AKAP4

Summary

AKAP4 (A-kinase anchoring protein 4, HGNC:374) is a protein-coding gene on chromosome Xp11.22, encoding A-kinase anchor protein 4 (Q5JQC9). Major structural component of sperm fibrous sheath.

The A-kinase anchor proteins (AKAPs) are a group of structurally diverse proteins, which have the common function of binding to the regulatory subunit of protein kinase A (PKA) and confining the holoenzyme to discrete locations within the cell. This gene encodes a member of the AKAP family. The encoded protein is localized to the sperm flagellum and may be involved in the regulation of sperm motility. Alternative splicing of this gene results in two transcript variants encoding different isoforms.

Source: NCBI Gene 8852 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 127 total — 25 pathogenic
• MANE Select transcript: NM_003886

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:374
Approved symbol	AKAP4
Name	A-kinase anchoring protein 4
Location	Xp11.22
Locus type	gene with protein product
Status	Approved
Aliases	p82, hAKAP82, AKAP82, Fsc1, HI, CT99
Ensembl gene	ENSG00000147081
Ensembl biotype	protein_coding
OMIM	300185
Entrez	8852

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 4 protein_coding, 2 protein_coding_CDS_not_defined

ENST00000358526, ENST00000376064, ENST00000437370, ENST00000448865, ENST00000480926, ENST00000481402

RefSeq mRNA: 2 — MANE Select: NM_003886 NM_003886, NM_139289

CCDS: CCDS14329, CCDS14330

Canonical transcript exons

ENST00000358526 — 6 exons

Exon	Start	End
ENSE00001317300	50192304	50194436
ENSE00003467784	50190777	50191115
ENSE00003494301	50200863	50201007
ENSE00003591544	50197544	50197594
ENSE00003667038	50196891	50196992
ENSE00003759971	50198657	50198752

Expression profiles

Bgee: expression breadth broad, 62 present calls, max score 98.98.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.3772 / max 309.0183, expressed in 25 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
199281	0.2825	17
199282	0.0607	5
199283	0.0293	9
199284	0.0048	2

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sperm	CL:0000019	98.98	gold quality
male germ cell	CL:0000015	97.94	gold quality
left testis	UBERON:0004533	97.86	gold quality
right testis	UBERON:0004534	97.74	gold quality
testis	UBERON:0000473	94.73	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	89.22	gold quality
adult organism	UBERON:0007023	87.55	gold quality
parotid gland	UBERON:0001831	70.10	gold quality
olfactory bulb	UBERON:0002264	69.74	gold quality
type B pancreatic cell	CL:0000169	68.03	gold quality
myocardium	UBERON:0002349	67.46	gold quality
diaphragm	UBERON:0001103	67.02	gold quality
vena cava	UBERON:0004087	66.29	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	65.42	gold quality
inferior olivary complex	UBERON:0002127	65.37	gold quality
thymus	UBERON:0002370	64.84	gold quality
buccal mucosa cell	CL:0002336	64.79	silver quality
medulla oblongata	UBERON:0001896	64.54	gold quality
pharyngeal mucosa	UBERON:0000355	64.37	gold quality
subthalamic nucleus	UBERON:0001906	64.35	gold quality
dorsal plus ventral thalamus	UBERON:0001897	64.26	gold quality
cerebellar vermis	UBERON:0004720	64.24	gold quality
saphenous vein	UBERON:0007318	64.13	gold quality
substantia nigra pars reticulata	UBERON:0001966	64.05	gold quality
pericardium	UBERON:0002407	64.05	gold quality
inferior vagus X ganglion	UBERON:0005363	64.05	gold quality
ventral tegmental area	UBERON:0002691	63.95	gold quality
body of tongue	UBERON:0011876	63.92	gold quality
cardiac muscle of right atrium	UBERON:0003379	63.90	gold quality
cardia of stomach	UBERON:0001162	63.81	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-GEOD-134144	yes	31.83
E-ANND-3	yes	3.61

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): GLI2

miRNA regulators (miRDB)

