106
7.30	IC50	50	nM	CHEMBL371543
7.16	IC50	70	nM	CHEMBL200027
7.10	IC50	80	nM	CHEMBL200229
7.10	Kd	80	nM	CHEMBL5180326
7.00	IC50	100	nM	CHEMBL200462
6.82	IC50	150	nM	CHEMBL372736
6.72	Kd	190	nM	CHEMBL5171411
6.70	IC50	200	nM	CHEMBL381041
6.70	IC50	200	nM	CHEMBL200106
6.60	IC50	250	nM	CHEMBL199980
6.52	IC50	300	nM	CHEMBL200832
6.52	IC50	300	nM	CHEMBL200229
6.52	IC50	300	nM	CHEMBL200027
6.40	IC50	400	nM	CHEMBL200462
6.40	IC50	400	nM	CHEMBL200229
6.35	IC50	450	nM	CHEMBL371543
6.30	IC50	500	nM	CHEMBL371967
6.30	IC50	500	nM	CHEMBL371543
6.30	IC50	500	nM	CHEMBL200027
6.30	IC50	500	nM	CHEMBL200832
6.30	IC50	500	nM	CHEMBL200462
6.22	IC50	600	nM	CHEMBL371543
6.22	IC50	600	nM	CHEMBL200462
6.10	IC50	800	nM	CHEMBL372160
6.00	IC50	1000	nM	CHEMBL200462
6.00	IC50	1000	nM	CHEMBL200027
5.70	IC50	2000	nM	CHEMBL371543
5.70	IC50	2000	nM	CHEMBL200106
5.70	IC50	2000	nM	CHEMBL200229
5.70	IC50	2000	nM	CHEMBL382752
5.66	IC50	2200	nM	CHEMBL1800969
5.56	IC50	2755	nM	BMS-345541
5.55	IC50	2800	nM	CHEMBL1800965
5.51	IC50	3091	nM	BMS-345541
5.48	IC50	3342	nM	BMS-345541
5.40	IC50	3982	nM	BMS-345541
5.37	IC50	4267	nM	BMS-345541
5.36	IC50	4400	nM	CHEMBL370166
5.34	IC50	4572	nM	BMS-345541
5.30	EC50	5000	nM	CHEMBL79004
5.30	IC50	5000	nM	CHEMBL200832
5.30	IC50	5000	nM	CHEMBL1800999
5.07	IC50	8500	nM	CHEMBL382752