18 targeting AKAP4, 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-4795-3P	100.00	74.62	4024
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-6513-3P	99.59	69.77	1102
HSA-MIR-4489	99.50	65.56	785
HSA-MIR-4505	99.27	67.81	2678
HSA-MIR-223-5P	99.24	68.82	1206
HSA-MIR-5787	99.22	67.86	2628
HSA-MIR-4426	99.17	66.74	1949
HSA-MIR-328-5P	99.08	64.65	1000
HSA-MIR-143-5P	98.98	68.87	946
HSA-MIR-6846-5P	98.81	65.86	1121
HSA-MIR-6848-5P	98.81	65.49	1126
HSA-MIR-6885-5P	98.71	64.33	902
HSA-MIR-767-3P	98.61	67.69	1192
HSA-MIR-193A-3P	98.59	66.36	769
HSA-MIR-193B-3P	98.59	66.62	748

Literature-anchored findings (GeneRIF, showing 21)

• AKAP4 is a novel target for protein S-nitrosylation in spermatozoa. (PMID:17683036)
• Role of AKAP4 in sperm motility is unclear, vut absent or weak AKAP4-labelling is associated with absent or weak sperm. motility. (PMID:17712481)
• We demonstrate the aberrant expression of AKAP-4 in prostate cancer, which will potentially be developed as a biomarker in prostate cancer. (PMID:21520158)
• data suggests that AKAP4 may be used as serum based diagnostic test for an early detection and diagnosis of breast cancer and may be a potential target for immunotherapeutic use (PMID:23451156)
• The putative role of AKAP4 in early tumorigenesis is implicated as a biomarker and immunotherapeutic target for cervical cancer. (PMID:23478221)
• Ablation of AKAP4 protein caused significant inhibition in cellular proliferation, colony-forming ability, migration and invasion ability of tumor cells. (PMID:23764900)
• SP17/AKAP4/PTTG1 are expressed in both human NSCLC cell lines and primary tumors and can elicit an immunogenic response in lung cancer patients. (PMID:25739119)
• AKAP4 is a highly accurate biomarker for the detection of early stage lung cancer. (PMID:26160834)
• AKAP4 appears to be a novel Colorectal cancer-associated antigen with a potential for developing as a new clinical therapeutic target (PMID:26590805)
• the physiological role of the negative crosstalk between the cAMP/PKA/AKAP4 and the PKC/ERK1/2 pathways is to regulate capacitation and acrosome reaction. (PMID:27901058)
• AKAP4 role in the proliferation and metastasis of thyroid cancer.AKAP4 is highly expressed in thyroid cancer. (PMID:27983916)
• A significant association was found between AKAP4 gene expression and metastasis (P-value: 0.045), expression of the CTAG1B (NY-ESO-1) gene was not observed in our cases. (PMID:29480665)
• High AKAP4 expression is associated with reduced sperm motility. (PMID:29581387)
• pro-AKAP4 protein in the fibrous sheath of human ejaculated spermatozoa and in elongating/elongated spermatids in the human testis. In normozoospermia, there were high interindividual variations in pro-AKAP4 levels, and these latter were associated with sperm motility. (PMID:29984477)
• Knockdown of AKAP4 inhibits hypoxia-induced epithelial-mesenchymal transition in human gastric cancer cells, at least in part, via inactivation of the Wnt/beta-catenin signaling pathway. (PMID:30145836)
• This study showed the role of Lactobacilli in down-regulation of TSGA10, AURKC, OIP5 and AKAP4 genes. Such expression change might be involved in the anticancer effects of these Lactobacilli. The underlying mechanisms of these observations are not clear but epigenetic modulatory mechanisms may participate in this process. (PMID:30545223)
• A-kinase anchor protein 4 downregulation inhibits various malignant properties and enhances the cytotoxic effect of paclitaxel, and this combinatorial approach could be useful for triple-negative breast cancer treatment. (PMID:32342732)
• A new hemizygous missense mutation, c.454TC (p.S152P), in AKAP4 gene is associated with asthenozoospermia. (PMID:34409659)
• Loss-of-function missense variant of AKAP4 induced male infertility through reduced interaction with QRICH2 during sperm flagella development. (PMID:34415320)
• Silencing of A-kinase anchor protein 4 inhibits the metastasis and growth of non-small cell lung cancer. (PMID:35253625)
• Identification of CD8(+) T-cell epitope from multiple myeloma-specific antigen AKAP4. (PMID:35967402)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Akap4	ENSMUSG00000050089
rattus_norvegicus	Akap4	ENSRNOG00000002921

Paralogs (3): AKAP11 (ENSG00000023516), AKAP3 (ENSG00000111254), SPHKAP (ENSG00000153820)

Protein

Protein identifiers

A-kinase anchor protein 4 — Q5JQC9 (reviewed: Q5JQC9)

Alternative names: A-kinase anchor protein 82 kDa, Major sperm fibrous sheath protein, Protein kinase A-anchoring protein 4

All UniProt accessions (4): Q5JQC9, A0A075B6Q6, A0A075B6R4, A0A384MQY7

UniProt curated annotations — full annotation on UniProt →

Function. Major structural component of sperm fibrous sheath. Plays a role in sperm motility.

Subunit / interactions. Interacts with PRKAR1A and PRKAR2A. Interacts with ENO4. Interacts with QRICH2.

Subcellular location. Cell projection. Cilium. Flagellum.

Tissue specificity. Testis specific; only expressed in round spermatids.

Post-translational modifications. Phosphorylated by STK33 during sperm flagella assembly.

Disease relevance. Spermatogenic failure. A male infertility disorder caused by spermatogenesis defects that result in non-obstructive azoospermia. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. RI-alpha binding site, predicted to form an amphipathic helix, could participate in protein-protein interactions with a complementary surface on the R-subunit dimer.

Similarity. Belongs to the AKAP110 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q5JQC9-1	1	yes
Q5JQC9-2	2

RefSeq proteins (2): NP_003877, NP_647450 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR008382	SPHK1-interactor_AKAP_110	Family
IPR018292	AKAP_110_C	Domain
IPR018459	RII-bd_1	Domain
IPR020799	AKAP_110	Family

Pfam: PF05716, PF10522

UniProt features (43 total): modified residue 23, sequence conflict 7, region of interest 4, sequence variant 4, compositionally biased region 2, propeptide 1, chain 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q5JQC9-F1	53.52	0.07

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 (23): 190, 213, 226, 272, 300, 303, 304, 307, 342, 432, 443, 445, 447, 450, 464, 492, 506, 536, 581, 627 …

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 90 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_MCMV_INFECTION_UP, GSE45365_NK_CELL_VS_CD8A_DC_MCMV_INFECTION_DN, GOBP_SINGLE_FERTILIZATION, MODULE_545, GOBP_MALE_GAMETE_GENERATION, GOBP_CILIUM_ORGANIZATION, GOBP_CILIUM_MOVEMENT, INGRAM_SHH_TARGETS_UP, GOBP_CILIUM_OR_FLAGELLUM_DEPENDENT_CELL_MOTILITY, GOBP_ORGANELLE_ASSEMBLY, TGACATY_UNKNOWN, GOBP_DEVELOPMENTAL_PROCESS_INVOLVED_IN_REPRODUCTION, GOBP_MOTILE_CILIUM_ASSEMBLY, GOBP_CELL_PROJECTION_ORGANIZATION, GOBP_FERTILIZATION

GO Biological Process (10): signal transduction (GO:0007165), cell surface receptor protein serine/threonine kinase signaling pathway (GO:0007178), spermatogenesis (GO:0007283), single fertilization (GO:0007338), intracellular protein localization (GO:0008104), flagellated sperm motility (GO:0030317), establishment of protein localization (GO:0045184), establishment of localization in cell (GO:0051649), sperm flagellum assembly (GO:0120316), cell projection organization (GO:0030030)

GO Molecular Function (3): protein kinase A binding (GO:0051018), protein binding (GO:0005515), kinase activity (GO:0016301)

GO Cellular Component (15): nucleus (GO:0005634), cytoplasm (GO:0005737), cytoskeleton (GO:0005856), cAMP-dependent protein kinase complex (GO:0005952), Z disc (GO:0030018), motile cilium (GO:0031514), sperm fibrous sheath (GO:0035686), sperm flagellum (GO:0036126), perinuclear region of cytoplasm (GO:0048471), sperm midpiece (GO:0097225), sperm principal piece (GO:0097228), sperm end piece (GO:0097229), sperm head-tail coupling apparatus (GO:0120212), cilium (GO:0005929), cell projection (GO:0042995)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	9
sperm flagellum	4
developmental process involved in reproduction	2
establishment of localization	2
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
enzyme-linked receptor protein signaling pathway	1
male gamete generation	1
fertilization	1
macromolecule localization	1
cilium-dependent cell motility	1
cilium movement involved in cell motility	1
sperm motility	1
cellular localization	1
spermatid development	1
flagellated sperm motility	1
motile cilium assembly	1
cellular component organization	1
protein binding	1
binding	1
transferase activity, transferring phosphorus-containing groups	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
intracellular membraneless organelle	1
intracellular protein-containing complex	1
serine/threonine protein kinase complex	1
I band	1
cilium	1
9+2 motile cilium	1
cytoplasm	1
intraciliary transport particle	1
membrane-bounded organelle	1
plasma membrane bounded cell projection	1