PubChem BioAssay actives

55 with measured affinity, of 92 total; 22 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
[4-[[4-[5-(3-amino-3-ethylpentyl)thiophen-2-yl]pyrimidin-2-yl]amino]phenyl]-(4-pyrrolidin-1-ylpiperidin-1-yl)methanone	258074: Inhibitory activity against IKK complex isolated from HeLa cells	ic50	0.0300	uM
[4-[[4-[5-(3-amino-3-methylbutyl)thiophen-2-yl]pyrimidin-2-yl]amino]phenyl]-(4-pyrrolidin-1-ylpiperidin-1-yl)methanone	258074: Inhibitory activity against IKK complex isolated from HeLa cells	ic50	0.0400	uM
[4-[[4-[5-(4-hydroxybutyl)thiophen-2-yl]pyrimidin-2-yl]amino]phenyl]-(4-pyrrolidin-1-ylpiperidin-1-yl)methanone	258074: Inhibitory activity against IKK complex isolated from HeLa cells	ic50	0.0400	uM
[4-[[4-[5-(3-hydroxy-3-methylbutyl)thiophen-2-yl]pyrimidin-2-yl]amino]phenyl]-(4-pyrrolidin-1-ylpiperidin-1-yl)methanone	258074: Inhibitory activity against IKK complex isolated from HeLa cells	ic50	0.0500	uM
[4-[[4-(1-benzothiophen-2-yl)pyrimidin-2-yl]amino]phenyl]-(4-pyrrolidin-1-ylpiperidin-1-yl)methanone	258074: Inhibitory activity against IKK complex isolated from HeLa cells	ic50	0.0700	uM
(2R,3S,3aR,6R,7R,7aR)-1’-methyl-3,6-bis(4-methylphenyl)-7-nitro-2’-oxospiro[1,3,3a,6,7,7a-hexahydroindene-2,3’-indole]-5-carbaldehyde	1845728: Binding affinity to full-length human NEMO (1 to 419 residues) assessed as dissociation constant	kd	0.0800	uM
[4-[[4-(1-benzothiophen-2-yl)pyrimidin-2-yl]amino]phenyl]-[4-(dimethylamino)piperidin-1-yl]methanone	258074: Inhibitory activity against IKK complex isolated from HeLa cells	ic50	0.0800	uM
[4-[[4-[5-(3-methoxypropyl)thiophen-2-yl]pyrimidin-2-yl]amino]phenyl]-(4-pyrrolidin-1-ylpiperidin-1-yl)methanone	258074: Inhibitory activity against IKK complex isolated from HeLa cells	ic50	0.1000	uM
[4-[[4-(1-benzothiophen-2-yl)pyrimidin-2-yl]amino]-2-methoxyphenyl]-(4-pyrrolidin-1-ylpiperidin-1-yl)methanone	258074: Inhibitory activity against IKK complex isolated from HeLa cells	ic50	0.1500	uM
(2S,3S,3aR,6R,7R,7aR)-1’-methyl-3,6-bis(4-methylphenyl)-7-nitro-2’-oxospiro[1,3,3a,6,7,7a-hexahydroindene-2,3’-indole]-5-carbaldehyde	1845728: Binding affinity to full-length human NEMO (1 to 419 residues) assessed as dissociation constant	kd	0.1900	uM
[4-[[4-[5-(3-amino-3-methylbut-1-ynyl)thiophen-2-yl]pyrimidin-2-yl]amino]phenyl]-(4-pyrrolidin-1-ylpiperidin-1-yl)methanone	258074: Inhibitory activity against IKK complex isolated from HeLa cells	ic50	0.2000	uM
[4-[[4-(1-benzothiophen-2-yl)pyrimidin-2-yl]amino]-2-chlorophenyl]-(4-pyrrolidin-1-ylpiperidin-1-yl)methanone	258074: Inhibitory activity against IKK complex isolated from HeLa cells	ic50	0.2500	uM
4-[[4-(1-benzothiophen-2-yl)pyrimidin-2-yl]amino]-N-[2-(dimethylamino)ethyl]benzamide	258074: Inhibitory activity against IKK complex isolated from HeLa cells	ic50	0.3000	uM
4-[[4-(1-benzothiophen-2-yl)pyrimidin-2-yl]amino]-N-(2-pyrrolidin-1-ylethyl)benzamide	258074: Inhibitory activity against IKK complex isolated from HeLa cells	ic50	0.5000	uM
N-[2-methyl-4-[5-[2-[4-(4-pyrrolidin-1-ylpiperidine-1-carbonyl)anilino]pyrimidin-4-yl]thiophen-2-yl]butan-2-yl]acetamide	258074: Inhibitory activity against IKK complex isolated from HeLa cells	ic50	0.8000	uM
[4-[[4-(1-benzothiophen-2-yl)pyrimidin-2-yl]amino]phenyl]-pyrrolidin-1-ylmethanone	258076: Inhibition of TNF-alpha-stimulated expression of E-selectin in HUVEC cells	ic50	2.0000	uM