Protein interactions and networks

STRING

1130 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
AKAP4	PRKACA	P17612	920
AKAP4	PRKACG	P22612	920
AKAP4	PRKACB	P22694	920
AKAP4	DDX17	Q92841	899
AKAP4	AKAP1	Q92667	802
AKAP4	TSN	Q15631	801
AKAP4	CCNB3	Q8WWL7	774
AKAP4	FSIP1	Q8NA03	755
AKAP4	FSIP2	Q5CZC0	751
AKAP4	SPANXA1	Q9NS26	745
AKAP4	CABYR	O75952	738
AKAP4	DDX5	P17844	718
AKAP4	ROPN1	Q9HAT0	633
AKAP4	ODF1	Q14990	626
AKAP4	CFAP44	Q96MT7	611

IntAct

5 interactions, top by confidence:

A	B	Type	Score
PPP1CC	AKAP4	psi-mi:“MI:0915”(physical association)	0.600
PPP1CC	AKAP4	psi-mi:“MI:0403”(colocalization)	0.600
PPP1CC	YWHAQ	psi-mi:“MI:0914”(association)	0.350

BioGRID (14): FSIP1 (Two-hybrid), AKAP3 (Two-hybrid), PRKAR1A (Two-hybrid), AKAP4 (Reconstituted Complex), PRKAR1A (Two-hybrid), PRKAR1A (Reconstituted Complex), PRKAR2A (Reconstituted Complex), HIST1H2BC (Cross-Linking-MS (XL-MS)), HIST1H2BK (Cross-Linking-MS (XL-MS)), SND1 (Cross-Linking-MS (XL-MS)), HENMT1 (Cross-Linking-MS (XL-MS)), HSP90AA1 (Cross-Linking-MS (XL-MS)), HSP90AB1 (Cross-Linking-MS (XL-MS)), FSIP2 (Two-hybrid)

ESM2 similar proteins: A0A0R4I9Y1, A0A0R4IBK5, A0A140LFM6, A0A1L8GSA2, A0JMD2, A0JP82, A2AKX3, A2ARZ3, A2RUR9, A6NKB5, D3ZJ47, F5H4B4, F5HCM1, K9JHZ4, O35774, O36397, O60284, O75969, O77797, O88987, P13202, P79269, Q0P4S0, Q18LF6, Q1LV19, Q29131, Q32LN6, Q4KLZ4, Q4V7H1, Q5CZC0, Q5JQC9, Q60662, Q62770, Q62924, Q6AXY9, Q6ZPK7, Q7TD10, Q80TY4, Q810N5, Q811D2

Diamond homologs: O35774, O75969, O77797, O88987, P0C6C0, Q1LV19, Q2M3C7, Q5JQC9, Q60662, Q6NSW3, Q9UKA4, Q62924

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
MAPK1	unknown	AKAP4	phosphorylation
STK33	“up-regulates quantity by stabilization”	AKAP4	phosphorylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	25
Likely pathogenic	0
Uncertain significance	74
Likely benign	13
Benign	0

Top pathogenic / likely-pathogenic (25)

Variant ID	HGVS	Classification
1180517	GRCh37/hg19 Xp11.23-11.22(chrX:47179068-54424785)x2	Pathogenic
145622	GRCh38/hg38 Xp11.3-11.22(chrX:43361870-50931794)x3	Pathogenic
146524	GRCh38/hg38 Xp11.23-11.22(chrX:48022053-52664916)x3	Pathogenic
146707	GRCh38/hg38 Xp11.23-11.21(chrX:48344666-58055036)x3	Pathogenic
147668	GRCh38/hg38 Xp11.23-11.22(chrX:48260861-52664916)x2	Pathogenic
149047	GRCh38/hg38 Xp11.23-11.22(chrX:48429509-52664916)x3	Pathogenic
149048	GRCh38/hg38 Xp11.23-11.22(chrX:48429509-52664916)x1	Pathogenic
150316	GRCh38/hg38 Xp11.23-11.22(chrX:48386298-52664916)x2	Pathogenic
153506	GRCh38/hg38 Xp11.23-11.22(chrX:48953927-53273903)x2	Pathogenic
219032	GRCh37/hg19 Xp11.23-11.22(chrX:48310313-52614698)x1	Pathogenic
2425308	NC_000023.10:g.(?48368209)(51241672_?)del	Pathogenic
2425881	NC_000023.10:g.(?46466387)(50659607_?)del	Pathogenic
2445496	NC_000023.10:g.(?46466387)(51241672_?)del	Pathogenic
2684980	GRCh37/hg19 Xp11.23-11.22(chrX:48224455-52832596)x3	Pathogenic
2685708	GRCh37/hg19 Xp21.1-11.22(chrX:36355238-54106257)x1	Pathogenic
395162	GRCh37/hg19 Xp11.23-11.22(chrX:48317353-51497588)x2	Pathogenic
395163	GRCh37/hg19 Xp11.23-11.22(chrX:48317353-51497588)x3	Pathogenic
443184	GRCh37/hg19 Xp11.23-11.22(chrX:48224454-52813336)x3	Pathogenic
564842	GRCh37/hg19 Xp11.23-11.22(chrX:48156672-52672728)x1	Pathogenic
57921	GRCh38/hg38 Xp11.23-11.22(chrX:50086006-54030240)x1	Pathogenic
58241	GRCh38/hg38 Xp11.23-11.22(chrX:48344666-52664916)x2	Pathogenic
58615	GRCh38/hg38 Xp11.23-11.22(chrX:47859417-52789530)x3	Pathogenic
687087	GRCh37/hg19 Xp11.23-11.22(chrX:48224266-52744574)x2	Pathogenic
816349	GRCh37/hg19 Xp11.23-11.22(chrX:48307437-50657313)x3	Pathogenic
979778	GRCh37/hg19 Xp11.23-11.22(chrX:48178413-52686510)x2	Pathogenic

SpliceAI

523 predictions. Top by Δscore:

Variant	Effect	Δscore
X:50191111:GGAAG:G	acceptor_gain	1.0000
X:50191112:GAAG:G	acceptor_gain	1.0000
X:50191114:AG:A	acceptor_gain	1.0000
X:50191116:C:CC	acceptor_gain	1.0000
X:50192301:TA:T	donor_loss	1.0000
X:50196989:CATC:C	acceptor_gain	1.0000
X:50196991:TC:T	acceptor_gain	1.0000
X:50196991:TCCTA:T	acceptor_loss	1.0000
X:50196992:CC:C	acceptor_gain	1.0000
X:50198656:CCA:C	donor_gain	1.0000
X:50198662:T:A	donor_gain	1.0000
X:50198748:GACAT:G	acceptor_gain	1.0000
X:50198749:ACAT:A	acceptor_gain	1.0000
X:50198750:CAT:C	acceptor_gain	1.0000
X:50198750:CATC:C	acceptor_gain	1.0000
X:50198751:AT:A	acceptor_gain	1.0000
X:50198752:TC:T	acceptor_loss	1.0000
X:50198753:C:CC	acceptor_gain	1.0000
X:50198753:C:CG	acceptor_loss	1.0000
X:50198754:T:A	acceptor_loss	1.0000
X:50191113:AAG:A	acceptor_gain	0.9900
X:50191118:G:C	acceptor_gain	0.9900
X:50192302:A:AC	donor_gain	0.9900
X:50192302:AC:A	donor_gain	0.9900
X:50192303:C:CA	donor_gain	0.9900
X:50192303:CC:C	donor_gain	0.9900
X:50192303:CCTT:C	donor_gain	0.9900
X:50196988:GCATC:G	acceptor_gain	0.9900
X:50196989:CATCC:C	acceptor_gain	0.9900
X:50196990:ATC:A	acceptor_gain	0.9900

AlphaMissense

5715 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:50192375:A:G	W780R	0.998
X:50192375:A:T	W780R	0.998
X:50192431:A:T	V761D	0.996
X:50192334:G:C	F793L	0.995
X:50192334:G:T	F793L	0.995
X:50192336:A:G	F793L	0.995
X:50192365:G:T	A783D	0.995
X:50192366:C:G	A783P	0.994
X:50192373:C:A	W780C	0.994
X:50192373:C:G	W780C	0.994
X:50194339:A:G	F125S	0.994
X:50194360:A:G	L118P	0.994
X:50198734:A:G	W16R	0.994
X:50198734:A:T	W16R	0.994
X:50192363:A:G	S784P	0.993
X:50192380:A:G	L778P	0.992
X:50197586:A:C	F44L	0.992
X:50197586:A:T	F44L	0.992
X:50197588:A:G	F44L	0.992
X:50192335:A:G	F793S	0.991
X:50192341:A:T	L791H	0.991
X:50193082:A:G	L544P	0.991
X:50192341:A:G	L791P	0.990
X:50194338:G:C	F125L	0.990
X:50194338:G:T	F125L	0.990
X:50194340:A:G	F125L	0.990
X:50194413:G:C	F100L	0.990
X:50194413:G:T	F100L	0.990
X:50194415:A:G	F100L	0.990
X:50190976:A:G	L850P	0.989