(1E,6E)-1,7-bis(3,4-dimethoxyphenyl)-4-[(4-fluorophenyl)methylidene]hepta-1,6-diene-3,5-dione	604786: Inhibition of IKK in human A549 cells assessed as inhibition of TNF-alpha-induced IkappaB phosphorylation preincubated for 30 mins before TNFalpha challenge	ic50	2.2000	uM
N’-(1,8-dimethylimidazo[1,2-a]quinoxalin-4-yl)ethane-1,2-diamine	2197127: Inhibition of IKK in human U-266 cells assessed as reduction of cell growth incubated for 72 hrs by CellTiter 96 aqueous one solution cell proliferation assay	ic50	2.7552	uM
(1E,6E)-1,7-bis(3,4-dimethoxyphenyl)-4-[(4-hydroxy-3-methoxyphenyl)methylidene]hepta-1,6-diene-3,5-dione	604786: Inhibition of IKK in human A549 cells assessed as inhibition of TNF-alpha-induced IkappaB phosphorylation preincubated for 30 mins before TNFalpha challenge	ic50	2.8000	uM
N-(2-aminoethyl)-4-[[4-(1-benzothiophen-2-yl)pyrimidin-2-yl]amino]benzamide	258074: Inhibitory activity against IKK complex isolated from HeLa cells	ic50	4.4000	uM
(1E,6E)-4-[(2,3-dimethoxyphenyl)methylidene]-1,7-bis(4-hydroxy-3-methoxyphenyl)hepta-1,6-diene-3,5-dione	604786: Inhibition of IKK in human A549 cells assessed as inhibition of TNF-alpha-induced IkappaB phosphorylation preincubated for 30 mins before TNFalpha challenge	ic50	5.0000	uM
N-(6-chloro-9H-pyrido[3,4-b]indol-8-yl)pyridine-3-carboxamide	86828: Inhibition of GST-IkB phosphorylation by TNF-alpha stimulated HeLa cell lysate (IP-IKKgamma)	ec50	5.0000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases expression	3
Resveratrol	increases expression, decreases expression, decreases phosphorylation, decreases reaction	3
Air Pollutants	affects expression, increases expression, affects cotreatment, increases abundance, increases oxidation	3
Benzo(a)pyrene	affects methylation, increases expression, increases methylation	3
Cadmium Chloride	increases abundance, increases expression	3
cupric chloride	increases expression	2
Vorinostat	decreases activity, increases reaction, affects cotreatment, decreases expression	2
Doxorubicin	affects reaction, increases phosphorylation, affects response to substance	2
Ozone	affects cotreatment, increases oxidation, increases abundance, affects expression	2
Valproic Acid	decreases expression, increases methylation	2
aristolochic acid I	increases expression	1
1-hydroxyalantolactone	increases ubiquitination, decreases reaction	1
FR900359	increases phosphorylation	1
bisphenol F	increases expression	1
moringin	affects cotreatment, decreases expression	1
2-anisidine	affects expression	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
bisphenol A	affects expression	1
lead acetate	increases expression	1
2,2’-methylenebis(4-methyl-6-tert-butylphenol)	affects expression, affects response to substance	1
beta-lapachone	increases expression	1
sulforaphane	increases expression	1
salvin	affects reaction, increases ubiquitination	1
potassium chromate(VI)	decreases expression, affects cotreatment	1
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
JHW 015	increases phosphorylation, decreases reaction	1
1,1-dimethylbutyl-1-deoxy-Delta(9)-THC	decreases reaction, increases phosphorylation	1
N-(oxo-5,6-dihydrophenanthridin-2-yl)-N,N-dimethylacetamide hydrochloride	affects cotreatment, increases reaction, affects reaction, increases phosphorylation, affects localization (+2 more)	1
capsiate	affects cotreatment, decreases reaction, increases activity	1