dbSNP variants (sampled 300 via entrez): RS1000463576 (X:50195934 C>T), RS1000664603 (X:50197586 A>G), RS1000795227 (X:50198227 G>A), RS1002301673 (X:50190688 C>T), RS1002335411 (X:50199976 T>C), RS1002469790 (X:50200448 C>T), RS1002809337 (X:50202838 A>G), RS1003084331 (X:50202305 C>T), RS1006474270 (X:50201729 C>T), RS1007050229 (X:50191630 G>A), RS1007490759 (X:50191332 T>A,C), RS1009067514 (X:50196381 A>G), RS1009813329 (X:50198632 C>T), RS1011113723 (X:50200566 C>G), RS1011446574 (X:50202956 G>C,T)

Disease associations

OMIM: gene MIM:300185 | disease phenotypes: MIM:300491, MIM:300894, MIM:300896, MIM:304790

GenCC curated gene-disease

Mondo (4): epilepsy, X-linked 1, with variable learning disabilities and behavior disorders (MONDO:0010339), neurodegeneration with brain iron accumulation 5 (MONDO:0010476), SLC35A2-congenital disorder of glycosylation (MONDO:0010478), immune dysregulation-polyendocrinopathy-enteropathy-X-linked syndrome (MONDO:0010580)

Orphanet (4): Beta-propeller protein-associated neurodegeneration (Orphanet:329284), SLC35A2-CDG (Orphanet:356961), X-linked epilepsy-learning disabilities-behavior disorders syndrome (Orphanet:85294), Immune dysregulation-polyendocrinopathy-enteropathy-X-linked syndrome (Orphanet:37042)

HPO phenotypes

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

GWAS associations

0 associations (top):

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
C564505	Epilepsy, X-Linked, with Variable Learning Disabilities and Behavior Disorders (supp.)
C580192	Immune Dysregulation, Polyendocrinopathy, Enteropathy, X-Linked Syndrome (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

9 total (human), top 9 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
CGP 52608	affects binding, increases reaction	1
abrine	increases expression	1
Benzo(a)pyrene	decreases methylation	1
Cadmium	decreases expression, increases abundance	1
Formaldehyde	decreases expression	1
T-2 Toxin	increases expression	1
Valproic Acid	decreases methylation	1
Aflatoxin B1	decreases methylation	1
Cadmium Chloride	decreases expression, increases abundance	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT01821781	PHASE2	ACTIVE_NOT_RECRUITING	Immune Disorder HSCT Protocol
NCT01998633	PHASE2	COMPLETED	Reduced Intensity Conditioning for Hemophagocytic Syndromes or Selected Primary Immune Deficiencies (BMT CTN 1204)
NCT07284641	PHASE2	RECRUITING	Hematopoietic Stem Cell Transplantation (HSCT) for Common Variable Immunodeficiency (CVID) and Other Autoimmune Manifestations of Primary Immune Regulatory Disorders (PIRD)
NCT05241444	PHASE1	RECRUITING	CD4^LVFOXP3 in Participants With IPEX
NCT02699190	Not specified	COMPLETED	LeukoSEQ: Whole Genome Sequencing as a First-Line Diagnostic Tool for Leukodystrophies
NCT03047369	Not specified	RECRUITING	The Myelin Disorders Biorepository Project
NCT03572114	Not specified	UNKNOWN	Imaging Neuromelanin and Iron in Dystonia/Parkinsonism
NCT05522374	Not specified	RECRUITING	TIRCON International NBIA Registry
NCT06938542	Not specified	ENROLLING_BY_INVITATION	Palliative Care Needs of Children With Rare Diseases and Their Families
NCT04902807	Not specified	RECRUITING	Conception of a Diagnosis, Prognosis and Therapeutic Decision Tool for Patients With Autoimmunity and Inflammation