ChEMBL screening assays

38 unique, capped per target: 30 binding, 8 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1805652	Binding	Inhibition of IKK in human A549 cells assessed as inhibition of TNF-alpha-induced IkappaB phosphorylation preincubated for 30 mins before TNFalpha challenge	Synthesis and identification of new 4-arylidene curcumin analogues as potential anticancer agents targeting nuclear factor-κB signaling pathway. — J Med Chem
CHEMBL3369239	Functional	Inhibition of IKKbeta expression in human THP1 cells at 20 to 100 uM by Western blotting method	Pyrano-isochromanones as IL-6 inhibitors: synthesis, in vitro and in vivo antiarthritic activity. — J Med Chem

Cellosaurus cell lines

11 cell lines: 5 cancer cell line, 3 transformed cell line, 2 embryonic stem cell, 1 induced pluripotent stem cell

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_A824	CHB-13	Embryonic stem cell	Male
CVCL_A825	CHB-14	Embryonic stem cell	Female
CVCL_B2Z9	Abcam HEK293T IKBKG KO	Transformed cell line	Female
CVCL_D7GM	Ubigene HEK293T IKBKG KO	Transformed cell line	Female
CVCL_D7RY	Ubigene A-549 IKBKG KO	Cancer cell line	Male
CVCL_D8MZ	Ubigene HCT 116 IKBKG KO	Cancer cell line	Male
CVCL_D9GX	Ubigene HEK293 IKBKG KO	Transformed cell line	Female
CVCL_E0ET	Ubigene HeLa IKBKG KO	Cancer cell line	Female
CVCL_SS40	HAP1 IKBKG (-) 1	Cancer cell line	Male
CVCL_SS41	HAP1 IKBKG (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT07531251	PHASE4	NOT_YET_RECRUITING	Clinical Trial in Patients With Barth Syndrome- 4TAZPower
NCT00520494	PHASE4	COMPLETED	Efficacy and Safety of Vivaglobin® in Previously Untreated Patients With Primary Immunodeficiency
NCT01289847	PHASE4	COMPLETED	A Study to Find Out How Safe and Effective Gammaplex® is in Young People With Primary Immunodeficiency
NCT01946906	PHASE4	COMPLETED	The Rifaximin Study in CVID
NCT05193552	PHASE4	RECRUITING	Usage of Spirometry in Managing IgG Therapy in CVID With Airway Disease
NCT00168012	PHASE3	COMPLETED	Efficacy and Safety of Intravenous Immunoglobulin IVIG-F10 in Patients With Primary Immunodeficiencies (PID)
NCT00168025	PHASE3	COMPLETED	Efficacy and Safety of Intravenous Immunoglobulin IgPro10 in Patients With Primary Immunodeficiencies (PID)
NCT00220766	PHASE3	COMPLETED	Rapid Infusion of Immune Globulin Intravenous (Human) In Primary Immunodeficiency Patients
NCT00322556	PHASE3	COMPLETED	Safety and Efficacy of Intravenous Immunoglobulin IgPro10 in Patients With Primary Immunodeficiencies (PID)
NCT00542997	PHASE3	COMPLETED	Study of Subcutaneous Immune Globulin in Patients Requiring IgG Replacement Therapy
NCT01884311	PHASE3	COMPLETED	Pharmacokinetics (PK) and Safety of Subgam-VF in Primary Immunodeficiency Diseases
NCT01963143	PHASE3	COMPLETED	Bioequivalence Study to Evaluate the Pharmacokinetics, Safety, and Tolerability of Gammaplex® 10 and Gammaplex® 5% in Primary Immunodeficiency Diseases
NCT02247141	PHASE3	COMPLETED	A Multi-centre Open Study to Assess the Safety and Efficacy of Subgam®
NCT01489618	PHASE2	TERMINATED	Prime Boost Vaccination Strategy Combining Conjugated Anti- Pneumococcal Vaccine (s0) and Polysaccharide Anti- Pneumococcal Vaccine (s4) Compared to Polysaccharide Anti- Pneumococcal Vaccine Alone (s4) In Patients With Common Variable Immunodeficiency
NCT01821781	PHASE2	ACTIVE_NOT_RECRUITING	Immune Disorder HSCT Protocol
NCT02579967	PHASE2	RECRUITING	Pilot Trial of Allogeneic Blood or Marrow Transplantation for Primary Immunodeficiencies
NCT03663933	PHASE2	ACTIVE_NOT_RECRUITING	Allogeneic Hematopoietic Cell Transplantation for Disorders of T-cell Proliferation and/or Dysregulation
NCT04339777	PHASE2	RECRUITING	Allogeneic Hematopoietic Stem Cell Transplant for Patients With Inborn Errors of Immunity
NCT04925375	PHASE2	RECRUITING	Abatacept for the Treatment of Common Variable Immunodeficiency With Interstitial Lung Disease
NCT05593588	PHASE2	ENROLLING_BY_INVITATION	Senolytics Treatment of Interstitial Lung Disease in Common Variable Immunodeficiency
NCT06897358	PHASE2	ACTIVE_NOT_RECRUITING	Leniolisib for Immune Dysregulation in CVID
NCT07284641	PHASE2	RECRUITING	Hematopoietic Stem Cell Transplantation (HSCT) for Common Variable Immunodeficiency (CVID) and Other Autoimmune Manifestations of Primary Immune Regulatory Disorders (PIRD)
NCT00263237	PHASE1	COMPLETED	STA-5326 Meslylate to Treat Gut Inflammation Associated With Common Variable Immunodeficiency
NCT00976586	Not specified	COMPLETED	Role of Pseudogene in Incontinentia Pigmenti, and Its Potential Treatment
NCT05954416	Not specified	RECRUITING	FARD (RaDiCo Cohort) (RaDiCo-FARD)
NCT03815357	Not specified	COMPLETED	What is the Incidence of an Immune Disorder in Children With Invasive Pneumococcal Disease (IPD)?
NCT03098797	PHASE2/PHASE3	COMPLETED	A Trial to Evaluate Safety, Tolerability and Efficacy of Elamipretide in Subjects With Barth Syndrome
NCT01194141	Not specified	COMPLETED	Exercise Training in Barth Syndrome
NCT01461304	Not specified	NO_LONGER_AVAILABLE	Compassionate Use of Triheptanoin (C7) for Inherited Disorders of Energy Metabolism
NCT01625663	Not specified	COMPLETED	Heart and Muscle Metabolism in Barth Syndrome
NCT01629459	Not specified	COMPLETED	Resistance Exercise in Barth Syndrome
NCT03655223	Not specified	ENROLLING_BY_INVITATION	Early Check: Expanded Screening in Newborns
NCT04689360	Not specified	AVAILABLE	An Intermediate Size Expanded Access Protocol of Elamipretide
NCT05554835	Not specified	RECRUITING	Global Registry and Natural History Study for Mitochondrial Disorders
NCT01852370	PHASE1/PHASE2	ENROLLING_BY_INVITATION	Sequential Cadaveric Lung and Bone Marrow Transplant for Immune Deficiency Diseases
NCT03513328	PHASE1/PHASE2	COMPLETED	Conditioning Regimen for Allogeneic Hematopoietic Stem-Cell Transplantation
NCT00004695	Not specified	COMPLETED	Randomized Study of Polyethylene-Glycol-Conjugated Interleukin 2 in Patients With Common Variable Immunodeficiency
NCT00006054	Not specified	TERMINATED	Allogeneic Bone Marrow Transplantation in Patients With Primary Immunodeficiencies
NCT00015431	Not specified	COMPLETED	Immune System and Gut Abnormalities in Patients With Common Variable Immunodeficiency With and Without Gastrointestinal Symptoms
NCT00661401	Not specified	COMPLETED	Specific IgG Antibody in Patients With Primary Antibody Deficiencies Treated With Subcutaneous Immunoglobulin